[
  {
    "reaction_id": "ord-1689e7993af44ed99334b50a757d688f",
    "procedure_text": "A solution of 25.0 g (144 mmol) of 2-amino-5-bromopyridine in 50 mL of acetic acid and 250 mL of acetic anhydride was heated at reflux for about 2 hours. The reaction mixture was then cooled and poured into 750 mL of water with stirring. After about 1 hour, the solution was adjusted to pH=10 with 50% sodium hydroxide solution and the precipitate was filtered, washed with water and dried to give 26.5 g of the title product as a white flaky solid, mp 175-176\u00b0 C. 1H nmr (deuteriochloroform): \u03b4=8.29 (d, 1 H); 8.12 (d, 1 H); 7.96 (br, 1 H); 7.78 (d of d, 1 H); 2.19 (s, 3 H). MS (El): m/z=214, 216 (M+, Br isotopes).",
    "reference_string": "{\"inputs\": {\"m1_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-amino-5-bromopyridine\"}], \"amount\": {\"mass\": {\"value\": 25.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic anhydride\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 750.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"with stirring\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"at reflux for about 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"The reaction mixture was then cooled\"}, {\"type\": \"FILTRATION\", \"details\": \"the precipitate was filtered\"}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 26.5, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c6ecb9d826ba4ea2aeb9f82ca6dddc19",
    "procedure_text": "(R)-3-O-Benzyl-2-O-(diisopropyl phosphonomethoxyl)-1-O-(methanesulfonyl)glycerol (15, 9 g, 20.53 mmol) (J. J. Bronson, etc. J. Med. Chem. 1989, 32, 1457) and sodium azide (4 g, 61.58 mmol) were mixed in 40 mL of anhydrous N',N'-dimethylformamide. The resulting mixture was stirred at 105\u00b0 C. for 5 hours. After the solvent was removed under reduced presuure, the residue was added 100 mL of methylene chloride. The mixture was filtered, and the solid was washed with methylene chloride. The filtrate was evaporated, and the residue was purified by flash chromatography on silica gel (methylene chloride:acetone=10:1 to 3:1) to give 6.15 g (78% yield) of the title compound as an oil.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-3-O-Benzyl-2-O-(diisopropyl phosphonomethoxyl)-1-O-(methanesulfonyl)glycerol\"}], \"amount\": {\"mass\": {\"value\": 9.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium azide\"}], \"amount\": {\"mass\": {\"value\": 4.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N',N'-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 105.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The resulting mixture was stirred at 105\\u00b0 C. for 5 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"After the solvent was removed\"}, {\"type\": \"ADDITION\", \"details\": \"the residue was added 100 mL of methylene chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"The mixture was filtered\"}, {\"type\": \"WASH\", \"details\": \"the solid was washed with methylene chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The filtrate was evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was purified by flash chromatography on silica gel (methylene chloride:acetone=10:1 to 3:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 5.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 6.15, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 78.0}}], \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b8b94d1023304f77ba3c492b5f4331e8",
    "procedure_text": "4-amino-2-chloro-benzoic acid was converted to product in 79% yield, using the procedure described for the synthesis of 4-tert-Butoxyamino-3-methyl-benzoic acid. 1H NMR (DMSO-d6): \u03b4 1.49 (s, 9 H), 7.46 (d of d, 1 H), 7.71 (br s, 1 H), 7.80 (d, 1 H), 9.87 (s, 1 H) and 13.00 (br s, 1 H).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-amino-2-chloro-benzoic acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-tert-Butoxyamino-3-methyl-benzoic acid\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 79.0}}]}]}]}"
  },
  {
    "reaction_id": "ord-3e697dd0b9304d75873c4fa489003e9f",
    "procedure_text": "To a suspension of Mg (3 g, 0.123 mol) in THF (40 ml) was added a small amount of solid I2 (20 mg). The mixture was heated to reflux under nitrogen. To the mixture was then added the 2-bromothiophene solution (5 ml) (19.6 g of 2-bromothiophene in 40 ml of THF). After the iodine color disappeared, to the suspension was added the rest of 2-bromothiophene solution dropwise keeping reflux. After the addition, the mixture was heated under reflux for 2 h., then was cooled to room temperature. To this mixture was added 4-fluorobenzyl iodide (or 4-fluorobenzyl bromide) followed by Li2CuCl4 (5 ml) solution keeping the temperature under 40\u00b0 C. using a cool water bath. The mixture was stirred at room temperature for 2 h. To the mixture was added sat. NH4Cl solution (100 ml), the mixture was stirred for 30 min., the organic layer was separated and washed with 10% sodium thiosulfate solution (50 ml), followed by distilled water (100 ml). The organic layer was then dried over MgSO4 and concentrated to give 19 g of 2-(4-fluorobenzyl)thiophene as an oil. Purification was achieved by vacuum distillation (110\u00b0 C., 5 mm Hg).",
    "reference_string": "{\"inputs\": {\"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-bromothiophene\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-bromothiophene\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"iodine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Li2CuCl4\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m6_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-fluorobenzyl iodide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-fluorobenzyl bromide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m9\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH4Cl\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"I2\"}], \"amount\": {\"mass\": {\"value\": 20.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m10\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Mg\"}], \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at room temperature for 2 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The mixture was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to reflux under nitrogen\"}, {\"type\": \"TEMPERATURE\", \"details\": \"dropwise keeping reflux\"}, {\"type\": \"ADDITION\", \"details\": \"After the addition\"}, {\"type\": \"TEMPERATURE\", \"details\": \"the mixture was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"under reflux for 2 h.\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"under 40\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 40.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"STIRRING\", \"details\": \"the mixture was stirred for 30 min.\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}}, {\"type\": \"CUSTOM\", \"details\": \"the organic layer was separated\"}, {\"type\": \"WASH\", \"details\": \"washed with 10% sodium thiosulfate solution (50 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium thiosulfate\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"by distilled water (100 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layer was then dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(4-fluorobenzyl)thiophene\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 19.0, \"units\": \"GRAM\"}}}], \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-acf87e69a6a146ed983bba7ce1f9e29f",
    "procedure_text": "2,6-dibromo-4H-cyclopenta[def]phenanthrene (2.6 g, 7.7 mmol) and octyl bromide (3.6 g, 18.5 mmol) in a 50 ml round bottom flask were dissolved with toluene (10 ml), and tetrabutylammoniumbromide (TBAB) (0.125 g, 0.385 mmol) was added thereto. A solution of NaOH (3.1 g, 77 mmol) in water (50 ml) was added to the reaction mixture, and the resultant solution was refluxed for two days. After the reaction was terminated, the reaction solution was extracted with chloroform. The organic phase was dried over MgSO4, concentrated, and purified by silica gel column chromatography (eluent: n-hexane). The eluate was distilled under a reduced pressure to remove unreacted octyl bromide, thereby giving a compound 2 (3.6 g, 80%).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"resultant solution\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,6-dibromo-4H-cyclopenta[def]phenanthrene\"}], \"amount\": {\"mass\": {\"value\": 2.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"octyl bromide\"}], \"amount\": {\"mass\": {\"value\": 3.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrabutylammoniumbromide\"}], \"amount\": {\"mass\": {\"value\": 0.125, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m3_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"amount\": {\"mass\": {\"value\": 3.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"CUSTOM\", \"details\": \"After the reaction was terminated\"}, {\"type\": \"EXTRACTION\", \"details\": \"the reaction solution was extracted with chloroform\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic phase was dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"purified by silica gel column chromatography (eluent: n-hexane)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-hexane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"The eluate was distilled under a reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"to remove unreacted octyl bromide\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"octyl bromide\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound 2\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 3.6, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 80.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-5264f0225b5b46c9a3d4f4eccbcf80d3",
    "procedure_text": "100 mg (0.53 mmol) of 2-methyl-4-oxo-4H-chromene-8-carbaldehyde are dissolved with 93.1 mg (0.93 mmol) of 2,4-pentanedione, 89.9 mg (0.53 mmol) of cyclopentyl 3-aminocrotonate and 31.9 mg (0.53 mmol) of acetic acid in 5 ml of 2-propanol and heated to reflux under argon for 10 h. The solvent is removed in vacuo, and the residue is purified by preparative HPLC. 84 mg (37.5% of theory) of the title compound are obtained as a yellow solid.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-methyl-4-oxo-4H-chromene-8-carbaldehyde\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,4-pentanedione\"}], \"amount\": {\"mass\": {\"value\": 93.1, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cyclopentyl 3-aminocrotonate\"}], \"amount\": {\"mass\": {\"value\": 89.9, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"mass\": {\"value\": 31.9, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-propanol\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to reflux under argon for 10 h\", \"duration\": {\"value\": 10.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The solvent is removed in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue is purified by preparative HPLC\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-60a9259a50764af89726c9c3a92eac9b",
    "procedure_text": "1-(3,4-dichlorobenzyl)-3-(4-(iodomethyl)thiazol-2-yl)urea (Intermediate 6) was taken up in tetrahydrofuran and an excess of the 2,4-dimethoxy-benzylamine (20 eq.) was added. The reaction was allowed to stir overnight at room temperature. The volatiles were removed in vacuo. Resulting oil triturated with water to give a gooey solid. Water was decanted off and resulting residue was purified by column chromatography using 0-8% gradient of 7 N ammonia/MeOH and DCM to give 1-(3,4-Dichloro-benzyl)-3-{4-[(2,4-dimethoxy-benzylamino)-methyl]-thiazol-2-yl}-urea.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(3,4-dichlorobenzyl)-3-(4-(iodomethyl)thiazol-2-yl)urea\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Intermediate 6\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,4-dimethoxy-benzylamine\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"to stir overnight at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The volatiles were removed in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"Resulting oil\"}, {\"type\": \"CUSTOM\", \"details\": \"triturated with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"to give a gooey solid\"}, {\"type\": \"CUSTOM\", \"details\": \"Water was decanted off\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"resulting residue\"}, {\"type\": \"CUSTOM\", \"details\": \"was purified by column chromatography\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(3,4-Dichloro-benzyl)-3-{4-[(2,4-dimethoxy-benzylamino)-methyl]-thiazol-2-yl}-urea\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3ac89d410bd346f4bcb103fd3aa9b2d8",
    "procedure_text": "To a solution of 4-(6-chloronaphthalene-2-sulfonyl)-1-[2-(4-piperidyl)ethyl]-2-piperazinone hydrochloride (118 mg) in methanol (10 ml) was added a solution of S-methylisothiourea hemisulfate (315 mg) and 28% sodium methoxide. in methanol (482 mg), and the mixture was stirred at room temperature for 3 days. The solvent was concentrated and purified with CHP20 column chromatography (water:acetonitrile:1 N hydrochloric acid=70:30:1), and then purified with LH20 (methanol) to give colorless amorphous of the title compound (66 mg).",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(6-chloronaphthalene-2-sulfonyl)-1-[2-(4-piperidyl)ethyl]-2-piperazinone hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 118.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"S-methylisothiourea hemisulfate\"}], \"amount\": {\"mass\": {\"value\": 315.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium methoxide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"mass\": {\"value\": 482.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"The solvent was concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"purified with CHP20 column chromatography (water:acetonitrile:1 N hydrochloric acid=70:30:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"purified with LH20 (methanol)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 66.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c371081bbefe4160bcb2e6e27899a68f",
    "procedure_text": "Morpholine (35.15 g, 0.4 mol) and water (30 mL) were added under stirring at room temperature to a mixture of 5-chloro-3-ethyl-1-methyl-1H-pyrazole-4-carbaldehyde from Step 2 (35 g, 0.202 mol) in HMPA (30 mL). The reaction mixture was heated at 90\u00b0 C. for 8 h, then diluted with water and extracted with ethyl acetate (3\u00d7100 mL). The organic extracts were washed with water to obtain a weak alkaline media, dried over Na2SO4 and evaporated. The residue was purified by chromatography (hexane/ethyl acetate) on silica gel to afford 37.2 g (82.6%) of the title product. Satisfactory C,H,N-analysis was obtained.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-chloro-3-ethyl-1-methyl-1H-pyrazole-4-carbaldehyde\"}], \"amount\": {\"mass\": {\"value\": 35.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HMPA\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Morpholine\"}], \"amount\": {\"mass\": {\"value\": 35.15, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 90.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate (3\\u00d7100 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic extracts were washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"to obtain a weak alkaline media\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by chromatography (hexane/ethyl acetate) on silica gel\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 37.2, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 82.6}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 82.5}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0055ae4d18f74f75912e8ca592f59415",
    "procedure_text": "Powdered anhydrous aluminum chloride (0.78 g) was slowly added to a stirred mixture of 1,2-dimethoxybenzene (0.64 g, 4.66 mmol) and 3,4-dimethoxyphenylacetyl chloride (1.0 g, 4.66 mmol) in 10 mL freshly distilled dry dichloromethane. An exothermic reaction occurred. The orange solution became brown as the mixture refluxed. The reaction mixture was heated to reflux for an additional 2 h and then allowed to cool to room temperature. The cooled solution was poured into a mixture containing of 5 g crushed ice and 5.5 mL 7.5 N HCl. The organic phase was separated and the aqueous phase was extracted three times with 10 mL dichloromethane. The combined dichloromethane extract was dried (Na2SO4), filtered, and evaporated to give a white solid, which was crystallized from ethanol to give pure white needles of 11a in 98% yield; mp 105-107\u00b0 C. (lit.30 mp 104-106\u00b0 C.); 1H NMR \u03b4 3.85 (s, 6H), 3.91 (s, 3H), 3.94 (s, 3H), 4.18 (s, 2H), 6.81 (m, 2H), 6.91 (m, 2H), 7.56 (d, 1H, J=2.0), 7.66 (dd, 1H, J=8.4,2.0); 13C NMR \u03b4 45.2, 56.3, 56.4, 56.5, 110.4, 111.1, 111.8, 112.8, 121.3, 121.9, 123.9, 127.9, 130.2, 148.4, 149.5, 153.8, 197.0.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 5.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aluminum chloride\"}], \"amount\": {\"mass\": {\"value\": 0.78, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,2-dimethoxybenzene\"}], \"amount\": {\"mass\": {\"value\": 0.64, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,4-dimethoxyphenylacetyl chloride\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"DISTILLATION\", \"details\": \"freshly distilled dry dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"An exothermic reaction\"}, {\"type\": \"TEMPERATURE\", \"details\": \"refluxed\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The reaction mixture was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to reflux for an additional 2 h\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"ADDITION\", \"details\": \"The cooled solution was poured into a mixture\"}, {\"type\": \"ADDITION\", \"details\": \"containing of 5 g\"}, {\"type\": \"CUSTOM\", \"details\": \"The organic phase was separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"the aqueous phase was extracted three times with 10 mL dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The combined dichloromethane extract\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"was dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a white solid, which\"}, {\"type\": \"CUSTOM\", \"details\": \"was crystallized from ethanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"11a\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 98.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-27baba8c80ea4b7a86dab2935641fd66",
    "procedure_text": "The Grignard compound was prepared under an argon atmosphere from 4.00 g of 2-bromo-6,7,8,9-tetrahydro-9,9-dimethyl-5H-benzocycloheptene, as described in EP-A2-0315071, and 456 mg of Mg shavings in 20 ml of absolute tetrahydrofuran. After carrying out the metallation a vigorous CO2 stream was introduced at -10\u00b0 C. The mixture was hydrolyzed with dil. HCl, extracted with ether and washed with a small amount of water. The acid was then purified by extraction in 1N NaOH, acidification to pH 1 (HCl) and re-extraction in ether. After washing with water, drying over Na2SO4 and evaporating there were obtained 2.64 g of 6,7,8,9-tetrahydro-9,9-dimethyl-5H-benzocycloheptene-2-carboxylic acid as colorless crystals of melting point 155\u00b0-156\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-bromo-6,7,8,9-tetrahydro-9,9-dimethyl-5H-benzocycloheptene\"}], \"amount\": {\"mass\": {\"value\": 4.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Mg\"}], \"amount\": {\"mass\": {\"value\": 456.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CO2\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was introduced at -10\\u00b0 C\", \"temperature\": {\"setpoint\": {\"value\": -10.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with a small amount of water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The acid was then purified by extraction in 1N NaOH\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"acidification to pH 1 (HCl) and re-extraction in ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"After washing with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"drying over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporating there\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6,7,8,9-tetrahydro-9,9-dimethyl-5H-benzocycloheptene-2-carboxylic acid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.64, \"units\": \"GRAM\"}}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b10173ed970240b89ac29b0e78147e86",
    "procedure_text": "The title compound, brown oil, MS (ISP): m/e=359.3 (M+H+), was prepared in accordance with the general method of example 163, step B from (6-bromo-quinolin-2-yl)-(R)-indan-1-yl-amine (see example 163, step A) and commercially available 1-methyl-piperazine.",
    "reference_string": "{\"inputs\": {\"m0_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(6-bromo-quinolin-2-yl)-(R)-indan-1-yl-amine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-methyl-piperazine\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-1e2e6d10d2a340c1976af3681ec6828a",
    "procedure_text": "To a solution of 125 mg (0.467 mmol) 2-chloro-N-methyl-4-(4-methyl-piperazin-1-yl)-benzamide and 0.22 ml (1.5 mmol) N,N,N\u2032,N\u2032-tetramethylethylenediamine in 2 ml THF a solution of o-tolyllithium, prepared by addition of 2.5 ml (3.8 mmol) of a 1.5 M solution of tert.-butyllithium in pentane to a solution of 0.23 ml (1.9 mmol) 2-bromotoluene in 2 ml diethyl ether at \u221278\u00b0, was added dropwise at \u221278\u00b0. The reaction mixture was allowed to warm to \u221225\u00b0 C. over a period of 2 h. After quenching with 1 ml water at \u221225\u00b0 the mixture was warmed to room temperature followed by dilution with 10 ml ethyl acetate and washing with 10 ml 1 N NaOH solution. The layers were separated and the aqueous layer was extracted with 2 10-ml portions of ethyl acetate. The combined organic layers were dried (Na2SO4) and evaporated. Chromatography (SiO2, CH2Cl2/methanol 19:1) afforded 55 mg (36%) 2\u2032-Methyl-5-(4-methyl-piperazin-1-yl)-biphenyl-2-carboxylic acid methylamide as a colorless oil MS 5 (EI): 324 (M+).",
    "reference_string": "{\"inputs\": {\"m1_m2_m7_m3_m4_m5_m8_m6_m9\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloro-N-methyl-4-(4-methyl-piperazin-1-yl)-benzamide\"}], \"amount\": {\"mass\": {\"value\": 125.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N,N\\u2032,N\\u2032-tetramethylethylenediamine\"}], \"amount\": {\"volume\": {\"value\": 0.22, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"o-tolyllithium\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert.-butyllithium\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-bromotoluene\"}], \"amount\": {\"volume\": {\"value\": 0.23, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pentane\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -25.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added dropwise at \\u221278\\u00b0\"}, {\"type\": \"CUSTOM\", \"details\": \"After quenching with 1 ml water at \\u221225\\u00b0 the mixture\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"was warmed to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"WASH\", \"details\": \"washing with 10 ml 1 N NaOH solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The layers were separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"the aqueous layer was extracted with 2 10-ml portions of ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic layers were dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2\\u2032-Methyl-5-(4-methyl-piperazin-1-yl)-biphenyl-2-carboxylic acid methylamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 55.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 36.0}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c84ef35aeb3d49af89cda9fe642172df",
    "procedure_text": "A mixture of 2-(bromomethyl)-1,3,4-trichlorobenzene (576 mg, 2.1 mmol), 3,6-dimethyl-2-sulfanyl-3,4-dihydropyrimidin-4-one (300 mg, 1.9 mmol), and triethylamine (280 \u03bcl, 2.0 mmol) in absolute ethanol (10 mL) was stirred at room temperature overnight. The solvent was evaporated under reduced pressure. The solid product was suspended in water (30 mL). The solid material was recovered by filtration, washed with water (2\u00d710 mL) and hexanes (2\u00d720 mL), and dried in vacuo, affording the title compound (475 mg, 72% yield); 1H NMR (400 MHz, DMSO-d6): \u03b4 2.20 (s, 3H), 3.31 (s, 3H), 4.77 (s, 2H), 6.08 (s, 1H), 7.57 (d, 1H, J=8.8 Hz), 7.68 (d, 1H, J=8.8 Hz); M+350; HPLC purity: 95.8%.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(bromomethyl)-1,3,4-trichlorobenzene\"}], \"amount\": {\"mass\": {\"value\": 576.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,6-dimethyl-2-sulfanyl-3,4-dihydropyrimidin-4-one\"}], \"amount\": {\"mass\": {\"value\": 300.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 280.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at room temperature overnight\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The solvent was evaporated under reduced pressure\"}, {\"type\": \"FILTRATION\", \"details\": \"The solid material was recovered by filtration\"}, {\"type\": \"WASH\", \"details\": \"washed with water (2\\u00d710 mL) and hexanes (2\\u00d720 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 475.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 72.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-29dbc10421c94db297032da8cb79c533",
    "procedure_text": "The title compound is prepared from methyl 2-((S)-6-((R)-7-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate and N-(4-bromo-3,5-dimethylphenethyl)methanesulfonamide following a procedure analogous to that described in Step 5 of Intermediate 1. LC (method 8): tR=0.58 min; Mass spectrum (ESI+): m/z=568 [M+H]+.",
    "reference_string": "{\"inputs\": {\"m0_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 2-((S)-6-((R)-7-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(4-bromo-3,5-dimethylphenethyl)methanesulfonamide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Intermediate 1\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0c1f4adf06874259be82761078af931c",
    "procedure_text": "Prepared by the same method as for 4-hydroxy-6-(2-phenylethyl)pyridazin-3(2H)-one (Example 1) from 3,4-bis(benzyloxy)-6-[1-(4-fluorophenyl)cyclopropyl]pyridazine (Intermediate 42) except that the solvent used for the hydrogenation was ethyl acetate and the product was recrystallised from a mixture of ethyl acetate and MTBE.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-hydroxy-6-(2-phenylethyl)pyridazin-3(2H)-one\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,4-bis(benzyloxy)-6-[1-(4-fluorophenyl)cyclopropyl]pyridazine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Intermediate 42\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the product was recrystallised from a mixture of ethyl acetate and MTBE\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MTBE\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-ba6a309b581d42a999ba4fe73b55b587",
    "procedure_text": "m-(3-Chloropropyloxy)benzyl alcohol (14 g), phthalimide potassium salt (13 g) and tetra-n-butyl ammonium hydrogen sulfate (2 g) were suspended in 200 g of acetonitrile. The suspension was refluxed for 18 hours. After cooling, the insoluble matter was removed by filtration, and the filtrate was concentrated. The concentrate was taken into ethyl acetate, washed with a 1N aqueous solution of sodium hydroxide and water, and then dried. The solvent was evaporated, and the residue was recrystallized from ethanol to give 16.7 g (yield 76.9%) of N-[3-(3-hydroxymethylphenoxy)propyl]phthalimide.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"m-(3-Chloropropyloxy)benzyl alcohol\"}], \"amount\": {\"mass\": {\"value\": 14.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"phthalimide potassium salt\"}], \"amount\": {\"mass\": {\"value\": 13.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetra-n-butyl ammonium hydrogen sulfate\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The suspension was refluxed for 18 hours\", \"duration\": {\"value\": 18.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"After cooling\"}, {\"type\": \"CUSTOM\", \"details\": \"the insoluble matter was removed by filtration\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate was concentrated\"}, {\"type\": \"WASH\", \"details\": \"washed with a 1N aqueous solution of sodium hydroxide and water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aqueous solution\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"CUSTOM\", \"details\": \"The solvent was evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was recrystallized from ethanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-[3-(3-hydroxymethylphenoxy)propyl]phthalimide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 16.7, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 76.9}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 76.9}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4364c2c3a9a24ba9aa51ccf6def7c34c",
    "procedure_text": "A 0.76 g portion of imidazole was added to 7 ml of N,N-dimethylformamide and mixed with 0.2 g of 90% lithium hydride under ice-cooling and then the mixture was stirred for 40 minutes. Next, 2.17 g of 2-bromopyridine N-oxide hydrochloride was gradually added thereto, the mixture was stirred at room temperature for about 1 hour and further heated at 80\u00b0 C. for about 1 hour, and then the solvent was evaporated and the thus obtained mixture was subjected to a silica gel column chromatography and eluted with chloroform-methanol-28% aqueous ammonia (10:0.9:0.1, v/v/v) to obtain 1.21 g of the title compound as light yellow crystals.",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"imidazole\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 7.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium hydride\"}], \"amount\": {\"mass\": {\"value\": 0.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-bromopyridine N-oxide hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 2.17, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 80.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred for 40 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooling\"}, {\"type\": \"STIRRING\", \"details\": \"the mixture was stirred at room temperature for about 1 hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was evaporated\"}, {\"type\": \"WASH\", \"details\": \"eluted with chloroform-methanol-28% aqueous ammonia (10:0.9:0.1, v/v/v)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 40.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.21, \"units\": \"GRAM\"}}}], \"isolated_color\": \"light yellow\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c68836ac96ba44e3941fcfd3f2f0f56a",
    "procedure_text": "To a stirred solution of Ethyl 2-(3-(2,6-dimethylbenzyloxy)phenyl)acetate (Step A, 4.79 g, 16.0 mmol) in dry THF (60 ml) was added drop wise a solution of lithium diisopropylamide (1.0 M in THF, 25 ml) at \u221278\u00b0 C. under argon followed by addition of hexamethylphosphoramide (HMPA, 15 ml). After 15 minutes of stirring at \u221278\u00b0 C., Iodoethane (12.53 g, 80.3 mmol) was added rapidly. The reaction mixture was warmed to room temperature for 16 hours. The crude mixture was quenched with sat. NH4Cl and extracted with ether (2\u00d7). The combined organic layers were washed with brine, dried over Na2SO4, filtered, concentrated and purified by flash chromatography on a silica gel column (ethyl acetate:hexane, 1:4) to provide the title compound.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Iodoethane\"}], \"amount\": {\"mass\": {\"value\": 12.53, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ethyl 2-(3-(2,6-dimethylbenzyloxy)phenyl)acetate\"}], \"amount\": {\"mass\": {\"value\": 4.79, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium diisopropylamide\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexamethylphosphoramide\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -78.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After 15 minutes of stirring at \\u221278\\u00b0 C.\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The reaction mixture was warmed to room temperature for 16 hours\", \"duration\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The crude mixture was quenched with sat. NH4Cl\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude mixture\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH4Cl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ether (2\\u00d7)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined organic layers were washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"purified by flash chromatography on a silica gel column (ethyl acetate:hexane, 1:4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-875d52d029364f18b1a83001893928f8",
    "procedure_text": "To a solution of methyl 1-methyl-6-oxo-5-(5-phenyl-4,5-dihydroisoxazol-3-yl)-1,6-dihydropyridazine-3-carboxylate (200 mg, 0.638 mmol, Preparation #33) in a mixture of methanol (2 mL) and THF (4 mL) was added lithium hydroxide (30.6 mg, 1.277 mmol, Spectrochem) dissolved in water (2 mL). The reaction mixture was stirred at RT for about 3 h. The reaction mixture was concentrated under vacuum and dissolved in water (10 mL). Further it was acidified to pH 2 with 2N HCl and the solids obtained were collected by filtration to afford 1-methyl-6-oxo-5-(5-phenyl-4,5-dihydroisoxazol-3-yl)-1,6-dihydropyridazine-3-carboxylic acid 0.150 g (79%) as light brown solids. 1H NMR (400 MHz, DMSO) \u03b4 13.8 (br s, 1H), 8.122 (s, 1H), 7.405-7.331 (m, 5H), 5.806-5.757 (m, 1H), 3.958-3.886 (m, 1H) 3.762 (s, 3H), 3.506-3.441 (m, 1H). MS m/z: 298.0 (M\u2212H)\u2212",
    "reference_string": "{\"inputs\": {\"m1_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 1-methyl-6-oxo-5-(5-phenyl-4,5-dihydroisoxazol-3-yl)-1,6-dihydropyridazine-3-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium hydroxide\"}], \"amount\": {\"mass\": {\"value\": 30.6, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred at RT for about 3 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"The reaction mixture was concentrated under vacuum\"}, {\"type\": \"DISSOLUTION\", \"details\": \"dissolved in water (10 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solids obtained\"}, {\"type\": \"FILTRATION\", \"details\": \"were collected by filtration\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-methyl-6-oxo-5-(5-phenyl-4,5-dihydroisoxazol-3-yl)-1,6-dihydropyridazine-3-carboxylic acid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.15, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 79.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a507bb17ab1c4d1686c2cc057b310c31",
    "procedure_text": "In a 500 ml three-necked bottle, 34.1 g of 7-bromo-3-methoxy-2-naphthylcarbinol (0.128 mol) and 350 ml of acetone were added, and the mixture was stirred vigorously to form a solution. 167 g of active manganese dioxide (1.92 mol) was added to the solution, and the mixture was stirred at room temperature for 48 h to complete the reaction. The mixture was filtered, and the manganese dioxide filter cake was washed with ethyl acetate (200 ml*6). The filtrates were combined, and dried under vacuum in a rotary dryer to obtain a crude product as a yellow solid, which was recrystallized from methanol to obtain 29.3 g with a yield of the two steps of 86%.",
    "reference_string": "{\"inputs\": {\"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-bromo-3-methoxy-2-naphthylcarbinol\"}], \"amount\": {\"mass\": {\"value\": 34.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"amount\": {\"volume\": {\"value\": 350.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"manganese dioxide\"}], \"amount\": {\"mass\": {\"value\": 167.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred vigorously\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"to form a solution\"}, {\"type\": \"STIRRING\", \"details\": \"the mixture was stirred at room temperature for 48 h\", \"duration\": {\"value\": 48.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"the reaction\"}, {\"type\": \"FILTRATION\", \"details\": \"The mixture was filtered\"}, {\"type\": \"FILTRATION\", \"details\": \"the manganese dioxide filter cake\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"manganese dioxide\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"was washed with ethyl acetate (200 ml*6)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried under vacuum in a rotary dryer\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a329899f93af4451805695351c04cac2",
    "procedure_text": "To a suspension of 9 g of sodium hydride (50 percent in oil) in 150 ml of anhydrous dimethylformamide were added drop-by-drop and while stirring 22.2 g (0.15 mol) of 2-methyl-3-hydroxy-benzofuran, care being taken to maintain the temperature at about 30\u00b0-35\u00b0C. The reaction medium was stirred for a further 15 minutes and then 27.2 g (0.15 mol) of methyl \u03b1-bromoisobutyrate were added, the temperature being maintained at 35\u00b0-40\u00b0C. Stirring was continued for 24 hours at room temperature, the reaction mixture was poured into water and extracted several times with ether. The ethereal extracts were collected, washed with water and dried over anhydrous sodium sulphate.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-methyl-3-hydroxy-benzofuran\"}], \"amount\": {\"mass\": {\"value\": 22.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydride\"}], \"amount\": {\"mass\": {\"value\": 9.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl \\u03b1-bromoisobutyrate\"}], \"amount\": {\"mass\": {\"value\": 27.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction medium was stirred for a further 15 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"were added drop-by-drop and\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to maintain the temperature at about 30\\u00b0-35\\u00b0C\"}, {\"type\": \"TEMPERATURE\", \"details\": \"the temperature being maintained at 35\\u00b0-40\\u00b0C\"}, {\"type\": \"STIRRING\", \"details\": \"Stirring\"}, {\"type\": \"WAIT\", \"details\": \"was continued for 24 hours at room temperature\", \"duration\": {\"value\": 24.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted several times with ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The ethereal extracts were collected\"}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous sodium sulphate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulphate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-d615b9e18b4d43e8af49a6bcb4338c0e",
    "procedure_text": "To a suspension of 7-bromo-5H-furo[3,2-c]pyridin-4-one (250 mg, 1.17 mmol) in DMF (5 mL) cooled to 0\u00b0 C. was added HNa (56 mg, 1.4 mmol, 60% dispersion in mineral oil) in three portions. After stirring at room temperature for 45 min, MeI (87 \u03bcl, 1.4 mmol) was added drop wise over five minutes. The reaction was allowed to warm up to rt stirred for 2 h. It was then cooled to 0\u00b0 C. followed by addition of sat. aq. NH4Cl (5 mL) drop wise. The resulting mixture was extracted with EtOAc (3\u00d75 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to afford the title compound. LCMS: 227.9 (M+H)+",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-bromo-5H-furo[3,2-c]pyridin-4-one\"}], \"amount\": {\"mass\": {\"value\": 250.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeI\"}], \"amount\": {\"volume\": {\"value\": 87.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH4Cl\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring at room temperature for 45 min\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added HNa (56 mg, 1.4 mmol, 60% dispersion in mineral oil) in three portions\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to warm up to rt\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"STIRRING\", \"details\": \"stirred for 2 h\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"It was then cooled to 0\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"The resulting mixture was extracted with EtOAc (3\\u00d75 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic layers were dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by silica gel column chromatography\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 45.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-34eb154bf317491f8a1556dbd61a96e1",
    "procedure_text": "1-[2-(2-Fluoro-6-methoxy-phenoxy)-5-morpholin-4-ylmethyl-phenyl]-3-thiazol-2-yl-urea (35 mg, 78%) was prepared from 1-[2-(2-fluoro-6-methoxy-phenoxy)-5-formyl-phenyl]-3-thiazol-2-yl-urea (39 mg, 0.1 mmol) and morpholine following the general procedure O.",
    "reference_string": "{\"inputs\": {\"m0_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-[2-(2-fluoro-6-methoxy-phenoxy)-5-formyl-phenyl]-3-thiazol-2-yl-urea\"}], \"amount\": {\"mass\": {\"value\": 39.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"morpholine\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-[2-(2-Fluoro-6-methoxy-phenoxy)-5-morpholin-4-ylmethyl-phenyl]-3-thiazol-2-yl-urea\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 35.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 78.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-1146d7e83d974b508a18bc1f3798dcc3",
    "procedure_text": "To a solution of 7.51 g (0.1 mole) of 2-methoxyethylamine in 20 ml of water 5.21 g (0.02 mole) of 1,2,3,4-tetrahydro-2,3-dioxo-6-quinoxalinesulfonyl chloride are added in small portions, under stirring, and the mixture is stirred at room temperature for 16 hours. It is allowed to stand further for 2 days, and then 15 ml of acetic acid and 10 ml of water are added to it. The separated crystals are filtered, washed successively with water and acetone, dried, dissolved in a slight amount of hot dimethyl sulfoxide and precipitated from the solution with water. Thus 3.80 g (63%) of 1,2,3,4-tetra-hydro-N-(2-methoxy-ethyl)-2,3-dioxo-6-quinoxaline sulfonamide are obtained, m.p.: 264-267\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m5_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-methoxyethylamine\"}], \"amount\": {\"mass\": {\"value\": 7.51, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,2,3,4-tetrahydro-2,3-dioxo-6-quinoxalinesulfonyl chloride\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"under stirring\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"the mixture is stirred at room temperature for 16 hours\", \"duration\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"The separated crystals are filtered\"}, {\"type\": \"WASH\", \"details\": \"washed successively with water and acetone\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"DISSOLUTION\", \"details\": \"dissolved in a slight amount of hot dimethyl sulfoxide\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethyl sulfoxide\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"precipitated from the solution with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"DAY\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,2,3,4-tetra-hydro-N-(2-methoxy-ethyl)-2,3-dioxo-6-quinoxaline sulfonamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 3.8, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 63.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a6899c2311c44e2ab07f825eb595a55e",
    "procedure_text": "A mixture of 4-chloro-1H-imidazole (5.0 g, 48.8 mmol), 1-chloro-2-methoxy-4-nitrobenzene (9.15 g, 48.8 mmol), and potassium hydroxide flakes (2.74 g, 48.8 mmol) in anhydrous DMSO (50 mL) was heated at 80\u00b0 C. for 20 h. The reaction mixture was allowed to cool to rt and was poured into 800 mL of water with vigorous stirring. The resulting yellow-orange precipitate was collected by vacuum filtration using a coarse sintered glass funnel The crude wet solid was transferred to a 1 L Erlenmeyer flask. Absolute ethanol (250 mL) was added to the flask and the resulting suspension was heated until all of the solids dissolved. The clear solution was cooled to rt and the desired product slowly crystallized. After 2 h, the crystalline solid was collected by vacuum filtration and rinsed with 100 mL of fresh ethanol. The solid was dried under high vacuum to afford 4-chloro-1-(2-methoxy-4-nitrophenyl)-1H-imidazole (5.2 g, 42% yield) as an off-white crystalline solid. LC-MS (M+H)+=254.0. 1H NMR (500 MHz, CDCl3) \u03b4 ppm 7.94-8.01 (m, 2H) 7.76 (d, J=1.53 Hz, 1H) 7.45 (d, J=8.55 Hz, 1H) 7.21 (d, J=1.53 Hz, 1H) 4.02 (s, 3H).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 800.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-chloro-1H-imidazole\"}], \"amount\": {\"mass\": {\"value\": 5.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-chloro-2-methoxy-4-nitrobenzene\"}], \"amount\": {\"mass\": {\"value\": 9.15, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium hydroxide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMSO\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 80.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"to cool to rt\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"The resulting yellow-orange precipitate was collected by vacuum filtration\"}, {\"type\": \"ADDITION\", \"details\": \"Absolute ethanol (250 mL) was added to the flask\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"the resulting suspension was heated until all of the solids\"}, {\"type\": \"DISSOLUTION\", \"details\": \"dissolved\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The clear solution was cooled to rt\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"the desired product slowly crystallized\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"the crystalline solid was collected by vacuum filtration\"}, {\"type\": \"WASH\", \"details\": \"rinsed with 100 mL of fresh ethanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The solid was dried under high vacuum\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-chloro-1-(2-methoxy-4-nitrophenyl)-1H-imidazole\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 5.2, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 42.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 42.0}}], \"isolated_color\": \"off-white crystalline\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3d0e929f0b7b4cdaa00c520698e82113",
    "procedure_text": "A solution of 2-({2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-5-fluoro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluoro-N-methylbenzamide (102 mg, 0.15 mmol) in dioxane (10 mL) and a 1N aqueous KOH solution (2 mL, 2.0 mmol) was heated at 80\u00b0 C. for 6 h. The resulting mixture was allowed to cool to rt and diluted with EtOAc (50 mL) and a saturated NaHCO3 solution (50 mL). The organic layer was washed with a saturated NaCl solution (50 mL), concentrated onto Celite and purified by silica gel chromatography using 1-10% MeOH (containing 0.2% NH3)/CH2Cl2 to obtain 2-[(2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-5-fluoro-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-6-fluoro-N-methylbenzamide as a brown solid (44 mg, 55%). 1H NMR (400 MHz, THF-d8) \u03b4 ppm 2.31 (s, 6H), 2.93 (d, J=4.58 Hz, 3H), 3.06 (t, J=8.24 Hz, 2H), 3.14 (s, 2H), 3.84 (s, 3H), 4.18 (t, J=8.33 Hz, 2H), 6.64 (s, 1H), 6.67-6.85 (m, 2H), 7.22-7.49 (m, 2H), 7.77 (br s, 1H), 8.75 (d, J=8.61 Hz, 1H), 9.35 (s, 1H), 10.50 (s, 1H), 10.76 (s, 1H); ESIMS (M+H)+=551.24.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-({2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-5-fluoro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluoro-N-methylbenzamide\"}], \"amount\": {\"mass\": {\"value\": 102.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"KOH\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dioxane\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WASH\", \"details\": \"The organic layer was washed with a saturated NaCl solution (50 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaCl\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated onto Celite\"}, {\"type\": \"CUSTOM\", \"details\": \"purified by silica gel chromatography\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-[(2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-5-fluoro-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-6-fluoro-N-methylbenzamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 44.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 55.0}}], \"isolated_color\": \"brown\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-55f70253dee94a0a979e4ad18792b519",
    "procedure_text": "Oxalyl chloride (0.5 mL, 5.9 mmol) was added to a suspension of (4-bromophenoxy)acetic acid (0.462 g, 2.0 mmol) in methylene chloride (10 mL) and 2 drops of N,N-dimethylformamide. The mixture was stirred at RT for 2 h. The solvent was evaporated under reduced pressure. The residue was diluted with methylene chloride (10 mL), cooled with ice-water bath, and 1M of sodium hydroxide aqueous solution (3.0 mL) was added. To the mixture was added pyrrolidine (167 \u03bcL, 2.0 mmol). The mixture was stirred and allowed to warm to RT. The organic layer was separated, washed with water and brine, dried over Na2SO4, filtered, and concentrated. The residue was directly used in next step without further purification (550 mg, 96.7%). LCMS: (M+H)=286.0/284.0",
    "reference_string": "{\"inputs\": {\"m1_m2_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Oxalyl chloride\"}], \"amount\": {\"volume\": {\"value\": 0.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(4-bromophenoxy)acetic acid\"}], \"amount\": {\"mass\": {\"value\": 0.462, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"reaction_role\": \"CATALYST\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyrrolidine\"}], \"amount\": {\"volume\": {\"value\": 167.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at RT for 2 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The solvent was evaporated under reduced pressure\"}, {\"type\": \"ADDITION\", \"details\": \"The residue was diluted with methylene chloride (10 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"cooled with ice-water bath\"}, {\"type\": \"ADDITION\", \"details\": \"1M of sodium hydroxide aqueous solution (3.0 mL) was added\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"STIRRING\", \"details\": \"The mixture was stirred\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to warm to RT\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The organic layer was separated\"}, {\"type\": \"WASH\", \"details\": \"washed with water and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was directly used in next step without further purification (550 mg, 96.7%)\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-a27e2d3e0405447ca2a4dc6570daf8c0",
    "procedure_text": "A mixture of {5-[5-(2,6-dichloro-phenylmethanesulfonyl)-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrol-3-yl}-acetic acid (208 mg, 0.4 mmol), HOBt (54 mg, 1 eq.) and EDAC (153 mg, 2 eq.) in DMF (1.5 mL) was stirred at rt for 30 mins. To the mixture was added 1-cyclopropyl-piperazine (101 mg, 2 eq.) in DMF (1.5 mL). After stirring at rt for overnight, the precipitate was collected by vacuum filtration, washed with water, sodium bicarbonate and ether to give 108 mg (43%) of the titled compound.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"{5-[5-(2,6-dichloro-phenylmethanesulfonyl)-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrol-3-yl}-acetic acid\"}], \"amount\": {\"mass\": {\"value\": 208.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HOBt\"}], \"amount\": {\"mass\": {\"value\": 54.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EDAC\"}], \"amount\": {\"mass\": {\"value\": 153.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 1.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-cyclopropyl-piperazine\"}], \"amount\": {\"mass\": {\"value\": 101.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 1.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at rt for 30 mins\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"After stirring at rt for overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"the precipitate was collected by vacuum filtration\"}, {\"type\": \"WASH\", \"details\": \"washed with water, sodium bicarbonate and ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"titled compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 108.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 43.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 43.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0bc4ce0359cc4fe5a5c6139ee262a01a",
    "procedure_text": "In a 250 mL round-bottom flask was placed 2,2-dimethyl-Chroman-7-ol (1.76 g, 9.87 mmol, from Step 4-1-2) in 30 mL of dry dichloroethane under argon. The solution was cooled to 0\u00b0 C. where boron trichloride (10.8 mL, 1M in CH2Cl2, 10.8 mmol, 1.1 eq) was added dropwise. At this point, methyl thiocyanate (0.80 g, 10.8 mmol, 1.1 eq) was added followed by aluminum trichloride (1.32 g, 9.87 mmol, 1 eq). The reaction was allowed to warm up to rt and stirred for 17 h. The reaction mixture was cooled down to 0\u00b0 C. and 10 mL of 50% w/w NaOH was added to adjust the solution to PH\u201414, followed by 40 mL of water. The solution was then refluxed at 65\u00b0 C. for 2 h. The solution was allowed to cool to ambient temperature. The aqueous layer was washed with dichloromethane (20 mL). The aqueous solution was transferred to an Erlenmeyer flask and acidified to pH\u02dc1 with conc. HCl. This solution was then extracted with EtOAc (3\u00d720 mL) and the combined organic layers were dried over Na2SO4, filtered and evaporated. The residue was purified on silica gel (flash column chromatography) eluting with 5% ethyl acetate-hexane followed by 20% ethyl acetate-hexane to provide the desired product as white solid. The desired product was white solid (0.33 g, 16.5%). 1H-NMR (CD3CN) \u03b4 7.93 (broad s, 1H, OH), 7.26 (s, 1H), 6.28 (s, 1H), 2.69 (t, 2H), 1.80 (t, 2H), 1.32 (s, 6H).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,2-dimethyl-Chroman-7-ol\"}], \"amount\": {\"mass\": {\"value\": 1.76, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl thiocyanate\"}], \"amount\": {\"mass\": {\"value\": 0.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aluminum trichloride\"}], \"amount\": {\"mass\": {\"value\": 1.32, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloroethane\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"boron trichloride\"}], \"amount\": {\"volume\": {\"value\": 10.8, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred for 17 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"In a 250 mL round-bottom flask was placed\"}, {\"type\": \"ADDITION\", \"details\": \"was added dropwise\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The reaction mixture was cooled down to 0\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"The solution was then refluxed at 65\\u00b0 C. for 2 h\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 65.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"to cool to ambient temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"WASH\", \"details\": \"The aqueous layer was washed with dichloromethane (20 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"This solution was then extracted with EtOAc (3\\u00d720 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"the combined organic layers were dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified on silica gel (flash column chromatography)\"}, {\"type\": \"WASH\", \"details\": \"eluting with 5% ethyl acetate-hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 17.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-501f06f403e14e6f9c560b4f7b3c468b",
    "procedure_text": "Isopropyl bromide (0.246 g) was added to a stirred mixture of 7-hydroxy-6-methoxy-4-(3'-methylanilino)quinazoline (0.281 g), potassium carbonate (0.414 g) and DMA (3 ml). The mixture was stirred at ambient temperature for 30 minutes and then heated to 70\u00b0 C. for 1 hour. The mixture was partitioned between ethyl acetate and water. The organic phase was dried (MgSO4) and evaporated to give 7-isopropoxy-6-methoxy-4-(3'-methylanilino)quinazoline (0.28 g), m.p. 218\u00b0-221\u00b0 C. NMR Spectrum: (CD3SOCD3) 1.36 (d, 6H), 2.34 (s, 3H), 3.94 (s, 3H), 4.83 (m, 1H), 6.94 (d, 1H), 7.17 (s, 1H), 7.27 (t, 1H), 7.57 (s, 1H), 7.64 (d, 1H), 7.82 (s, 1H), 8.43 (s, 1H); Elemental Analysis: Found C, 69.4; H, 6.7; N, 12.0; C19H21N3O2. 0.3H2O. 0.1EtOAc requires C, 69.0; H, 6.6; N, 12.4%.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Isopropyl bromide\"}], \"amount\": {\"mass\": {\"value\": 0.246, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-hydroxy-6-methoxy-4-(3'-methylanilino)quinazoline\"}], \"amount\": {\"mass\": {\"value\": 0.281, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 0.414, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMA\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at ambient temperature for 30 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"heated to 70\\u00b0 C. for 1 hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 70.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The mixture was partitioned between ethyl acetate and water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic phase was dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-isopropoxy-6-methoxy-4-(3'-methylanilino)quinazoline\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.28, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0a3ea4d8e68f4c49a100d2ab5a78f30e",
    "procedure_text": "Prepared according to the procedure described in Example 33, Step 4, using the following starting materials: (5-chloro-2\u2032-formyl-4\u2032-trifluoromethyl-biphenyl-3-yl)-acetic acid ethyl ester and ethylamine (2M in THF).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(5-chloro-2\\u2032-formyl-4\\u2032-trifluoromethyl-biphenyl-3-yl)-acetic acid ethyl ester\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethylamine\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Prepared\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-6dbd6a9c488f47278857100863dc9190",
    "procedure_text": "To a 1-L flask was added a magnetic stir bar, 85 g of sodium sulfate, and 100 mL of water. The mixture was magnetically stirred until all the solids were dissolved. To the resultant aqueous solution was added a solution of 6-aminobenzothiazole (4.96 g, 33.0 mmol) in 50 mL of 1N aqueous hydrochloric acid and 10 mL of ethanol. The mixture was stirred, and chloral (6.0 9, (36 mmol) was added. To the resultant solution was added a solution of hydroxyl amine hydrochloride (7.50 g, 108 mmol) in 30 mL of water. The final mixture was heated with stirring to a gentle boil until all solids dissappeared, and heating was continued for an additional 15 min. The flask was removed from the heat, and the solution was poured onto 500 g of ice. The mixture was stirred as the product precipatated from solution. The precipatate was collected by suction filtration, washed thoroughly with water, filtered, and air dried to provide 6.9 g (94%) of N-benzothiazol-6yl-2-hydroxyimino-acetamide: 1H NMR (DMSO-d6): \u03b4 12.2 (s, 1H), 10.4 (s, 1H), 9.2 (s, 1H), 8.5 (s, 1H), 7.9 (d, 1H), 7.7 (m, 1H), 7.7 (s 1H); APCI\u2212MS m/z 220 (M\u2212H)\u2212. To a 1-L 3-neck round bottom flask was placed a magnetic stir bar and 100 ml of concentrated sulfuric acid. The flask was fitted with a thermometer to monitor the temperature of the reaction. The sulfuric acid was heated to 100\u00b0 C., and 10.0 g (45.2 mmol) of N-benzothiazol-6-yl-2-hydroxyimino-acetamide was added slowly. The solution was heated for \u02dc1 h, and the reaction mixture was poured into 750 g of ice and water. The residual reaction mixture in the reaction vessel was washed out with an additional 20 mL of cold water. The aqueous slurry was stirred for about 1 h and filtered. The solid was washed thoroughly with water, filtered, and air dried to yield 4.3 g (46%) of 6-H-1-thia-3,6-diaza-as-indacen-7,8-dione: 1H NMR (DMSO-d6): \u03b4 11.1 (s, 1H), 9.2 (s, 1H), 8.2 (d, 1H), 7.0 (d, 1H); APCI\u2212MS m/z 203 (M\u2212H)\u2212.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sulfuric acid\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sulfuric acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice\"}], \"amount\": {\"mass\": {\"value\": 750.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-benzothiazol-6-yl-2-hydroxyimino-acetamide\"}], \"amount\": {\"mass\": {\"value\": 10.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The aqueous slurry was stirred for about 1 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"To a 1-L 3-neck round bottom flask was placed\"}, {\"type\": \"CUSTOM\", \"details\": \"The flask was fitted with a thermometer\"}, {\"type\": \"CUSTOM\", \"details\": \"the temperature of the reaction\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The solution was heated for \\u02dc1 h\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The residual reaction mixture in the reaction vessel\"}, {\"type\": \"WASH\", \"details\": \"was washed out with an additional 20 mL of cold water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"WASH\", \"details\": \"The solid was washed thoroughly with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"air dried\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-H-1-thia-3,6-diaza-as-indacen-7,8-dione\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 4.3, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 46.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f43ae6d82d244984a4b166d59ac8fcc3",
    "procedure_text": "In 10 ml of tetrahydrofuran was dissolved 488 mg (0.82 mmol) of 5-[2-[4-dibutylamino-2-(tert-butyldiphenylsiloxy)phenyl]vinyl]thiophene-2-carboaldehyde, and 2.5 ml of tetrabutylammonium fluoride (1 mol solution in tetrahydrofuran) was added dropwise thereto with stirring at room temperature. The mixture was stirred for 35 minutes. After the reaction mixture was poured into water, extraction with ethyl acetate, washing with a saturated saline solution, drying over anhydrous sodium sulfate, and concentration were performed. The residue was purified by silica gel column chromatography to give 274 mg of a blackish brown crystal (yield: 93.6%).",
    "reference_string": "{\"inputs\": {\"m5_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-[2-[4-dibutylamino-2-(tert-butyldiphenylsiloxy)phenyl]vinyl]thiophene-2-carboaldehyde\"}], \"amount\": {\"mass\": {\"value\": 488.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrabutylammonium fluoride\"}], \"amount\": {\"volume\": {\"value\": 2.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"with stirring at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added dropwise\"}, {\"type\": \"STIRRING\", \"details\": \"The mixture was stirred for 35 minutes\", \"duration\": {\"value\": 35.0, \"units\": \"MINUTE\"}}, {\"type\": \"WASH\", \"details\": \"washing with a saturated saline solution\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"drying over anhydrous sodium sulfate, and concentration\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by silica gel column chromatography\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"blackish brown crystal\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 274.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 93.6}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 93.5}}], \"isolated_color\": \"blackish brown\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystal\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3473922d6b974e70a42997fc9c59ec44",
    "procedure_text": "The title compound was prepared from (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-((2-(trimethylsilyl)ethoxy)methyl)piperidin-2-one (Example 414, Step B) and N-methylcyclopropanesulfonamide by a procedure similar to the one described in Example 201, Step A. The product was purified by chromatography through a RediSep\u00ae pre-packed silica gel column (Teledyne Isco, Lincoln, Nebr.) (12 g), eluting with a gradient of 0% to 80% EtOAc in hexane, to provide the title compound as an oil. Mass Spectrum (ESI) m/z=665.2 (M+1).",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-((2-(trimethylsilyl)ethoxy)methyl)piperidin-2-one\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-methylcyclopropanesulfonamide\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The product was purified by chromatography through a RediSep\\u00ae pre-packed silica gel column (Teledyne Isco, Lincoln, Nebr.) (12 g)\"}, {\"type\": \"WASH\", \"details\": \"eluting with a gradient of 0% to 80% EtOAc in hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2de5e19e8e9647d495960c174f777dd0",
    "procedure_text": "Benzylchloroformate (44.95 kg, 263.5 mol, 1.0 eq.) was added over a 2 hour period at room temperature to a solution of ethanolamine (16.1 kg, 263.5 mol, 1.0 eq.) in water (34 gal). After stirring for 30 minutes, this was added to a cold (5-10\u00b0 C.) solution of NaHCO3 (33.2 kg, 395.25 mol, 1.5 eq) in H2O (330 L) over a 30 min period and then allowed to stir at room temperature overnight. Ethyl acetate (22 gal) was added, the layers separated, and the aqueous layer extracted again with 22 gal. ethyl acetate. The combined organic extracts were concentrated under vacuum to a volume of 10 gal, and the remainder displaced with isopropyl ether. The resulting slurry was stirred and cooled to +10\u00b0 C. for 2 hours, then filtered. The solids were washed with isopropyl ether and vacuum dried to give the title compound(39.1 kg, 71.1%). mp 61-63\u00b0 C. NMR (300 MHz, d6 -DMSO): \u03b4=7.50-7.37 (m, 5H), 7.37-7.16 (m, 1H), 5.05 (s, 2H), 4.70-4.63 (m, 1H), 3.46-3.37 (m, 2H), 3.13-3.03 (m, 2H).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ethyl acetate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Benzylchloroformate\"}], \"amount\": {\"mass\": {\"value\": 44.95, \"units\": \"KILOGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanolamine\"}], \"amount\": {\"mass\": {\"value\": 16.1, \"units\": \"KILOGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"amount\": {\"mass\": {\"value\": 33.2, \"units\": \"KILOGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"amount\": {\"volume\": {\"value\": 330.0, \"units\": \"LITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring for 30 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"to stir at room temperature overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"the layers separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"the aqueous layer extracted again with 22 gal\"}, {\"type\": \"CONCENTRATION\", \"details\": \"The combined organic extracts were concentrated under vacuum to a volume of 10 gal\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"10\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"STIRRING\", \"details\": \"The resulting slurry was stirred\"}, {\"type\": \"TEMPERATURE\", \"details\": \"cooled to +10\\u00b0 C. for 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"WASH\", \"details\": \"The solids were washed with isopropyl ether and vacuum\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isopropyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 39.1, \"units\": \"KILOGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 71.1}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d779de5181ec462b887d44e5eb4602cf",
    "procedure_text": "A solution of potassium hydroxide (1.6 g, 29.2 mmol) in methanol (9.8 ml) was added to a solution of hydroxylamine hydrochloride (1.02 g, 14.6 mmol) in methanol (9.8 ml) at 0\u00b0 C. After 5 min., a solution of methyl 2-(R)-{benzyl-[4-(4-chlorophenyl)piperazine-1-sulfonyl]amino}-propionate (1.101 g, 2.44 mmol) in methanol (9.8 ml), [prepared as described in Example 2, Step, 2, but replacing D-valinesulfamoyl chloride methyl ester and 4-(5-chloropyridin-2-yloxy)piperidine with D-alaninesulfamoyl chloride methyl ester and 4-(4-chlorophenyl)-piperazine respectively, followed by benzylation as described in Example 4] was added and the reaction temperature was allowed to rise to RT. After 5 h, the reaction mixture was diluted with methylene chloride (147 ml) and neutralized with 10% aqueous HCl. The solvent was removed in vacuo and the residue was dissolved in methanol. The insoluble salts were filtered off and N-hydroxy-2-(R)-{benzyl-[4-(4-chlorophenyl)piperazine-1-sulfonyl]amino}-propionamide was isolated using reverse phase preparative HPLC (20-70% acetonitrile/0.1% aqueous trifluoroacetic acid) as a crystalline solid (23%).",
    "reference_string": "{\"inputs\": {\"m1_m9_m2_m10\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium hydroxide\"}], \"amount\": {\"mass\": {\"value\": 1.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydroxylamine hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 1.02, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 9.8, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 9.8, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m12\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 147.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(5-chloropyridin-2-yloxy)piperidine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3_m11\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 2-(R)-{benzyl-[4-(4-chlorophenyl)piperazine-1-sulfonyl]amino}-propionate\"}], \"amount\": {\"mass\": {\"value\": 1.101, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 9.8, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloride methyl ester\"}], \"reaction_role\": \"REACTANT\"}]}, \"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloride methyl ester\"}], \"reaction_role\": \"REACTANT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(4-chlorophenyl)-piperazine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"CUSTOM\", \"details\": \"to rise to RT\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"WAIT\", \"details\": \"After 5 h\", \"duration\": {\"value\": 5.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The solvent was removed in vacuo\"}, {\"type\": \"DISSOLUTION\", \"details\": \"the residue was dissolved in methanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"The insoluble salts were filtered off\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 5.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-hydroxy-2-(R)-{benzyl-[4-(4-chlorophenyl)piperazine-1-sulfonyl]amino}-propionamide\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-29e8ceb103954c80b1398f330265441e",
    "procedure_text": "A mixture of 3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)benzohydrazide (4.10 g), 3,4-difluorophenylacetic acid (3.15 g), HATU (7.57 g) and triethylamine (2.77 mL) in DMF (77 mL,) was stirred at room temperature for 16 hr. Water was added to the reaction mixture, and the resultant precipitate was collected by filtration and washed with hexane and acetone to give the title compound (4.69 g).",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)benzohydrazide\"}], \"amount\": {\"mass\": {\"value\": 4.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,4-difluorophenylacetic acid\"}], \"amount\": {\"mass\": {\"value\": 3.15, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HATU\"}], \"amount\": {\"mass\": {\"value\": 7.57, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 2.77, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 77.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at room temperature for 16 hr\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"the resultant precipitate was collected by filtration\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"resultant precipitate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with hexane and acetone\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 4.69, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-cd656bfe9a854b84bc3ffeafd56442bf",
    "procedure_text": "Ethyl 4-[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butanoate (6.25 g, 18.3 mmol) and morpholine (16.0 g, 184 mmol) were sealed and heated in a high-pressure vessel at 130\u00b0 C. overnight. An analysis by TLC indicated the reaction was incomplete. Pyridinium p-toluenesulfonate (100 mg) was added, and the reaction was heated for three days at 105\u00b0 C. and for one day at 125\u00b0 C. The solution was allowed to cool and then poured into water (100 mL). The resulting solution was extracted with dichloromethane (3\u00d775 mL), and the combined extracts were dried over potassium carbonate, filtered, and concentrated under reduced pressure. The residue was mixed with ethyl acetate (50 mL) and hexane (200 mL) and sonicated. The solvent was decanted away to afford 6.9 g of 2-(ethoxymethyl)-1-(4-morpholin-4-yl-4-oxobutyl)-1H-imidazo[4,5-c]quinoline as an oil.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ethyl 4-[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butanoate\"}], \"amount\": {\"mass\": {\"value\": 6.25, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"morpholine\"}], \"amount\": {\"mass\": {\"value\": 16.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pyridinium p-toluenesulfonate\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 130.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"the reaction was heated for three days at 105\\u00b0 C. and for one day at 125\\u00b0 C\", \"duration\": {\"value\": 1.0, \"units\": \"DAY\"}, \"temperature\": {\"setpoint\": {\"value\": 125.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"to cool\"}, {\"type\": \"EXTRACTION\", \"details\": \"The resulting solution was extracted with dichloromethane (3\\u00d775 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 75.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"the combined extracts were dried over potassium carbonate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"ADDITION\", \"details\": \"The residue was mixed with ethyl acetate (50 mL) and hexane (200 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"sonicated\"}, {\"type\": \"CUSTOM\", \"details\": \"The solvent was decanted away\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(ethoxymethyl)-1-(4-morpholin-4-yl-4-oxobutyl)-1H-imidazo[4,5-c]quinoline\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 6.9, \"units\": \"GRAM\"}}}], \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e827c00bc27e4ba08d4231e3fc47766b",
    "procedure_text": "A solution of 2,3-quinolinedicarboxylic anhydride (0.37 mol) in tetrahydrofuran (THF, 250 mL) is stirred at 5\u00b0 C. under a drying tube, and a solution of 2-amino-2,3-dimethylbutyramide (0.37 mol) in THF (50 mL) added thereto, in small increments, over a 15 minute period. The reaction mixture is allowed to warm slowly to room temperature for an extended period of time, i.e. about 17 hours. The solvent is evaporated in vacuo to afford a gummy residue, which is triturated with hot ethyl acetate (400 mL) and then filtered to afford the desired 2-[(1-carbamoyl-1,2-dimethylpropyl)carbamoyl]-3-quinolinecarboxylic acid, mp 172.5\u00b0-173.5\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,3-quinolinedicarboxylic anhydride\"}], \"amount\": {\"moles\": {\"value\": 0.37, \"units\": \"MOLE\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-amino-2,3-dimethylbutyramide\"}], \"amount\": {\"moles\": {\"value\": 0.37, \"units\": \"MOLE\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The solvent is evaporated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"to afford a gummy residue, which\"}, {\"type\": \"CUSTOM\", \"details\": \"is triturated with hot ethyl acetate (400 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 400.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-[(1-carbamoyl-1,2-dimethylpropyl)carbamoyl]-3-quinolinecarboxylic acid\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a0d97e51d6c347a181facba8807526cb",
    "procedure_text": "(4-Mercapto-phenyl)-acetic acid methyl ester (1.8 g, 9.89 mmol) was dissolved in DMF (20 ml) at 0\u00b0 C. Triethylamine (1.5 g, 14.83 mmol) was added and stirred for 15 minutes followed by addition of 4-iodo-tetrahydropyan (3.14 g, 14.83 mmol). The reaction mixture was stirred overnight at room temperature. Solvent was removed under reduced pressure, the resulting residue was taken into water and extracted with ethyl acetate (50 ml\u00d72) washed with water and brine (50 ml each) dried over anhydrous sodium sulfate, filtered and concentrated to obtain a crude product which was purified by column chromatography over silica gel using 15% ethyl acetate in hexanes as eluent to provide [4-(Tetrahydro-pyran-4-ylsulfanyl)-phenyl]acetic acid methyl ester (2.1 gm).",
    "reference_string": "{\"inputs\": {\"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(4-Mercapto-phenyl)-acetic acid methyl ester\"}], \"amount\": {\"mass\": {\"value\": 1.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Triethylamine\"}], \"amount\": {\"mass\": {\"value\": 1.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred for 15 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"followed by addition of 4-iodo-tetrahydropyan (3.14 g, 14.83 mmol)\"}, {\"type\": \"STIRRING\", \"details\": \"The reaction mixture was stirred overnight at room temperature\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"Solvent was removed under reduced pressure\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate (50 ml\\u00d72)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with water and brine (50 ml each)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"to obtain a crude product which\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"was purified by column chromatography over silica gel using 15% ethyl acetate in hexanes as eluent\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"[4-(Tetrahydro-pyran-4-ylsulfanyl)-phenyl]acetic acid methyl ester\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.1, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c963745c300b48fa94f121d885dfe89a",
    "procedure_text": "Formic acid (230 g, 5.0 mol) is added dropwise to acetic anhydride (383 g, 3.75 mol) at 0\u00b0 C. This mixture is stirred for 2 hours at +55\u00b0 C. and subsequently cooled again to 0\u00b0 C. Tetrahydrofuran (500 ml) is added at this temperature followed by 4-(2-amino-ethyl)-2-methoxy-phenol hydrochloride (50 g, 0.25 mol). The resulting white suspension is stirred for 18 hours at +75\u00b0 C., changing into a yellow solution. The reaction mixture is evaporated and the residue is submitted to flash-chromatography to yield N-[2-(4-hydroxy-3-methoxy-phenyl)-ethyl]-formamide. 1H-NMR (300 MHz, CDCl3, \u03b4(ppm)): 2.85 (t, 2H, CH2CH2), 3.57 (t, 2H, CH2CH2), 3.82 (s, 3H, OCH3), 5.69 (bs, 1H, NH), 6.67\u20137.09 (m, 3H, CH arom.), 8.12 (s, 1H, CHO).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Formic acid\"}], \"amount\": {\"mass\": {\"value\": 230.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic anhydride\"}], \"amount\": {\"mass\": {\"value\": 383.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(2-amino-ethyl)-2-methoxy-phenol hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"This mixture is stirred for 2 hours at +55\\u00b0 C.\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"The resulting white suspension is stirred for 18 hours at +75\\u00b0 C.\", \"duration\": {\"value\": 18.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture is evaporated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-[2-(4-hydroxy-3-methoxy-phenyl)-ethyl]-formamide\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-8219429150f643b0b48213d64ac967a7",
    "procedure_text": "1-(4\u2032-Phthalimidobutoxy)3,5-dibromobenzene (1.0 g, 2.20 mmol) was dissolved in ethanol (45 mL) for 5 minutes under nitrogen. Hydrazine monohydrate (610 mg, 12.1 mmol) was added and the reaction was refluxed at 80\u00b0 C. for 2 hours. To the reaction aqueous 1M HCl (17.7 mL, 17.7 mmol) was added and refluxed at 105\u00b0 C. for another 2 hours. The aqueous layer was extracted with dichloromethane (2\u00d7150 mL). The organic layers were combined, washed with saturated NaHCO3 (3\u00d7), water, and brine, then dried over MgSO4, and filtered. Removal of solvent yielded a yellow oil (560 mg, 78%).",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(4\\u2032-Phthalimidobutoxy)3,5-dibromobenzene\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 45.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Hydrazine monohydrate\"}], \"amount\": {\"mass\": {\"value\": 610.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 17.7, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 80.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"refluxed at 105\\u00b0 C. for another 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 105.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"The aqueous layer was extracted with dichloromethane (2\\u00d7150 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with saturated NaHCO3 (3\\u00d7), water, and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"Removal of solvent\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"oil\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 560.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 78.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 78.8}}], \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-9a4d5baae8064d5aac0a7606d59f1d28",
    "procedure_text": "Combine 2-chloro-1-(2-ethoxyethyl)-1H-benzimidazole (22.3 g, 99.4 mmol), 1-methyl[1,4]diazepane (19 mL, 152.8 mmol), and triethylamine (75 mL). Heat to 70\u00b0 C. After 18 hours, add 1-methyl[1,4]diazepane (10 mL) and continue to heat at reflux. After 96 hours, cool to ambient temperature and partition the reaction mixture between water and ethyl acetate. Separate the layers and extract the organic layer with a saturated aqueous sodium bicarbonate solution and then brine. Dry the organic layer over MgSO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting sequentially with 50% ethyl acetate/hexane and then 10% methanol/dichloromethane to give 1-methyl-4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepane: Rf=0.52 (silica gel, dichloromethane/methanol/concentrated aqueous ammonia, 90/10/0.1).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-methyl[1,4]diazepane\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5_m6_m0\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate hexane\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol dichloromethane\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloro-1-(2-ethoxyethyl)-1H-benzimidazole\"}], \"amount\": {\"mass\": {\"value\": 22.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-methyl[1,4]diazepane\"}], \"amount\": {\"volume\": {\"value\": 19.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 75.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 70.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"to heat\"}, {\"type\": \"TEMPERATURE\", \"details\": \"at reflux\"}, {\"type\": \"WAIT\", \"details\": \"After 96 hours\", \"duration\": {\"value\": 96.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"cool to ambient temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"partition the reaction mixture between water and ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Separate the layers\"}, {\"type\": \"EXTRACTION\", \"details\": \"extract the organic layer with a saturated aqueous sodium bicarbonate solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"Dry the organic layer over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filter\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporate in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a residue\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 18.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-methyl-4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepane\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f8df416800c74f0cbf4ceeaeb53d0356",
    "procedure_text": "A solution of 2-ethyl-4-nitro-phenol (3.34 g, 20.00 mmol) in MeOH (40 ml) and aqueous 1M HCl (20 ml, 20.00 mmol) was hydrogenated in the presence of 10% Pd/C (0.33 g) for 4 h. After removal of the catalyst the reaction was evaporated and suspended in CH2Cl2 and a small amount of MeOH, dried (Na2SO4) and evaporated to give 3.35 g (96%) of 4-amino-2-ethyl-phenol.HCl, MS: 138 (MH+), MP: 239-240\u00b0 C., dec.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-ethyl-4-nitro-phenol\"}], \"amount\": {\"mass\": {\"value\": 3.34, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd/C\"}], \"amount\": {\"mass\": {\"value\": 0.33, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"After removal of the catalyst the reaction\"}, {\"type\": \"CUSTOM\", \"details\": \"was evaporated\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"a small amount of MeOH, dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-amino-2-ethyl-phenol\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 3.35, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 96.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-555fa250ebb047cdab157d5cad4bace3",
    "procedure_text": "Chloromethyl phenylacetate (Neuenschwander, Markus et. al., Helv. Chin. Acta, 61 (1978) 2047) (1.59 g. 8.6 mmol) in dry DMF (20 ml) is added dropwise at 50\u00b0 C. to a solution of cesium 5-(N-acetylamino)-3-(N-acetyl-N-methylamino)-2,4,6-triiodobenzenecarboxylate (7.28 g, 9.6 mmol) and sodium iodide (64 mg, 0.42 mmol) in dry DMF (100 ml). The precipitate is removed by filtration after stirring for 20 hours and the solvent is removed at reduced pressure. The residue is dissolved in chloroform (200 ml) and washed twice with a saturated sodium hydrogen carbonate solution and twice with water. After drying with magnesium sulfate the solvent is removed at reduced pressure to give the title compound:",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Chloromethyl phenylacetate\"}], \"amount\": {\"mass\": {\"value\": 1.59, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cesium 5-(N-acetylamino)-3-(N-acetyl-N-methylamino)-2,4,6-triiodobenzenecarboxylate\"}], \"amount\": {\"mass\": {\"value\": 7.28, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium iodide\"}], \"amount\": {\"mass\": {\"value\": 64.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"after stirring for 20 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The precipitate is removed by filtration\"}, {\"type\": \"CUSTOM\", \"details\": \"the solvent is removed at reduced pressure\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue is dissolved in chloroform (200 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed twice with a saturated sodium hydrogen carbonate solution and twice with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydrogen carbonate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"After drying with magnesium sulfate the solvent\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"is removed at reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 20.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-db74311bd1fc41858e66dec60dfa7074",
    "procedure_text": "3-(3-Chloro-phenyl)-1-[1-(1,1-dioxo-tetrahydro-thiophene-3-sulfonyl)-piperidin-4-yl]-7-methoxy-1H-pyrimido[5,4-c]quinoline-2,4-dione (51 mg) was prepared according to general procedure H from 3-(3-chloro-phenyl)-7-methoxy-1-piperidin-4-yl-1H-pyrimido[5,4-c]quinoline-2,4-dione.dihydrochloride (50 mg, 0.1 mmol) and 1,1-dioxo-tetrahydro-thiophene-3-sulfonyl chloride. LCMS: m/z 619 [M+1]+.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(3-chloro-phenyl)-7-methoxy-1-piperidin-4-yl-1H-pyrimido[5,4-c]quinoline-2,4-dione.dihydrochloride\"}], \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,1-dioxo-tetrahydro-thiophene-3-sulfonyl chloride\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(3-Chloro-phenyl)-1-[1-(1,1-dioxo-tetrahydro-thiophene-3-sulfonyl)-piperidin-4-yl]-7-methoxy-1H-pyrimido[5,4-c]quinoline-2,4-dione\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 51.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-30077d7c5c7a4980ab8fc3340c62f031",
    "procedure_text": "A mixture consisting of 11.3 g (0.046 mole) of 1-ethyl-7-fluoro-4-methoxy-[1,2,4]triazolo[4,3-a]quinoxaline, 115 ml. of 1N hydrochloric acid and 345 ml. of glacial acetic acid was refluxed for a period of three hours. Upon completion of this step, the reaction mixture was cooled to room temperature and poured over ice/water. The resulting mixture was then stirred for a period of 30 minutes, filtered and the recovered solid product subsequently washed with water and air-dried to ultimately afford 6.6 g. (62%) of pure 1-ethyl-7-fluoro-4-hydroxy-[1,2,4]triazolo[4,3-a]quinoxaline, m.p.>300\u00b0 C. Mass Spectrum: m/e, 232 (P); m/e, 231 (P-1).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-ethyl-7-fluoro-4-methoxy-[1,2,4]triazolo[4,3-a]quinoxaline\"}], \"amount\": {\"mass\": {\"value\": 11.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The resulting mixture was then stirred for a period of 30 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"WASH\", \"details\": \"the recovered solid product subsequently washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"air-dried to ultimately afford 6.6 g\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-ef82957925b84e55a9b109e3e8937307",
    "procedure_text": "A mixture of 5-{4-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrole-3-carboxylic acid (50 mg, 0.11 mmol), ethylene glycol (1 ml), 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC.HCl, 25 mg, 0.13 mmol) and 4-dimethylaminopyridine (DMAP, 5 mg, 0.04 mmol) in anhydrous THF (10 ml) was stirred at 60\u00b0 C. for 16 hours. The mixture was poured into 100 ml of water. 2M HCl was added dropwise until pH=4. The precipitates were filtered, washed with water and dried in vacuo to give the crude, which was purified by silica gel chromatography with a gradient of 3\u02dc5% MeOH/CHCl3 to give 2-hydroxyethyl 5-{4-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrole-3-carboxylate as white solid. Yield: 36 mg, 67%.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-{4-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrole-3-carboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethylene glycol\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 25.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-dimethylaminopyridine\"}], \"amount\": {\"mass\": {\"value\": 5.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at 60\\u00b0 C. for 16 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The precipitates were filtered\"}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"to give the crude, which\"}, {\"type\": \"CUSTOM\", \"details\": \"was purified by silica gel chromatography with a gradient of 3\\u02dc5% MeOH/CHCl3\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH CHCl3\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-hydroxyethyl 5-{4-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrole-3-carboxylate\"}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-22f8833845da41d8900c4e6335b90971",
    "procedure_text": "To a 0\u00b0 solution of 54.30 g (0.30 moles) of 2-methyl-6-nitrobenzoic acid in 500 ml of anhydrous tetrahydrofuran was added dropwise under a nitrogen atmosphere, 380 ml (0.38 moles) of a stock IM boran/THF solution at such a rate that the temperature did not exceed 5\u00b0. Upon complete addition, the ice bath was removed, the solution allowed to stir at room temperature for 14 hours, heated to reflux for 4 hrs. and then cooled to 0\u00b0 in an ice bath. The reaction was quenched by the dropwise addition of 400 ml of 10% hydrochloric acid, the solution heated to reflux on a steam bath for 0.5 hrs., the THF solvent distilled at atmospheric pressure and the insoluble precipitate extracted into methylene chloride. The methylene chloride extracts were combined, washed with satd. sodium bicarbonate solution, dried (Na2SO4) and the solvent removed in vacuo affording a reddish colored semi solid. Purification was effected from 300 ml of carbon tetrachloride resulting in 41.35 g (84% yield) of yellow flakes; mp 67\u00b0-8\u00b0.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-methyl-6-nitrobenzoic acid\"}], \"amount\": {\"mass\": {\"value\": 54.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"to stir at room temperature for 14 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"did not exceed 5\\u00b0\"}, {\"type\": \"ADDITION\", \"details\": \"Upon complete addition\"}, {\"type\": \"CUSTOM\", \"details\": \"the ice bath was removed\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to reflux for 4 hrs\", \"duration\": {\"value\": 4.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"and then cooled to 0\\u00b0 in an ice bath\"}, {\"type\": \"CUSTOM\", \"details\": \"The reaction was quenched by the dropwise addition of 400 ml of 10% hydrochloric acid\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 400.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"the solution heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to reflux on a steam bath for 0.5 hrs\", \"duration\": {\"value\": 0.5, \"units\": \"HOUR\"}}, {\"type\": \"DISTILLATION\", \"details\": \", the THF solvent distilled at atmospheric pressure\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"the insoluble precipitate extracted into methylene chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with satd\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"sodium bicarbonate solution, dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent removed in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"affording a reddish colored semi solid\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 14.0, \"units\": \"HOUR\"}, \"products\": [{\"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 84.0}}]}]}]}"
  },
  {
    "reaction_id": "ord-ce0e9afc00dd47a7a029614f30151c5f",
    "procedure_text": "To 2,4-difluoro-3-[hydroxy-(5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-phenol (P-0009, 45.0 mg, 1.27 mmol) in tetrahydrofuran (15 mL) and N,N-dimethylformamide (5 mL) was added dichlorodicyanoquinone (87 mg, 3.8 mmol). The reaction was stirred at room temperature for 50 hours. The reaction was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated. The desired compound was isolated by silica eel column chromatography eluting with 5% methanol in methylene chloride to give a white solid (P-0066, 7 mg, 15.6%). MS(ESI) [M+H+]+=352.1.",
    "reference_string": "{\"inputs\": {\"m1_m5_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,4-difluoro-3-[hydroxy-(5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-phenol\"}], \"amount\": {\"mass\": {\"value\": 45.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichlorodicyanoquinone\"}], \"amount\": {\"mass\": {\"value\": 87.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction was stirred at room temperature for 50 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 50.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-466a68ffcd0945c38d6378829ad628cb",
    "procedure_text": "Ethanethiol (0.0389 ml) was added to a mixture of 4-(2,3-dihydro-6-methyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-4-methylpent-1-en-3-one (100 mg) and potassium carbonate (4.85 mg) in N,N-dimethylformamide, and then stirred overnight at 20\u00b0 C., and for 24 hours at 40\u00b0 C. The mixture was purified by silica gel column chromatography eluting with isohexane/ethyl acetate (4:1) to give 5-ethylthio-2-(2,3-dihydro-6-methyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-2-methylpentan-3-one (Compound 1083, 45 mg), NMR 1.2(t,3H), 1.4(s,6H), 1.9(s,3H), 2.5(q,2H), 2.8(s,4H), 5.3(s,2H),7.2-7.4(m,5H).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ethanethiol\"}], \"amount\": {\"volume\": {\"value\": 0.0389, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(2,3-dihydro-6-methyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-4-methylpent-1-en-3-one\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 4.85, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 20.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred overnight at 20\\u00b0 C.\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WAIT\", \"details\": \"for 24 hours at 40\\u00b0 C\", \"duration\": {\"value\": 24.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 40.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The mixture was purified by silica gel column chromatography\"}, {\"type\": \"WASH\", \"details\": \"eluting with isohexane/ethyl acetate (4:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isohexane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-ethylthio-2-(2,3-dihydro-6-methyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-2-methylpentan-3-one\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 45.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-29f3594dc9da41aa81020feba0367a01",
    "procedure_text": "Combine 1-ethoxycarbonyl-4-(1H-benzimidazol-2-yl)[1,4]diazepane (10 mmol) and sodium hydride (10 mmol) in dimethylformamide (20 mL). After gas evolution ceases, add ethyl 5-chloromethyl-2-furoate (10 mmol) and stir. After 3 days, evaporate in vacuo to give a residue. Combine the residue and ethyl acetate. Extract with water and brine. Dry the the organic layer over Na2SO4, filter, and evaporate in vacuo to give 1-ethoxycarbonyl-4-(1-(5-(ethoxycarbonyl)fur-2-ylmethyl)-1H-benzimidazol-2-yl)[1,4]diazepane.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-ethoxycarbonyl-4-(1H-benzimidazol-2-yl)[1,4]diazepane\"}], \"amount\": {\"moles\": {\"value\": 10.0, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydride\"}], \"amount\": {\"moles\": {\"value\": 10.0, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 5-chloromethyl-2-furoate\"}], \"amount\": {\"moles\": {\"value\": 10.0, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stir\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"evaporate in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a residue\"}, {\"type\": \"EXTRACTION\", \"details\": \"Extract with water and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"Dry the the organic layer over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filter\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporate in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"DAY\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-ethoxycarbonyl-4-(1-(5-(ethoxycarbonyl)fur-2-ylmethyl)-1H-benzimidazol-2-yl)[1,4]diazepane\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3221fd17c5e44505bf3678f8a8deea4f",
    "procedure_text": "To a suspension of 8.15 g (214.8 mmol) of lithium aluminium hydride (LiAlH4) in 800 mL of methyl tert-butyl ether (MTBE) there are added 101.2 g of the ditosyl compound obtained in Step A (214.8 mmol) dissolved in 200 mL of MTBE. The batch is then heated at 50\u00b0 C. for 2 hours. It is allowed to cool and placed at 0\u00b0 C., and there are then added, dropwise, 12 mL of 5N NaOH solution. The batch is stirred at ambient temperature for 45 minutes. The solid thereby obtained is then filtered off and washed with MTBE and then with dichloromethane. The filtrate is then concentrated to dryness. The title product is then obtained in the form of a solid.",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium aluminium hydride\"}], \"amount\": {\"mass\": {\"value\": 8.15, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl tert-butyl ether\"}], \"amount\": {\"volume\": {\"value\": 800.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ditosyl\"}], \"amount\": {\"mass\": {\"value\": 101.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MTBE\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"amount\": {\"volume\": {\"value\": 12.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 50.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The batch is stirred at ambient temperature for 45 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"to cool\"}, {\"type\": \"CUSTOM\", \"details\": \"placed at 0\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"ADDITION\", \"details\": \"there are then added\"}, {\"type\": \"CUSTOM\", \"details\": \"The solid thereby obtained\"}, {\"type\": \"FILTRATION\", \"details\": \"is then filtered off\"}, {\"type\": \"WASH\", \"details\": \"washed with MTBE\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MTBE\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"The filtrate is then concentrated to dryness\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 45.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title product\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3f0d16ec04c64c18b9568e8e45b85c21",
    "procedure_text": "Grignard reagent was prepared in an oven-dried three necked flask outfitted with a reflux condenser, dropping funnel, and magnetic stirrer. Approximately \u00bc of a solution of 3,5-bromoveratrole (10 g, 46.1 mmol) in anhydrous THF (60 mL) was added to a mixture of magnesium turnings (1.12 g, 46.1 mmol) in THF (10 mL) with a small piece of iodine. As soon as the solution became colorless (heating sometimes necessary), the remaining 3,5-bromoveratrole solution was added dropwise to the reaction mixture under mild reflux, over 30 min. The resulting mixture was refluxed for 3 h then cooled to room temperature for 30 min. The (3,5-dimethoxy-phenyl) magnesium bromide was then added slowly to a stirred solution of 4-methoxy-3-nitro-benzaldehyde (6.95 g, 38.4 mmol) in THF (60 mL) at 0\u00b0 C. After complete addition, the reaction mixture was stirred at cold for 10 min and then at room temperature for 2 h. The solution was cooled to 0\u00b0 C. and quenched with saturated NH4Cl solution (90 mL). The aqueous layer was extracted with ether (3\u00d790 mL). The combined organic layers were washed with water (2\u00d7120 mL), brine (120 mL) and dried (MgSO4). Removal of solvent gave the crude (3,5-dimethoxy-phenyl)-(4-methoxy-3-nitro-phenyl)-methanol, which was used in the next step without further purification.",
    "reference_string": "{\"inputs\": {\"m2_m8_m3_m9_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,5-bromoveratrole\"}], \"amount\": {\"mass\": {\"value\": 10.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium\"}], \"amount\": {\"mass\": {\"value\": 1.12, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"iodine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,5-bromoveratrole\"}], \"reaction_role\": \"REACTANT\"}]}, \"m6_m7_m10\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(3,5-dimethoxy-phenyl) magnesium bromide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-methoxy-3-nitro-benzaldehyde\"}], \"amount\": {\"mass\": {\"value\": 6.95, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture was stirred at cold for 10 min\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"an oven-dried three necked flask\"}, {\"type\": \"CUSTOM\", \"details\": \"outfitted with a reflux condenser\"}, {\"type\": \"ADDITION\", \"details\": \"was added dropwise to the reaction mixture under mild reflux, over 30 min\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"The resulting mixture was refluxed for 3 h\", \"duration\": {\"value\": 3.0, \"units\": \"HOUR\"}}, {\"type\": \"ADDITION\", \"details\": \"After complete addition\"}, {\"type\": \"WAIT\", \"details\": \"at room temperature for 2 h\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"The solution was cooled to 0\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"quenched with saturated NH4Cl solution (90 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH4Cl\"}], \"amount\": {\"volume\": {\"value\": 90.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The aqueous layer was extracted with ether (3\\u00d790 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"amount\": {\"volume\": {\"value\": 90.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined organic layers were washed with water (2\\u00d7120 mL), brine (120 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 120.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 120.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Removal of solvent\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 10.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Grignard reagent\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(3,5-dimethoxy-phenyl)-(4-methoxy-3-nitro-phenyl)-methanol\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3aea12f660ae42a595950e40397af94a",
    "procedure_text": "The title compound was prepared according to General Method A starting from 2-((R)-1-chloro-ethyl)-isonicotinonitrile (46 mg, 0.28 mmol) and (2R)-2-[(2-amino-5-mercapto[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]-4-methylpentan-1-ol (69 mg, 0.23 mmol). Purification by chiral HPLC (Column: Chiralpak AD 50\u00d7150 mm, eluent: heptane:isopropanol 85:15), flowrate 60 ml/min) yielded the title compound (20 mg, 20% yield).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-((R)-1-chloro-ethyl)-isonicotinonitrile\"}], \"amount\": {\"mass\": {\"value\": 46.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2R)-2-[(2-amino-5-mercapto[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]-4-methylpentan-1-ol\"}], \"amount\": {\"mass\": {\"value\": 69.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The title compound was prepared\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Purification by chiral HPLC (Column: Chiralpak AD 50\\u00d7150 mm, eluent: heptane:isopropanol 85:15), flowrate 60 ml/min)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"heptane isopropanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 20.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 20.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 20.2}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-225a0a7545e24717a4ea3d58050b1e41",
    "procedure_text": "The operation was as in Example 1, except that 14 g of 1-(2-phenyl-4-quinolyl)-3-(4-piperidyl)-1-propanone and 2.3 g of sodium borohydride in 300 ml of methanol were used. After recrystallization of the crude product in isopropanol, 7 g of 1-(2-phenyl-4-quinolyl)-3-(4-piperidyl)-1-propanol (racemic) were obtained, which melted at 162\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(2-phenyl-4-quinolyl)-3-(4-piperidyl)-1-propanone\"}], \"amount\": {\"mass\": {\"value\": 14.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium borohydride\"}], \"amount\": {\"mass\": {\"value\": 2.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 300.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"After recrystallization of the crude product in isopropanol, 7 g of 1-(2-phenyl-4-quinolyl)-3-(4-piperidyl)-1-propanol (racemic)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isopropanol\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(2-phenyl-4-quinolyl)-3-(4-piperidyl)-1-propanol\"}], \"amount\": {\"mass\": {\"value\": 7.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"were obtained\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(2-PHENYL-4-QUINOLYL)-3-(4-PIPERIDYL)-1-PROPANOL\"}]}]}]}"
  },
  {
    "reaction_id": "ord-6720839f8c324baf93ffc7d4c15fbbeb",
    "procedure_text": "A solution of 4 N hydrochloric acid in ethyl acetate (1 mL) was added to a solution of tert-butyl[2-oxo-3-(3,4,5-trifluorophenyl)piperidin-1-yl]carbamate (134 mg) in chloroform (1 mL), and the reaction solution was stirred at room temperature for three hours. The reaction solution was concentrated under reduced pressure to obtain 109 mg of the title compound. The property value of the compound is as follows.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl[2-oxo-3-(3,4,5-trifluorophenyl)piperidin-1-yl]carbamate\"}], \"amount\": {\"mass\": {\"value\": 134.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction solution was stirred at room temperature for three hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"The reaction solution was concentrated under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 109.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-7750079b85e64aaeb0b3cc9aa6ebbb67",
    "procedure_text": "ca) 50 ml of 33 percent hydrobromic acid in acetic acid are added dropwise within 15 minutes at 10\u00b0 to 20 g of 4-(benzyloxy)-3-methoxyphenyl 3-pyridyl ketone dissolved in 200 ml of methylene chloride. After stirring at 20\u00b0 for 3 hours, the reaction mixture is poured into a mixture of 100 ml of conc. aqueous ammonia and ice. The pH is adjusted to 6 by adding acetic acid. The methylene chloride phase is separated: the aqueous phase is extracted twice more with 100 ml of methylene chloride each time. The combined methylene chloride phases are dried over sodium sulfate and evaporated. The residue is recrystallized from methylene chloride/hexane. There is obtained 4-hydroxy-3-methoxyphenyl 3-pyridyl ketone of m.p. 150\u00b0-151\u00b0.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrobromic acid\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(benzyloxy)-3-methoxyphenyl 3-pyridyl ketone\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonia\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring at 20\\u00b0 for 3 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The methylene chloride phase is separated\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"the aqueous phase is extracted twice more with 100 ml of methylene chloride each time\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined methylene chloride phases are dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue is recrystallized from methylene chloride/hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-hydroxy-3-methoxyphenyl 3-pyridyl ketone\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-72e9bd4c60f24615ba6a8b476be84dff",
    "procedure_text": "The title compound (Sarges, R. et al., J. Med. Chem. 33:2240 (1990)) was prepared using an adaptation of the method of Cheeseman. (Cheeseman, G. W. H. J. Chem. Soc. 1171 (1962)). A mixture of diethyl oxalate (1.11 g, 7.63 mmol and 4,5-difluoro-1,2-diaminobenzene (110 mg, 0.763 mmol) was heated to reflux under N2 for 2 h. The reaction was allowed to cool to room temperature and the solid was collected by vacuum filtration, rinsed with hexanes, and air dried. This gray brown solid was recrystallized from 20 mL of EtOH and the brown-white crystals collected by vacuum filtration and the crystals further dried under vacuum (0.5 torr, 25\u00b0 C.) to yield 45.3 mg (30.0%); mp>360\u00b0 C. (lit.>310\u00b0 C.); 1H NMR (d6 -acetone) \u03b4 7.19 (t, 2H, ArH, JH-F =9.3), 10.9 (br s, 2H, NH).",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl oxalate\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4,5-difluoro-1,2-diaminobenzene\"}], \"amount\": {\"mass\": {\"value\": 110.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to reflux under N2 for 2 h\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"the solid was collected by vacuum filtration\"}, {\"type\": \"WASH\", \"details\": \"rinsed with hexanes, and air\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"CUSTOM\", \"details\": \"This gray brown solid was recrystallized from 20 mL of EtOH\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOH\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"the brown-white crystals collected by vacuum filtration\"}, {\"type\": \"CUSTOM\", \"details\": \"the crystals further dried under vacuum (0.5 torr, 25\\u00b0 C.)\", \"temperature\": {\"setpoint\": {\"value\": 25.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"to yield 45.3 mg (30.0%)\"}, {\"type\": \"CUSTOM\", \"details\": \"mp>360\\u00b0 C. (lit.>310\\u00b0 C.)\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2f03f86e82c54fe2b75ef364dc7adb49",
    "procedure_text": "20 parts of 2-iodofluorene was dissolved in a mixed solution of 114 parts of dimethyl sulfoxide (DMSO) and 23 parts of tetrahydrofuran (THF), and the thus obtained mixture was then stirred at 25\u00b0 C. for 10 minutes. Thereafter, while stirring, 8.6 parts of potassium-tert-butoxide was added to the mixture. Twenty minutes later, 14.6 parts of butyl iodide was added to the mixture, and further twenty minutes later, 8.6 parts of potassium-tert-butoxide was added thereto. Further, twenty minutes later, 14.6 parts of butyl iodide was added thereto, and the obtained mixture was then stirred at 25\u00b0 C. for 2 hours. After completion of the stirring, THF was distilled away from the reaction solution, and it was then extracted with toluene-water. The toluene phase was dried over magnesium sulfate, and toluene was then distilled away, thereby obtaining a brown tarry solid. This brown tarry solid was separated and purified by column chromatography (hexane-ethyl acetate) to obtain 25 parts of 9,9-dibutyl-2-iodofluorene in the form of a colorless crystal.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"butyl iodide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"butyl iodide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2_m8_m7_m9\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-iodofluorene\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethyl sulfoxide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"114\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium-tert-butoxide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium-tert-butoxide\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 25.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the thus obtained mixture was then stirred at 25\\u00b0 C. for 10 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"Thereafter, while stirring\"}, {\"type\": \"STIRRING\", \"details\": \"the obtained mixture was then stirred at 25\\u00b0 C. for 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 25.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"DISTILLATION\", \"details\": \"After completion of the stirring, THF was distilled away from the reaction solution, and it\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"was then extracted with toluene-water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The toluene phase was dried over magnesium sulfate, and toluene\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"was then distilled away\"}, {\"type\": \"CUSTOM\", \"details\": \"obtaining a brown tarry solid\"}, {\"type\": \"CUSTOM\", \"details\": \"This brown tarry solid was separated\"}, {\"type\": \"CUSTOM\", \"details\": \"purified by column chromatography (hexane-ethyl acetate)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 10.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"25\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"9,9-dibutyl-2-iodofluorene\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a93947a9ce4f4082884d3f199442879e",
    "procedure_text": "To a solution of (+)-trans-3-hydroxymethyl-4-phenylcyclopentan-1-one from Example 8, Step F (3.3 g, 16 mmol) in methylene chloride (100 mL) was added t-butyldimethylsilyl chloride (11 g, 49 mmol) and DIPEA (22 mL, 74 mmol). The reaction was stirred at rt for 16 h, poured into dilute aq. hydrochloric acid and extracted twice with ether. The organic layers were washed with brine, dried over sodium sulfate, a combined and concentrated. The residue was purified by FC (5% ethyl acetate in hexanes) to afford of (+)-trans-1-t-butyldimethylsilyloxymethyl-4-oxo-2-phenylcyclopentane (6.3 g) as a oil.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m5_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(+)-trans-3-hydroxymethyl-4-phenylcyclopentan-1-one\"}], \"amount\": {\"mass\": {\"value\": 3.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"t-butyldimethylsilyl chloride\"}], \"amount\": {\"mass\": {\"value\": 11.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DIPEA\"}], \"amount\": {\"volume\": {\"value\": 22.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction was stirred at rt for 16 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted twice with ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layers were washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by FC (5% ethyl acetate in hexanes)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(+)-trans-1-t-butyldimethylsilyloxymethyl-4-oxo-2-phenylcyclopentane\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 6.3, \"units\": \"GRAM\"}}}], \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-ae48fa0c7ab04ecaab746eb88e454ffa",
    "procedure_text": "2-methylthioethylchloride (18.0 g, 0.16 mole), o-nitrophenol (20.8 g, 0.15 mole) and potassium carbonate (24.7 g, 0.18 mole) was refluxed in acetonitrile for 24 h. The reaction mixture was filtered and the solvent was evaporated. The residue was dissolved in methylene chloride and washed with water once and thereafter twice with a saturated sodium carbonate solution. The organic layer was dried over sodium sulfate and the solvent was evaporated giving 20.2 g (63%) of the title compound as an oily residue.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-methylthioethylchloride\"}], \"amount\": {\"mass\": {\"value\": 18.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"o-nitrophenol\"}], \"amount\": {\"mass\": {\"value\": 20.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 24.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The reaction mixture was filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was evaporated\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue was dissolved in methylene chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with water once\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layer was dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was evaporated\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 20.2, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 63.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 63.1}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-ddaa1b34cfc343a98004e9f2bd09e58b",
    "procedure_text": "A mixture of 4-bromo-6-chloro-2-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole (3.2 g, 9.70 mmol), Zn(CN)2 (2.3 g, 19.40 mmol), and Pd(PPh3)4 (1.1 g, 0.97 mmol) in NMP (20 mL) was stirred at 90\u00b0 C. for 3 h. The reaction mixture was filtered and the filtrate diluted with EtOAc (50 mL). The organic layer was washed with water (50 mL\u00d73), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by SiO2 chromatography eluting with a DCM:MeOH gradient (0 to 6% MeOH) to afford 6-chloro-2-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole-4-carbonitrile as a white solid (1.0 g, 37.2%). MS (ESI): m/z=276.2 [M+1]+.",
    "reference_string": "{\"inputs\": {\"m1_m3_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-bromo-6-chloro-2-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole\"}], \"amount\": {\"mass\": {\"value\": 3.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NMP\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Zn(CN)2\"}], \"amount\": {\"mass\": {\"value\": 2.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd(PPh3)4\"}], \"amount\": {\"mass\": {\"value\": 1.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 90.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at 90\\u00b0 C. for 3 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The reaction mixture was filtered\"}, {\"type\": \"ADDITION\", \"details\": \"the filtrate diluted with EtOAc (50 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with water (50 mL\\u00d73)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by SiO2 chromatography\"}, {\"type\": \"WASH\", \"details\": \"eluting with a DCM\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-chloro-2-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole-4-carbonitrile\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 37.2}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2302dda86ed84f9894aae5953b2be09f",
    "procedure_text": "To a solution of 1-(3-amino-2-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)-propyl)cyclohexanol (21 mg, 0.064 mmol) in CH2Cl2 (2 mL) were added Et3N (0.2 mL) and Me3SiCl (13.9 mg, 16 \u03bcL, 0.13 mmol). The resulting solution was stirred for 1 h and evaporated under vacuum. The residue was dissolved in CH2Cl2 (2 mL) and pyridine (0.05 mL) was added, followed by 4-nitrophenyl chloroformate (15 mg, 0.077 mmol). The mixture was stirred for 30 min to afford a solution of 1-(2-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)-3-(p-nitrophenoxycarbonylamino)propyl)-1-(trimethylsilyloxy)cyclohexane which was used directly without isolation.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-nitrophenyl chloroformate\"}], \"amount\": {\"mass\": {\"value\": 15.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(3-amino-2-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)-propyl)cyclohexanol\"}], \"amount\": {\"mass\": {\"value\": 21.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Et3N\"}], \"amount\": {\"volume\": {\"value\": 0.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Me3SiCl\"}], \"amount\": {\"volume\": {\"value\": 16.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The resulting solution was stirred for 1 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"evaporated under vacuum\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue was dissolved in CH2Cl2 (2 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"pyridine (0.05 mL) was added\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"amount\": {\"volume\": {\"value\": 0.05, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"STIRRING\", \"details\": \"The mixture was stirred for 30 min\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(2-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)-3-(p-nitrophenoxycarbonylamino)propyl)-1-(trimethylsilyloxy)cyclohexane\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3a4d3ba17dd24a73b8eb1b8917631480",
    "procedure_text": "Acetyl cyanide (4.55 ml, 64.3 mmol) was added to a mixture of N-benzyl-N-benzyloxycarbonyl-L-phenylalaninal (20.0 g, 53.6 mmol), zinc chloride (8.76 g, 64.3 mmol) and tetrahydrofuran (70 ml) at 5\u00b0 C. with stirring, and the whole was stirred at 25\u00b0 C. for 12 hours. After the reaction was finished, tetrahydrofuran was evaporated under reduced pressure. Water was added to the residue, and the whole was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give 19.6 g (yield 83%, erythro:threo=94:6) of titled (2S, 3S)-3-[N-(benzyl)-N-(benzyloxycarbonyl) amino]-2-acetyloxy-4-phenylbutyronitrile.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Acetyl cyanide\"}], \"amount\": {\"volume\": {\"value\": 4.55, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-benzyl-N-benzyloxycarbonyl-L-phenylalaninal\"}], \"amount\": {\"mass\": {\"value\": 20.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 70.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"zinc chloride\"}], \"amount\": {\"mass\": {\"value\": 8.76, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"with stirring\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"the whole was stirred at 25\\u00b0 C. for 12 hours\", \"duration\": {\"value\": 12.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 25.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"tetrahydrofuran was evaporated under reduced pressure\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"Water was added to the residue\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"the whole was extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by silica gel column chromatography\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2S, 3S)-3-[N-(benzyl)-N-(benzyloxycarbonyl) amino]-2-acetyloxy-4-phenylbutyronitrile\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 19.6, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 83.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fd9173d6d90944fa82e3d31de23492ea",
    "procedure_text": "To a stirred solution of 3-(1-(3-fluorobenzyl)-1H-pyrazol-4-yl)-5-(4-(piperazin-1-yl)phenyl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine (product of step 1 of example 124) (75 mg, 0.123 mmol), potassium carbonate (24 mg, 0.185 mmol) and DMF (5 ml) was added 2-bromoethanol (24 mg, 0.185 mmol) and the mixture stirred at RT for overnight. Then water was added, this was then extracted into 10% methanol in DCM, organic portion was dried over sodium sulfate and concentrated to give 60 mg (75% yield) of the titled compound. MS: m/z=651.2 (M+1).",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(1-(3-fluorobenzyl)-1H-pyrazol-4-yl)-5-(4-(piperazin-1-yl)phenyl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine\"}], \"amount\": {\"mass\": {\"value\": 75.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 24.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-bromoethanol\"}], \"amount\": {\"mass\": {\"value\": 24.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture stirred at RT for overnight\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"this was then extracted into 10% methanol in DCM, organic portion\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"was dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"titled compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 60.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 75.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 75.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-8a90f92c8b5f4054ba246788d41df462",
    "procedure_text": "Compound 11 (6.2 g, 20.5 mmol) was dissolved in methanol (70 mL), H2SO4 concentrated (4 mL) was added and the solution heated to reflux for 9 h. After cooling to r.t., the mixture was poured into ice (600 mL) and the precipitate formed was collected by filtration. Drying under hv gave 5.0 g (94%) of 12 as a yellow solid. Data of 12: Rf 0.85 (hexane/EtOAc 1:4). 1H NMR (300 MHz, DMSO-d6): \u03b4 3.77 (s, 6H), 6.85 (brs, 2H), 7.82 (s, 1H). 13C NMR (75 MHz, DMSO-d6): \u03b4 52.80, 64.68, 110.40, 114.21, 133.80, 142.29, 153.60, 163.48. MS (ESI): m/z (rel intensity) 261 (100). HRMS (FAB): m/z calcd for C9H9N2O5Cl, 260.0200; found, 260.0197.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Compound 11\"}], \"amount\": {\"mass\": {\"value\": 6.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 70.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"H2SO4 concentrated (4 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"TEMPERATURE\", \"details\": \"the solution heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to reflux for 9 h\", \"duration\": {\"value\": 9.0, \"units\": \"HOUR\"}}, {\"type\": \"ADDITION\", \"details\": \"the mixture was poured into ice (600 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice\"}], \"amount\": {\"volume\": {\"value\": 600.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the precipitate formed\"}, {\"type\": \"FILTRATION\", \"details\": \"was collected by filtration\"}, {\"type\": \"CUSTOM\", \"details\": \"Drying under hv\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"12\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 5.0, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 94.0}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fdce5d5343454896af4d0210372ca2a1",
    "procedure_text": "To an ice cold solution of 1-(2-t-butyloxycarbonyl-3-dibenzylaminopropyl)-1-cyclopentane carboxylic acid (12.7 g, 27 mmole) in dry dichloromethane (100 ml) was added 1-hydroxybenztriazole (4.2 g,.31 mmole), and 1-ethyl-3-(dimethylaminopropyl)-carbodiimide (7 g, 36 mmole) and the resulting solution stirred at 0\u00b0 C. for 30 minutes. To this solution was added 0-t-butyltyrosine t-butyl ester (8.4 g, 28.6 mmole) and N-methylmorpholine (5.25 g, 52 mmole) and the solution allowed to stand overnight at room temperature. The solvent was evaporated under reduced pressure and the resultant mobile oil was dissolved in methylene chloride and washed with water (2 x ), 2M hydrochloric acid and saturated aqueous sodium bicarbonate (1 x) dried (MgSO4), and the solution filtered and evaporated to yield the crude product as a gum. Recrystallization from n-hexane gave the title compound as a solid (13 g, 69%), m.p. 82-87\u00b0 C. A further batch of material was obtained by evaporation of the supernatant liquors and further recrystallisation. Found: C,74.12; H,8.69; N,3.87. C45H62N2O6 requires C,74.34; H,8.59; N,3.85%.",
    "reference_string": "{\"inputs\": {\"m1_m2_m7_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(2-t-butyloxycarbonyl-3-dibenzylaminopropyl)-1-cyclopentane carboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 12.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-hydroxybenztriazole\"}], \"amount\": {\"mass\": {\"value\": 4.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-ethyl-3-(dimethylaminopropyl)-carbodiimide\"}], \"amount\": {\"mass\": {\"value\": 7.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"0-t-butyltyrosine t-butyl ester\"}], \"amount\": {\"mass\": {\"value\": 8.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-methylmorpholine\"}], \"amount\": {\"mass\": {\"value\": 5.25, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the resulting solution stirred at 0\\u00b0 C. for 30 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WAIT\", \"details\": \"to stand overnight at room temperature\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The solvent was evaporated under reduced pressure\"}, {\"type\": \"DISSOLUTION\", \"details\": \"the resultant mobile oil was dissolved in methylene chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with water (2 x ), 2M hydrochloric acid and saturated aqueous sodium bicarbonate (1 x)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"the solution filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"to yield the crude product as a gum\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Recrystallization from n-hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 13.0, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 69.0}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fc8e4278023241ac8e2e77c808542cb0",
    "procedure_text": "Using (+)-N-((3R)-3-(4-isopropylphenyl)-4,6-dimethyl-2,3-dihydro-1-benzofuran-5-yl)-3,3-dimethylbutanamide obtained in Example 37 and benzoyl chloride, the title compound was obtained in the same manner as in Example 38.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(+)-N-((3R)-3-(4-isopropylphenyl)-4,6-dimethyl-2,3-dihydro-1-benzofuran-5-yl)-3,3-dimethylbutanamide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzoyl chloride\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-141d5bec10724f79add39cee804b5cf3",
    "procedure_text": "1,1\u2032-Bis(diphenylphosphino)ferrocene (1.5 g, 2.7 mmol), palladium acetate (616 mg, 2.7 mmol) and sodium tert-butoxide (22.9 g, 238 mmol) are added to a solution of biphenyl-2-ylamine (31.0 g, 183 mmol) and 2-bromo-9,9-dimethyl-9H-fluorene (50.0 g, 183 mmol) in degassed toluene (400 ml), and the mixture is heated under reflux for 20 h. The reaction mixture is cooled to room temperature, diluted with toluene and filtered through Celite. The filtrate is diluted with water and re-extracted with toluene, and the combined organic phases are dried and evaporated in vacuo. The residue is filtered through silica gel (heptane/dichloromethane) and crystallised from isopropanol, giving biphenyl-2-yl-(9,9-dimethyl-9H-fluoren-2-yl)amine in the form of a pale-yellow solid (63.0 g, 95% of theory).",
    "reference_string": "{\"inputs\": {\"m6_m7_m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium tert-butoxide\"}], \"amount\": {\"mass\": {\"value\": 22.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"biphenyl-2-ylamine\"}], \"amount\": {\"mass\": {\"value\": 31.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-bromo-9,9-dimethyl-9H-fluorene\"}], \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 400.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,1\\u2032-Bis(diphenylphosphino)ferrocene\"}], \"amount\": {\"mass\": {\"value\": 1.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"palladium acetate\"}], \"amount\": {\"mass\": {\"value\": 616.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"the mixture is heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"under reflux for 20 h\", \"duration\": {\"value\": 20.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"filtered through Celite\"}, {\"type\": \"ADDITION\", \"details\": \"The filtrate is diluted with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"re-extracted with toluene\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the combined organic phases are dried\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated in vacuo\"}, {\"type\": \"FILTRATION\", \"details\": \"The residue is filtered through silica gel (heptane/dichloromethane)\"}, {\"type\": \"CUSTOM\", \"details\": \"crystallised from isopropanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isopropanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"biphenyl-2-yl-(9,9-dimethyl-9H-fluoren-2-yl)amine\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-8530d8d5d4c14a44854897876ad058f3",
    "procedure_text": "To a stirred solution of 1-ethyl-4-(5-methyl-3-pyridyl)-6-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid (18 mg) and 4-methoxybenzyl amine (10.3 mg) in DMF (1 ml) was added O-(7-azabenzotriazol-1-yl)-N,N,N\u2032,N\u2032-tetramethyluronium hexafluorophosphate (28.6 mg) and N,N-dimethylaminopyridine (9.2 mg). The reaction mixture was stirred at room temperature for 18 hours and at 50\u00b0 for 5 hours. After cooling, the reaction mixture was diluted with water and extracted with EtOAc. The organic layer was washed with diluted HCl, water, saturated aqueous NaHCO3, water, brine, dried over anhydrous MgSO4 and concentrated in vacuo. The crystalline residue was recrystallized from EtOAc and n-hexane to give 1-ethyl-N-(4-methoxybenzyl)-4-(5-methyl-3-pyridyl)-6-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide (15.8 mg) as a colorless crystal.",
    "reference_string": "{\"inputs\": {\"m1_m2_m5_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-ethyl-4-(5-methyl-3-pyridyl)-6-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 18.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-methoxybenzyl amine\"}], \"amount\": {\"mass\": {\"value\": 10.3, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"O-(7-azabenzotriazol-1-yl)-N,N,N\\u2032,N\\u2032-tetramethyluronium hexafluorophosphate\"}], \"amount\": {\"mass\": {\"value\": 28.6, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylaminopyridine\"}], \"amount\": {\"mass\": {\"value\": 9.2, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred at room temperature for 18 hours and at 50\\u00b0 for 5 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"After cooling\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with diluted HCl, water, saturated aqueous NaHCO3, water, brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The crystalline residue was recrystallized from EtOAc and n-hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 5.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-ethyl-N-(4-methoxybenzyl)-4-(5-methyl-3-pyridyl)-6-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 15.8, \"units\": \"MILLIGRAM\"}}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystal\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-61b2267382714fbe977925970a95701c",
    "procedure_text": "A mixture of 1-benzoyl-1,2,3,4,5,6-hexahydro-4-phenyl[1,3,6]-triazocino[1,2-a]benzimidazole (10.00 g) from Example 2 and methanolic ammonia (1150 ml), presaturated at 0\u00b0, was stirred magnetically and heated in a sealed bomb at 100\u00b0 for 4 days. The resulting cooled solution was filtered and the filtrate was evaporated to a syrup which crystallized. The residue was dissolved in dichloromethane-methanol and the solution was evaporated to a syrup. Crystallization from methanol gave crude titled product; wt. 5.24 g (72%), mp=158\u00b0-159\u00b0. The mother liquor was evaporated to a crystalline residue which was subjected to an oil pump vacuum. A solution of the residue in a minimum volume of warm dichloromethane was applied to a column (56\u00d73.2 cm) of dry column grade neutral alumina prepacked in toluene. Elution was with toluene (400 ml), toluene-dichloromethane (4:1, 500 ml) followed by dichloromethane. The product was eluted with dichloromethane. The fractionation was monitored by t.l.c. on Alox-25 uv254 plates with dichloromethane-methanol (19:1) as developer. Fractions which contained only product were evaporated to a syrup which crystallized. Recrystallization with decolorization from methanol gave product; wt. 0.93 g (13%), mp=158\u00b0-160\u00b0. This material, combined with material obtained above, was recrystallized with decolorization from methanol to give pure titled product; wt. 5.46 g, mp=159\u00b0-160\u00b0.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-benzoyl-1,2,3,4,5,6-hexahydro-4-phenyl[1,3,6]-triazocino[1,2-a]benzimidazole\"}], \"amount\": {\"mass\": {\"value\": 10.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonia\"}], \"amount\": {\"volume\": {\"value\": 1150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred magnetically\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"presaturated at 0\\u00b0\"}, {\"type\": \"TEMPERATURE\", \"details\": \"heated in a sealed bomb at 100\\u00b0 for 4 days\", \"duration\": {\"value\": 4.0, \"units\": \"DAY\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"The resulting cooled solution\"}, {\"type\": \"FILTRATION\", \"details\": \"was filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"the filtrate was evaporated to a syrup which\"}, {\"type\": \"CUSTOM\", \"details\": \"crystallized\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue was dissolved in dichloromethane-methanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane methanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solution was evaporated to a syrup\"}, {\"type\": \"CUSTOM\", \"details\": \"Crystallization from methanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"gave crude titled product\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude titled product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The mother liquor was evaporated to a crystalline residue which\"}, {\"type\": \"WASH\", \"details\": \"Elution\"}, {\"type\": \"WASH\", \"details\": \"The product was eluted with dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"were evaporated to a syrup which\"}, {\"type\": \"CUSTOM\", \"details\": \"crystallized\"}, {\"type\": \"CUSTOM\", \"details\": \"Recrystallization with decolorization from methanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"gave product\"}, {\"type\": \"CUSTOM\", \"details\": \"obtained above,\"}, {\"type\": \"CUSTOM\", \"details\": \"was recrystallized with decolorization from methanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"titled product\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0428ae5044894c3294885d91f1996253",
    "procedure_text": "As described in Example 9, 0.471 g (1.5 mmol) of 5-(4-aminobenzoyl)-6,11-dihydro-5H-dibenz[b,e]azepine is reacted with 0.303 g (1.8 mmol) of 2,4-dimethylbenzoyl chloride in 10 ml of dichloromethane. The product is recrystallized from hexane-dichloromethane to give 0.38 g of crystals, m.p. 197\u00b0-199\u00b0 C. Anal. Calc'd for C30H26N2O2 1/2 H2O: C,79.1; H,6.0; N,6.2. Found: C,79.0; H,5.8; N,6.2.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-(4-aminobenzoyl)-6,11-dihydro-5H-dibenz[b,e]azepine\"}], \"amount\": {\"mass\": {\"value\": 0.471, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,4-dimethylbenzoyl chloride\"}], \"amount\": {\"mass\": {\"value\": 0.303, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The product is recrystallized from hexane-dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crystals\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.38, \"units\": \"GRAM\"}}}], \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-365b3035c4ba4780bca8ca317caea587",
    "procedure_text": "To a disposable sealed tube was charged 2-bromo-6-(3-(4-fluorophenoxy)azetidin-1-yl)pyridine (100.0 mg, 0.309 mmol), 3-amino-N-methylbenzamide (69.7 mg, 0.464 mmol), potassium carbonate (59.9 mg, 0.433 mmol) followed by X-Phos (2.95 mg, 6.19 \u03bcmol) and Pd2(dba)3 (1.417 mg, 1.547 \u03bcmol). The tube was fitted with a septum with an argon inlet for 5-10 min, when t-BuOH (1.0 mL) was added. The reaction mixture was then heated to 100\u00b0 C. for 7 h, cooled to RT, diluted with EtOAc, and filtered through Celite\u00ae (diatomaceous earth) with EtOAc. The filtrate was concentrated and purified using MPLC (5 g cartridge, 12 g column, 0 to 75% EtOAc-hexanes) giving 3-(6-(3-(4-fluorophenoxy)azetidin-1-yl)pyridin-2-ylamino)-N-methylbenzamide (112.8 mg).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"t-BuOH\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-bromo-6-(3-(4-fluorophenoxy)azetidin-1-yl)pyridine\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-amino-N-methylbenzamide\"}], \"amount\": {\"mass\": {\"value\": 69.7, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 59.9, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd2(dba)3\"}], \"amount\": {\"mass\": {\"value\": 1.417, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"X-Phos\"}], \"amount\": {\"mass\": {\"value\": 2.95, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The tube was fitted with a septum with an argon inlet for 5-10 min\", \"duration\": {\"value\": 7.5, \"precision\": 2.5, \"units\": \"MINUTE\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"cooled to RT\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"filtered through Celite\\u00ae (diatomaceous earth) with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"The filtrate was concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"purified\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(6-(3-(4-fluorophenoxy)azetidin-1-yl)pyridin-2-ylamino)-N-methylbenzamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 112.8, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-817ace154e7448cf9985afefcdd1a24a",
    "procedure_text": "The tricarboxylic ester of Example 6 (35 g, 0.1 mol) in EtOH (400 ml) was stirred at room temperature with a solution of KOH (13.2 g of 85%, 0.2 mol) in EtOH (100 ml) for 96 hours. The mixture was evaporated to dryness. The solid foam was broken up, treated with Et2O (200 ml) and filtered. The residue was dissolved in H2O (100 ml), acidified with 5 N HCl to give an oil which was extracted with Et2O. The Et2O was dried (Na2SO4) filtered and evaporated to give an oily solid. The solid was shaken with a mixture of CHCl3 -light petroleum (b.p. 40\u00b0-60\u00b0 C.) (100 ml of 50:50), filtered, the residue washed with the same solvent mixture (100 ml) and the filtrate evaporated to leave an oil which was distilled to give the title product, b.p. 175\u00b0-7\u00b0 C./0.25 mm.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ester\"}], \"amount\": {\"mass\": {\"value\": 35.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"KOH\"}], \"amount\": {\"mass\": {\"value\": 13.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOH\"}], \"amount\": {\"volume\": {\"value\": 400.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOH\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CHCl3 light petroleum\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The mixture was evaporated to dryness\"}, {\"type\": \"ADDITION\", \"details\": \"treated with Et2O (200 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Et2O\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue was dissolved in H2O (100 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"to give an oil which\"}, {\"type\": \"EXTRACTION\", \"details\": \"was extracted with Et2O\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Et2O\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The Et2O was dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Et2O\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"to give an oily solid\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"WASH\", \"details\": \"the residue washed with the same solvent mixture (100 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"mixture\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the filtrate evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"to leave an oil which\"}, {\"type\": \"DISTILLATION\", \"details\": \"was distilled\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title product\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-9595b3fe4c364df49c8c14b4aa3d01bc",
    "procedure_text": "A suspension of anhydrous cerium chloride (43.88 g, 178.1 mmol) in THF (250 mL) was stirred at room temperature for 2 hours under nitrogen. A solution of 3,5-m-xylenylmagnesium bromide (178 mmol, prepared from magnesium (4.33 g, 178.1 mmol) and 5-bromo-m-xylene (24.2 mL, 178.1 mmol) in ether (60 mL) was added at 0\u00b0 C. and stirred for 3.5 h. A solution of 2-indanone (14.21 g, 107.7 mmol) in THF (20 mL) was added at the same temperature. After stirring at 0\u00b0 C. for 3 h, the mixture was allowed to warm to room temperature and kept at ambient temperature for 12 h. It was then treated with 5% aqueous hydrochloric solution. The solution was extracted with diethyl ether (4*200 mL). All etheral layers were combined, washed with water (100 mL), dried over anhydrous magnesium sulphate and concentrated to give the crude product. 2-Indanone was distilled out at 80\u00b0 C. (0.3 mm Hg). The residue was washed with pentane (50 mL) to yield 21.57 g of 2-(3,5-xylenyl)-2-indanol in solid form.",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aqueous hydrochloric solution\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2_m3_m4_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,5-m-xylenylmagnesium bromide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium\"}], \"amount\": {\"mass\": {\"value\": 4.33, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-bromo-m-xylene\"}], \"amount\": {\"volume\": {\"value\": 24.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5_m9\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-indanone\"}], \"amount\": {\"mass\": {\"value\": 14.21, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cerium chloride\"}], \"amount\": {\"mass\": {\"value\": 43.88, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at room temperature for 2 hours under nitrogen\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added at 0\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"STIRRING\", \"details\": \"stirred for 3.5 h\", \"duration\": {\"value\": 3.5, \"units\": \"HOUR\"}}, {\"type\": \"STIRRING\", \"details\": \"After stirring at 0\\u00b0 C. for 3 h\", \"duration\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"to warm to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"WAIT\", \"details\": \"kept at ambient temperature for 12 h\", \"duration\": {\"value\": 12.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"The solution was extracted with diethyl ether (4*200 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with water (100 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous magnesium sulphate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulphate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"to give the crude product\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"2-Indanone was distilled out at 80\\u00b0 C. (0.3 mm Hg)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-Indanone\"}], \"reaction_role\": \"WORKUP\"}]}, \"temperature\": {\"setpoint\": {\"value\": 80.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"WASH\", \"details\": \"The residue was washed with pentane (50 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pentane\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(3,5-xylenyl)-2-indanol\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 21.57, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-98f30c34b9974cee9bcb3c441f065335",
    "procedure_text": "To a mixture of Methyl 3,4-diaminobenzoate (1.91 g) and triethylamine (0.56 g) in N,N-dimethylformamide (20 ml) was added decanoyl chloride (2.31 g), and the mixture was stirred for an hour at 0\u00b0 C. The reaction mixture was diluted with ethyl acetate, and washed with water and brine. The separated organic layer was dried over magnesium sulfate. The magnesium sulfate was filtered off, and filtrate was evaporated under reduced pressure. The residue was dissolved in methanol (20 ml), and conc. sulfuric acid (0.05 ml) was added, and the mixture was stirred for 6 hours at 60\u00b0 C. After cooling, the reaction mixture was evaporated under reduced pressure. The residue was diluted with ethyl acetate, and washed with water and brine. The separated organic layer was dried over magnesium sulfate. The magnesium sulfate was filtered off, and filtrate was evaporated under reduced pressure. Purification of the residue by column chromatography on silica gel eluted with (n-hexane:ethyl acetate=3:1) gave 5-Methoxycarbonyl-2-nonylbenzimidazole (1.40 g).",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Methyl 3,4-diaminobenzoate\"}], \"amount\": {\"mass\": {\"value\": 1.91, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"mass\": {\"value\": 0.56, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"decanoyl chloride\"}], \"amount\": {\"mass\": {\"value\": 2.31, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred for an hour at 0\\u00b0 C\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WASH\", \"details\": \"washed with water and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The separated organic layer was dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"The magnesium sulfate was filtered off\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"filtrate was evaporated under reduced pressure\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue was dissolved in methanol (20 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"conc. sulfuric acid (0.05 ml) was added\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sulfuric acid\"}], \"amount\": {\"volume\": {\"value\": 0.05, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"STIRRING\", \"details\": \"the mixture was stirred for 6 hours at 60\\u00b0 C\", \"duration\": {\"value\": 6.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"After cooling\"}, {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture was evaporated under reduced pressure\"}, {\"type\": \"ADDITION\", \"details\": \"The residue was diluted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with water and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The separated organic layer was dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"The magnesium sulfate was filtered off\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"filtrate was evaporated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification of the residue by column chromatography on silica gel\"}, {\"type\": \"WASH\", \"details\": \"eluted with (n-hexane:ethyl acetate=3:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-hexane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-Methoxycarbonyl-2-nonylbenzimidazole\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.4, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 40.3}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c9a71fe1ce7a4dfeb8d6497345fa9dca",
    "procedure_text": "A mixture of 28.05 g (114.4 mmole) of 4-(4-trifluoromethyl-phenyl)-3H-thiazol-2-one and 85 mL (0.92 mole) of phosphorus oxychloride was heated at reflux for 5 hours. The mixture was cooled and the excess phosphorus oxychloride was removed under reduced pressure. The residue was diluted with ethyl acetate and the slurry was poured onto ice. The mixture was made basic by the addition of saturated aqueous sodium carbonate solution. The ethyl acetate layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with ethyl acetate-hexanes (gradient 10:90-20:80) to give 19.34 g of 2-chloro-4-(4-trifluoromethyl-phenyl)-thiazole as a light brown solid.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(4-trifluoromethyl-phenyl)-3H-thiazol-2-one\"}], \"amount\": {\"mass\": {\"value\": 28.05, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"phosphorus oxychloride\"}], \"amount\": {\"volume\": {\"value\": 85.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"at reflux for 5 hours\", \"duration\": {\"value\": 5.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"The mixture was cooled\"}, {\"type\": \"CUSTOM\", \"details\": \"the excess phosphorus oxychloride was removed under reduced pressure\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"phosphorus oxychloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"The residue was diluted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"the slurry was poured onto ice\"}, {\"type\": \"ADDITION\", \"details\": \"The mixture was made basic by the addition of saturated aqueous sodium carbonate solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium carbonate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The ethyl acetate layer was dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by silica gel chromatography\"}, {\"type\": \"WASH\", \"details\": \"eluting with ethyl acetate-hexanes (gradient 10:90-20:80)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate-hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloro-4-(4-trifluoromethyl-phenyl)-thiazole\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 19.34, \"units\": \"GRAM\"}}}], \"isolated_color\": \"light brown\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fdf8690e4db040deb6502f4d3c9f6958",
    "procedure_text": "To a flask containing (1R,3aS,5aR,5bR,7aR,11aS,11bR,13bR)-9-(4-(methoxycarbonyl)phenyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysene-3a-carboxylic acid (0.1-4.2 mmol scale) was added oxalyl chloride (2M in dichloromethane) (10-50 equiv.). The solution was stirred at rt for 2-5 h and was stripped of solvent. The residue was dissolved in dichloromethane and concentrated two additional times, then was used with no additional purification in the next step. 1H NMR (500 MHz, CHLOROFORM-d) \u03b4 ppm 7.92 (d, J=8.55 Hz, 2H), 7.19 (d, J=8.24 Hz, 2H), 5.26-5.30 (m, 1H), 4.73 (d, J=1.53 Hz, 1H), 4.62-4.64 (m, 1H), 3.90 (s, 3H), 2.81 (td, J=11.14, 4.58 Hz, 1H), 2.47 (ddd, J=13.58, 3.20, 3.05 Hz, 1H), 2.19-2.28 (m, 2H), 2.10 (dd, J=17.09, 6.41 Hz, 1H), 1.85-1.99 (m, 1H), 1.68 (s, 3H), 1.00 (s, 6H), 0.98 (s, 3H), 0.92 (s, 3H), 0.92 (s, 3H), 0.84-1.83 (m, 17H). 13C NMR (126 MHz, CHLOROFORM-d) \u03b4 ppm 177.49, 167.35, 149.46, 148.81, 146.39, 130.17 (s, 2C), 128.61 (s, 2C), 128.03, 124.12, 110.40, 68.00, 52.99, 52.11, 49.78, 49.67, 46.11, 42.54, 41.86, 40.70, 38.00, 37.60, 36.39, 36.31, 33.64, 32.3, 29.98, 29.72, 29.54, 25.60, 21.37, 21.13, 19.86, 19.48, 16.59, 15.71, 14.89.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(1R,3aS,5aR,5bR,7aR,11aS,11bR,13bR)-9-(4-(methoxycarbonyl)phenyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysene-3a-carboxylic acid\"}], \"amount\": {\"moles\": {\"value\": 2.15, \"precision\": 2.05, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"oxalyl chloride\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The solution was stirred at rt for 2-5 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"concentrated two additional times\"}, {\"type\": \"CUSTOM\", \"details\": \"was used with no additional purification in the next step\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.5, \"precision\": 1.5, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-0f9b643ce62d4e728acb0b4d719a90ad",
    "procedure_text": "A solution of 1-(2-nitro-1-imidazolyl)-3-(1-aziridino)-2-propanol (2.12 g, 10.0 mmol) in acetone (20 cm3) prepared as described in Example 1(a) was treated with ethanoic acid (2.5 mol equivalents) at 25\u00b0 C. then warmed to 50\u00b0 C. for 15 minutes. The resulting mixture was cooled to 20\u00b0 C., stirred with decolourising charcoal (0.3 g) and excess anhydrous potassium carbonate for 30 minutes, filtered and concentrated under reduced pressure to give 1-(2-nitro-1-imidazolyl)-3-(2-acetoxyethylamino)-2-propanol (1.58 g, 58.0%) in the form of a pale yellow crystalline solid.",
    "reference_string": "{\"inputs\": {\"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanoic acid\"}], \"amount\": {\"moles\": {\"value\": 2.5, \"units\": \"MOLE\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(2-nitro-1-imidazolyl)-3-(1-aziridino)-2-propanol\"}], \"amount\": {\"mass\": {\"value\": 2.12, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"charcoal\"}], \"amount\": {\"mass\": {\"value\": 0.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 50.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The resulting mixture was cooled to 20\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 20.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(2-nitro-1-imidazolyl)-3-(2-acetoxyethylamino)-2-propanol\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.58, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 58.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 58.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-cd38b82ad558422992bb93508b3ccb24",
    "procedure_text": "Prepared in analogy to that of Example 1(e) from 2,3-dichloro-7-cyano-1-(2-fluoro-benzyl)-4-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid ethyl ester, glycine and NaOMe/HOMe. The title compound, ESI MS (m/z): 437 (M+H)+.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,3-dichloro-7-cyano-1-(2-fluoro-benzyl)-4-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid ethyl ester\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"glycine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOMe HOMe\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4fb9fb2e7a314707ac63b07adfaacc58",
    "procedure_text": "Pyrrolidine-1-carboxylic acid (3-nitro-phenyl)-amide (850 mg, 3.40 mmol) was dissolved in 1:1 MeOH-EtOAc (100 mL). Raney\u00ae-Nickel was added (3 full spatulas) followed by hydrazine monohydrate (1.70 g, 34.0 mmol) over a 5 minute period. The reaction mixture was stirred at rt for 16 hours then filtered through celite, washing the precipitate with EtOAc (10\u00d710 mL). The filtrate was evaporated in vacuo and the residue dissolved in EtOAc (50 mL). The solution was washed with saturated brine solution (2\u00d750 mL), dried (Na2SO4), filtered, and the solvent evaporated in vacuo. The crude product was then purified by column chromatography (Flashmaster, 40-63 mesh silica gel, EtOAc\u219210% MeOH-EtOAc) to provide the title compound as a pale yellow solid (1.29 g, 92%); LC-MS, Rt=0.99 min (MeOH-FA), m/z 206 (MH+).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Nickel\"}], \"reaction_role\": \"CATALYST\"}]}, \"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pyrrolidine-1-carboxylic acid (3-nitro-phenyl)-amide\"}], \"amount\": {\"mass\": {\"value\": 850.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH EtOAc\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrazine monohydrate\"}], \"amount\": {\"mass\": {\"value\": 1.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred at rt for 16 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"then filtered through celite\"}, {\"type\": \"WASH\", \"details\": \"washing the precipitate with EtOAc (10\\u00d710 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The filtrate was evaporated in vacuo\"}, {\"type\": \"DISSOLUTION\", \"details\": \"the residue dissolved in EtOAc (50 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The solution was washed with saturated brine solution (2\\u00d750 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"the solvent evaporated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude product was then purified by column chromatography (Flashmaster, 40-63 mesh silica gel, EtOAc\\u219210% MeOH-EtOAc)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.29, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 92.0}}], \"isolated_color\": \"pale yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4ab1de73d3134259b73f40a5b60787fc",
    "procedure_text": "At first, 0.24 g (1.25 mmol) of p-toluenesulfonic acid monohydrate were added to a toluene solution (25 ml) containing 8.35 g (25 mmol) of 4-methylacetophenone (3c) as a ketone and 3.03 g (25 mmol) of (S)-1-phenylethylamine ((S)-2a) as an optically active primary amine, followed by heating under reflux for 24 hr and by removing water (formed as a by-product) with a Dean-Stark tube during the reaction, in order to conduct the reaction. Then, the reaction liquid after the reaction was washed with a saturated sodium hydrogencarbonate aqueous solution, followed by drying with sodium sulfate anhydride, then filtration, then concentration, and then vacuum drying, thereby obtaining as a crude product 5.66 g of (S)-N-(1-phenylethylidene)-1-(4-methylphenyl)-ethylamine ((S)-3ca, yield: 89%).",
    "reference_string": "{\"inputs\": {\"m2_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"p-toluenesulfonic acid monohydrate\"}], \"amount\": {\"mass\": {\"value\": 0.24, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m4_m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-methylacetophenone\"}], \"amount\": {\"mass\": {\"value\": 8.35, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ketone\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(S)-1-phenylethylamine\"}], \"amount\": {\"mass\": {\"value\": 3.03, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"primary amine\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"by heating\"}, {\"type\": \"TEMPERATURE\", \"details\": \"under reflux for 24 hr\", \"duration\": {\"value\": 24.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"by removing water (\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"formed as a by-product) with a Dean-Stark tube\"}, {\"type\": \"CUSTOM\", \"details\": \"during the reaction\"}, {\"type\": \"CUSTOM\", \"details\": \"the reaction\"}, {\"type\": \"CUSTOM\", \"details\": \"Then, the reaction liquid after the reaction\"}, {\"type\": \"WASH\", \"details\": \"was washed with a saturated sodium hydrogencarbonate aqueous solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydrogencarbonate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"by drying with sodium sulfate anhydride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate anhydride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtration\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentration\"}, {\"type\": \"CUSTOM\", \"details\": \"vacuum drying\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 5.66, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(S)-N-(1-phenylethylidene)-1-(4-methylphenyl)-ethylamine\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 89.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-bc5a5ab6c1ee4fcea28fbc69b3f8a2fc",
    "procedure_text": "To a solution of 4-[2-(4-benzyloxy-phenyl)-ethyl]-4-hydroxymethyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (25 mg, 0.05 mmol) in methanol (10 ml) is added a catalytic amount of paladium on charcoal (10% wt). The reaction mixture is stirred under H2 atmosphere at room temperature for 2 hours. 4-Hydroxymethyl-4-[2-(4-hydroxy-phenyl)-ethyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester is isolated as a white solid after filtration of the suspension through celite and concentration to dryness.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-[2-(4-benzyloxy-phenyl)-ethyl]-4-hydroxymethyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester\"}], \"amount\": {\"mass\": {\"value\": 25.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture is stirred under H2 atmosphere at room temperature for 2 hours\"}, \"conditions_are_dynamic\": true}, \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-Hydroxymethyl-4-[2-(4-hydroxy-phenyl)-ethyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d2219f776a274835b238a63554c380b2",
    "procedure_text": "A mixture of methyl 2-{[(benzyloxy)carbonyl]amino}-3-(dimethoxyphosphoryl)-propanoate (1 g, 30 mmol) in tetrahydrofuran (7 ml) was stirred at \u221240\u00b0 C. and tetramethylguanidine (380 mg, 33 mmol) was added. The reaction mixture was stirred at \u221240\u00b0 C. for 20 minutes and then imidazole-2-carboxaldehyde (317 mg, 33 mmol) was added. The reaction was then allowed to warm to room temperature and was stirred at room temperature for 18 h. The solvent was then removed by evaporation under reduced pressure and the residue dissolved in ethyl acetate and washed with water and then brine. The organic phase was then dried (MgSO4), filtered, and then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with a solvent gradient of ethyl acetate:pentane (30:70 to 80:20), to give the title compound, 366 mg, 40% yield.",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 2-{[(benzyloxy)carbonyl]amino}-3-(dimethoxyphosphoryl)-propanoate\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 7.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetramethylguanidine\"}], \"amount\": {\"mass\": {\"value\": 380.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"imidazole-2-carboxaldehyde\"}], \"amount\": {\"mass\": {\"value\": 317.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -40.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at \\u221240\\u00b0 C.\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"The reaction mixture was stirred at \\u221240\\u00b0 C. for 20 minutes\", \"duration\": {\"value\": 20.0, \"units\": \"MINUTE\"}, \"temperature\": {\"setpoint\": {\"value\": -40.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"to warm to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"STIRRING\", \"details\": \"was stirred at room temperature for 18 h\", \"duration\": {\"value\": 18.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The solvent was then removed by evaporation under reduced pressure\"}, {\"type\": \"DISSOLUTION\", \"details\": \"the residue dissolved in ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic phase was then dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by column chromatography on silica gel\"}, {\"type\": \"WASH\", \"details\": \"eluting with a solvent gradient of ethyl acetate:pentane (30:70 to 80:20)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate pentane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 40.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-039aaed079db4a71879948c858bc0d63",
    "procedure_text": "Under a nitrogen atmosphere, a solution of 2-aminobenzoic acid (100.0 g, 0.73 mol) in acetic anhydride (400 ml, 4.2 mol) was heated to reflux for 2 hours. The reaction was cooled to room temperature and the solvent was removed in vacuo. The residue was dissolved in glacial acetic acid (500 ml) and NaN3 (49.77 g, 0.77 mol) was added. The mixture was stirred overnight at room temperature followed by concentration of the acetic acid in vacuo. The residue was dissolved in 10% NaOH (500 ml) solution and heated to reflux for 3.5 hours. The reaction was cooled to room temperature and then poured over a mixture of ice water (2 L) and HCl (150 ml). A white solid precipitated and was collected by vacuum filtration. The solid was dried in vacuo to yield 130.5 g of 2-(5-methyl-1H-tetrazol-1-yl)benzoic acid.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-aminobenzoic acid\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic anhydride\"}], \"amount\": {\"volume\": {\"value\": 400.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"LITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaN3\"}], \"amount\": {\"mass\": {\"value\": 49.77, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred overnight at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"to reflux for 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was removed in vacuo\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue was dissolved in glacial acetic acid (500 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to reflux for 3.5 hours\", \"duration\": {\"value\": 3.5, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"The reaction was cooled to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"A white solid precipitated\"}, {\"type\": \"FILTRATION\", \"details\": \"was collected by vacuum filtration\"}, {\"type\": \"CUSTOM\", \"details\": \"The solid was dried in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(5-methyl-1H-tetrazol-1-yl)benzoic acid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 130.5, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-9b59d9176f6f4be8b11d7d8b6154410f",
    "procedure_text": "Combine dimethyl-[1-(5-nitro-benzooxazol-2-yl)-pyrrolidin-3-yl]-amine (1.00 g, 3.62 mmol) and Fe0 (1.98 g, 35.4 mmol) in acetic acid (20 mL) and stir at 40\u00b0 C. for 2 h. Dilute with water (50 mL) and filter through Celite\u00ae. Wash with copious amounts of water and MeOH. Make the filtrate alkaline with 5 N NaOH and extract twice with CH2Cl2 (2\u00d7). Concentrate in vacuo to afford the title compound (769 mg, 86%). 1H NMR (400 MHz, CDCl3): \u03b4 7.00 (d, 1H, J=8.4 Hz), 6.70 (d, 1H, J=2.2 Hz), 6.32 (dd, 1H, J=8.4, 2.6 Hz), 3.88 (dd, 1H, J=9.9, 7.1 Hz), 3.81 (m, 1H), 3.62-3.50 (m, 3H), 3.39 (dd, 1H, J=10.1, 8.8 Hz), 2.83 (m, 1H), 2.30 (s, 6H), 2.21 (m, 1H), 1.93 (m, 1H).",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethyl-[1-(5-nitro-benzooxazol-2-yl)-pyrrolidin-3-yl]-amine\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"filter through Celite\\u00ae\"}, {\"type\": \"WASH\", \"details\": \"Wash with copious amounts of water and MeOH\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extract twice with CH2Cl2 (2\\u00d7)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"Concentrate in vacuo\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 769.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 86.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 86.2}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-21c641558b9f423b91c0580f697bb11e",
    "procedure_text": "The diluted HCl/methanol solution was cooled (T<10\u00b0 C.). Fexofendine base (50 grams) (1.88% H2O) was reacted with the diluted HCl/methanol solution, to form a fexofenadine-HCl solution. The molar ratio between fexofenadine-base and HCl was 1:1.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl methanol\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Fexofendine\"}], \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl methanol\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-87a90cc0b09e4a50bbe7b8254c3b1919",
    "procedure_text": "As in Example 115, (E)-5,5-bis(3,4-dimethoxyphenyl)-2,4-pentadienoic acid (16 g) and 4-nitrophenol (6.6 g) in dichloromethane (160 mL) was treated with 1,3-dicyclohexylcarbodiimide (9.3 g). The mixture was stirred at 0.5\u00b0 C. for 1 hour, then at room temperature for 18 hours. After the usual work up, the crude product was triturated with ether to give 13.2 g of (E)-5,5-bis(3,4-dimethoxyphenyl)-2,4-pentadienoic acid 4-nitrophenyl ester. Crystallization of a portion from ether afforded the analytical sample, mp 140\u00b0-142\u00b0 C. Anal. Calculated for C27H25NO8 : C, 69.60; H, 4.91; N, 3.23 Found: C, 69.19; H, 4.94; N, 3.25.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(E)-5,5-bis(3,4-dimethoxyphenyl)-2,4-pentadienoic acid\"}], \"amount\": {\"mass\": {\"value\": 16.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-nitrophenol\"}], \"amount\": {\"mass\": {\"value\": 6.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,3-dicyclohexylcarbodiimide\"}], \"amount\": {\"mass\": {\"value\": 9.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 160.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.5, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at 0.5\\u00b0 C. for 1 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WAIT\", \"details\": \"at room temperature for 18 hours\", \"duration\": {\"value\": 18.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"After the usual work up, the crude product was triturated with ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(E)-5,5-bis(3,4-dimethoxyphenyl)-2,4-pentadienoic acid 4-nitrophenyl ester\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 13.2, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e881125df20f4cda85628ef8bd2a675d",
    "procedure_text": "A suspension of rac-8-benzyl-4-phenyl-2,8-diaza-spiro[4.5]decan-1-one (28.8 g, 90 mmol) in MeOH: DCM (4: 1, 500 ml) was hydrogenated in the presence of Pd (10% on C, 14 g, 132 mmol) at 2 bar for 48 h at room temperature. After filtration over celite, the reaction mixture was evaporated and the residue dissolved in NaOH (2 N, 200 mnL). The product was extracted with DCM (3\u00d7150 mL) and the combined organic extracts dried over sodium sulfate. Filtration and evaporation afforded the title compound (13.1 g, 63%) as a white solid after trituration from diethylether. MS: m/e=231.4 (M+H).",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"rac-8-benzyl-4-phenyl-2,8-diaza-spiro[4.5]decan-1-one\"}], \"amount\": {\"mass\": {\"value\": 28.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH DCM\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd\"}], \"amount\": {\"mass\": {\"value\": 14.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"After filtration over celite\"}, {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture was evaporated\"}, {\"type\": \"DISSOLUTION\", \"details\": \"the residue dissolved in NaOH (2 N, 200 mnL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The product was extracted with DCM (3\\u00d7150 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"the combined organic extracts dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"Filtration and evaporation\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 13.1, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 63.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 63.2}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-00d4186e303142b59f4d853a03d24712",
    "procedure_text": "6-Chloro-4-(3-pyridylmethyl)-1(2H)-phthalazinone (0.86 g) was suspended in 10 ml of phosphorus oxychloride. The obtained suspension was heated under reflux for 2 hours and freed from the phosphorus oxychloride by vacuum distillation. The residue was dissolved in tetrahydrofuran. The obtained solution was neutralized with triethylamine, followed by the addition of water. The obtained mixture was extracted with ethyl acetate. The organic phase was washed with water and a saturated aqueous solution of common salt, dried over anhydrous magnesium sulfate and freed from the solvent by vacuum distillation. The residue was purified by silica gel column chromatography to give 0.49 g of the title compound as a pale yellow crystal.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-Chloro-4-(3-pyridylmethyl)-1(2H)-phthalazinone\"}], \"amount\": {\"mass\": {\"value\": 0.86, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"phosphorus oxychloride\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The obtained suspension was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"under reflux for 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"DISTILLATION\", \"details\": \"freed from the phosphorus oxychloride by vacuum distillation\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"phosphorus oxychloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue was dissolved in tetrahydrofuran\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"followed by the addition of water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The obtained mixture was extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic phase was washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"a saturated aqueous solution of common salt, dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"freed from the solvent by vacuum distillation\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by silica gel column chromatography\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.49, \"units\": \"GRAM\"}}}], \"isolated_color\": \"pale yellow\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystal\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a514e0e0ed7546b7a49c7fc2e626d5f3",
    "procedure_text": "Under an argon atmosphere, to a solution of 2-[4-(tert-butyldimethylsilyloxy)phenyl]acetic acid (9) (1.07 g, 4.02 mmol) in CH2Cl2 (10 mL) was added DMF (3 drops) by a Pasteur pipette at room temperature. To this was added oxalyl dichloride (680 \u03bcL, 8.04 mmol) at 0\u00b0 C. and the mixture was stirred for 30 minutes while elevating to room temperature. The mixture was concentrated under reduced pressure to give crude 2-[4-(tert-butyldimethylsilyloxy)phenyl]acetyl chloride (10) as a colorless oil, which was used in the following reaction without further purification.",
    "reference_string": "{\"inputs\": {\"m1_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-[4-(tert-butyldimethylsilyloxy)phenyl]acetic acid\"}], \"amount\": {\"mass\": {\"value\": 1.07, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"reaction_role\": \"CATALYST\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"oxalyl dichloride\"}], \"amount\": {\"volume\": {\"value\": 680.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred for 30 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"while elevating to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CONCENTRATION\", \"details\": \"The mixture was concentrated under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-[4-(tert-butyldimethylsilyloxy)phenyl]acetyl chloride\"}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0cf21384b7114793ad4cb20befabdc3c",
    "procedure_text": "To a 10 mL microwave vial was added 5-chloro-1-methyl-4-nitro-1H-pyrazole from Example 1 (150 mg, 0.93 mmol), 3-(tert-butoxycarbonylamino)phenylboronic acid (440 mg, 1.86 mmol), dichloro[1,1\u2032-bis(diphenylphosphino)ferrocene]palladium(II) (152 mg, 0.019 mmol), a 1:1 M solution of Na2CO3/KOAc (1 mL) and acetonitrile (4 mL). The mixture was irradiated to 130\u00b0 C. with a microwave for 40 min and the mixture was cooled, concentrated and purified via flash chromatography, heptane/ethyl acetate 20% to 95% to afford a yellow oil. To a 50 mL round bottom flask was added the nitro compound (120 mg, 0.90 mmol), iron (156 mg, 2.8 mmol), ammonium chloride (200 mg, 3.7 mmol), ethanol (10 mL) and water (1.5 mL). The mixture was stirred for 1 h and the reaction was monitored by LCMS. Upon completion of the reaction, the mixture was filtered through a pad of Celite and was washed with ethyl acetate (30 mL) and a 10% aqueous solution of K3PO4 (30 mL). The organic layer was washed with water (30 mL), dried over Na2SO4 and the organic solvent was distilled off to yield tert-butyl 3-(4-amino-1-methyl-1H-pyrazol-5-yl)phenylcarbamate as a brown oil with a purity of >98% (120 mg, 45%) over two steps. ESIMS m/z=289.1 (M+1)",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2CO3 KOAc\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m11\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-chloro-1-methyl-4-nitro-1H-pyrazole\"}], \"amount\": {\"mass\": {\"value\": 150.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(tert-butoxycarbonylamino)phenylboronic acid\"}], \"amount\": {\"mass\": {\"value\": 440.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloro[1,1\\u2032-bis(diphenylphosphino)ferrocene]palladium(II)\"}], \"amount\": {\"mass\": {\"value\": 152.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m5_m8_m6_m10_m9\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"nitro\"}], \"amount\": {\"mass\": {\"value\": 120.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium chloride\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"iron\"}], \"amount\": {\"mass\": {\"value\": 156.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 1.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred for 1 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The mixture was irradiated to 130\\u00b0 C. with a microwave for 40 min\", \"duration\": {\"value\": 40.0, \"units\": \"MINUTE\"}, \"temperature\": {\"setpoint\": {\"value\": 130.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"the mixture was cooled\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"purified via flash chromatography, heptane/ethyl acetate 20% to 95%\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"heptane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"to afford a yellow oil\"}, {\"type\": \"CUSTOM\", \"details\": \"Upon completion of the reaction\"}, {\"type\": \"FILTRATION\", \"details\": \"the mixture was filtered through a pad of Celite\"}, {\"type\": \"WASH\", \"details\": \"was washed with ethyl acetate (30 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with water (30 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"the organic solvent was distilled off\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl 3-(4-amino-1-methyl-1H-pyrazol-5-yl)phenylcarbamate\"}], \"isolated_color\": \"brown\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-6222f316366c477c9d9909672367cb5f",
    "procedure_text": "To a 100 mL round-bottomed flask was added 2-(2-methoxyphenyl)ethylamine (1510 mg, 10 mmol, Aldrich), pyridine (10 mL), 4-(trifluoromethyl)benzoyl chloride (2 mL, 10 mmol, Fluka). The reaction mixture was stirred at RT for 1 h. The reaction mixture was diluted with water (20 mL) and extracted with EtOAc (2\u00d750 mL). The organic extract was washed with saturated NaHCO3 (20 mL), saturated NaCl (20 mL), dried over Na2SO4, filtered and concentrated in vacuo and the residue was purified by silica gel chromatography, eluting with 20% EtOAc/CH2Cl2 to give N-(2-methoxyphenethyl)-4-(trifluoromethyl)benzamide. MS (ESI pos. ion) m/z: 324 (M+1).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(2-methoxyphenyl)ethylamine\"}], \"amount\": {\"mass\": {\"value\": 1510.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(trifluoromethyl)benzoyl chloride\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred at RT for 1 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted with EtOAc (2\\u00d750 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The organic extract\"}, {\"type\": \"WASH\", \"details\": \"was washed with saturated NaHCO3 (20 mL), saturated NaCl (20 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaCl\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was purified by silica gel chromatography\"}, {\"type\": \"WASH\", \"details\": \"eluting with 20% EtOAc/CH2Cl2\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc CH2Cl2\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(2-methoxyphenethyl)-4-(trifluoromethyl)benzamide\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-19fd726250af49daa1609b2c45afad92",
    "procedure_text": "To a solution of methyl 2-bromonicotinate (5.6 g, 25.9 mmol) in toluene (140 mL) was added 4-chlorophenylboronic acid (6.1 g, 38.9 mmol), potassium carbonate (5.4 g, 39 mmol), and tetrakis(triphenylphosphine) palladium (1.53 g. 1.3 mmol). The mixture was heated to reflux for 3.5 hours, evaporated in vacuo and then purified on a silica gel column using a 1:4 mixture of ethyl acetate:hexane as mobile phase. Pure fractions were combined and the solvent was removed in vacuo to yield methyl 2-(4-chlorophenyl)nicotinate (6.0 g, HPLC RT=3.04 min, method A; LC-MS m/z=248).",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 2-bromonicotinate\"}], \"amount\": {\"mass\": {\"value\": 5.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-chlorophenylboronic acid\"}], \"amount\": {\"mass\": {\"value\": 6.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 5.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 140.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrakis(triphenylphosphine) palladium\"}], \"amount\": {\"mass\": {\"value\": 1.53, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The mixture was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to reflux for 3.5 hours\", \"duration\": {\"value\": 3.5, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"purified on a silica gel column\"}, {\"type\": \"ADDITION\", \"details\": \"a 1:4 mixture of ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was removed in vacuo\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 2-(4-chlorophenyl)nicotinate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 6.0, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a5a33240802e4867a54fa1e428fc6e8d",
    "procedure_text": "To a solution of (2-chloro-5-((3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxy-methyl)tetrahydro-2H-pyran-2-yl)benzyloxy)triisopropylsilane (198 mmol) from Step 5 in tetrahydrofuran (500 mL) was added tetrabutylammonium fluoride (1.0 M in tetrahydrofuran, 594 mL, 594 mmol) and the reaction mixture stirred at ambient temperature for 2 h. After removal of organic volatiles under reduced pressure, the residue was partitioned between ethyl acetate and saturated ammonium chloride solution. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The crude residue was purified on Biotage\u00ae purification apparatus (silica gel, 10 to 60% ethyl acetate in hexanes) to yield the title compound (130 g, 195 mmol, 98%, mixture of \u03b1,\u03b2-anomer in about 1:2 ratio) as a white solid.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2-chloro-5-((3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxy-methyl)tetrahydro-2H-pyran-2-yl)benzyloxy)triisopropylsilane\"}], \"amount\": {\"moles\": {\"value\": 198.0, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrabutylammonium fluoride\"}], \"amount\": {\"volume\": {\"value\": 594.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture stirred at ambient temperature for 2 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"After removal of organic volatiles under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was partitioned between ethyl acetate and saturated ammonium chloride solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The organic layer was separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"the aqueous layer was extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined organic layers were washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude residue was purified on Biotage\\u00ae purification apparatus (silica gel, 10 to 60% ethyl acetate in hexanes)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude residue\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 195.0, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 130.0, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 98.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 98.5}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-befa043881be4da5b8c273d5c95fe733",
    "procedure_text": "In an egg-plant type flask were charged 7.66 g of 85% potassium hydroxide, 3 ml of water, 60 ml of ethanol, and 3.0 g of the compound obtained in Step 6, and the mixture was refluxed for 10 hours. Ethanol was removed by distillation under reduced pressure, and 30 ml of water was added to the residue. The mixture was adjusted to pH 1 with concentrated hydrochloric acid and then extracted with ethyl acetate. The extract was washed with water, and the solvent was removed by distillation under reduced pressure to obtain 2.6 g of a crude product. Purification by silica gel column chromatography gave 1.8 g (59.77%) of the titled compound.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium hydroxide\"}], \"amount\": {\"mass\": {\"value\": 7.66, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound\"}], \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"the mixture was refluxed for 10 hours\", \"duration\": {\"value\": 10.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"Ethanol was removed by distillation under reduced pressure, and 30 ml of water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ethanol\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"was added to the residue\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The extract was washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was removed by distillation under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"to obtain 2.6 g of a crude product\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"amount\": {\"mass\": {\"value\": 2.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Purification by silica gel column chromatography\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"titled compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.8, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 59.77}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 59.8}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f509a64986d042528b7adaba812e5bdd",
    "procedure_text": "To a solution of tert-butyl 3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)phenyl(methyl)carbamate (31) (450 mg, 0.86 mmol) in DCM (8 mL) was added TFA (2 mL) dropwise. The reaction mixture was stirred at rt for 1 h and then concentrated. The residue was purified by column chromatography (silica gel, 0 to 10% methanol in methylene chloride (0.3% Et3N)) to give 6-amino-9-(3-(methylamino)phenyl)-7-(4-phenoxyphenyl)-7H-purin-8(9H)-one (32) (364 mg, 100%). LC-MS (ESI): m/z (M+1) 425.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl 3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)phenyl(methyl)carbamate\"}], \"amount\": {\"mass\": {\"value\": 450.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TFA\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"amount\": {\"volume\": {\"value\": 8.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred at rt for 1 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by column chromatography (silica gel, 0 to 10% methanol in methylene chloride (0.3% Et3N))\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Et3N\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-amino-9-(3-(methylamino)phenyl)-7-(4-phenoxyphenyl)-7H-purin-8(9H)-one\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 364.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 100.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f037756b0a444bdabcd4ebc5d0d19261",
    "procedure_text": "A carousel tube was charged with sulfuric acid mono-[2-(2-sulfooxy-ethylamino)-ethyl]ester (1 g) and D2O (3 mL). To the resulting stirred solution was added then added cyclopropylamin (0.7 mL). The resulting mixture was observed to form a stirrable thick slurry, which was heated at 50\u00b0 C. overnight. Comparison of the 1H NMR of the title compound with the 1H NMR of the di-hydrochloride salt of the title compound confirmed that the title compound was prepared and present in the resulting solution.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sulfuric acid mono-[2-(2-sulfooxy-ethylamino)-ethyl]ester\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cyclopropylamin\"}], \"amount\": {\"volume\": {\"value\": 0.7, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 50.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"To the resulting stirred solution\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"CUSTOM\", \"details\": \"to form a stirrable thick slurry, which\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-883c845d9ead478aa65ac82f3de80cd1",
    "procedure_text": "To a solution of 3.46 g (10 mmol) of 3-(S)-(3,4-dichlorophenyl)-4-(t-butoxycarbonyl-methylamino)butanal (Example 1) in 20 mL of methanol were added 3.11 g (14 mmol) of spiro(1H-indene-1,4'-piperidine) hydrochloride and 3 g of powdered 4 \u212b molecular sieves. After 15 min a solution of 2.52 g (40 mmol) of NaCNBH3 in 30 mL of THF was dropwise added. Some gas evolution was observed. After stirring the reaction overnight, the mixture was filtered through a pad of celite, the reaction flask and the pad were rinsed with methanol. The filtrate was concentrated to approximately 10 ml and the residue was partitioned between saturated NaHCO3 and Et2O:EtOAC. The organic layer was washed with water, brine and dried over NA2SO4. The filtrate was concentrated and the residue was chromatographed on a flash column using a gradient of 49:49:2 to 98:0:2 EtOAc:Hexane:triethylamine to furnish 4.05 g (79%) of the title compound as a foam.",
    "reference_string": "{\"inputs\": {\"m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaCNBH3\"}], \"amount\": {\"mass\": {\"value\": 2.52, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(S)-(3,4-dichlorophenyl)-4-(t-butoxycarbonyl-methylamino)butanal\"}], \"amount\": {\"mass\": {\"value\": 3.46, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"spiro(1H-indene-1,4'-piperidine) hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 3.11, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the reaction overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"the mixture was filtered through a pad of celite\"}, {\"type\": \"WASH\", \"details\": \"the reaction flask and the pad were rinsed with methanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"The filtrate was concentrated to approximately 10 ml\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was partitioned between saturated NaHCO3 and Et2O\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Et2O\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with water, brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried over NA2SO4\"}, {\"type\": \"CONCENTRATION\", \"details\": \"The filtrate was concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was chromatographed on a flash column\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 4.05, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 79.0}}], \"texture\": {\"type\": \"FOAM\", \"details\": \"foam\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-7da7d6f307e24982acac6448264b9fee",
    "procedure_text": "To a mixture of tert-butyl 2-hydroxyethyl (methyl)carbamate (1.75 g) obtained in Reference Example 1 and ethyl acetate (20 mL) were added pyridine (0.97 mL) and 4-dimethylaminopyridine (catalytic amount), and ethyl chlorocarbonate (1.25 mL) was dropwise added. The mixture was stirred overnight at room temperature and ethyl acetate (50 mL) was added. The mixture was washed with water (50 mL), a 5% aqueous citric acid solution (50 mL) and saturated brine (50 mL), and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, a 4N hydrogen chloride-ethyl acetate solution (10 mL) was added to the residue. After stirring at room temperature for 2 hrs., diethyl ether (10 mL) was added, and the precipitated solid was collected by filtration. The solid was dried under reduced pressure to give the title compound (1.66 g) as a white solid.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2_m6_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"amount\": {\"volume\": {\"value\": 0.97, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl chlorocarbonate\"}], \"amount\": {\"volume\": {\"value\": 1.25, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-dimethylaminopyridine\"}], \"reaction_role\": \"CATALYST\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl 2-hydroxyethyl (methyl)carbamate\"}], \"amount\": {\"mass\": {\"value\": 1.75, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred overnight at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was dropwise added\"}, {\"type\": \"WASH\", \"details\": \"The mixture was washed with water (50 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"a 5% aqueous citric acid solution (50 mL) and saturated brine (50 mL), and dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"citric acid\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"After concentration under reduced pressure\"}, {\"type\": \"ADDITION\", \"details\": \"a 4N hydrogen chloride-ethyl acetate solution (10 mL) was added to the residue\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrogen chloride-ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"STIRRING\", \"details\": \"After stirring at room temperature for 2 hrs\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"ADDITION\", \"details\": \", diethyl ether (10 mL) was added\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"the precipitated solid was collected by filtration\"}, {\"type\": \"CUSTOM\", \"details\": \"The solid was dried under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.66, \"units\": \"GRAM\"}}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b8afb5521a7b43cba946b0a0176db700",
    "procedure_text": "A tetrahydrofuran solution of 6.78 g of 1-(4-benzyloxy-3-methoxy-phenyl)-2-nitropropene is added dropwise to a suspension of 2.15 g of lithium aluminum hydride in tetrahydrofuran. The mixture is stirred at room temperature and then refluxed. After the reaction, excess lithium aluminum hydride is decomposed with ice water, and inorganic materials are filtered off. The filtrate is washed, dried and then condensed to dryness. 6 g of 1-(4-benzyloxy-3-methoxyphenyl)-2-aminopropane are obtained as pale yellow viscous oil.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"reaction_role\": \"REACTANT\"}]}, \"m6_m1_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(4-benzyloxy-3-methoxy-phenyl)-2-nitropropene\"}], \"amount\": {\"mass\": {\"value\": 6.78, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium aluminum hydride\"}], \"amount\": {\"mass\": {\"value\": 2.15, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium aluminum hydride\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture is stirred at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"refluxed\"}, {\"type\": \"FILTRATION\", \"details\": \"are filtered off\"}, {\"type\": \"WASH\", \"details\": \"The filtrate is washed\"}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"CUSTOM\", \"details\": \"condensed to dryness\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(4-benzyloxy-3-methoxyphenyl)-2-aminopropane\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 6.0, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-db7af0a0c5f14de4b55a0c6772f87793",
    "procedure_text": "The procedures of Example 6 (1) and (2) were repeated but substituting the 1-(2-pyrimidinyl)-4-acetyl-5-methylpyrazole and 1,2,3,4-tetrahydroisoquinoline hydrochloride employed in Example 6 (1) respectively by 1-(4-methyl-6-methoxy-2-pyrimidinyl)-4-acetyl-5-methylpyrazole and 1-(2-methylphenyl)piperazine hydrochloride. After the completion of the post treatment, the title compound was obtained.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"( 1 )\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Example 6 ( 1 )\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(2-pyrimidinyl)-4-acetyl-5-methylpyrazole\"}], \"reaction_role\": \"REACTANT\"}]}, \"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,2,3,4-tetrahydroisoquinoline hydrochloride\"}], \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(4-methyl-6-methoxy-2-pyrimidinyl)-4-acetyl-5-methylpyrazole\"}], \"reaction_role\": \"REACTANT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(2-methylphenyl)piperazine hydrochloride\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"( 2 )\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-6bbf57bc04be4ff9b5c8005032b086f3",
    "procedure_text": "A mixture of (+)-cis-2-(4-methoxyphenyl)-3-hydroxy-8-chloro-2,3-dihydro-1,5-benzothiazepin-4(5H)-one (6.8 g), 2-(dimethylamino)ethyl chloride hydrochloride (3.02 g), potassium carbonate (6.1 g) and acetone (150 ml) is stirred under refluxing for 20 hours. After the completion of the reaction, the insoluble materials are removed by filtration and the filtrate is concentrated under reduced pressure. The resulting residue is dissolved in ethyl acetate, washed with water, dried and the ethyl acetate is distilled off. The resulting residue is recrystallized from a mixture of ethyl acetate and n-hexane to give (+)-cis-2-(4-methoxyphenyl)-3-hydroxy-5-[2-(dimethylamino)ethyl]-8-chloro-2,3-dihydro-1,5-benzothiazepin-4(5H)-one (7.13 g) as colorless needles, m.p. 122\u00b0-124\u00b0 C. (decomposed).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(+)-cis-2-(4-methoxyphenyl)-3-hydroxy-8-chloro-2,3-dihydro-1,5-benzothiazepin-4(5H)-one\"}], \"amount\": {\"mass\": {\"value\": 6.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(dimethylamino)ethyl chloride hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 3.02, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 6.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"is stirred\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"under refluxing for 20 hours\", \"duration\": {\"value\": 20.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"After the completion of the reaction\"}, {\"type\": \"CUSTOM\", \"details\": \"the insoluble materials are removed by filtration\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate is concentrated under reduced pressure\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The resulting residue is dissolved in ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"DISTILLATION\", \"details\": \"the ethyl acetate is distilled off\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The resulting residue is recrystallized from a mixture of ethyl acetate and n-hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(+)-cis-2-(4-methoxyphenyl)-3-hydroxy-5-[2-(dimethylamino)ethyl]-8-chloro-2,3-dihydro-1,5-benzothiazepin-4(5H)-one\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 7.13, \"units\": \"GRAM\"}}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"needles\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fa71248bb219462281d3a76ddae61759",
    "procedure_text": "A 1:1 mixture of 5-bromo-3,6-dimethyl-1H-indole-2-carboxylic acid and 5-bromo-3,4-dimethyl-1H-indole-2-carboxylic acid (4.39 g, 16.4 mmol) in quinoline (10 mL) with copper powder (250 mg) was stirred at 240\u00b0 C. for 3 h to give the corresponding mixture of the decarboxylated products. Upon cooling, ether (200 mL) was added and the mixture acidified with 5N HCl. The layers were separated, the organics were washed with brine, dried and evaporated. Chromatography (silica, 15% CH2Cl2 in hexane) and crystallization from a CH2Cl2/hexane mixture afforded the title compound (1.35 g 37%). 1H NMR (300 MHz, CDCl3). 7.74 (s, 1H), 7.21 (is, 1H), 6.90 (s, 1H), 2.48 (s, 3H), 2.27 (s, 3H).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-bromo-3,6-dimethyl-1H-indole-2-carboxylic acid\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-bromo-3,4-dimethyl-1H-indole-2-carboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 4.39, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"quinoline\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"copper\"}], \"amount\": {\"mass\": {\"value\": 250.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 240.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at 240\\u00b0 C. for 3 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"to give\"}, {\"type\": \"ADDITION\", \"details\": \"the corresponding mixture of the decarboxylated products\"}, {\"type\": \"TEMPERATURE\", \"details\": \"Upon cooling\"}, {\"type\": \"CUSTOM\", \"details\": \"The layers were separated\"}, {\"type\": \"WASH\", \"details\": \"the organics were washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"Chromatography (silica, 15% CH2Cl2 in hexane) and crystallization from a CH2Cl2/hexane mixture\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2 hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.35, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 37.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-9a9dce2bf1754d9b9108eefb190f458b",
    "procedure_text": "Isopropyl bromide (19.0 mL, 200 mmol) was added to a suspension of K2CO3 (42.0 g, 302 mmol) and isovanillin (23 g, 151.3 mmol) in DMF (100 gmL) and the stirring slurry heated to 80\u00b0 C. for 13 h. The reaction mixture was then cooled to room temperature, diluted with ether (200 mL) and washed with H2O (4\u00d7200 mL), dried (MgSO4) and concentrated under reduced pressure giving the title compound as a slightly tan oil (29.3 g, 100%) which required no further purification. The spectra of this material are identical with those previously reported (H. Ishii, I.-S. Chen and T. Ishikawa J. Chem. Soc., Perkin Trans. 1, 1987, 671.).",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Isopropyl bromide\"}], \"amount\": {\"volume\": {\"value\": 19.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"K2CO3\"}], \"amount\": {\"mass\": {\"value\": 42.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isovanillin\"}], \"amount\": {\"mass\": {\"value\": 23.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 80.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The reaction mixture was then cooled to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"WASH\", \"details\": \"washed with H2O (4\\u00d7200 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"oil\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 29.3, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 100.0}}], \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-9bf3202b43844610852c9d67408e26a0",
    "procedure_text": "A solution of 0.55 g (1.6 mmol) (S)-7-amino-5-(4-methoxy-benzyl)-5H,7H-dibenzo[b,d]azepin-6-one, 3.74 ml (50 mmol) trifluoroacetic acid and 1.4 ml (16 mmol) trifluormethane sulfonic acid in 38 ml dichloromethane was stirred at room temperature for 4 hours. The solvent was distilled off and extraction with aqueous sodium bicarbonate solution/ethyl acetate followed by chromatography on silicagel with ethylacetate/methanol (100-95/0-5) yielded 0.35 g (96%) (S)-7-amino-5H,7H-dibenzo[b,d]azepin-6-one as orange solid; MS: m/e: 225.4 (M+H+).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(S)-7-amino-5-(4-methoxy-benzyl)-5H,7H-dibenzo[b,d]azepin-6-one\"}], \"amount\": {\"mass\": {\"value\": 0.55, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trifluoroacetic acid\"}], \"amount\": {\"volume\": {\"value\": 3.74, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trifluormethane sulfonic acid\"}], \"amount\": {\"volume\": {\"value\": 1.4, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 38.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"DISTILLATION\", \"details\": \"The solvent was distilled off\"}, {\"type\": \"EXTRACTION\", \"details\": \"extraction with aqueous sodium bicarbonate solution/ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(S)-7-amino-5H,7H-dibenzo[b,d]azepin-6-one\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.35, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 96.0}}], \"isolated_color\": \"orange\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-76311e5b0419429d86ab764c6998baab",
    "procedure_text": "In a similar manner to that described in Example (2-2b), a reaction was carried out using 5-{4-[1-methyl-6-(4-methoxyphenoxy)-1H-benzimidazole-2-ylmethoxy]benzyl}thiazolidine-2,4-dione (1.8 g) and 4N hydrogen chloride/ethyl acetate (50 ml) and the reaction mixture was purified to give the title compound (1.85 g).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-{4-[1-methyl-6-(4-methoxyphenoxy)-1H-benzimidazole-2-ylmethoxy]benzyl}thiazolidine-2,4-dione\"}], \"amount\": {\"mass\": {\"value\": 1.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrogen chloride ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the reaction mixture was purified\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.85, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f069efdd17614bd193813fdbf2fd760e",
    "procedure_text": "To a solution of 4,6-dichloro-2-methylsulfanylpyrimidine (500 mg, 2.56 mmol) in anhydrous DMF (6 mL) was added sodium ethoxide (174 mg, 2.56 mmol). The reaction mixture was stirred at 70\u00b0 C. for overnight. The resulting mixture was poured into 30 mL of water and was extracted with diethyl ether (20 mL\u00d73) three times. The ether layer was separated and dried with anhydrous MgSO4 and concentrated in vacuo to give crude product 4-chloro-6-ethoxy-2-methylsulfanylpyrimidine (525 mg). 1H-NMR (CDCl3): \u03b4 6.39 (s, 1H), 4.43 (q, J=7.1 Hz, 2H), 2.54 (s, 3H), 1.38 (t, J=7.1H, 3H).",
    "reference_string": "{\"inputs\": {\"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4,6-dichloro-2-methylsulfanylpyrimidine\"}], \"amount\": {\"mass\": {\"value\": 500.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium ethoxide\"}], \"amount\": {\"mass\": {\"value\": 174.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 6.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 70.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred at 70\\u00b0 C. for overnight\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"was extracted with diethyl ether (20 mL\\u00d73) three times\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The ether layer was separated\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried with anhydrous MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-chloro-6-ethoxy-2-methylsulfanylpyrimidine\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 525.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0e70df2446234590b2d35ee7d285125f",
    "procedure_text": "The title compound was prepared according to the general procedure described in Steps 3 and 4 of Method F starting from 4-[3-[6-(3-bromo-5-dimethylcarbamoyl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester and 4-chlorophenylboronic acid. LC/MS indicated a purity of 100% as measured by UV 214 nM.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-[3-[6-(3-bromo-5-dimethylcarbamoyl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-chlorophenylboronic acid\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c12676b3e0654bb4951a01b5b4b68e96",
    "procedure_text": "To a solution of 5.00 g (21.9 mmol) of 4-(tert-butyl-dimethyl-silanyloxy)-cyclohexanone in 100 mL THF was added 9.18 mL (43.8 mmol) of Ti(OEt)4 and 2.78 g (23.0 mmol) of 2-methyl-2-propanesulfinamide. The resulting mixture was stirred under reflux for 12 h, before being poured into an equal volume of saturated aqueous NaHCO3 with rapid stirring and filtered through celite. The filter cake was washed with ethyl acetate, the aqueous layer was separated and extracted twice with ethyl acetate. The combined organic layers were dried over MgSO4, filtered, and concentrated under vacuum. The crude product was purified by silica gel chromatography to yield 5.12 g of the title compound (25) as diastereomeric mixture. Rt=1.87 min, 1.92 min (Method C). Detected mass: 332.3 (M+H+).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m5_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(tert-butyl-dimethyl-silanyloxy)-cyclohexanone\"}], \"amount\": {\"mass\": {\"value\": 5.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ti(OEt)4\"}], \"amount\": {\"volume\": {\"value\": 9.18, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-methyl-2-propanesulfinamide\"}], \"amount\": {\"mass\": {\"value\": 2.78, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The resulting mixture was stirred\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"under reflux for 12 h\", \"duration\": {\"value\": 12.0, \"units\": \"HOUR\"}}, {\"type\": \"STIRRING\", \"details\": \"with rapid stirring\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered through celite\"}, {\"type\": \"WASH\", \"details\": \"The filter cake was washed with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the aqueous layer was separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted twice with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic layers were dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under vacuum\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude product was purified by silica gel chromatography\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 5.12, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4791538f23c34f109afb5e3663829483",
    "procedure_text": "To 20 mL of stirring chlorosulfonic acid cooled to \u22125\u00b0 C. was added 3,4-diphenyl-2-(5H)-furanone (Step 1)(3.160 g, 13.4 mmol) portion-wise over 30 minutes. The solution was warmed to room temperature and maintained at that temperature for 16 hours. The reaction mixture was diluted with dichloromethane and quenched into ice water. The phases were separated and the aqueous phase extracted with dichloromethane, the combined dichloromethane extract was dried over anhydrous MgSO4, filtered and concentrated in vacuo. The residue was diluted with dichloromethane and added to excess concentrated NH4OH. The mixture was stirred for 1 hour. The phases were separated and the aqueous phase was extracted with dichloromethane. The organic extract was dried over anhydrous MgSO4, filtered and concentrated in vacuo to give a white solid that was crystallized from aqueous ethanol to afford pure 3-[(4-aminosulfonyl)phenyl)]-4-phenyl-2-(5H)-furanone (2.110 g, 50%): mp 225.5-226.5\u00b0 C. 1H NMR (CDCl3/300 MHz) 7.79 (d, 2H, J=8.4 Hz), 7.41 (d, 2H, J=8.4 Hz), 6.38 (brs, 2H), 5.09 (s, 2H). FABLRMS m/z 316 (m+H). Anal. Calc'd for C16H13NO4S: C, 60.94; H, 4.16; N, 4.44. Found: C, 60.86; H, 4.18; N, 4.40.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chlorosulfonic acid\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,4-diphenyl-2-(5H)-furanone\"}], \"amount\": {\"mass\": {\"value\": 3.16, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred for 1 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"maintained at that temperature for 16 hours\", \"duration\": {\"value\": 16.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"quenched into ice water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The phases were separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"the aqueous phase extracted with dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"the combined dichloromethane extract\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"was dried over anhydrous MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"ADDITION\", \"details\": \"The residue was diluted with dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"added to excess concentrated NH4OH\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH4OH\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The phases were separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"the aqueous phase was extracted with dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The organic extract\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"was dried over anhydrous MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a white solid\"}, {\"type\": \"CUSTOM\", \"details\": \"that was crystallized from aqueous ethanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-phenyl-2-(5H)-furanone\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.11, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 50.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fc6fb0b9dde640f1bf18744b978b8f55",
    "procedure_text": "15.2 g (0.1 mol) of salicylic acid hydrazide and 20.0 g (0.1 mol) of lauric acid are suspended in 200 ml of chlorobenzene, 2.0 g (0.025 mol) of pyridine are added and the mixture is heated to the boil. 13.1 g (0.11 mol) of thionyl chloride are added dropwise at this temperature. The product separates out initially as a turbidity and then as a flocculent precipitate. After boiling for 1 hour the mixture is cooled and the product is filtered off and washed with a little benzene and then with petroleum ether. N-Salicyloyl-N'-lauroyl-hydrazine of melting point 158\u00b0 C is thus obtained in a yield of 53%. The product can be recrystallised from ethylene glycol monomethyl ether.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"thionyl chloride\"}], \"amount\": {\"mass\": {\"value\": 13.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"salicylic acid hydrazide\"}], \"amount\": {\"mass\": {\"value\": 15.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lauric acid\"}], \"amount\": {\"mass\": {\"value\": 20.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chlorobenzene\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"the mixture is heated to the boil\"}, {\"type\": \"TEMPERATURE\", \"details\": \"the mixture is cooled\"}, {\"type\": \"FILTRATION\", \"details\": \"the product is filtered off\"}, {\"type\": \"WASH\", \"details\": \"washed with a little benzene\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzene\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-Salicyloyl-N'-lauroyl-hydrazine\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 53.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c19af088cac24e75b2d62f82f2dc7351",
    "procedure_text": "3-chloro-6-ethynylisoquinoline (Preparation 50, 120 mg, 0.64 mmol) was dissolved in dry DMF (1 mL). Azidotrimethylsilane (1 mL, 7.5 mmol) was added and the reaction stirred at 120\u00b0 C. for 2 hours. The reaction was cooled to room temperature and diluted with ethyl acetate (20 mL). The organic solution was washed with water (20 mL), brine (20 mL), dried over sodium sulphate and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 2% 7N NH3 in methanol in DCM followed by elution through an SCX-2 column using 50% methanol in chloroform followed by 50% 7N NH3 in methanol in chloroform to afford the title compound as a pale brown powder (90 mg, 61%).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-chloro-6-ethynylisoquinoline\"}], \"amount\": {\"mass\": {\"value\": 120.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Azidotrimethylsilane\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 120.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction stirred at 120\\u00b0 C. for 2 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The reaction was cooled to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"WASH\", \"details\": \"The organic solution was washed with water (20 mL), brine (20 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulphate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulphate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified\"}, {\"type\": \"WASH\", \"details\": \"eluting with 2% 7N NH3 in methanol in DCM\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH3\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"followed by elution through an SCX-2 column\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 90.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 61.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 61.0}}], \"isolated_color\": \"pale brown\", \"texture\": {\"type\": \"POWDER\", \"details\": \"powder\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-ad9de76693e242618ac1f457a08391e5",
    "procedure_text": "3-(3,4-Diacetoxyphenyl)-2-(diethoxyphosphinyl) acrylonitrile (Table 1, No. 56; 2.5 g; 0.0066 mol) was hydrogenated in 100 ml of acetic anhydride over 0.5 g of 10 percent Pd/C catalyst in a Parr hydrogenation apparatus under an initial pressure of 3.45 bar until hydrogen uptake was complete (16 hours), adding an additional 0.3 g of catalyst after 8 hours had elapsed. Finally, the catalyst was filtered off and the filtrate was evaporated under reduced pressure. The residue was chromatographed on silica gel, eluted with the solvent mixture dichloromethane:ethyl acetate (7:3). This results in the title compound as a pale oil in a yield of 1.7 g (67.7% of theory).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd/C\"}], \"amount\": {\"mass\": {\"value\": 0.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(3,4-Diacetoxyphenyl)-2-(diethoxyphosphinyl) acrylonitrile\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrogen\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"catalyst\"}], \"amount\": {\"mass\": {\"value\": 0.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic anhydride\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"(16 hours)\", \"duration\": {\"value\": 16.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"Finally, the catalyst was filtered off\"}, {\"type\": \"CUSTOM\", \"details\": \"the filtrate was evaporated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was chromatographed on silica gel\"}, {\"type\": \"WASH\", \"details\": \"eluted with the solvent mixture dichloromethane:ethyl acetate (7:3)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"isolated_color\": \"pale\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-51e5a15da9db422784ba0e82a3365bad",
    "procedure_text": "Fluoroalkylation conditions were based on a paper by Timperley et al. J. Fluorine Chem. 2006, 127, 249. A solution of 4-[1-(5-hydroxy-pyridin-2-yl)-1H-[1,2,4]triazol-3-yl]-benzaldehyde O-((2S,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl)-oxime in 10 mL anhydrous DMF/THF (1:1) under a N2 atmosphere was cooled at 0\u00b0 C. while an excess of hexafluoropropylene gas was added over 15 min. Following addition, triethylamine (15 uL, 0.109 mmol) was added and the reaction mixture warmed to ambient temperature before concentration to dryness. Chromatography (EtOAc/hexanes, 1:1) afforded Compound 94 (16 mg, 24%). 1H NMR (CDCl3) \u03b4 9.17 (s, 1H), 8.39 (d, J=7.68 Hz, 1H), 8.21 (d, J=8.22 Hz, 2H), 8.19 (s, 1H), 8.08 (d, J=7.68 Hz, 1H), 7.74 (d, J=8.22 Hz, 2H), 6.97 (s, 1H), 5.63 (d, J=1.85 Hz, 1H), 5.17 (m, 1H), 3.78 (dd, J=3.28, 1.99 Hz, 1H), 3.63 (m, 1H), 3.59 (s, 3H), 3.57 (s, 3H), 3.56 (s, 3H), 3.43 (dd, J=9.31, 3.36 Hz, 1H), 3.18 (t, J=9.48 Hz, 1H), 1.29 (d, J=6.26 Hz, 3H); EIMS 619 m/z (M+).",
    "reference_string": "{\"inputs\": {\"m3_m6_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-[1-(5-hydroxy-pyridin-2-yl)-1H-[1,2,4]triazol-3-yl]-benzaldehyde O-((2S,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl)-oxime\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexafluoropropylene\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF THF\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Fluorine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added over 15 min\", \"duration\": {\"value\": 15.0, \"units\": \"MINUTE\"}}, {\"type\": \"ADDITION\", \"details\": \"was added\"}], \"outcomes\": [{\"products\": [{\"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Compound 94\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 16.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 24.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-78bcaebe602245449fe3a2ea7d50a69f",
    "procedure_text": "To a stirring solution of 4-[2-(3-Aminomethyl-oxetan-3-ylmethoxy)-3,4-dimethoxy-phenyl]-indan-1-one (Compound 191) (150 mg, 0.3916 mmol) in dichloromethane (15 mL), were added diisopropylethylamine (50 mg, 0.390 mmol) and butyryl chloride (41 mg, 0.391 mmol) and the resultant reaction mixture was subjected to the conditions used in the preparation of Compound 193 and purification by column chromatography (silica gel, 0-3% methanol in dichloromethane) afforded the title compound as a solid.",
    "reference_string": "{\"inputs\": {\"m1_m2_m6_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-[2-(3-Aminomethyl-oxetan-3-ylmethoxy)-3,4-dimethoxy-phenyl]-indan-1-one\"}], \"amount\": {\"mass\": {\"value\": 150.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Compound 191\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropylethylamine\"}], \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"butyryl chloride\"}], \"amount\": {\"mass\": {\"value\": 41.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5_m8_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Compound 193\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the resultant reaction mixture\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-244e89b002de49da88c323eb152c2554",
    "procedure_text": "Prepared from 2-amino-5-bromophenyl methyl ketone and 2-pyridyllithium generally according to the procedure described in example 1. 1H NMR (DMSO-d6): \u03b4 8.5 (d, J=3.99 Hz, 1H), 7.77 (dt, J=7.77, 1.79 Hz, 1H), 7.64 (d, J=7.96 Hz, 1H), 7.30 (d, J=2.37 Hz, 1H), 7.21-7.25 (m, 1H), 7.06 (dd, J=8.49, 2.36 Hz, 1H), 6.47 (d, J=8.51 Hz, 1H), 6.18 (s, 1H), 5.26 (s, 2H), 1.8 (s, 3H); MS (ESI) m/z 293/295, 1 Br pattern ([M+H]+).",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-amino-5-bromophenyl methyl ketone\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-pyridyllithium\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-11528d974ea74b82a6e25f3d8d90ef4f",
    "procedure_text": "A solution of 4.7 g (12.0 mmole) of 9-fluoro-16\u03b2-methyl-11\u03b2,17,21-trihydroxypregna-1,4-diene-3,20-dione in 50% acetic acid (600 ml) was stirred with 18 g of sodium bismuthate at room temperature for 2 hours. The brown suspension was filtered through a bed of deactivated silica powder and washed with 100 ml of 50% acetic acid. The filtrate was concentrated in vacuo to 100 ml, diluted with 100 ml of 20% hydrochloric acid and extracted with chloroform. The chloroform solution was washed with 20% hydrochloric acid and water, dried over anhydrous Na2SO4 and evaporated in vacuo to give a solid. This was dissolved in chloroform and chromatographed on a 30 g silica gel column, eluting successively with chloroform and 1:4 ethyl acetate-chloroform to give 2.6 g of the title compound, melting point 281\u00b0-283\u00b0 C., dec.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"9-fluoro-16\\u03b2-methyl-11\\u03b2,17,21-trihydroxypregna-1,4-diene-3,20-dione\"}], \"amount\": {\"mass\": {\"value\": 4.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bismuthate\"}], \"amount\": {\"mass\": {\"value\": 18.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 600.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The brown suspension was filtered through a bed of deactivated silica powder\"}, {\"type\": \"WASH\", \"details\": \"washed with 100 ml of 50% acetic acid\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"The filtrate was concentrated in vacuo to 100 ml\"}, {\"type\": \"ADDITION\", \"details\": \"diluted with 100 ml of 20% hydrochloric acid\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with chloroform\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The chloroform solution was washed with 20% hydrochloric acid and water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a solid\"}, {\"type\": \"CUSTOM\", \"details\": \"chromatographed on a 30 g silica gel column\"}, {\"type\": \"WASH\", \"details\": \"eluting successively with chloroform and 1:4 ethyl acetate-chloroform\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.6, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-bd0538b662c64ed0a312f41c2caed84d",
    "procedure_text": "N-(4-tert-butylbenzyl)-2-methyl-1,8-naphthyridine-3-carboxamide (150 mg, 0.45 mmol) was dissolved in THF (anh, 8.0 ml) under N2. Methylmagnesium bromide (4.5 ml of a 1M sln) was added dropwise. The mixture was stirred at r.t. for 2.0 h. The reaction was quenched with NH4Cl (sat). The product was extracted with EtOAc, dried (MgSO4), filtered and concentrated. The residue was dissolved in CHCl3 and O2 (94%) was bubbled through the solution for 3.0 h. The mixture was concentrated and purified by flash chromatography CH2Cl2/MeOH (96:4\u219295:5) yielding 50.0 mg of the title compound (32%). 1H NMR (CDCl3) \u03b4 8.80 (m, 1H), 8.13 (m, 1H), 7.44 (d, 2H), 7.41 (d, 2H), 7.35 (m, 1H), 7.02 (t, 1H), 4.74 (d, 2H), 2.73 (s, 3H), 2.49 (s, 3H), 1.34 (s, 9H).",
    "reference_string": "{\"inputs\": {\"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(4-tert-butylbenzyl)-2-methyl-1,8-naphthyridine-3-carboxamide\"}], \"amount\": {\"mass\": {\"value\": 150.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 8.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Methylmagnesium bromide\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at r.t. for 2.0 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The reaction was quenched with NH4Cl (sat)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH4Cl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The product was extracted with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue was dissolved in CHCl3\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CHCl3\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"O2 (94%) was bubbled through the solution for 3.0 h\", \"duration\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"O2\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"The mixture was concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"purified by flash chromatography CH2Cl2/MeOH (96:4\\u219295:5)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2 MeOH\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 32.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e8571ea9c24d4f77b6e950243aa7472a",
    "procedure_text": "A 2.0 g quantity of benzyl 2-(3-phenoxyacetamido-4-benzenesulfonylthio-2-azetidinone-1-yl)-3-methyl-3-butenate was dissolved in 10 ml of dichloromethane and to the solution was added 5 to ml of water. The mixture was cooled in an ice bath with stirring while thereto was added dropwise over 30 minutes about 10 ml of methylene chloride having dissolved therein 6.9 mmol of chlorine gas. After the addition, the organic layer was separated and the aqueous layer was extracted with dichloromethane. The organic layer thus separated and the dichloromethane layer were washed successively with aqueous solutions each of NaHCO3, Na2S2O3 and NaCl and dried over anhydrous magnesium sulfate. The solvent was distilled off at reduced pressure. The resulting residue was separated and purified by silica gel column chromatography, giving 1.87 g of benzyl 2-(3-phenoxyacetamido-4-benzenesulfonylthio-2-azetidinone-1-yl)-3-chloromethyl-3-butenate in 88% yield.",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzyl 2-(3-phenoxyacetamido-4-benzenesulfonylthio-2-azetidinone-1-yl)-3-methyl-3-butenate\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chlorine\"}], \"amount\": {\"moles\": {\"value\": 6.9, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"with stirring\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The mixture was cooled in an ice bath\"}, {\"type\": \"DISSOLUTION\", \"details\": \"dissolved\"}, {\"type\": \"ADDITION\", \"details\": \"After the addition\"}, {\"type\": \"CUSTOM\", \"details\": \"the organic layer was separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"the aqueous layer was extracted with dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The organic layer thus separated\"}, {\"type\": \"WASH\", \"details\": \"the dichloromethane layer were washed successively with aqueous solutions each of NaHCO3, Na2S2O3 and NaCl\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2S2O3\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaCl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"The solvent was distilled off at reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The resulting residue was separated\"}, {\"type\": \"CUSTOM\", \"details\": \"purified by silica gel column chromatography\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzyl 2-(3-phenoxyacetamido-4-benzenesulfonylthio-2-azetidinone-1-yl)-3-chloromethyl-3-butenate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.87, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 88.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-ec9f99a978234dce811b1918022ddc39",
    "procedure_text": "To a stirred solution of 1,4,7,10-tetra(p-toluenesulfonyl)-1,4,7,10-tetraazadecane prepared as in Example 15B (66.5 g, 0.0872 mole) in anhydrous DMF (1 l) was added sodium hydride (5.22 g--80% in mineral oil, 0.174 mole) in portions under a dry nitrogen blanket. The resulting mixture was stirred for 30 minutes under a dry argon atmosphere. The solution was then heated to 100\u00b0 C. and a solution of N-methylbis(2-chloroethyl)amine freshly prepared as in Example 15A (13.6 g, 0.0872 mole) in anhydrous DMF (200 ml) was added dropwise over a 1.5 h period, maintaining the temperature at 100\u00b0 C. After stirring an additional 45 minutes at 100\u00b0 C., the solution was concentrated in vacuo to a volume of 750 ml. H2O was slowly added at room temperature to crystallize the product. The resulting brown solid was filtered, washed thoroughly with H2O and dried in vacuo over P2O, to give 62.9 g (85% yield) of the crude product as a brown solid. The product was purified by crystallization from DMF-H2O to give a yellow solid: mp 170-1\u00b0 C.; 1H NMR (CDCl3) \u03b4 2.15 (s, 3 H), 2.43 (s, 6 H), 2.44 (s, 6 H), 2.51 (t, J=5.5 Hz, 4 H), 3.15 (t, J=5.5 Hz, 4 H), 3.29 (m, 8 H), 3.36 (s, 4 H), 7.32 (m, 8 H), 7.69 (m, 8 H).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,4,7,10-tetra(p-toluenesulfonyl)-1,4,7,10-tetraazadecane\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Example 15A\"}], \"amount\": {\"mass\": {\"value\": 13.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydride\"}], \"amount\": {\"moles\": {\"value\": 0.174, \"units\": \"MOLE\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-methylbis(2-chloroethyl)amine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"LITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Example 15B\"}], \"amount\": {\"mass\": {\"value\": 66.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The resulting mixture was stirred for 30 minutes under a dry argon atmosphere\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added dropwise over a 1.5 h period\", \"duration\": {\"value\": 1.5, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"maintaining the temperature at 100\\u00b0 C\", \"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"STIRRING\", \"details\": \"After stirring an additional 45 minutes at 100\\u00b0 C.\", \"duration\": {\"value\": 45.0, \"units\": \"MINUTE\"}, \"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CONCENTRATION\", \"details\": \"the solution was concentrated in vacuo to a volume of 750 ml\"}, {\"type\": \"ADDITION\", \"details\": \"H2O was slowly added at room temperature\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"reaction_role\": \"WORKUP\"}]}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"to crystallize the product\"}, {\"type\": \"FILTRATION\", \"details\": \"The resulting brown solid was filtered\"}, {\"type\": \"WASH\", \"details\": \"washed thoroughly with H2O\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried in vacuo over P2O\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 62.9, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 85.0}}], \"isolated_color\": \"brown\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-20069deb61654190894675a14b1784de",
    "procedure_text": "To a mixture of 1.9 g (3.71 mmol) of methyl 4-(4-methoxybenzenesulfonyl)-1-(2-methyl-5-fluorobenzoyl)-2,3,4,5-tetrahydro-1H-[1,4]benzodiazepine-3-carboxylate in 10 ml of tetrahydrofuran was added 5 ml (4.82 mmol) of 1 N NaOH. The mixture was stirred at room temperature for 1.5 hours and the solvent removed under vacuum. To the residue was added ethyl acetate and the mixture neutralized with 1 N HCl. The organic layer was separated, washed with brine and dried with Na2SO4. The solvent was removed under vacuum to give 1.41 g of white solid. Anal. for C25H23FN2O6S: Calc'd: C,60.2; H,4.7; N,5.6; Found: C,60.2; H,4.8; N,5.4 S,6.4; F,3.6; Mass spectrum (ES) 497.5 (M-H).",
    "reference_string": "{\"inputs\": {\"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 4-(4-methoxybenzenesulfonyl)-1-(2-methyl-5-fluorobenzoyl)-2,3,4,5-tetrahydro-1H-[1,4]benzodiazepine-3-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 1.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at room temperature for 1.5 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the solvent removed under vacuum\"}, {\"type\": \"ADDITION\", \"details\": \"To the residue was added ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The organic layer was separated\"}, {\"type\": \"WASH\", \"details\": \"washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried with Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The solvent was removed under vacuum\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.5, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"white solid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.41, \"units\": \"GRAM\"}}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-eca9bde9de43448b9db0ef25b1d736c8",
    "procedure_text": "Using general procedure A with 4-(trifluoromethoxy)-aniline (0.21 mL, 1.55 mmol) and (R)-3-(4-oxo-piperidin-1-yl]-butyronitrile (310 mg, 1.87 mmol) followed by general procedure J afforded [1-((R)-3-amino-1-methyl-propyl)-piperidin-4-yl]-(4-trifluoromethoxy-phenyl)-amine as a white solid (277 mg, 55% over 2 steps).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(trifluoromethoxy)-aniline\"}], \"amount\": {\"volume\": {\"value\": 0.21, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-3-(4-oxo-piperidin-1-yl]-butyronitrile\"}], \"amount\": {\"mass\": {\"value\": 310.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"[1-((R)-3-amino-1-methyl-propyl)-piperidin-4-yl]-(4-trifluoromethoxy-phenyl)-amine\"}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-5b3f35573b28427b807879c342f432f3",
    "procedure_text": "Phthalonitrile (1100 grams) and titanium tetrachloride (813 grams) were suspended in 6800 milliliters (ml) of 1-chloronaphthalene and heated to 215-220\u00b0 C. and maintained for 2.5 hours at this temperature. The reaction mixture was cooled to 140\u00b0 C., and the dark solid was collected and washed with acetone and methanol. After drying, the dark blue solid (1090 grams) was slurried twice in refluxing 10 liters of distilled water for two hours, filtered hot each time, and washed with acetone to yield crude phthalocyanine. The X-ray diffraction spectrum exhibits major peaks of the Bragg angle at 7.5, 8.3, 10.5, 12.7, 14.2, 14.6, 18.9, 22.1, 24.3, 26.1, and 29.9 (all +/-0.2 degrees).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Phthalonitrile\"}], \"amount\": {\"mass\": {\"value\": 1100.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-chloronaphthalene\"}], \"amount\": {\"volume\": {\"value\": 6800.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"titanium tetrachloride\"}], \"amount\": {\"mass\": {\"value\": 813.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 217.5, \"precision\": 2.5, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"maintained for 2.5 hours at this temperature\", \"duration\": {\"value\": 2.5, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"The reaction mixture was cooled to 140\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 140.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"the dark solid was collected\"}, {\"type\": \"WASH\", \"details\": \"washed with acetone and methanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"After drying\"}, {\"type\": \"TEMPERATURE\", \"details\": \"in refluxing 10 liters of distilled water for two hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"LITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered hot each time\"}, {\"type\": \"WASH\", \"details\": \"washed with acetone\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"phthalocyanine\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c765470b21964013a886c7b402f42a02",
    "procedure_text": "Prepared according to general procedure B from 72.4 mg (0.27 mmol) 7,8-dihydro-5H-pyrido[3,2-b]azepine-6,9-dione 9-(phenylhydrazone) in 30 ml diphenyl ether. Recrystallization from ethanol afforded a brown solid. Yield: 17 mg (25%); m.p. >330\u00b0 C.; IR (KBr): 3054 cm\u22121 (CH-arom.), 2974 cm\u22121 (CH-aliph.), 1675 cm\u22121 (C\u2550O), 1H-NMR (d6-DMSO, 400 MHz): \u03b4 (ppm)=3.66 (s, 2H, azepine-CH2), 7.06-7.09 (m, 1H, arom. H), 7.18-7.22 (m, 1H, arom. H), 7.40 (dd, 1H, 8.2/4.5 Hz, arom. H), 7.47 (d, 1H, 8.2 Hz, arom. H), 7.62 (dd, 1H, 8.2/1.4 Hz, arom. H), 7.70 (d, 1H, 8.0 Hz, arom. H), 8.48 (dd, 1H, 4.5/1.4 Hz, arom. H), 10.22 (s, 1H, NH), 11.70 (s, 1H, NH); 13C-NMR (DMSO-d6, 100.6 MHz): \u03b4 (ppm)=31.9 (azepine-CH2), 111.9, 118.4, 119.1, 122.5, 122.8, 129.3, 144.3 (tert. arom. C), 108.9, 126.3, 132.0, 132.5, 137.5, 140.5 (quat. arom. C), 171.1 (C\u2550O); C15H11N3O (249.27); purity (HPLC): 98.8% (ts=3.25 min, acetonitrile/water 35:65).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile water\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7,8-dihydro-5H-pyrido[3,2-b]azepine-6,9-dione 9-(phenylhydrazone)\"}], \"amount\": {\"mass\": {\"value\": 72.4, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"KBr\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diphenyl ether\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"C15H11N3O\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Prepared\"}, {\"type\": \"CUSTOM\", \"details\": \"Recrystallization from ethanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"afforded a brown solid\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-78ed05de7dea4fecb889ed520c4a38db",
    "procedure_text": "{2-Amino-5-bromo-3-methylphenyl}(1-pyrrolidinyl)methanone (prepared from pyrrolidine and 6-bromo-8-methyl-2H-3,1-benzoxazine-2,4-(1H)-dione using the methods described in Example 17) and CMI were reacted using conditions described in the general procedure for CMI coupling to give {5-bromo-2-[(4,5-dihydro-1H-imidazol-2-ylmethyl)amino]-3-methylphenyl}(1-pyrrolidinyl)methanone.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"{2-Amino-5-bromo-3-methylphenyl}(1-pyrrolidinyl)methanone\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyrrolidine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-bromo-8-methyl-2H-3,1-benzoxazine-2,4-(1H)-dione\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"were reacted\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"{5-bromo-2-[(4,5-dihydro-1H-imidazol-2-ylmethyl)amino]-3-methylphenyl}(1-pyrrolidinyl)methanone\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-895c38f1c72c46c9af15a708d511c14a",
    "procedure_text": "A mixture of ethyl (4-hydroxy-3-methoxy-phenyl)-acetic acid ethyl ester (11.22 g, 53.4 mmol) and K2CO3 (22.13 g, 160 mmol) in DMF (100 ml) was heated at 60\u00b0 C. 2-Iodopropane (9.06 ml, 91 mmol) was added and the mixture was vigorously stirred at 60\u00b0 C. for 5 h. The reaction mixture was cooled to RT, diluted with AcOEt and washed with water. The aqueous phase was separated and further extracted with AcOEt. The combined organic fractions were dried over Na2SO4, filtered and evaporated to dryness. The resulting crude material was purified by Combi-Flash Companion\u2122 (Isco Inc.) column chromatography (SiO2; gradient elution, heptane/AcOEt 98:2\u21923:1) to yield the title compound (11.94 g, 47.3 mmol, 89%) as a colorless oil. TLC: RF=0.44 (heptane/AcOEt 7:3); HPLC: AtRet=2.14 min; LC-MS: m/z 253.4 [M+H]+; 1H NMR (400 MHz, CDCl3): 1.28 (t, J=7.1, 3H), 1.38 (d, J=6.1, 6H), 3.56 (s, 2H), 3.87 (s, 3H), 4.17 (q, J=7.1, 2H), 4.50 (h, J=6.1, 1H), 6.77-6.89 (m, 3H).",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl (4-hydroxy-3-methoxy-phenyl)-acetic acid ethyl ester\"}], \"amount\": {\"mass\": {\"value\": 11.22, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"K2CO3\"}], \"amount\": {\"mass\": {\"value\": 22.13, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"AcOEt\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-Iodopropane\"}], \"amount\": {\"volume\": {\"value\": 9.06, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was vigorously stirred at 60\\u00b0 C. for 5 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The reaction mixture was cooled to RT\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The aqueous phase was separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"further extracted with AcOEt\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"AcOEt\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic fractions were dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated to dryness\"}, {\"type\": \"CUSTOM\", \"details\": \"The resulting crude material was purified by Combi-Flash Companion\\u2122 (Isco Inc.) column chromatography (SiO2; gradient elution, heptane/AcOEt 98:2\\u21923:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude material\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"heptane AcOEt\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 5.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 47.3, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 11.94, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 89.0}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e1a142618bcf4bfaa529b9d80e7bc35f",
    "procedure_text": "(a)(b) To a stirred solution of (S)-2,2-dimethyl-3-(1-methyl-1H-indazol-5-yl)-3-phenylpropanenitrile (24 mg, 0.078 mmol) in anhydrous THF (10 mL) was added 1.0M lithium aluminum hydride in diethyl ether (0.5 mL, 0.5 mmol) portionwise at RT under nitrogen. After stirring at RT for 3 hr, the mixture was carefully quenched with MeOH, poured into brine, extracted with ethyl acetate (2\u00d7100 mL), dried (MgSO4) and concentrated. The crude product was coupled with 2,2,2-trifluoroethanesulfonyl chloride (14 mg, 0.073 mmol) using General Coupling Method B to give (S)\u2014N-(2,2-dimethyl-3-(1-methyl-1H-indazol-5-yl)-3-phenylpropyl)-3,3,3-trifluoropropanamide. MS found: (M+H)+=468.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,2,2-trifluoroethanesulfonyl chloride\"}], \"amount\": {\"mass\": {\"value\": 14.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(S)-2,2-dimethyl-3-(1-methyl-1H-indazol-5-yl)-3-phenylpropanenitrile\"}], \"amount\": {\"mass\": {\"value\": 24.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium aluminum hydride\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"amount\": {\"volume\": {\"value\": 0.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring at RT for 3 hr\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the mixture was carefully quenched with MeOH\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"poured into brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate (2\\u00d7100 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(S)\\u2014N-(2,2-dimethyl-3-(1-methyl-1H-indazol-5-yl)-3-phenylpropyl)-3,3,3-trifluoropropanamide\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4a4da1c340db49a1a133fcdc335d4749",
    "procedure_text": "A stirred mixture of 6-fluoro-3-(4-piperidinyl)-1,2- benzisoxazole (3.9 g, 17.7 mmoles). N,N-dimethyl-4- bromopropoxy-3-methoxybenzamide (5.54 g, 17.5 mmoles) and K2CO3 (3g) in acetonitrile (250 ml) was heated at reflux for one hour. At the end of the reaction, the insolubles were filtered and washed with dichloromethane. The solvent was removed on a rotary evaporator. The residue was purified by flash chromatography over a silica gel column. The product thus obtained as an oil weight 7 g. Crystallization from hot ethanol (45 ml) afforded analytically pure N,N-dimethyl-4- [3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] propoxy]-3-methoxybenzamide, 3.95 g, 50%, as light yellow crystals, m.p.=126\u00b0-127\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-fluoro-3-(4-piperidinyl)-1,2- benzisoxazole\"}], \"amount\": {\"mass\": {\"value\": 3.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethyl-4- bromopropoxy-3-methoxybenzamide\"}], \"amount\": {\"mass\": {\"value\": 5.54, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"K2CO3\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"at reflux for one hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"At the end of the reaction\"}, {\"type\": \"FILTRATION\", \"details\": \"the insolubles were filtered\"}, {\"type\": \"WASH\", \"details\": \"washed with dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The solvent was removed on a rotary evaporator\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by flash chromatography over a silica gel column\"}, {\"type\": \"CUSTOM\", \"details\": \"The product thus obtained as an oil weight 7 g\"}, {\"type\": \"CUSTOM\", \"details\": \"Crystallization from hot ethanol (45 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 45.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethyl-4- [3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] propoxy]-3-methoxybenzamide\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e8fed43ffcc74153aae0b172cb781dc4",
    "procedure_text": "To a solution of 7-benzyloxy-3-(4-chlorophenyl)-8-hydroxy-2-isopropyl-chromen-4-one (3.01 g, 7.15 mmol) and iodomethane (1.17 g, 8.22 mmol) in N,N-dimethylformamide (60 ml) is added K2CO3 (1.98 g, 14.3 mmol). The reaction mixture is stirred at room temperature for 72 h. The mixture is diluted with ethyl acetate and water, and the organic phase is washed with sodium thiosulfate solution and brine, dried (MgSO4) and concentrated in vacuo. The resulting off-white solid residue is triturated with ethyl acetate to afford the title compound as a white solid.",
    "reference_string": "{\"inputs\": {\"m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m4_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-benzyloxy-3-(4-chlorophenyl)-8-hydroxy-2-isopropyl-chromen-4-one\"}], \"amount\": {\"mass\": {\"value\": 3.01, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"iodomethane\"}], \"amount\": {\"mass\": {\"value\": 1.17, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"K2CO3\"}], \"amount\": {\"mass\": {\"value\": 1.98, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture is stirred at room temperature for 72 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WASH\", \"details\": \"the organic phase is washed with sodium thiosulfate solution and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium thiosulfate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The resulting off-white solid residue is triturated with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 72.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3c65c86c0c774a43a1074f157c493239",
    "procedure_text": "A solution of 20 g (0.102 mol) of (S)-5-cyclohexylmethyl)-2,4-pyrrolidinedione in 800 ml of 10% methanol-ethyl acetate is exposed to hydrogen gas in the presence of platinum oxide (this solution is charcoaled and filtered before reduction). After hydrogen uptake is complete, the catalyst is filtered and the filtrate concentrated under reduced pressure. The remaining white solid is triturated with 100 ml of diethyl ether, filtered and washed with diethyl ether to afford 19.3 g of (4S-cis)-5-(cyclohexylmethyl)-4-hydroxy-2-pyrrolidinone after recrystallization from ethyl acetate; mp 141\u00b0-143\u00b0 C.; [\u03b1]D23 =-19.9\u00b0 (c=0.98% methanol).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"platinum oxide\"}], \"reaction_role\": \"CATALYST\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,4-pyrrolidinedione\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrogen\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 800.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"filtered before reduction)\"}, {\"type\": \"FILTRATION\", \"details\": \"the catalyst is filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The remaining white solid is triturated with 100 ml of diethyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"WASH\", \"details\": \"washed with diethyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(4S-cis)-5-(cyclohexylmethyl)-4-hydroxy-2-pyrrolidinone\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 19.3, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b4d9f5a00e294ca5b31e1de78e00a956",
    "procedure_text": "A suspension of lithium aluminum hydride (1.56 g, 41.1 mmol) in ether (150 mL) was stirred at room temperature for 30 minutes. The solution was cooled to -55\u00b0 C. under nitrogen, and a solution of the product from Step E (11.10 g, 41.1 mmol) in ether (150 mL) was added over 15 min, maintaining the temperature below -50\u00b0 C. When the addition was complete, the reaction was warmed to 5\u00b0 C., then recooled to -40\u00b0 C. A solution of potassium hydrogen sulfate (21.8 g) in 25 mL water was slowly added, maintaining the temperature below -35\u00b0 C. The mixture was warmed to room temperature and stirred for one hour, filtered through Celite, and concentrated in vacuo to provide the title aldehyde.",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium aluminum hydride\"}], \"amount\": {\"mass\": {\"value\": 1.56, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium hydrogen sulfate\"}], \"amount\": {\"mass\": {\"value\": 21.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"amount\": {\"mass\": {\"value\": 11.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at room temperature for 30 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The solution was cooled to -55\\u00b0 C. under nitrogen\", \"temperature\": {\"setpoint\": {\"value\": -55.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"maintaining the temperature below -50\\u00b0 C\"}, {\"type\": \"ADDITION\", \"details\": \"When the addition\"}, {\"type\": \"TEMPERATURE\", \"details\": \"the reaction was warmed to 5\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 5.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"recooled to -40\\u00b0 C\", \"temperature\": {\"setpoint\": {\"value\": -40.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"maintaining the temperature below -35\\u00b0 C\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The mixture was warmed to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"STIRRING\", \"details\": \"stirred for one hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"filtered through Celite\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aldehyde\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-93ae9d1a466b4e7288548fc5bc2c41e1",
    "procedure_text": "An aqueous solution (2.0 mL) of potassium hydroxide (0.11 g) was added to a THF (2.0 mL)-methanol (2.0 mL) solution of 4-{2-[(4\u2032-{[(2S)-1-ethoxy-2-methyl-3-(methylamino)-1,3-dioxopropan-2-yl](methyl)carbamoyl}biphenyl-4-yl)oxy]ethyl}morpholine (93 mg) as obtained in Example 19-(3), and the mixture was stirred for 16 hours at room temperature. The reaction mixture was adjusted to pH 6 with a 10% aqueous solution of citric acid, and extracted with chloroform. The organic layer was separated using a phase separator, and the solvent was distilled off under reduced pressure to obtain 4-{2-[(4\u2032-{[(2S)-2-carboxy-1-(methylamino)-1-oxopropan-2-yl](methyl)carbamoyl}biphenyl-4-yl)oxy]ethyl}morpholine (light brown oil) (58 mg, 65%).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aqueous solution\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"citric acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m6_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium hydroxide\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-{2-[(4\\u2032-{[(2S)-1-ethoxy-2-methyl-3-(methylamino)-1,3-dioxopropan-2-yl](methyl)carbamoyl}biphenyl-4-yl)oxy]ethyl}morpholine\"}], \"amount\": {\"mass\": {\"value\": 93.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred for 16 hours at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"as obtained in Example 19-(3)\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with chloroform\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The organic layer was separated\"}, {\"type\": \"DISTILLATION\", \"details\": \"the solvent was distilled off under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-{2-[(4\\u2032-{[(2S)-2-carboxy-1-(methylamino)-1-oxopropan-2-yl](methyl)carbamoyl}biphenyl-4-yl)oxy]ethyl}morpholine\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 58.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 65.0}}], \"isolated_color\": \"brown\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-91513605f0cd40b888afac0097e68913",
    "procedure_text": "Following the same procedure as described in Preparation 18, 3.4 g of 6-acetoxy-2-(4-aminophenoxymethyl)-2-hydroxy-5,7,8-trimethylchroman-4-one (prepared as described in Preparation 44), 40 ml of acetone, 5 ml of 35% w/v aqueous hydrochloric acid, 1.2 g of sodium nitrite, 1.6 ml of water, 13 g of ethyl acrylate and 0.32 g of cuprous oxide were reacted, to give the title compound.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acrylate\"}], \"amount\": {\"mass\": {\"value\": 13.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 1.6, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-acetoxy-2-(4-aminophenoxymethyl)-2-hydroxy-5,7,8-trimethylchroman-4-one\"}], \"amount\": {\"mass\": {\"value\": 3.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cuprous oxide\"}], \"amount\": {\"mass\": {\"value\": 0.32, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium nitrite\"}], \"amount\": {\"mass\": {\"value\": 1.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"were reacted\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-21a37df3e79b4738932ec3887865ba31",
    "procedure_text": "To a solution of 1-[1-(6-aminoindan-1-ylmethyl)piperidin-4-yl]-5-chloro-1H-indole, 10h (0.9 g) in dichloromethane (10 mL) was added methylisocyanate (0.2 mL). The mixture was stirred at room temperature for 16 hours. Dichloromethane was evaporated. Upon addition of ethyl acetate the title compound 19a crystallized. The crystalline product was filtered off and dried overnight at 80\u00b0 C. in vacua. Yield 0.6 g. mp: 193-195\u00b0 C. 1H NMR (DMSO-d6): \u03b4 1.70-1.85 (m, 1H); 1.90-2.35 (m, 7H); 2.35-2.85 (m, 4H); 2.65 (d, 3H); 3.05-3.15 (m, 2H); 3.25 (quin, 1H); 4.35-4.45 (m, 1H); 5.95 (dt, 1H); 6.45 (d, 1H); 7.00-7.20 (m, 3H); 7.50-7.65 (m, 4H); 8.35 (s, 1H).",
    "reference_string": "{\"inputs\": {\"m1_m2_m4_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-[1-(6-aminoindan-1-ylmethyl)piperidin-4-yl]-5-chloro-1H-indole\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"10h\"}], \"amount\": {\"mass\": {\"value\": 0.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylisocyanate\"}], \"amount\": {\"volume\": {\"value\": 0.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at room temperature for 16 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Dichloromethane was evaporated\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"Upon addition of ethyl acetate the title compound 19a\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound 19a\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"crystallized\"}, {\"type\": \"FILTRATION\", \"details\": \"The crystalline product was filtered off\"}, {\"type\": \"CUSTOM\", \"details\": \"dried overnight at 80\\u00b0 C. in vacua\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 80.0, \"units\": \"CELSIUS\"}}}], \"outcomes\": [{\"reaction_time\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-5ccebfc77e6641aea9ff11c8b30c9550",
    "procedure_text": "To a 500 ml. flask, fitted with a condenser and containing a solution of 1.84 g. of sodium hydroxide in 150 ml. of ethanol was added 14 g. of 8-chloro-dibenzothiophene-3-acetic acid ethyl ester. After the solution was refluxed for 1 hour, the solvent was removed in vacuo (steam bath, rotary evaporator), the residue dissolved in 100 ml. of water, and the aqueous solution acidified with dilute hydrochloric acid. The 8-chloro-dibenzothiophene-3-acetic acid was removed by filtration, washed with water and dried at 60\u00b0 in a vacuum oven overnight. The yield of 8-chloro-dibenzothiophene-3-acetic acid, after crystallization from i-propanol, was 8 g., mp 220\u00b0-221\u00b0.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"8-chloro-dibenzothiophene-3-acetic acid ethyl ester\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"flask, fitted with a condenser\"}, {\"type\": \"ADDITION\", \"details\": \"containing a solution of 1.84 g\"}, {\"type\": \"TEMPERATURE\", \"details\": \"After the solution was refluxed for 1 hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was removed in vacuo (steam bath, rotary evaporator)\"}, {\"type\": \"DISSOLUTION\", \"details\": \"the residue dissolved in 100 ml\"}, {\"type\": \"CUSTOM\", \"details\": \"The 8-chloro-dibenzothiophene-3-acetic acid was removed by filtration\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"8-chloro-dibenzothiophene-3-acetic acid\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried at 60\\u00b0 in a vacuum oven overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The yield of 8-chloro-dibenzothiophene-3-acetic acid, after crystallization from i-propanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"8-chloro-dibenzothiophene-3-acetic acid\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"i-propanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"8-chloro-dibenzothiophene-3-acetic acid\"}]}]}]}"
  },
  {
    "reaction_id": "ord-69ead50a870a4ec3aeecbcec6a22f5e8",
    "procedure_text": "16 g of histidine hydrochloride was dissolved in 50 g of a 6% solution of hydrochloric acid. To this solution, 25 g of powdery menadione sodium bisulfite was added within about 1/2 hour. A white, very fine precipitate was obtained, which, after filtering, washing and vacuum drying, weighed 26 g and had the following analysis:",
    "reference_string": "{\"inputs\": {\"m1_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"histidine hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 16.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"menadione sodium bisulfite\"}], \"amount\": {\"mass\": {\"value\": 25.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"A white, very fine precipitate was obtained\"}, {\"type\": \"FILTRATION\", \"details\": \"which, after filtering\"}, {\"type\": \"WASH\", \"details\": \"washing\"}, {\"type\": \"CUSTOM\", \"details\": \"vacuum drying\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-c0e082e97012495bad9ca0d577ad8b5f",
    "procedure_text": "37.2 g of commercial 5-chloro vanillin and 800 ml of dichloromethane were mixed together under nitrogen and cooled to 0\u00b0 C. 300 ml of a molar solution of boron tribromide in dichloromethane were added and the mixture stood for one night at ambient temperature. It was concentrated, cooled again to 0\u00b0 C. and acidified. The crystallized product was separated, washed with water, dried and crystallized from an isopropanol-water mixture (1-2 by volume) to obtain 26.6 g of the expected product melting at>260\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-chloro vanillin\"}], \"amount\": {\"mass\": {\"value\": 37.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 800.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"molar solution\"}], \"amount\": {\"volume\": {\"value\": 300.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"boron tribromide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WAIT\", \"details\": \"the mixture stood for one night at ambient temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CONCENTRATION\", \"details\": \"It was concentrated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"cooled again to 0\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The crystallized product was separated\"}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"CUSTOM\", \"details\": \"crystallized from an isopropanol-water mixture (1-2 by volume)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isopropanol water\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"expected product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 26.6, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-dd964b479a76481eb7019da5d42ba403",
    "procedure_text": "A stirred solution of sodium 2-(2-tritylaminothiazol-4-yl)-2-(Z)-trityloxyiminoacetate (762 mg) in dimethylformamide (4 ml) was cooled to -55\u00b0 C. to -60\u00b0 C. and methanesulphonyl chloride (0.085 ml) was added. The mixture was stirred at the same temperature for 30 mins and then a solution of diphenylmethyl 7\u03b2-amino-3-(2,5-dihydro-2-oxofuran-4-ylthiomethyl)ceph-3-em-4-carboxylate (494 mg) in dimethylformamide (4 ml) was added followed by pyridine (0.08 ml). The mixture was then stirred at 0\u00b0 C. for 90 mins and then partitioned between ethyl acetate and aqueous citric acid solution. The organic phase was washed successively with water, sodium bicarbonate solution, water, and brine. The solution was dried over magnesium sulphate and evaporated. The title compound (744 mg) was isolated by column chromatography of the residue using gradient elution (Kieselgel 2:1 going to 1:1 hexane:ethyl acetate). \u03c5max (CHCl3) 3400, 1785, 1745 and 1685cm-1 . \u03b4H(CDCl3) 3.23 (1H, d, J 18.2Hz), 3.52 (1H, d, J 18.2Hz), 3.93 (1H, d, J 12.6Hz), 3.99 (1H, d, J 12.5Hz), 4.70 (2H, s), 5.08 (1H, d, J 5.0Hz),5.65 (1H, s), 6.11 (1H, dd, J 5.0 and 8.9Hz), 6.43 (1H, s), 6.75 (1H, s), 6.98 (1H, s), 7.15-7.5 (41H, m). [mass spectrum: +ve ion (thioglycerol) MH+ 1148].",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"amount\": {\"volume\": {\"value\": 0.08, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanesulphonyl chloride\"}], \"amount\": {\"volume\": {\"value\": 0.085, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium 2-(2-tritylaminothiazol-4-yl)-2-(Z)-trityloxyiminoacetate\"}], \"amount\": {\"mass\": {\"value\": 762.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diphenylmethyl 7\\u03b2-amino-3-(2,5-dihydro-2-oxofuran-4-ylthiomethyl)ceph-3-em-4-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 494.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at the same temperature for 30 mins\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"The mixture was then stirred at 0\\u00b0 C. for 90 mins\", \"duration\": {\"value\": 90.0, \"units\": \"MINUTE\"}, \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"partitioned between ethyl acetate and aqueous citric acid solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"citric acid\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic phase was washed successively with water, sodium bicarbonate solution, water, and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The solution was dried over magnesium sulphate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulphate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 744.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fa64d8f772a34f74be068f58d834722c",
    "procedure_text": "14.5 g of the compound obtained in Stage B are refluxed with 50 ml of methanol and 30 ml of 6N hydrochloric acid for 20 hours. After evaporation the hydrochloride of the desired product is obtained.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound\"}], \"amount\": {\"mass\": {\"value\": 14.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"After evaporation the hydrochloride of the desired product\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloride\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"is obtained\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-dbdf59c5e6884bcca9a1048e6914c3eb",
    "procedure_text": "(5Z)-5-({1-[2,4-Bis(trifluoromethyl)benzyl]-1H-indazol-5-yl}methylidene)-3-[trans-3-fluoropiperidin-4-yl]-1,3-thiazolidine-2,4-dione was prepared from [2,4-bis(trifluoromethyl)benzyl]-1H-indazol-5-carbaldehyde (from Example 6) and 1,1-dimethylethyl trans-4-(2,4-dioxo-1,3-thiazolidin-3-yl)-3-fluoropiperidine-1-carboxylate (from Example 273) following General Procedure F.",
    "reference_string": "{\"inputs\": {\"m0_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"[2,4-bis(trifluoromethyl)benzyl]-1H-indazol-5-carbaldehyde\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,1-dimethylethyl trans-4-(2,4-dioxo-1,3-thiazolidin-3-yl)-3-fluoropiperidine-1-carboxylate\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(5Z)-5-({1-[2,4-Bis(trifluoromethyl)benzyl]-1H-indazol-5-yl}methylidene)-3-[trans-3-fluoropiperidin-4-yl]-1,3-thiazolidine-2,4-dione\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f535b760ff3f48e09063e865c9ebec65",
    "procedure_text": "To a mixture of 2-bromo-5-fluoroaniline (35.00 g, 184 mmol, Aldrich), palladium (II) acetate (2.06 g, 9.18 mmol, Strem) and tri(o-tolyl)phosphine (5.60 g, 18.40 mmol; Strem) in acetonitrile (350 ml) at RT was added methyl acrylate (33.00 ml, 365 mmol, Aldrich) and triethylamine (64.00 ml, 460 mmol, Aldrich). The reaction was heated at 80\u00b0 C. for 24 h. The reaction mixture was diluted with EtOAc (500 mL) and the resulting colorless crystalline solid was filtered and washed with EtOAc. The organic solution was concentrated to dryness and the solids were slurried in 10% EtOAc/hexane at 60\u00b0 C. for 1 h. The slurry was cooled to RT and filtered. The solid was washed with 10% EtOAc/hexane and sucked dry with air to give 18.30 g (51%) of a light-yellow crystalline solid. m/z=195.9 (M+1).",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m7_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-bromo-5-fluoroaniline\"}], \"amount\": {\"mass\": {\"value\": 35.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tri(o-tolyl)phosphine\"}], \"amount\": {\"mass\": {\"value\": 5.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 350.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"palladium (II) acetate\"}], \"amount\": {\"mass\": {\"value\": 2.06, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl acrylate\"}], \"amount\": {\"volume\": {\"value\": 33.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 64.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 80.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"the resulting colorless crystalline solid was filtered\"}, {\"type\": \"WASH\", \"details\": \"washed with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"The organic solution was concentrated to dryness\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The slurry was cooled to RT\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"WASH\", \"details\": \"The solid was washed with 10% EtOAc/hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc hexane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"sucked dry with air\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"light-yellow crystalline solid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 18.3, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 51.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 51.0}}], \"isolated_color\": \"light-yellow crystalline\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-760ebf0ea2264cd3a5e2e56550388425",
    "procedure_text": "211 g (1.13 moles) of 2-(2,2-dichlorovinyl)-toluene, 251 g (1.41 moles) of N-bromosuccinimide and 2 g of azoisobutyronitrile in 1300 ml of dry 1,1,1-trichloroethane are refluxed, an additional 1 g of azoisobutyronitrile is added to the reaction mixture after one hour, and heating is continued for a further hour.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"azoisobutyronitrile\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(2,2-dichlorovinyl)-toluene\"}], \"amount\": {\"mass\": {\"value\": 211.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-bromosuccinimide\"}], \"amount\": {\"mass\": {\"value\": 251.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"azoisobutyronitrile\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,1,1-trichloroethane\"}], \"amount\": {\"volume\": {\"value\": 1300.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"heating\"}, {\"type\": \"WAIT\", \"details\": \"is continued for a further hour\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-afe1d64d88df42dfb71c051d1640df24",
    "procedure_text": "In 59.69 g of methanol were dissolved 18.15 g (67.41 mmol) of 11-methacrylamidoundecanoic acid (MAU), 1.85 g (7.49 mmol) of potassium 3-methacryloxypropanesulfonate (Tokyo Chemical industry Co.), and 0.31 g (1.89 mmol) of azobisisobutyronitrile (Nacalai Tesque, Inc.). The solution was deaerated by bubbling nitrogen for 60 minutes. The container was covered with a septum, and the polymerization was conducted by heating at 60\u00b0 C. for 20 hours. After the completion of the polymerization reaction, the reaction solution was dropwise added into a large excess of ethyl acetate, and the resulting precipitate was collected by filtration under suction. After drying under reduced pressure, 18.47 g of random MAU/potassium 3-methacryloxypropanesulfonate copolymer (90/10) was obtained (yield: 92.4%). The weight average molecular weight was 240000.",
    "reference_string": "{\"inputs\": {\"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m4_m1_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"11-methacrylamidoundecanoic acid\"}], \"amount\": {\"mass\": {\"value\": 18.15, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium 3-methacryloxypropanesulfonate\"}], \"amount\": {\"mass\": {\"value\": 1.85, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"mass\": {\"value\": 59.69, \"units\": \"GRAM\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"azobisisobutyronitrile\"}], \"amount\": {\"mass\": {\"value\": 0.31, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"by bubbling nitrogen for 60 minutes\", \"duration\": {\"value\": 60.0, \"units\": \"MINUTE\"}}, {\"type\": \"CUSTOM\", \"details\": \"After the completion of the polymerization reaction\"}, {\"type\": \"FILTRATION\", \"details\": \"the resulting precipitate was collected by filtration under suction\"}, {\"type\": \"CUSTOM\", \"details\": \"After drying under reduced pressure\"}], \"outcomes\": [{\"products\": [{\"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 18.47, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 92.4}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d7cb6e6fbdc8408b8fd13af33f73c559",
    "procedure_text": "To a solution of 36.45 g (200 mmol) of 10-undecynoic acid in 200 ml 1N NaOH at 0\u00b0 C. was added a solution of alkaline sodium hypobromite dropwise over 30 minutes, maintaining the temperature below 5\u00b0 C. (the hypobromite solution was prepared by the dropwise addition of 35.16 g (220 mmol) of bromine to 55 ml of 20N NaOH at 0\u00b0-5\u00b0 C.). The mixture was stirred four hours at 0\u00b0-5\u00b0 C., and was then acidified to pH 1 with 9M H2SO4. The solution was extracted with three 150 ml portions of ether. The combined extracts were dried (Na2SO4) and evaporated yielding 50.159 (96% crude) of a pale yellow solid. This was used without further purification.",
    "reference_string": "{\"inputs\": {\"m1_m6_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"10-undecynoic acid\"}], \"amount\": {\"mass\": {\"value\": 36.45, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hypobromite\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"bromine\"}], \"amount\": {\"mass\": {\"value\": 35.16, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"amount\": {\"volume\": {\"value\": 55.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2SO4\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hypobromite\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred four hours at 0\\u00b0-5\\u00b0 C.\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"The solution was extracted with three 150 ml portions of ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"three\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined extracts were dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"yielding 50.159 (96% crude) of a pale yellow solid\"}, {\"type\": \"CUSTOM\", \"details\": \"This was used without further purification\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-9a75f8db99e1449d8044a9b4d5dade9e",
    "procedure_text": "Fifty-three grams (0.25 mole) of 3,4-dinitrobenzoic acid, 500 ml. of benzene, 65 g. (0.51 mole) of oxalyl chloride and 1 ml. of pyridine were reacted according to Example 2 (A), first paragraph, to provide 3,4-dinitrobenzoyl chloride as a crude oil.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Example 2 ( A )\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,4-dinitrobenzoic acid\"}], \"amount\": {\"moles\": {\"value\": 0.25, \"units\": \"MOLE\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzene\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"oxalyl chloride\"}], \"amount\": {\"moles\": {\"value\": 0.51, \"units\": \"MOLE\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,4-dinitrobenzoyl chloride\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3c2969fca3244ab59ac2c2714416fc6d",
    "procedure_text": "Dichlorobis(triphenylphosphine)palladium(II) (170 mg, 0.24 mmol) was added to 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1.376 g, 6.28 mmol) and 2-chloro-4-[2-(4-fluorophenyl)sulfonylpropan-2-yl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine (2 g, 4.83 mmol), and sodium carbonate (5 mL, 10.00 mmol) in 18% DMF in DME:water:ethanol (7:3:2) (20 mL). The resulting solution was stirred at 90\u00b0 C. for 4 hours. The reaction mixture was diluted with ethyl acetate (20 mL), and washed with water (2\u00d720 mL1). The organic layer was dried (MgSO4), filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 5 to 60% ethyl acetate in isohexane, to give the desired material as a cream solid (1.80 g).",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m7_m1_m2_m3_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline\"}], \"amount\": {\"mass\": {\"value\": 1.376, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloro-4-[2-(4-fluorophenyl)sulfonylpropan-2-yl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium carbonate\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DME water ethanol\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Dichlorobis(triphenylphosphine)palladium(II)\"}], \"amount\": {\"mass\": {\"value\": 170.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 90.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The resulting solution was stirred at 90\\u00b0 C. for 4 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WASH\", \"details\": \"washed with water (2\\u00d720 mL1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layer was dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"to afford crude product\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude product was purified by flash silica chromatography, elution gradient 5 to 60% ethyl acetate in isohexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isohexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired material\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.8, \"units\": \"GRAM\"}}}], \"isolated_color\": \"cream\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3bc60bece80d4de994b3bb15ce6531d6",
    "procedure_text": "To 335 mg (5.5 mmol) trans-N-[4-(5-{[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-ethyl-amino}-pentyl)-cyclohexyl]-N-methyl-4-trifluoromethyl-benzenesulfonamide N-oxide in 8 ml THF were added 0.83 ml 1M TBAF at 0\u00b0 C. The solution was stirred at RT for 1 h, partitioned between EtOAc and an aqueous solution of Na2CO3. The organic phase was washed with brine and dried over Na2SO4. Column chromatography with CH2Cl2/MeOH 9:1 yielded 190 mg (44%, 3 steps) trans-N-(4-{5-[Ethyl-(2-hydroxy-ethyl)-amino]-pentyl}-cyclohexyl)-N-methyl-4-trifluoromethyl-benzenesulfonamide N-oxide as colorless oil, MS: 495 (MH+).",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trans-N-[4-(5-{[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-ethyl-amino}-pentyl)-cyclohexyl]-N-methyl-4-trifluoromethyl-benzenesulfonamide N-oxide\"}], \"amount\": {\"mass\": {\"value\": 335.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TBAF\"}], \"amount\": {\"volume\": {\"value\": 0.83, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 8.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The solution was stirred at RT for 1 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"partitioned between EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic phase was washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trans-N-(4-{5-[Ethyl-(2-hydroxy-ethyl)-amino]-pentyl}-cyclohexyl)-N-methyl-4-trifluoromethyl-benzenesulfonamide N-oxide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 190.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 44.0}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b3eabd096e3a4bc1a6e1faee5c0aa745",
    "procedure_text": "Trifluoroacetic acid (0.3 mL) was added to a solution of (R)-t-butoxycarbonylamino-[4\u2032-(1-{4-[3-(t-butyldimethyl-silanyloxy)-4,4-dimethyl-pentyl]-3-methyl-phenyl}-1-ethyl-propyl)-2\u2032-methyl-biphenyl-4-yl]-acetic acid methyl ester (Example 167-(2); 28.5 mg, 0.038 mmol) in dichloromethane (3 mL) at 0\u00b0 C., and the mixture was stirred at room temperature for one hour. Then, the reaction mixture was concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (chloroform:methanol=10:1) to give the target compound as a colorless oil (16.6 mg, 83%).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Trifluoroacetic acid\"}], \"amount\": {\"volume\": {\"value\": 0.3, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-t-butoxycarbonylamino-[4\\u2032-(1-{4-[3-(t-butyldimethyl-silanyloxy)-4,4-dimethyl-pentyl]-3-methyl-phenyl}-1-ethyl-propyl)-2\\u2032-methyl-biphenyl-4-yl]-acetic acid methyl ester\"}], \"amount\": {\"mass\": {\"value\": 28.5, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at room temperature for one hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"Then, the reaction mixture was concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The resulting residue was purified by silica gel chromatography (chloroform:methanol=10:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 16.6, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 83.0}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0969d848989f4e08adb2ea521baa1961",
    "procedure_text": "To (3-methoxyphenyl)acetonitrile (1.0 g, 6.79 mmol) and iodomethane (0.42 mL, 6.79 mmol) in THF (10 mL) at 0\u00b0 C. was added sodium bis(trimethylsilyl)amide (1M in THF; 6.8 mL, 6.8 mmol). The reaction was warmed to room temperature and stirred for 1 hour. The mixture was partitioned between H2O and EtOAc and acidified with 1N aqueous HCl, and then extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated to give the desired product.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(3-methoxyphenyl)acetonitrile\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"iodomethane\"}], \"amount\": {\"volume\": {\"value\": 0.42, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bis(trimethylsilyl)amide\"}], \"amount\": {\"volume\": {\"value\": 6.8, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred for 1 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The mixture was partitioned between H2O and EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic layers were dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d199417382d24f8da905888b7a62bce4",
    "procedure_text": "A mixture of 43 parts by mass of the polymer (white solid) obtained through the production of an intermediate, 20 parts by mass of n-octadecylamine, 1 part by mass of pyridine, and 420 parts by mass of toluene is stirred at a temperature of 100\u00b0 C. for 3 hours. After the mixture is cooled, the reaction solution is added to 8000 parts by mass of methanol in 15 minutes while stirring and is further stirred for 1 hour. The precipitated solid is filtered and is dried under depressurization, whereby 43 parts by mass of light yellowish white solid (specific copolymer) is obtained. The molecular weight measured through the use of a high-speed liquid chromatography method is 14,000. As the result of neutralization titration using a potassium hydroxide ethanol solution, the ratio of the semi-maleic acid amide component and the maleinimide component is 6:4.",
    "reference_string": "{\"inputs\": {\"m0_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"43\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-octadecylamine\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-7ae3614a6345407a895ed2ff26be545b",
    "procedure_text": "o-Cresol (0.36 g) is dissolved in dimethylsulfoxide (4 ml) containing sodium hydroxide powder (0.18 g) and thereto is added 1-[4-(2-chloroacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (1.03 g). The mixture is stirred at 90\u00b0 C. for 7.5 hours. The reaction mixture is poured into ice-water (300 ml) and the precipitated crystal is collected by filtration, washed with water, and purified by silica gel column chromatography (eluent; n-hexane:ethyl acetate=2:1), and recrystallized from ethyl acetate to give 1-{4-[2-(2-methylphenoxy)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine (546 mg) as colorless scales, m.p. 172.5-175\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"amount\": {\"volume\": {\"value\": 300.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"mass\": {\"value\": 0.18, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"o-Cresol\"}], \"amount\": {\"mass\": {\"value\": 0.36, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylsulfoxide\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-[4-(2-chloroacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine\"}], \"amount\": {\"mass\": {\"value\": 1.03, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 90.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture is stirred at 90\\u00b0 C. for 7.5 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"the precipitated crystal is collected by filtration\"}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"purified by silica gel column chromatography (eluent; n-hexane:ethyl acetate=2:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-hexane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"recrystallized from ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 7.5, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-{4-[2-(2-methylphenoxy)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 546.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e1c0b3c7bcd94f79a2acae3169fdbe0b",
    "procedure_text": "Tert-butyl 4-(3-(methoxycarbonyl)benzyl)piperazine-1-carboxylate (1.25 g, 3.74 mmol) was stirred with a 4/1 solution of dichloromethane/trifluoroacetic acid (20 mL) for 1 hour at room temperature. The solution was then concentrated under vacuum to afford the title compound (1.73 g). MS (ESI) m/z 235.1 [M+H]+",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Tert-butyl 4-(3-(methoxycarbonyl)benzyl)piperazine-1-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 1.25, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane trifluoroacetic acid\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"The solution was then concentrated under vacuum\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.73, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-295e9b1dac8344a1932cf017c7c11d2e",
    "procedure_text": "Sodium hydroxide (22.5 g, 0.56 mol) in water (100 ml) was added to the amine from example 26 (26.0 g, 0.09 mol) in dichloromethane (400 ml) and the solution vigorously stirred at room temperature. Chloroacetylchloride (8.6 ml, 0.11 mol) was then added and the reaction mixture stirred for a further 60 minutes. The layers were separated and the aqueous layer re-extracted with dichloromethane (200 ml). The organic extracts were combined, dried over anhydrous magnesium sulphate, filtered and concentrated in vacuo to give a colourless oil. Potassium hydroxide (15.0 g, 0.27 mol), isopropyl alcohol (400 ml) and the colourless oil residue were stirred together as an opaque solution with water (30 ml) for 2 hours. The reaction mixture was concentrated in vacuo and the yellow residue dissolved in ethyl acetate (200 ml). This was partitioned with water (200 ml) then brine (200 ml). The organic fraction was dried over anhydrous magnesium sulphate, filtered and concentrated in vacuo to give the title compound as a white solid (19.9 g, 0.06 mol, 67%). 1H NMR (CDCl3, 400 MHz) \u03b4: 0.95 (t 3H), 1.62 (m, 2H), 3.34 (m, 2H), 3.51 (m, 2H), 4.32 (d, 1H), 4.41 (d, 1H), 4.72 (dd, 1H), 5.04 (s, 2H), 6.98 (d, 2H), 7.31-7.43 (m, 7H). LRMS: m/z 326 (M-H+).",
    "reference_string": "{\"inputs\": {\"m4_m8_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Potassium hydroxide\"}], \"amount\": {\"mass\": {\"value\": 15.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isopropyl alcohol\"}], \"amount\": {\"volume\": {\"value\": 400.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m5_m2_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Sodium hydroxide\"}], \"amount\": {\"mass\": {\"value\": 22.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"amine\"}], \"amount\": {\"mass\": {\"value\": 26.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 400.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Chloroacetylchloride\"}], \"amount\": {\"volume\": {\"value\": 8.6, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the solution vigorously stirred at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"the reaction mixture stirred for a further 60 minutes\", \"duration\": {\"value\": 60.0, \"units\": \"MINUTE\"}}, {\"type\": \"CUSTOM\", \"details\": \"The layers were separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"the aqueous layer re-extracted with dichloromethane (200 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous magnesium sulphate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulphate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a colourless oil\"}, {\"type\": \"CONCENTRATION\", \"details\": \"The reaction mixture was concentrated in vacuo\"}, {\"type\": \"DISSOLUTION\", \"details\": \"the yellow residue dissolved in ethyl acetate (200 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"This was partitioned with water (200 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic fraction was dried over anhydrous magnesium sulphate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulphate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 0.06, \"units\": \"MOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 19.9, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 67.0}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fc9cf28c0b3845f1a9bead206d3c31ee",
    "procedure_text": "5-HT2A receptor binding assay was performed in reference to a method described by Hirose et al. (Japan. J. Pharmacol., 53, 321-329, 1990). After a reaction in a total volume of 200 \u03bcL of 50 mM Tris-HCl (pH=7.6) buffer solution containing 50 \u03bcL of [3H]-ketanserin (final concentration 1 nM), 1 \u03bcL of test drug in DMSO, and 149 \u03bcL of human 5-HT2A receptor-expressing CHO cell membrane sample, human 5-HT2A receptor binding activity of [3H]-ketanserin was measured. The reaction solution let stand for 15 minutes at 37\u00b0 C., and then it was quickly added on a glass fiber filter plate (Multiscreen FB, Millipore inc.) coated with 0.05% Brij 35 and filtered under reduced pressure. The glass fiber filter was washed with 200 \u03bcL of ice-cooled 50 mM Tris-HCl (pH=7.6) twice, repeatedly filtered under reduced pressure, and then transferred to a vial containing 4 mL of Ecoscint A (National Diagnostics inc.). The residual radioactivity on the glass fiber filter was measured by a liquid scintillation counter. Nonspecific binding was measured in the presence of 10 \u03bcM of MDL-100907, and [3H]-ketanserin binding inhibition rate in the presence of 1 nM or 10 nM of test drug was determined. The results are shown in Tables 8 to 13.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Tris-HCl\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"[3H]-ketanserin\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMSO\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"[3H]-ketanserin\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"for 15 minutes\", \"duration\": {\"value\": 15.0, \"units\": \"MINUTE\"}}, {\"type\": \"CUSTOM\", \"details\": \"at 37\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 37.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"ADDITION\", \"details\": \"it was quickly added on a glass fiber\"}, {\"type\": \"FILTRATION\", \"details\": \"filter plate (Multiscreen FB, Millipore inc.) coated with 0.05% Brij 35\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Brij 35\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered under reduced pressure\"}, {\"type\": \"FILTRATION\", \"details\": \"The glass fiber filter\"}, {\"type\": \"WASH\", \"details\": \"was washed with 200 \\u03bcL of ice-\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"cooled 50 mM Tris-HCl (pH=7.6) twice\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Tris-HCl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"repeatedly filtered under reduced pressure\"}, {\"type\": \"ADDITION\", \"details\": \"a vial containing 4 mL of Ecoscint A (National Diagnostics inc.)\"}, {\"type\": \"FILTRATION\", \"details\": \"The residual radioactivity on the glass fiber filter\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-f86a0cd8ee3b479eaa06f7abed52eb1c",
    "procedure_text": "A mixture of 0.76 g (3.4 mmol) of 2-methyl-6-phenyl-5-propargyl-4(3H)-pyrimidinone, 0.72 g (5.2 mmol) of anhydrous potassium carbonate, 0.32 mL (5.1 mmol) of methyl iodide and 20 mL of methyl ethyl ketone was heated at reflux for 6 h. The mixture was cooled, diluted with 40 mL of water and extracted with two 60 mL portions of ethyl acetate. The ethyl acetate extracts were dried and rotovaped to leave 0.75 g of crude product. This material was purified by flash chromatography on silica gel to afford 0.71 g of 2,3-dimethyl-6-phenyl-5-propargyl-4(3H)-pyrimidinone as a white solid, mp 142\u00b0-144\u00b0 C., 1H-NMR (CDCl3) \u03b42.10(3H,t,J=4), 2.60(3H, s), 3.40(2H,d,J=4), 3.60(3H,s), 7.45(3H,m), 7.65(2H, m); IR(nujol) 3200, 1650 cm-1. Calculated for C15H14N2O: C 75.61, H 5.92, N 11.76. Found: C 75.33, H 5.72, N 11.63.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-methyl-6-phenyl-5-propargyl-4(3H)-pyrimidinone\"}], \"amount\": {\"mass\": {\"value\": 0.76, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 0.72, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl iodide\"}], \"amount\": {\"volume\": {\"value\": 0.32, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl ethyl ketone\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"at reflux for 6 h\", \"duration\": {\"value\": 6.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"The mixture was cooled\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with two 60 mL portions of ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"two\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The ethyl acetate extracts were dried\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"to leave 0.75 g of crude product\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"amount\": {\"mass\": {\"value\": 0.75, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"This material was purified by flash chromatography on silica gel\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,3-dimethyl-6-phenyl-5-propargyl-4(3H)-pyrimidinone\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.71, \"units\": \"GRAM\"}}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fa303dd3d2164d519d781b2bc703333b",
    "procedure_text": "To a solution of Example D (8.5 g, 30 mmol) in MeOH (80 mL) was slowly added solid NaBH4 (3.42 g, 90 mmol) while the reaction temperature was controlled below 20\u00b0 C. After stirring for 2 h, the reaction was quenched with H2O, extracted with EtOAc (3\u00d7100 mL) and the combined organic layers were washed with brine, dried (Na2SO4), concentrated in vacuo. The residue was purified via flash column chromatography to yield methyl 4-(((t-butoxycarbonyl)methylamino)methyl)benzoate (6.55 g, 77% yield). 1H NMR (CDCl3) \u03b4 7.98 (d, J=8.4 Hz, 2H), 7.40 (d, J=8.4 Hz, 2H), 3.90 (s, 3H,) 3.84 (s, 2H) 3.29 (s, 2H) 1.46 (s, 9H).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"amount\": {\"mass\": {\"value\": 8.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaBH4\"}], \"amount\": {\"mass\": {\"value\": 3.42, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"amount\": {\"volume\": {\"value\": 80.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring for 2 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"was controlled below 20\\u00b0 C\"}, {\"type\": \"CUSTOM\", \"details\": \"the reaction was quenched with H2O\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with EtOAc (3\\u00d7100 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"the combined organic layers were washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified via flash column chromatography\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 4-(((t-butoxycarbonyl)methylamino)methyl)benzoate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 6.55, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 77.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a6b35b2aa2874c4f9304cf003986c90b",
    "procedure_text": "Add a solution of 3\u2032,4\u2032,5\u2032-Trimethoxy-biphenyl-2-carbonyl chloride (57) (0.18 mmol) in DCM (11.0 mL) to an ice cooled solution of [5-(2-Amino-phenyl)-thiophen-2-yl]-acetic acid methyl ester (36) (46 mg, 0.18 mmol) in anhydrous DCM (2.0 mL) and anhydrous pyridine (0.5 mL). Stir the reaction mixture for 1 h at 0\u00b0 C. and additional 20 h at rt. Pour the reaction mixture into ice cooled 1 M aqu. HCl, extract with EtOAc (2\u00d7) and DCM (2\u00d7), wash the combined organic layer with brine and dry with Na2SO4. Purify the crude product by preparative radial chromatography (silica gel, EtOAc/CyH 1+2) to obtain (5-{2-[(3\u2032,4\u2032,5\u2032-Trimethoxy-biphenyl-2-carbonyl)-amino]-phenyl}-thiophen-2-yl)-acetic acid methyl ester (58) as a light brown solid (58 mg, 59%). 1H NMR (400 MHz, CDCl3): 3.70 (s, 3H); 3.76 (s, 6H); 3.78 (s, 2H); 3.80 (s, 3H); 6.29 (d, 1H, J=3.4 Hz); 6.60 (s, 2H); 6.75 (d, 1H, J=3.4 Hz); 7.07 (t, 1H, J=7.6 Hz); 7.23 (d, 1H, J=7.6 Hz); 7.31 (t, 1H, J=8.0 Hz); 7.37-7.43 (m, 2H); 7.48 (t, 1H, J=7.6 Hz); 7.52 (s, 1H); 7.69 (d, 1H, J=8.0 Hz); 8.45 (d, 1H, J=8.0 Hz).",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m3_m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3\\u2032,4\\u2032,5\\u2032-Trimethoxy-biphenyl-2-carbonyl chloride\"}], \"amount\": {\"moles\": {\"value\": 0.18, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"[5-(2-Amino-phenyl)-thiophen-2-yl]-acetic acid methyl ester\"}], \"amount\": {\"mass\": {\"value\": 46.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"amount\": {\"volume\": {\"value\": 11.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"amount\": {\"volume\": {\"value\": 0.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"Stir the reaction mixture for 1 h at 0\\u00b0 C.\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"additional 20 h\", \"duration\": {\"value\": 20.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"at rt\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"ADDITION\", \"details\": \"Pour the reaction mixture into ice\"}, {\"type\": \"TEMPERATURE\", \"details\": \"cooled 1 M aqu\"}, {\"type\": \"EXTRACTION\", \"details\": \"HCl, extract with EtOAc (2\\u00d7) and DCM (2\\u00d7)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"wash the combined organic layer with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dry with Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Purify the crude product by preparative radial chromatography (silica gel, EtOAc/CyH 1+2)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc CyH\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(5-{2-[(3\\u2032,4\\u2032,5\\u2032-Trimethoxy-biphenyl-2-carbonyl)-amino]-phenyl}-thiophen-2-yl)-acetic acid methyl ester\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 58.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 59.0}}], \"isolated_color\": \"light brown\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f24dac7f984340688114a34124144344",
    "procedure_text": "Methyl hydrogen isophthalate (1.5 g, 8.2 mmol), 2-amino-4-(benzyloxy)butan-1-ol hydrochloride (2 g, 8.6 mmol), diisopropylethylamine (4.2 mL, 24.7 mmol), and HATU (3.8 mg, 9.9 mmol), in DMF (15 mL) are stirred at room temperature 1 h. The reaction is diluted in ethyl acetate and washed with water, 1N hydrochloric acid (aq), saturated sodium bicarbonate, brine, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica gel, 4% methanol/chloroform) provides the title compound. 1H NMR (400 MHz, CDCl3) \u03b4 8.44 (s, 1H), 8.18 (d, 1H, J=7.9 Hz), 7.86 (d, 1H, J=7.9 Hz), 7.43 (t, 1H, J=7.6 Hz), 7.42\u20137.35 (m, 5H), 4.59 (s, 2H), 4.33 (m, 1H), 3.96 (s, 3H), 3.88\u20133.72 (m, 4H), 3.53 (s, 1H), 2.08 (m, 2H).",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Methyl hydrogen isophthalate\"}], \"amount\": {\"mass\": {\"value\": 1.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-amino-4-(benzyloxy)butan-1-ol hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropylethylamine\"}], \"amount\": {\"volume\": {\"value\": 4.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HATU\"}], \"amount\": {\"mass\": {\"value\": 3.8, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WASH\", \"details\": \"washed with water, 1N hydrochloric acid (aq), saturated sodium bicarbonate, brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (magnesium sulfate)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification by flash column chromatography (silica gel, 4% methanol/chloroform)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c526efb4ca7142119ca3b3bd7a588a3d",
    "procedure_text": "tert-Butyl 1,3,4,8-tetrahydro-2H-[1,4]oxazepino[6,7-e]indole-2-carboxylate (Intermediate 18, 14 mg, 0.050 mmol), NaH (60% in mineral oil, 6.4 mg, 0.10 mmol) and dry DMF (0.2 mL) were shaken at room temperature for 10 minutes. 4-Methylbenzenesulfonyl chloride (19 mg, 0.10 mmol, in 0.15 mL of dry DMF) was added to the solution. The reaction mixture was shaken at room temperature for another 20 minutes and a mixture of MeOH/1 M HCl (3:1, 1 mL) was added. The reaction mixture was stirred overnight and evaporated. The residue was dissolved in 1 M NH3 in MeOH (1 mL, 1 mmol) and MeOH (1 mL). The crude product was purified by preparative HPLC (XTerra C18, 50 mM NH4HCO3 pH 10-CH3CN) to give the title compound as an off-white solid (4.9 mg). MS m/z 343 [M+H]+.",
    "reference_string": "{\"inputs\": {\"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m6_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH3\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m9\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-Butyl 1,3,4,8-tetrahydro-2H-[1,4]oxazepino[6,7-e]indole-2-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 14.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Intermediate 18\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaH\"}], \"amount\": {\"mass\": {\"value\": 6.4, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 0.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-Methylbenzenesulfonyl chloride\"}], \"amount\": {\"volume\": {\"value\": 0.15, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was shaken at room temperature for another 20 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"STIRRING\", \"details\": \"The reaction mixture was stirred overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude product was purified by preparative HPLC (XTerra C18, 50 mM NH4HCO3 pH 10-CH3CN)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH4HCO3\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH3CN\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 20.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 4.9, \"units\": \"MILLIGRAM\"}}}], \"isolated_color\": \"off-white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c2f844975da0402cbe3c51f97dd0fb00",
    "procedure_text": "To a cooled (0\u00b0 C.) solution of 4-amino-2-bromopyridine (346 mg, 2.0 mmol) and diisopropylethylamine (461 mg, 4.0 mmol) in dichloromethane (5 mL) and CH3CN (0.5 mL) was added a solution of 2-chloro-4-cyano-6-fluorobenzoyl chloride (484 mg, 2.2 mmol) in dichlormethane (5 mL) drop wise. The reaction mixture was warmed up to room temperature and stirred for 16 hours. The reaction was quenched with saturated NH4Cl (40 mL) and extracted with EtOAc (3\u00d750 mL). The combined organic extractss were dried with Na2SO4 and concentrated under reduced pressure. The residue wars purified by silica gel column chromatography (0-50% EtOAc/hexane) to give N-(2-bromopyridin-4-yl)-2-chloro-4-cyano-6-fluorobenzamide as an off-white solid (379 mg, yield: 53%).",
    "reference_string": "{\"inputs\": {\"m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloro-4-cyano-6-fluorobenzoyl chloride\"}], \"amount\": {\"mass\": {\"value\": 484.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichlormethane\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-amino-2-bromopyridine\"}], \"amount\": {\"mass\": {\"value\": 346.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropylethylamine\"}], \"amount\": {\"mass\": {\"value\": 461.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH3CN\"}], \"amount\": {\"volume\": {\"value\": 0.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred for 16 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The reaction was quenched with saturated NH4Cl (40 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH4Cl\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with EtOAc (3\\u00d750 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic extractss were dried with Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue wars purified by silica gel column chromatography (0-50% EtOAc/hexane)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(2-bromopyridin-4-yl)-2-chloro-4-cyano-6-fluorobenzamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 379.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 53.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 53.4}}], \"isolated_color\": \"off-white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a304a923cc50493f8fb04bdf1a26a063",
    "procedure_text": "The title compound was prepared from 1-benzyl-4-hydroxypiperidine and 4-chloropyridine (979 mg, 8.62 mmol), using the same method as that described for preparation 25, as an oil in 52% yield. 1H NMR (CDCl3, 400 MHz): 1.81-1.96 (m, 2H), 1.98-2.18 (m, 2H), 2.30-2.48 (m, 2H), 2.70-2.83 (m, 2H), 3.52-3.70 (m, 2H), 4.40-4.50 (m, 1H), 6.72-6.80 (m, 2H), 7.22-7.39 (m, 5H), 8.40 (m, 2H); LRMS APCI m/z 269 [M+H]+",
    "reference_string": "{\"inputs\": {\"m0_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-benzyl-4-hydroxypiperidine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-chloropyridine\"}], \"amount\": {\"mass\": {\"value\": 979.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"that described for preparation 25, as an oil in 52% yield\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 52.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2aaf5dbcffbe42a3bdfad3bf20802b35",
    "procedure_text": "2-chloro-2-methylpropane (75 g, 0.8 mol) was slowly added to magnesium pellets (19.5 g, 0.8 mol) in 800 mL of THF to make the Grignard reagent, tBuMgCl. This was added slowly to a mixture of cuprous chloride (49.5 g, 0.50 mol) and tertbutylacetylchloride (67.25 g, 0.50 mol), cooled to \u221250\u00b0 C. in dry ice. After addition, the mixture was allowed to warm up to room temperature overnight. Most of the THF was removed by decreased pressure, followed by the addition of 500 mL of hexanes and 200 mL of 2M HCl. This mixture was filtered to remove the solid byproducts. The aqueous layer was washed 3\u00d7 with 100 mL of hexanes, the hexanes layer washed 3\u00d7 with 200 mL of 2M HCl, 2\u00d7 with 200 mL of NaHCO3/water, 1\u00d7 with 200 mL of water, and finally 1\u00d7 with 200 mL of NaCl/water. The product mixture was then dried for an hour in MgSO4, which was subsequently removed by filtration. The hexane was then removed by atmospheric distillation.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tBuMgCl\"}], \"reaction_role\": \"REACTANT\"}]}, \"m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dry ice\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloro-2-methylpropane\"}], \"amount\": {\"mass\": {\"value\": 75.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 800.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cuprous chloride\"}], \"amount\": {\"mass\": {\"value\": 49.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tertbutylacetylchloride\"}], \"amount\": {\"mass\": {\"value\": 67.25, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Grignard reagent\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"After addition\"}, {\"type\": \"CUSTOM\", \"details\": \"Most of the THF was removed\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"followed by the addition of 500 mL of hexanes and 200 mL of 2M HCl\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"This mixture was filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"to remove the solid byproducts\"}, {\"type\": \"WASH\", \"details\": \"The aqueous layer was washed 3\\u00d7 with 100 mL of hexanes\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"the hexanes layer washed 3\\u00d7 with 200 mL of 2M HCl, 2\\u00d7 with 200 mL of NaHCO3/water, 1\\u00d7 with 200 mL of water, and finally 1\\u00d7 with 200 mL of NaCl/water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3 water\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaCl water\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The product mixture was then dried for an hour in MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"which was subsequently removed by filtration\"}, {\"type\": \"CUSTOM\", \"details\": \"The hexane was then removed by atmospheric distillation\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-85df06d7b7284d26ab495fe3b9b687c8",
    "procedure_text": "A mixture of 2.22 gm (0.03 mole) of acetic acid hydrazide, 3.63 gm (0.03 mole) of 4-acetylpyridine and 100 ml of absolute ethanol is refluxed 2 hr. The hot solution is filtered. The filtrate is diluted with water to the cloud point. The mixture is cooled to room temperature and then chilled in the refrigerator. The product is collected, washed with water and dried to yield 3.63 gm (69%) of the title compound having a melting point of 178.1\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid hydrazide\"}], \"amount\": {\"mass\": {\"value\": 2.22, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-acetylpyridine\"}], \"amount\": {\"mass\": {\"value\": 3.63, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"is refluxed 2 hr\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"The hot solution is filtered\"}, {\"type\": \"ADDITION\", \"details\": \"The filtrate is diluted with water to the cloud point\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"chilled in the refrigerator\"}, {\"type\": \"CUSTOM\", \"details\": \"The product is collected\"}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 3.63, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 69.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3a76c2ac45a3465382591ed0185de999",
    "procedure_text": "To a solution of 3-amino-N-cyclopropyl-4-methylbenzamide (2 g) in acetonitrile (10 ml) was added with potassium carbonate (2.6 g). The mixture was heated to 80\u00b0 C. and a solution of allyl bromide (1.1 ml) in acetonitrile (6 ml) was added dropwise and heating was continued for 17 hours. The insoluble material was removed by filtration. The filtrate was concentrated and the residue was recrystallised from 50% ethyl acetate/hexane. The mother liquors was concentrated and by column chromatography on a silica column eluting using a gradient of iso-hexane to 50% ethyl acetate/iso-hexane to yield 3-(allylamino)-N-cyclopropyl-4-methylbenzamide as a colourless oil which solidified to a white solid (688 mg); NMR Spectrum: (DMSOd6) 0.53 m, 2H), 0.78 (m, 2H), 2.10 (s, 3H), 2.81 (m, 1H), 3.67 (s, 1H), 3.81 (d, 2H), 5.13 (d, 1H), 5.23 (d, 1H), 5.93 (m, 1H), 6.11 (s, 1H), 6.83 (d, 1H), 6.98 (m, 2H); Mass Spectrum: M+H+ 231.",
    "reference_string": "{\"inputs\": {\"m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"allyl bromide\"}], \"amount\": {\"volume\": {\"value\": 1.1, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 6.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-amino-N-cyclopropyl-4-methylbenzamide\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 2.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 80.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"heating\"}, {\"type\": \"CUSTOM\", \"details\": \"The insoluble material was removed by filtration\"}, {\"type\": \"CONCENTRATION\", \"details\": \"The filtrate was concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was recrystallised from 50% ethyl acetate/hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate hexane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"The mother liquors was concentrated and by column chromatography on a silica column\"}, {\"type\": \"WASH\", \"details\": \"eluting\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 17.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(allylamino)-N-cyclopropyl-4-methylbenzamide\"}], \"isolated_color\": \"colourless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d0b9d0890a0c4208b0d7f883c011e030",
    "procedure_text": "2-Isopropyl-thiazole-4-carboxylic acid [6-acetyl-2-chloro-3-(2,2-dimethoxy-ethoxy)-phenyl]-amide (5.5 g, 12.91 mmol) and KOtBu (3.04 g, 27.11 mmol) were dissolved in tBuOH (100 mL) under an atmosphere of nitrogen. The reaction was heated to 75\u00b0 C. for 4 hours. The reaction was cooled to rt and the pH was adjusted to 4 with 2N HCl(aq). The reaction mixture was concentrated and taken up in EtOAc (100 mL). The mixture was washed with \u00bd sat. brine. The organic layer was dried with Na2SO4, filtered and was concentrated. 8-Chloro-7-(2,2-dimethoxy-ethoxy)-2-(2-isopropyl-thiazol-4-yl)-quinolin-4-ol (4.49 g, 85%) was isolated by silica gel chromatography as a yellow solid.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-Isopropyl-thiazole-4-carboxylic acid [6-acetyl-2-chloro-3-(2,2-dimethoxy-ethoxy)-phenyl]-amide\"}], \"amount\": {\"mass\": {\"value\": 5.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"KOtBu\"}], \"amount\": {\"mass\": {\"value\": 3.04, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tBuOH\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 75.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The reaction was cooled to rt\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CONCENTRATION\", \"details\": \"The reaction mixture was concentrated\"}, {\"type\": \"WASH\", \"details\": \"The mixture was washed with \\u00bd sat. brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layer was dried with Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"was concentrated\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"8-Chloro-7-(2,2-dimethoxy-ethoxy)-2-(2-isopropyl-thiazol-4-yl)-quinolin-4-ol\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 4.49, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 85.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 85.1}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-390da6494e7b419eac2dc5ef8c661421",
    "procedure_text": "3-Dimethylcarbamoyloxypyridine (1.66 g) and chloromethylhexanoate (2.0 g) were heated to 90\u00b0 C. with stirring for 3 hours. The reaction mixture was treated in a similar manner as described in Example 1 to give 2.65 g of 3-(dimethylcarbamoyloxy)-1-(hexanoyloxymethyl)-pyridinium chloride as colorless powdery crystals. It was impossible to precisely measure the melting point because of high hygroscopicity. The structure was determined by N.M.R.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-Dimethylcarbamoyloxypyridine\"}], \"amount\": {\"mass\": {\"value\": 1.66, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloromethylhexanoate\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"with stirring for 3 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"The reaction mixture was treated in a similar manner\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(dimethylcarbamoyloxy)-1-(hexanoyloxymethyl)-pyridinium chloride\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.65, \"units\": \"GRAM\"}}}], \"isolated_color\": \"colorless powdery\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-51c366a69a6f4c2c804cf23898ab5690",
    "procedure_text": "According to the similar procedure in Synthesis Example 1, by using 4-amino-2-hydroxybenzene sulfonic acid (1.00 g, 5.30 mmole), DMF (10 ml), TEA (1.0 ml), and 2,3,5,6-tetrafluoro-4-trifluoromethylbenzyl bromide (0.88 g, 5.30 mmole), 0.61 g (28.0% yield) of 2-hydroxy-5-(2,3,5,6-tetrafluoro-4-trifluoromethylbenzylamino)benzene sulfonic acid was obtained as a yellow solid.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-amino-2-hydroxybenzene sulfonic acid\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TEA\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,3,5,6-tetrafluoro-4-trifluoromethylbenzyl bromide\"}], \"amount\": {\"mass\": {\"value\": 0.88, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"According to the similar procedure in Synthesis Example 1\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-hydroxy-5-(2,3,5,6-tetrafluoro-4-trifluoromethylbenzylamino)benzene sulfonic acid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.61, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 28.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f1f2e628b7c049ba8349cf0fd2461f90",
    "procedure_text": "36 g of 1,5-undecadien-4-ol is stirred and heated to reflux with 32.6 g of acetic acid anhydride for 1 hour. The excess anhydride and the resulting acetic acid are removed by distillation under reduced pressure. The residue is fractionated. Yield: 33.8 g (76%) 1,5-undecadien-4-yl acetate; b.p. 70\u00b0-80\u00b0 C/2 Torr; n20D = 1.4468. 1,5-Nonadien-4-yl acetate was prepared in a similar way; yield: 75%; b.p. 85\u00b0 C/10 Torr; n22D = 1.4403.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,5-undecadien-4-ol\"}], \"amount\": {\"mass\": {\"value\": 36.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid anhydride\"}], \"amount\": {\"mass\": {\"value\": 32.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"heated\"}, {\"type\": \"CUSTOM\", \"details\": \"The excess anhydride and the resulting acetic acid are removed by distillation under reduced pressure\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"anhydride\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,5-Nonadien-4-yl acetate\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 75.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c64770c734a845a1aa82838330b66966",
    "procedure_text": "A solution of N-(4-chloroquinolin-3-yl)-2-methylpropanamide (6.0 g, 24 mmol), O-methylhydroxylamine hydrochloride (2.5 g, 0.030 mol), and ethanol (75 mL) was heated at reflux for five hours, allowed to cool to room temperature, stirred overnight, and concentrated under reduced pressure. The residue was dissolved in dichloromethane (100 mL), and the solution was washed with saturated aqueous sodium carbonate (2\u00d750 mL) dried over potassium carbonate, filtered, and concentrated under reduced pressure to provide 4.9 g of 2-isopropyl-1-methoxy-1H-imidazo[4,5-c]quinoline as a dark oil.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(4-chloroquinolin-3-yl)-2-methylpropanamide\"}], \"amount\": {\"mass\": {\"value\": 6.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"O-methylhydroxylamine hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 2.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 75.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred overnight\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"at reflux for five hours\", \"duration\": {\"value\": 5.0, \"units\": \"HOUR\"}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue was dissolved in dichloromethane (100 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"the solution was washed with saturated aqueous sodium carbonate (2\\u00d750 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium carbonate\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over potassium carbonate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-isopropyl-1-methoxy-1H-imidazo[4,5-c]quinoline\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 4.9, \"units\": \"GRAM\"}}}], \"isolated_color\": \"dark\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f6d72131818c48fba4cab079dcff8ec5",
    "procedure_text": "The product was obtained starting from 3-((E)-3-Dimethylamino-acryloyl)-1-[4-(2,2,2-trifluoro-ethoxy)-phenyl]-1H-pyridazin-4-one (A-32) and 3-chloro-phenylhydrazine according to the method described for example 43. MS: M=447.1 (M+H)+",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-((E)-3-Dimethylamino-acryloyl)-1-[4-(2,2,2-trifluoro-ethoxy)-phenyl]-1H-pyridazin-4-one\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-chloro-phenylhydrazine\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The product was obtained\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-cbe139c0ccf84feb820b16ea16bb62f0",
    "procedure_text": "600 mg 4-Iodo-3-methoxy-6-pyridin-4-yl-pyridazine, 974 mg 1-(tert-butoxycarbonyl)-6-(tert-butyldimethylsiloxy)indole-2-boronic acid, 2.5 g cesium carbonate, and 78 mg [1,1\u2032-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) are dissolved in a mixture of 18 mL dioxane and 5.4 mL water. Argon is bubbled through the solution for 5 minutes. The mixtures is heated to reflux for 2 hours. After diluting with EtOAc, the organic phase is ished with water and brine, dried with MgSO4 and concentrated in vacuo. The crude product is dissolved in 30 mL THF. After addition of 1.51 g tetrabutylammonium fluoride trihydrate, the red solution is stirred for 2 hours. The reaction mixture is diluted with EtOAc, ished with saturated aqueous ammonium chloride, water, and brine, dried with MgSO4 and concentrated in vacuo. Purification by HPLC afforded 760 mg (95%) 6-hydroxy-2-(3-methoxy-6-pyridin-4-yl-pyridazin-4-yl)-indole-1-carboxylic acid tert-butyl ester.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4_m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-Iodo-3-methoxy-6-pyridin-4-yl-pyridazine\"}], \"amount\": {\"mass\": {\"value\": 600.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(tert-butoxycarbonyl)-6-(tert-butyldimethylsiloxy)indole-2-boronic acid\"}], \"amount\": {\"mass\": {\"value\": 974.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cesium carbonate\"}], \"amount\": {\"mass\": {\"value\": 2.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dioxane\"}], \"amount\": {\"volume\": {\"value\": 18.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 5.4, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the red solution is stirred for 2 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Argon is bubbled through the solution for 5 minutes\", \"duration\": {\"value\": 5.0, \"units\": \"MINUTE\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"The mixtures is heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to reflux for 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"ADDITION\", \"details\": \"After diluting with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried with MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The crude product is dissolved in 30 mL THF\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"After addition of 1.51 g tetrabutylammonium fluoride trihydrate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrabutylammonium fluoride trihydrate\"}], \"amount\": {\"mass\": {\"value\": 1.51, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"The reaction mixture is diluted with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried with MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification by HPLC\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-hydroxy-2-(3-methoxy-6-pyridin-4-yl-pyridazin-4-yl)-indole-1-carboxylic acid tert-butyl ester\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 760.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 95.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-5b5e2341276e49ab86648b66994bb32c",
    "procedure_text": "1.14 g (2.7 mmol) of trans-3-{4-[methyl-(4-trifluoromethyl-benzenesulfonyl)-amino]-cyclohexyloxy}-propionic acid methyl ester in 27 mL of THF were treated with 27 mL of 1M LiOH at RT for 1 h. By adding 1M KHSO4 the solution was acidified, and the mixture was extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4 and evaporated to give 1.1 g (quantitative) of trans-3-{4-[methyl-(4-trifluoromethyl-benzenesulfonyl)-amino]-cyclohexyloxy}-propionic acid as colorless oil, MS: 408 (M\u2212H)\u2212.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trans-3-{4-[methyl-(4-trifluoromethyl-benzenesulfonyl)-amino]-cyclohexyloxy}-propionic acid methyl ester\"}], \"amount\": {\"mass\": {\"value\": 1.14, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"LiOH\"}], \"amount\": {\"volume\": {\"value\": 27.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 27.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"KHSO4\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"the mixture was extracted with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic phase was washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trans-3-{4-[methyl-(4-trifluoromethyl-benzenesulfonyl)-amino]-cyclohexyloxy}-propionic acid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.1, \"units\": \"GRAM\"}}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-04095f1b8be34b428e858a38774dc18f",
    "procedure_text": "75 g of a 25% aqueous ammonia solution are placed together with 10 g of Raney nickel and 20 ml of 1N aqueous NaOH as well as 52.2 g (0.2 mol) of 3,3-dimethyl-12- isopropyl-1-aza-1,5,9-cyclododecatriene into an autoclave with magnetic stirrer. After the reaction mixture has been heated to 175\u00b0 C., hydrogen gas is injected up to a total pressure of 50 bar. After a reaction time of 9 hours, the mixture is cooled and distilled. There is obtained 65% of the theoretical yield of 1-isopropyl-10,10-dimethyl-1,11-diaminoundecane.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Raney nickel\"}], \"amount\": {\"mass\": {\"value\": 10.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonia\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,3-dimethyl-12- isopropyl-1-aza-1,5,9-cyclododecatriene\"}], \"amount\": {\"mass\": {\"value\": 52.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrogen\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 175.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"After a reaction time of 9 hours, the mixture is cooled\", \"duration\": {\"value\": 9.0, \"units\": \"HOUR\"}}, {\"type\": \"DISTILLATION\", \"details\": \"distilled\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-isopropyl-10,10-dimethyl-1,11-diaminoundecane\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4e799fdee7074410945cf58461b62fb9",
    "procedure_text": "To a solution of (3RS,4SR)-1-benzyl-3-(3,4-dichloro-phenyl)-4-[(RS)-1-(4-trifluoromethyl-phenoxy)-ethyl]-pyrrolidine (XIV-B-1) 0.99 g (2.00 mmol) dissolved in CH3CN (25 mL) was added 0.40 mL (3.00 mmol) of 2,2,2-trichloroethyl chloroformate and stirring was continued for 4 hours at RT. Volatiles were removed under vacuo, and the crude was dissolved in AcOH (20 mL) before a total of 800 mg of Zn dust was added portion wise. After three hours at RT, the reaction mixture was filtered on celite, the solvent removed under vacuo, followed by an extraction with EtOAc/aq. NaHCO3 (basic pH). The organic phases were dried on Na2SO4 and column chromatography (SiO2, CH2Cl2/MeOH 9:1) yielded 0.54 g (67%) of the title compound as a colorless oil. ES-MS m/e: 404.2 (M+H+).",
    "reference_string": "{\"inputs\": {\"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(3RS,4SR)-1-benzyl-3-(3,4-dichloro-phenyl)-4-[(RS)-1-(4-trifluoromethyl-phenoxy)-ethyl]-pyrrolidine\"}], \"amount\": {\"mass\": {\"value\": 0.99, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH3CN\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,2,2-trichloroethyl chloroformate\"}], \"amount\": {\"volume\": {\"value\": 0.4, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirring\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Volatiles were removed under vacuo\"}, {\"type\": \"DISSOLUTION\", \"details\": \"the crude was dissolved in AcOH (20 mL) before a total of 800 mg of Zn dust\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"AcOH\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Zn\"}], \"amount\": {\"mass\": {\"value\": 800.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"was added portion wise\"}, {\"type\": \"WAIT\", \"details\": \"After three hours at RT\", \"duration\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"the reaction mixture was filtered on celite\"}, {\"type\": \"CUSTOM\", \"details\": \"the solvent removed under vacuo\"}, {\"type\": \"EXTRACTION\", \"details\": \"followed by an extraction with EtOAc/aq\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic phases were dried on Na2SO4 and column chromatography (SiO2, CH2Cl2/MeOH 9:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2 MeOH\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.54, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 67.0}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2435a354b9d64ebb9aed5763a2f06ca0",
    "procedure_text": "1-(3-Cyanopropyl)-4-(2-fluoro phenyl)piperazine (2 g) was dissolved in a mixture of methanol and aqueous ammonia 28% (1-1, 20 ml) and the mixture is introduced in a Parr bottle. Then, Raney nickel (500 mg) is added as catalyst, and the mixture is hydrogenated in a Parr apparatus for 12 h under 60 psi. The catalyst is filtered of. The filtrate is evaporated in vacuo and the residue is taken of with AcOEt, the organic layer is washed three times with H2O, dried over anhydrous Na2SO4 and evaporated. The residue is taken with EtOH and concentrated HCl (15 mL 37%) is added. The mixture is evaporated and the hydrochloride is crystallized in a mixture of EtOH-Et2O (1-1) to yield the title compound B3 (99%). 1H NMR (200 MHz, CDCl3) \u03b4: 1.44-1.61 (m, 4H), 1.88 (s, 2H), 2.37-2.45 (t, 2H), 2.60-2.65 (t, 4H), 2.65-2.72 (t, 2 H), 3.09-3.14 (t, 4H), 6.90-7.08 (m, 4H). RMN 13C (50 MHz, CDCl3): \u03b4 24.2, 31.6, 42.0, 50.4, 53.2, 58.4, 115.7, 118.8, 122.3, 124.4, 142.8, 158.1.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Raney nickel\"}], \"amount\": {\"mass\": {\"value\": 500.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(3-Cyanopropyl)-4-(2-fluoro phenyl)piperazine\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonia\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"the mixture is introduced in a Parr bottle\"}, {\"type\": \"FILTRATION\", \"details\": \"The catalyst is filtered of\"}, {\"type\": \"CUSTOM\", \"details\": \"The filtrate is evaporated in vacuo\"}, {\"type\": \"WASH\", \"details\": \"the organic layer is washed three times with H2O\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"ADDITION\", \"details\": \"is added\"}, {\"type\": \"CUSTOM\", \"details\": \"The mixture is evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"the hydrochloride is crystallized in a mixture of EtOH-Et2O (1-1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloride\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOH Et2O\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 12.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound B3\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 99.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-54aa6a3d681244bdadba331d55191a1c",
    "procedure_text": "60 mg (0.45 mmol) K2CO3 and 0.7 ml (1.36 mmol, 2M in THF) dimethylamine were added at RT to a solution of 200 mg (0.45 mmol) 4-chloro-2-ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-7-(trifluoromethyl)-quinoline-3-carboxamide (example 122) in DMF (3 ml) and the mixture was then heated in a closed vessel for 150 min at 80\u00b0. Then it was diluted with water and extracted with EE. The organic phase was washed with water and brine, dried over Na2SO4, filtered and concentrated to small volume under vacuum. Column chromatography (hexane/EE 17:3) of the residue yielded 120 mg (0.27 mmol, 60%) 4-dimethylamino-2-ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-7-(trifluoromethyl)-quinoline-3-carboxamide. MS: m/z 452.1 [M+H]+.",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m4_m0\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"K2CO3\"}], \"amount\": {\"mass\": {\"value\": 60.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylamine\"}], \"amount\": {\"volume\": {\"value\": 0.7, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-chloro-2-ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-7-(trifluoromethyl)-quinoline-3-carboxamide\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"the mixture was then heated in a closed vessel for 150 min at 80\\u00b0\", \"duration\": {\"value\": 150.0, \"units\": \"MINUTE\"}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with EE\"}, {\"type\": \"WASH\", \"details\": \"The organic phase was washed with water and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated to small volume under vacuum\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-dimethylamino-2-ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-7-(trifluoromethyl)-quinoline-3-carboxamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 0.27, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 120.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 60.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 60.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-7f5059bfc63a4f7c8c201eff0253daba",
    "procedure_text": "A slurry containing 24.6 g of zinc dust in 100 ml dry toluene was treated dropwise with a solution containing 73.5 g of ethyl bromoisobutyrate and 65 g of 4-acetoxybenzaldehyde in 200 ml dry toluene. A crystal of iodine was added to initiate the reaction and the mixture was heated to reflux overnight. An additional equivalent of ethyl bromoisobutyrate was added and reflux was continued for 24 hours. After cooling, the filtrate was hydrogenated over palladium and the residue purified by flash chromatography to give 12.2 g of 3-(4-hydroxyphenyl)-2,2-dimethylpropanoic acid ethyl ester as an oil.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl bromoisobutyrate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"palladium\"}], \"reaction_role\": \"CATALYST\"}]}, \"m1_m2_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl bromoisobutyrate\"}], \"amount\": {\"mass\": {\"value\": 73.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-acetoxybenzaldehyde\"}], \"amount\": {\"mass\": {\"value\": 65.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m7_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"zinc\"}], \"amount\": {\"mass\": {\"value\": 24.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"iodine\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was treated dropwise with a solution\"}, {\"type\": \"CUSTOM\", \"details\": \"the reaction\"}, {\"type\": \"TEMPERATURE\", \"details\": \"the mixture was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to reflux overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"reflux\"}, {\"type\": \"TEMPERATURE\", \"details\": \"After cooling\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue purified by flash chromatography\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 24.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(4-hydroxyphenyl)-2,2-dimethylpropanoic acid ethyl ester\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 12.2, \"units\": \"GRAM\"}}}], \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3de7abf0b95e4367827bfc0e5354eedf",
    "procedure_text": "To a solution of Compound 47 (1 ml) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (19 mg, 0.099 mmol) and 1-hydroxybenzotriazole (catalytic amount). Dimethylamine (0.04 ml, M=2 in tetrahydrofuran) and diisopropylethylamine (0.1 ml) were added to the above solution at ice bath. The resulted solution was stirred at room temperature for 3 days. The reaction was quenched with 1 N HCl and extracted with dichloromethane. The combined organic extracts were dried over anhydrous sodium sulfate, filtrated through silica gel, and concentrated by rotary evaporation. Purification by radial preparative-layer chromatography (ethyl acetate/hexanes 50/50 to methanol/chloroform 2/98) provided 12 mg of Compound 48 as a yellow solid.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Compound 47\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 19.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-hydroxybenzotriazole\"}], \"reaction_role\": \"REACTANT\"}]}, \"m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Dimethylamine\"}], \"amount\": {\"volume\": {\"value\": 0.04, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropylethylamine\"}], \"amount\": {\"volume\": {\"value\": 0.1, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The resulted solution was stirred at room temperature for 3 days\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The reaction was quenched with 1 N HCl\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic extracts were dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtrated through silica gel\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated by rotary evaporation\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification by radial preparative-layer chromatography (ethyl acetate/hexanes 50/50 to methanol/chloroform 2/98)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate hexanes\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"DAY\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Compound 48\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 12.0, \"units\": \"MILLIGRAM\"}}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3e0588d488ab4356bd3055ead7776472",
    "procedure_text": "According to the Step 22-1 in synthetic method for EXAMPLE 22, compound 106-2 (30 mg) and [2-[2-[[(1,1-dimethylethyl)dimethylsilyl]oxy]ethyl]phenyl]boronic acid (31.4 mg) were used instead of 14-4 and 2-thiopheneboronic acid to obtain compound 106-3 (10 mg) as a colorless amorphous solid.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound 106-2\"}], \"amount\": {\"mass\": {\"value\": 30.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"[2-[2-[[(1,1-dimethylethyl)dimethylsilyl]oxy]ethyl]phenyl]boronic acid\"}], \"amount\": {\"mass\": {\"value\": 31.4, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-thiopheneboronic acid\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound 106-3\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 10.0, \"units\": \"MILLIGRAM\"}}}], \"isolated_color\": \"colorless amorphous\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2afc91b2f882430facf8de2146485e63",
    "procedure_text": "To the above resin bound 4-[(4-tert-butylcyclohexylamino)methyl]-N-(2H-tetrazol-5-yl)-benzamide was added a solution of benzo[b]thiophene-2-carboxylic acid (400 \u03bcmol) in a mixture of NMP, DCP and diisopropylethylamine (4.5:4.5:1, 1 mL) followed by a solution of PyBrOP (400 \u03bcmol) in DCP (500 \u03bcL). The mixture was allowed to react 3 hours at 50\u00b0 C. The resin was cooled to 25\u00b0 C. while washed with NMP (4\u00d71 mL), and DCM (10\u00d71 mL).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"PyBrOP\"}], \"amount\": {\"moles\": {\"value\": 400.0, \"units\": \"MICROMOLE\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropylethylamine\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NMP\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-[(4-tert-butylcyclohexylamino)methyl]-N-(2H-tetrazol-5-yl)-benzamide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzo[b]thiophene-2-carboxylic acid\"}], \"amount\": {\"moles\": {\"value\": 400.0, \"units\": \"MICROMOLE\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 25.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"to react 3 hours at 50\\u00b0 C\", \"duration\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 50.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"WASH\", \"details\": \"while washed with NMP (4\\u00d71 mL), and DCM (10\\u00d71 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NMP\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-95fdf596400646a39bae522b1bc8ec86",
    "procedure_text": "The title compound was prepared by using a similar procedure as described for the preparation of 25 except that (2-(2-(2-(4-butyrylphenoxy)ethoxy)ethoxy)ethyl)imidodicarbonic acid, 1,3-bis-tert-butyl ester (44) was used instead of 1-(4-(2-(diethylamino)ethoxy)phenyl)butan-1-one (21). This produced the crude product which was purified by flash silica gel column chromatography, eluting with ethyl acetate, to give 45 (730 mg, 73%) as a clear oil: MS (ES+) m/z 497.3 (M+H)+.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"25\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2-(2-(2-(4-butyrylphenoxy)ethoxy)ethoxy)ethyl)imidodicarbonic acid, 1,3-bis-tert-butyl ester\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"This produced the crude product which\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-34435fc6530f4cbea848ce346d6f4222",
    "procedure_text": "A mixture of 2-chloromethylquinoline hydrochloride (488 mg), methyl E-4-(4-hydroxybenzyloxyimino)-4-phenylbutyrate (650 mg), potassium carbonate (1.00 g) and N,N-dimethylformamide (10 ml) was stirred at room temperature for 13 hours. Water was added to the reaction mixture and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. The residue was subjected to silica gel chromatography to obtain methyl E-4-phenyl-4-[4-(2-quinolinylmethoxy)benzyloxyimino]butyrate (655 mg, yield 70%) as a colorless oil from an ethyl acetate-hexane (1:4, v/v)-eluted fraction.",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m0_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate hexane\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloromethylquinoline hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 488.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl E-4-(4-hydroxybenzyloxyimino)-4-phenylbutyrate\"}], \"amount\": {\"mass\": {\"value\": 650.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at room temperature for 13 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 13.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl E-4-phenyl-4-[4-(2-quinolinylmethoxy)benzyloxyimino]butyrate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 655.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 70.0}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-6342e69523b841cfa69345cbb00a7462",
    "procedure_text": "6-[4-Chloro-6-(5-cyclopropyl-2H-pyrazol-3-ylamino)-[1,3,5]triazin-2-ylamino]-1,2-dihydro-indazol-3-one (60 mg, 0.121 mmol) was dissolved in 5 ml of a 2 M solution of dimethylamine in THF and stirred at room temperature for 2 hours. The reaction was concentrated in vacuo and purified on prep HPLC to afford 38 mg (62% yield) of the desired product as a white solid (62.2% yield). H-NMR(DMSO-d6, 500 mHz) \u03b4 11.20(s, 1H), 10.48(s br, 1H), 10.08(s, 1H), 7.92(s, 1H), 7.55(d, 1H), 7.13(s, 1H), 5.93(s, 1H), 3.20(d, 6H), 1.92(m, 1H), 0.96(m, 2H), 0.72(m, 2H). MS (ES+): m/e=393.2 (M+H), 391.2 (M\u2212H); LC/Method A/3.835 min, 98.0% purity by area %.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-[4-Chloro-6-(5-cyclopropyl-2H-pyrazol-3-ylamino)-[1,3,5]triazin-2-ylamino]-1,2-dihydro-indazol-3-one\"}], \"amount\": {\"mass\": {\"value\": 60.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylamine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred at room temperature for 2 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"The reaction was concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"purified on prep HPLC\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 38.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 62.0}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-228183850090488ca9c9b2e23bea7792",
    "procedure_text": "Compound (59) is repeatedly dried by evaporating off anhydrous pyridine. 400 mg (0.87 mmol) of compound (59) which has been dried in this way are dissolved in 5 ml of anhydrous pyridine. After adding 4,4'-dimethoxytrityl chloride (328 mg, 0.95 mmol) at room temperature, the reaction mixture is stirred overnight. MeOH (3 ml) and 5% aq. NaHCO3 (30 ml) are then added. The aqueous phase is extracted 3 times with CH2Cl2. The organic phase is dried (Na2SO4) and evaporated, and the residue is subjected to flash chromatography (column: 10\u00d75 cm, solvent CH2Cl2 /acetone, 9:1). Isolating the material from the main zone affords the colorless, amorphous title compound (61). (600 mg, 91%). 1H-NMR ([D6 ] DMSO: \u03b4=1.13 (m, 4 CH3), 2.24 (m, H--C(2')), 2.77 (m, CH), 3.12 (m, H--C(5')), 3.75 (s, 2 CH3O), 3.93 (m, H--C(4')), 4.35 (m, H--C(3')), 5.30 (d, 3'-OH), 6.39 (dd, H--C(1')), 6.86-7.39 (m, aromatic H +H--C(6)), 11.54, 11.82 (2s, 2 NH). Anal. calculated for C36H37JN4O7 (764.6): C, 56.55, H, 4.88, N, 7.33: found C, 56.42, H, 4.82, N, 7.30.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound ( 59 )\"}], \"amount\": {\"mass\": {\"value\": 400.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4,4'-dimethoxytrityl chloride\"}], \"amount\": {\"mass\": {\"value\": 328.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture is stirred overnight\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"Compound (59) is repeatedly dried\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Compound ( 59 )\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"by evaporating off anhydrous pyridine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The aqueous phase is extracted 3 times with CH2Cl2\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic phase is dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"Isolating the material from the main zone\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-019640bbf80f4f72a79f204621db630b",
    "procedure_text": "To a solution of 5-bromo-2-chloropyridin-3-amine (7.93 g, 38.2 mmol) in pyridine (76 mL) was drop wise added 2,4-difluorobenzene-1-sulfonyl chloride (20.3 g, 96.0 mmol) at 0\u00b0 C. The mixture was stirred for 1 h at room temperature. The resulting solid was filtered, and washed with water, and dried under vacuum oven to give the N-(5-bromo-2-chloropyridin-3-yl)-N-(2,4-difluorophenylsulfonyl)-2,4-difluorobenzenesulfonamide (19.6 g, 90%) as a white solid, which was used for the next step without further purification.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-bromo-2-chloropyridin-3-amine\"}], \"amount\": {\"mass\": {\"value\": 7.93, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,4-difluorobenzene-1-sulfonyl chloride\"}], \"amount\": {\"mass\": {\"value\": 20.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"amount\": {\"volume\": {\"value\": 76.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred for 1 h at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"at 0\\u00b0 C\", \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"FILTRATION\", \"details\": \"The resulting solid was filtered\"}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried under vacuum oven\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(5-bromo-2-chloropyridin-3-yl)-N-(2,4-difluorophenylsulfonyl)-2,4-difluorobenzenesulfonamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 19.6, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 90.0}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e4637182e36247888c7b686d71c1495b",
    "procedure_text": "A solution of catechol (3.30 g, 30.0 mmol) and toluene (45 ml) was dehydrated by distilling 5 mL of the solution. Thereafter, 4.08 g (20.0 mmol) of aluminum(III) isopropoxide was added to the solution while stirring. The mixed solution was refluxed for 1 hour, and then, while the distillation temperature was 100\u00b0 C. or higher, distilled until the amount of the solution became half. After the distillation, volatile components of the residual mixed solution were vaporized under reduced pressure by a rotary evaporator. The residual solid content was further heated to 100\u00b0 C. under vacuum using a vacuum dryer so that the remaining volatile components were completely removed. The solid content (catechol-aluminum complex) was green in color. The yield amount was 3.78 g (20.0 mmol), and the yield percentage was 100%. 1.89 g of catechol-aluminum complex was dissolved into 100 mL of 1:4 acetylacetone/toluene to produce a coating liquid.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"catechol\"}], \"amount\": {\"mass\": {\"value\": 3.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aluminum(III) isopropoxide\"}], \"amount\": {\"mass\": {\"value\": 4.08, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 45.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"while stirring\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"DISTILLATION\", \"details\": \"by distilling 5 mL of the solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"The mixed solution was refluxed for 1 hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"was 100\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"DISTILLATION\", \"details\": \"higher, distilled until the amount of the solution\"}, {\"type\": \"DISTILLATION\", \"details\": \"After the distillation, volatile components of the residual mixed solution\"}, {\"type\": \"CUSTOM\", \"details\": \"were vaporized under reduced pressure by a rotary evaporator\"}, {\"type\": \"CUSTOM\", \"details\": \"were completely removed\"}, {\"type\": \"DISSOLUTION\", \"details\": \"1.89 g of catechol-aluminum complex was dissolved into 100 mL of 1:4 acetylacetone/toluene\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetylacetone toluene\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"to produce a coating liquid\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-80c10a116cdf47a78f5ea984ecd04386",
    "procedure_text": "In a preferred embodiment 2-(azidomethyl)-1,3- difluorobenzene is treated with methyl 2-bromoacrylate in mixture of t-butanol and water to produce methyl 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxylate.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(azidomethyl)-1,3- difluorobenzene\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 2-bromoacrylate\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"t-butanol\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxylate\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-af79fa19069d425faa2a83b5e963b6eb",
    "procedure_text": "To a 5 ml microwave vial equipped with a stir bar was added ethyl 3-pyridin-4-yl-1-trityl-1H-indazole-5-carboxylate (816 mg, 1.601 mmol), LOH (2402 \u03bcl, 2.402 mmol), and THF (8006 \u03bcl). The vial was sealed and heated to 50\u00b0 C. for 19 hours, after which the LCMS indicates formation of the desired product. Crude was quenched with HCl (2402 \u03bcl, 2.402 mmol) and the reaction was concentrated in vacuo. Material was dry loaded onto a 100 g column; was run from 100% dichloromethane to 25% methanol. Desired product eluted; fractions were collected and concentrated in vacuo to a white solid.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 3-pyridin-4-yl-1-trityl-1H-indazole-5-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 816.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 8006.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 50.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"To a 5 ml microwave vial equipped with a stir bar\"}, {\"type\": \"CUSTOM\", \"details\": \"The vial was sealed\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-30727a82afbd4cfb8cde18df1147a5ed",
    "procedure_text": "To a suspension of 5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-amine hydrochloride (0.10 g, 0.35 mmol) and 2-bromo-1-cyclohexylethanone (0.078 g, 0.38 mmol, 3B Pharmachem) in n-BuOH (1.5 mL) was added DIEA (0.067 g, 0.52 mmol) and the resulting solution was heated at about 170\u00b0 C. in the CEM\u2122 microwave for about 30 min. The solvent was removed under reduced pressure to afford 7-cyclohexyl-3-tosyl-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazine as a crude solid that was used in Step D without further purification: LC/MS (Table 2, Method a) Rt=2.71 min; MS m/z: 395 (M+H)+.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-amine hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 0.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-bromo-1-cyclohexylethanone\"}], \"amount\": {\"mass\": {\"value\": 0.078, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-BuOH\"}], \"amount\": {\"volume\": {\"value\": 1.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DIEA\"}], \"amount\": {\"mass\": {\"value\": 0.067, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 170.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The solvent was removed under reduced pressure\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-cyclohexyl-3-tosyl-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazine\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-27d3d6d5c85c4fd3979869aae584ae2b",
    "procedure_text": "A mixture of 6-(3-fluoro-phenyl)-2H-[1,2,4]triazin-3-one (15.2 g, 79.5 mmol, crude) and 2 ml of DMF in 250 ml of 1:1 phosphorous oxychloride-chloroform was maintained at reflux overnight. The mixture was then concentrated at reduced pressure, diluted with methylene chloride and poured onto ice with stirring. When the ice melted the mixture was neutralized with sodium bicarbonate solution, and the layers were separated, the aqueous layer was extracted with dichloromethane once, the combined organic layer was washed with water, dried and concentrated to a brown oil which was purified by column chromatography (eluting with pure petroleum) to give title compound as a pale yellow solid (3.5 g, 21.0%): 1H NMR (CDCl3): \u03b4 8.88 (s, 1H), 7.87-7.82 (m, 2H), 7.60-7.52 (m, 1H), 7.32-7.27 (m, 1H).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-(3-fluoro-phenyl)-2H-[1,2,4]triazin-3-one\"}], \"amount\": {\"mass\": {\"value\": 15.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"phosphorous oxychloride chloroform\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"with stirring\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"was maintained\"}, {\"type\": \"TEMPERATURE\", \"details\": \"at reflux overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"CONCENTRATION\", \"details\": \"The mixture was then concentrated at reduced pressure\"}, {\"type\": \"ADDITION\", \"details\": \"diluted with methylene chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"poured onto ice\"}, {\"type\": \"CUSTOM\", \"details\": \"the layers were separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"the aqueous layer was extracted with dichloromethane once\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"the combined organic layer was washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated to a brown oil which\"}, {\"type\": \"CUSTOM\", \"details\": \"was purified by column chromatography (eluting with pure petroleum)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"petroleum\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 3.5, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 21.0}}], \"isolated_color\": \"pale yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-29cd370797774e51b221faf3e9f5209b",
    "procedure_text": "To a solution of tert-butyl(S)-(1-(3-acetyl-5-chloropyridin-2-yl)-2-methylpropyl)carbamate (62.3 mg, 191 \u03bcmol) in EtOH (1 mL) at 0\u00b0 C. was added sodium borohydride (7.2 mg, 191 \u03bcmol) as a solid. The mixture was stirred at 0\u00b0 C. for 90 min, then it was quenched with saturated aqueous ammonium chloride (10 mL). The mixture was extracted with EtOAc (20 mL), then the organic phase was washed with brine (10 mL), dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluting with 10% EtOAc in hexanes, gradient to 100%) to afford 53.4 mg of tert-butyl((1S)-1-(5-chloro-3-(1-hydroxyethyl)pyridin-2-yl)-2-methylpropyl)carbamate (85% yield). LC-MS tR=1.01 min in 1 min chromatography, MS (ESI) m/z 329.4 [M+H]+. 1H NMR (CDCl3, 400 MHz, mixture of diastereomers): \u03b4 8.44 (d, J=2.4 Hz, 0.3H), 8.41 (d, J=2.4 Hz, 0.7H), 7.86 (d, J=2.4 Hz, 0.7H), 7.77 (d, J=2.4 Hz, 0.3H), 5.44 (d, J=9.6 Hz, 0.7H), 5.31 (m, 0.7H), 5.23 (m, 0.7H), 4.73 (t, J=8.8 Hz, 0.3H), 4.63 (t, J=9.6 Hz, 0.3H), 4.56 (s, 0.3H), 2.18-2.12 (m, 0.3H), 2.08-2.00 (m, 0.7H), 1.56 (d, J=6.8 Hz, 0.9H), 1.52 (d, J=6.8 Hz, 2.1H), 1.40 (s, 9H), 1.11 (d, J=6.8 Hz, 0.9H), 1.00 (d, J=6.8 Hz, 2.1H), 0.80 (d, J=6.8 Hz, 2.1H), 0.69 (d, J=6.8 Hz, 0.9H).",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl(S)-(1-(3-acetyl-5-chloropyridin-2-yl)-2-methylpropyl)carbamate\"}], \"amount\": {\"mass\": {\"value\": 62.3, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium borohydride\"}], \"amount\": {\"mass\": {\"value\": 7.2, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOH\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at 0\\u00b0 C. for 90 min\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"it was quenched with saturated aqueous ammonium chloride (10 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium chloride\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The mixture was extracted with EtOAc (20 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"the organic phase was washed with brine (10 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by silica gel chromatography (eluting with 10% EtOAc in hexanes, gradient to 100%)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 90.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl((1S)-1-(5-chloro-3-(1-hydroxyethyl)pyridin-2-yl)-2-methylpropyl)carbamate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 53.4, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 85.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 85.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-61a4fd177f7f47f193231efab7616262",
    "procedure_text": "In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of (E)-2-methyl-3-phenylacrylic acid (19.0 g, 116 mmol) and Et3N (17.1 mL, 122 mmol) in THF (500 mL) at 0\u00b0 C. was treated with ethyl chloroformate (11.4 mL, 117 mmol) and the reaction mixture was stirred at 0\u00b0 C. for 15 min. A solution of NH4OH (250 mL of a 25% aq. solution) in THF (150 mL) was then added and the reaction mixture was stirred at rt for 90 min. The aq. layer was extracted twice with CH2Cl2 and the combined org. extracts were washed with water, dried over MgSO4, filtered, and the solvents were removed under reduced pressure to give the title compound as a white solid. TLC:rf (1000:50:4 CH2Cl2\u2014MeOH\u2014NH4OH)=0.25",
    "reference_string": "{\"inputs\": {\"m2_m3_m7_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(E)-2-methyl-3-phenylacrylic acid\"}], \"amount\": {\"mass\": {\"value\": 19.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Et3N\"}], \"amount\": {\"volume\": {\"value\": 17.1, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl chloroformate\"}], \"amount\": {\"volume\": {\"value\": 11.4, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N2\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5_m6_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH4OH\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aq. solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture was stirred at 0\\u00b0 C. for 15 min\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"the reaction mixture was stirred at rt for 90 min\", \"duration\": {\"value\": 90.0, \"units\": \"MINUTE\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"The aq. layer was extracted twice with CH2Cl2\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"extracts were washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"the solvents were removed under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e0798c9f573b4d15a1ab8f86bd28f5d5",
    "procedure_text": "To a solution of 2-allyloxy-3-hydroxy-pentenoic acid ethyl ester (200 mg, 1.00 mmol) in THF (5 mL) was added LiAlH4 (151 mg, 4.00 mmol). The resulting solution was stirred at ambient temperature for 15 min. H2O (10 mL) was added and the mixture was diluted with EtOAc (50 mL\u00d72), washed with brine (50 mL), dried over Na2SO4, concentrated in vacuo and purified by flash chromatography with 50% EtOAc-hexane",
    "reference_string": "{\"inputs\": {\"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-allyloxy-3-hydroxy-pentenoic acid ethyl ester\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"LiAlH4\"}], \"amount\": {\"mass\": {\"value\": 151.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The resulting solution was stirred at ambient temperature for 15 min\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WASH\", \"details\": \"washed with brine (50 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"purified by flash chromatography with 50% EtOAc-hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-d9fdfddf41c74c47ab758605f008997b",
    "procedure_text": "To a solution of 2-phenoxyisonicotinaldehyde (378 mg) in tetrahydrofuran (4 ml), 0.228 ml of diiodomethane and 3.8 ml of methyllithium (1.0M diethyl ether solution) were added under ice-cooling, and the reaction solution was stirred at the same temperature for 1 hour. To the reaction solution was added 10% aqueous citric acid, and the mixture was extracted with ethyl acetate. The combined organic layers were washed with a saturated saline solution and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue obtained was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (98:2-50/50)) to afford the title compound as a yellow oil.",
    "reference_string": "{\"inputs\": {\"m1_m3_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-phenoxyisonicotinaldehyde\"}], \"amount\": {\"mass\": {\"value\": 378.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diiodomethane\"}], \"amount\": {\"volume\": {\"value\": 0.228, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyllithium\"}], \"amount\": {\"volume\": {\"value\": 3.8, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"citric acid\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction solution was stirred at the same temperature for 1 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooling\"}, {\"type\": \"EXTRACTION\", \"details\": \"the mixture was extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined organic layers were washed with a saturated saline solution\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"The solvent was distilled off under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue obtained\"}, {\"type\": \"CUSTOM\", \"details\": \"was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (98:2-50/50))\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-85d567670d0c45269662ac89df01d2b8",
    "procedure_text": "A solution of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole (500 g) in triethyl orthoformate was treated with concentrated hydrochloric acid (10 ml) and heated at 50\u00b0 C. After 8 hours the reaction mixture was evaporated to give a solid which was washed (heptane) and air-dried to give 3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-ethoxymethylideneamino-4-trifluoromethylthiopyrazole (217 g), m.p. 68\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole\"}], \"amount\": {\"mass\": {\"value\": 500.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethyl orthoformate\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 50.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"After 8 hours the reaction mixture was evaporated\", \"duration\": {\"value\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"to give a solid which\"}, {\"type\": \"WASH\", \"details\": \"was washed (heptane)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"heptane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"air-dried\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-ethoxymethylideneamino-4-trifluoromethylthiopyrazole\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 217.0, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-98e75fd9c421455fa57ae44b588b5b18",
    "procedure_text": "The title compound, white solid (17 mg, 54.7%), MS (ISP) m/z=457.2 [(M+H)+], was prepared in accordance with the general method of example 1 from Trans-4-[2-(4-Benzo[1,3]dioxol-4-yl-piperidin-1-yl)-ethyl]-cyclohexylamine hydrochloride (intermediate A) (25 mg, 0.0681 mmol) and (R)-3,3,3-trifluoro-2-hydroxypropanoic acid",
    "reference_string": "{\"inputs\": {\"m0_m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solid\"}], \"amount\": {\"mass\": {\"value\": 17.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Trans-4-[2-(4-Benzo[1,3]dioxol-4-yl-piperidin-1-yl)-ethyl]-cyclohexylamine hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 25.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"intermediate A\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-3,3,3-trifluoro-2-hydroxypropanoic acid\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-dd1757c75b534b219247305412581efd",
    "procedure_text": "Prepared according to the procedure described in Example 1, Step 7, using [5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]-[3-(3-chloro-phenyl)-1-methyl-propyl]-amine and {1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropyl}-acetic acid ethyl ester.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"[5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]-[3-(3-chloro-phenyl)-1-methyl-propyl]-amine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"{1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropyl}-acetic acid ethyl ester\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Prepared\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-42cdc1643b2a4ffb9516c563a41073ce",
    "procedure_text": "Magnesium metal (0.29 g), 12 g atom) in dry THF (70 mL) was treated with (2-bromoethyl) benzene (0.44 mL) and an Iodine crystal. When the Iodine color had discharged additional (2-bromoethyl)benzene (1.2 mL) was added and the suspension was reacted for 24 hours. Solid imidazo[2,1-b]benzothiazole-3-carboxaldehyde (Formula J-3) (0.606 g, 3.0 mmol) was added and the mixture was reacted for 1.25 hours. The solution was decanted into 5% NH4Cl solution (250 mL) and the mixture was extracted with ethyl acetate. Drying and evaporation of the extract gave pure \u03b1-(2-phenylethyl)-imidazo[2,1-b]benzothiazole-3-methanol (Formula J-4) (0.81 g) after trituration of residue with acetonitrile. An aliquot of the triturated product was crystallized from acetonitrile solution to provide an analytical sample of \u03b1-(2-phenylethyl)-imidazo[2,1-b]benzothiazole-3-methanol (Formula J-4) (m.p. 174-175\u00b0).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Iodine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"imidazo[2,1-b]benzothiazole-3-carboxaldehyde\"}], \"amount\": {\"mass\": {\"value\": 0.606, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m7_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Magnesium\"}], \"amount\": {\"mass\": {\"value\": 0.29, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2-bromoethyl) benzene\"}], \"amount\": {\"volume\": {\"value\": 0.44, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 70.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2-bromoethyl)benzene\"}], \"amount\": {\"volume\": {\"value\": 1.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Iodine\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"CUSTOM\", \"details\": \"the suspension was reacted for 24 hours\", \"duration\": {\"value\": 24.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"the mixture was reacted for 1.25 hours\", \"duration\": {\"value\": 1.25, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The solution was decanted into 5% NH4Cl solution (250 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH4Cl\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"the mixture was extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Drying\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporation of the extract\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"\\u03b1-(2-phenylethyl)-imidazo[2,1-b]benzothiazole-3-methanol\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.81, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-40c682e84b644e8084256c888a4294b9",
    "procedure_text": "The title compound, MS: m/e=539.2 (M+H+), was prepared in analogy to example 16 from 7-amino-5-methyl-5H,7H-dibenzo[b,d]azepin-6-one and N-(3,5-difluoro-benzyl)-2-benzyl-malonamic acid.",
    "reference_string": "{\"inputs\": {\"m0_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-amino-5-methyl-5H,7H-dibenzo[b,d]azepin-6-one\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(3,5-difluoro-benzyl)-2-benzyl-malonamic acid\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fa06c9efde4e49a4bb36ec7fbf116e7d",
    "procedure_text": "4-(4-Methylphenyl)-1H-pyrazol-5-amine (170 mg) and ethyl 3-(4-fluorophenyl)-3-oxopropanoate (250 mg) are stirred overnight in a pyridine (10 mL) solvent at 95\u00b0 C. After cooling to room temperature, the reaction solvent is removed by distillation under reduced pressure. The remainder is extracted with ethyl acetate and water. The extracted organic layer is washed with brine and dehydrated with anhydrous MgSO4. The dehydrated organic layer is distilled under reduced pressure and purified by column chromatography to yield 180 mg of the target compound.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(4-Methylphenyl)-1H-pyrazol-5-amine\"}], \"amount\": {\"mass\": {\"value\": 170.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 3-(4-fluorophenyl)-3-oxopropanoate\"}], \"amount\": {\"mass\": {\"value\": 250.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the reaction solvent is removed by distillation under reduced pressure\"}, {\"type\": \"EXTRACTION\", \"details\": \"The remainder is extracted with ethyl acetate and water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The extracted organic layer is washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"The dehydrated organic layer is distilled under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"purified by column chromatography\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"target compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 180.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-8bb604c38d4f45dab41787efb36bc564",
    "procedure_text": "tert-Butyl 4-{4-[4-chloro-1-(cyclopropylmethyl)-1H-benzotriazol-5-yl]benzyl}piperazine-1-carboxylate (Example 52, 430 mg, 0.89 mmol) was dissolved in a dichloromethane (8.9 mL) and methanol (8.9 mL), cooled to 0\u00b0 C. and treated with a hydrochloric acid (2.2 mL, 4 M in dioxane, 8.9 mmol). The mixture was warmed to ambient temperature and treated with hydrochloric acid (200 \u03bcL, 12 N aqueous). The mixture was stirred at ambient temperatures until complete, at which time the mixture was treated with aqueous saturated sodium bicarbonate, diluted with water and extracted with ethyl acetate (3\u00d740 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (100:0 to 90:5; dichloromethane:methanol) to afford the product as a clear oil: 1H-NMR (400 MHz, CDCl3) \u03b4 7.51 (1H, d, J=1.9 Hz); 7.48-7.42 (5H, m); 4.56 (2H, d, J=7.0 Hz); 3.57 (2H, s); 2.93 (5H, t, J=4.8 Hz); 2.81 (3H, t, J=4.8 Hz); 1.49-1.38 (1H, m); 0.73-0.65 (2H, m); 0.57-0.48 (2H, m) ppm; high resolution mass spectrometry (ES+) m/z 382.1796 [(M+H)+; calculated for C21H25ClN5: 382.1793].",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-Butyl 4-{4-[4-chloro-1-(cyclopropylmethyl)-1H-benzotriazol-5-yl]benzyl}piperazine-1-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 430.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 8.9, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 8.9, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 2.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at ambient temperatures until complete, at which time the mixture\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The mixture was warmed to ambient temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate (3\\u00d740 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic extracts were dried with sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by silica gel chromatography (100:0 to 90:5; dichloromethane:methanol)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"isolated_color\": \"clear\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-eb16413276b94f1db387c8dacb18848f",
    "procedure_text": "5-[1-(2,4-Bis-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-thiazol-4-one was prepared from 5-[1-(2,4-Bis-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-methylsulfanyl-thiazol-4-one and 2-piperazin-1-yl-ethanol following General Procedure C.",
    "reference_string": "{\"inputs\": {\"m0_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-[1-(2,4-Bis-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-methylsulfanyl-thiazol-4-one\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-piperazin-1-yl-ethanol\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-[1-(2,4-Bis-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-thiazol-4-one\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-008f0e10d4bc4f3cb765b5e985b4c3e0",
    "procedure_text": "To a suspension of benzhydryl 7-[2-(2-formamidothiazol-5-yl)acetamido]-3-vinyl-3-cephem-4-carboxylate (11.48 g) in methylene chloride (57.4 ml) and anisole (15 ml) was added 2,2,2-trifluoroacetic acid (46 ml) under ice-cooling, and the mixture was stirred at 7\u00b0 to 8\u00b0 C. for 15 minutes. After the reaction mixture was poured into diisopropyl ether (600 ml), it was stirred under ice-cooling for 20 minutes, followed by collecting the insoluble substance by filtration and washing it with diisopropyl ether. This substance (11.4 g) was suspended in water (150 ml), adjusted to pH 6.5 with sodium bicarbonate and then treated with charcoal. The resultant filtrate was adjusted to pH 2.0 with 10% hydrochloric acid, and the precipitated substance was collected by filtration, washed with water and then dried to give 7-[2-(2-formamidothiazol-5-yl)acetamido]-3-vinyl-3-cephem-4-carboxylic acid (5.88 g), mp 200\u00b0 C. (dec.).",
    "reference_string": "{\"inputs\": {\"m1_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzhydryl 7-[2-(2-formamidothiazol-5-yl)acetamido]-3-vinyl-3-cephem-4-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 11.48, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 57.4, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"anisole\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,2,2-trifluoroacetic acid\"}], \"amount\": {\"volume\": {\"value\": 46.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropyl ether\"}], \"amount\": {\"volume\": {\"value\": 600.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at 7\\u00b0 to 8\\u00b0 C. for 15 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooling\"}, {\"type\": \"STIRRING\", \"details\": \"was stirred under ice-\"}, {\"type\": \"TEMPERATURE\", \"details\": \"cooling for 20 minutes\", \"duration\": {\"value\": 20.0, \"units\": \"MINUTE\"}}, {\"type\": \"CUSTOM\", \"details\": \"by collecting the insoluble substance\"}, {\"type\": \"FILTRATION\", \"details\": \"by filtration\"}, {\"type\": \"WASH\", \"details\": \"washing it with diisopropyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"treated with charcoal\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"charcoal\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"the precipitated substance was collected by filtration\"}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-[2-(2-formamidothiazol-5-yl)acetamido]-3-vinyl-3-cephem-4-carboxylic acid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 5.88, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4a844a40202e4196ae6a26f1b639b1e2",
    "procedure_text": "A mixture of 4-(2,2-dimethyl-4-oxo-1,2,3,4-tetrahydrothieno[3,2-d]pyrimidin-6-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazole-5-carbaldehyde (122 mg, 0.30 mmol), 2-phenylethanamine (0.151 mL, 1.20 mmol) and THF (5 mL) was stirred at room temperature overnight. Then, sodium borohydride (0.023 g, 0.60 mmol) and MeOH (2 mL) were added. After 30 min, the mixture was poured into saturated aqueous NaHCO3 and extracted with EtOAc, and the extract was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (Purif, NH, 95:5 hexane/EtOAc to EtOAc then to 80:20 EtOAc/MeOH) to afford 2,2-dimethyl-6-(5-{[(2-phenylethyl)amino]methyl}-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazol-4-yl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one (140 mg). 2,2-Dimethyl -6-(5-{[(2-phenylethyl)amino]methyl}-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazol-4-yl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one (140 mg) was dissolved with N,N,N,N-tetrabutylammonium fluoride (1.0 M in THF, 3.0 mL, 3.00 mmol) and the mixture was stirred at 60\u00b0 C. overnight. The mixture was filtered, and the filtrate was poured into saturated aqueous NaHCO3 and extracted with EtOAc, and the extract was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (Purif, NH, 95:5 hexane/EtOAc to EtOAc then to 80:20 EtOAc/MeOH) to afford the title compound (27.5 mg, 24%) as a colorless oil:",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,2-Dimethyl -6-(5-{[(2-phenylethyl)amino]methyl}-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazol-4-yl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one\"}], \"amount\": {\"mass\": {\"value\": 140.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N,N,N-tetrabutylammonium fluoride\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at 60\\u00b0 C. overnight\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The mixture was filtered\"}, {\"type\": \"ADDITION\", \"details\": \"the filtrate was poured into saturated aqueous NaHCO3\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"the extract was dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by column chromatography (Purif, NH, 95:5 hexane/EtOAc to EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 27.5, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 24.0}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-5659b7f3f12649d9bc3bd7bf643c97f9",
    "procedure_text": "Tetra-n-butylammonium fluoride (1M in tetrahydrofuran, 25.1 mL, 25.11 mmol) was added to a solution of 3-bromo-5-(2-pyridyl)-3-(trimethylsilyl)furan (4.96 g, 16.74 mmol) in tetrahydrofuran (50 mL). The reaction mixture was heated at 70\u00b0 C. (bath temperature) for six hours. The reaction mixture was evaporated, and the residue was purified by flash chromatography using hexane as the eluant to give the sub-title compound as a pale brown solid (3.02 g), m/z 224, 226 (MH+).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Tetra-n-butylammonium fluoride\"}], \"amount\": {\"volume\": {\"value\": 25.1, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-bromo-5-(2-pyridyl)-3-(trimethylsilyl)furan\"}], \"amount\": {\"mass\": {\"value\": 4.96, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 70.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was purified by flash chromatography\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sub-title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 3.02, \"units\": \"GRAM\"}}}], \"isolated_color\": \"pale brown\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-5f41de846f824db39bbf6b020fd6573f",
    "procedure_text": "To a solution of 3-morpholino-l-(2\u2032-nitrophenyl) propane-1-one (200 mg, 0.758 mmol) dissolved in 10 ml of 95% ethanol was added sodium dithionite (660 mg, 3.79 mmol) and the reaction mixture was stirred under reflux for 3 hrs. The reaction mixture was concentrated under reduced pressure. The residue was purified by flash column chromatography with ethanol-dichloromethane-triethylamine to yield the desired product (174 mg, 89%) as an oil.",
    "reference_string": "{\"inputs\": {\"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-morpholino-l-(2\\u2032-nitrophenyl) propane-1-one\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium dithionite\"}], \"amount\": {\"mass\": {\"value\": 660.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture was stirred\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"under reflux for 3 hrs\", \"duration\": {\"value\": 3.0, \"units\": \"HOUR\"}}, {\"type\": \"CONCENTRATION\", \"details\": \"The reaction mixture was concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by flash column chromatography with ethanol-dichloromethane-triethylamine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol dichloromethane triethylamine\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 174.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 89.0}}], \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-7d9e76ca8dfe499992cc66c682396a9b",
    "procedure_text": "4 g 1-(4-Bromobutyl)-4,4-dimethyl-2,6-piperidin-dione, 3.15 g 1-(4-(1,1-dimethylethyl)-2-thiazolyl)-piperazine, 2.7 g K2CO3, 70 ml dimethylformamide and 20 ml water are stirred at room temperature for about 35 hours. The mixture is diluted with water, extracted twice with ether, the combined extracts are washed with water, dried (Na2SO4) and evaporated. The residue is recrystallized from hexane/ethyl acetate, whereby the title compound is obtained, m.p. 93\u00b0-94\u00b0. M.p. of the hydrochloride is 199\u00b0-201\u00b0 (ethanol/ether).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloride\"}], \"reaction_role\": \"REACTANT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol ether\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3_m8_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(4-Bromobutyl)-4,4-dimethyl-2,6-piperidin-dione\"}], \"amount\": {\"mass\": {\"value\": 4.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(4-(1,1-dimethylethyl)-2-thiazolyl)-piperazine\"}], \"amount\": {\"mass\": {\"value\": 3.15, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"K2CO3\"}], \"amount\": {\"mass\": {\"value\": 2.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 70.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted twice with ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"the combined extracts are washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue is recrystallized from hexane/ethyl acetate, whereby the title compound\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"is obtained\"}, {\"type\": \"CUSTOM\", \"details\": \"is 199\\u00b0-201\\u00b0\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-da84338d18144d05a7559d4c55364d8b",
    "procedure_text": "To a solution of 1-(3-iodobenzyl)pyrrolidin-2-one (5.49 g, 16.8 mmol) in toluene (20 mL) was added N1,N2-dimethylcyclohexane-1,2-diamine (530 \u03bcL, 3.40 mmol), 3-(tert-butyl)-1H-pyrazol-5-amine (2.57 g, 18.5 mmol), potassium carbonate (4.64 g, 33.5 mmol) and copper(I) iodide (160 mg, 0.839 mmol), and the reaction mixture was heated to 110\u00b0 C. for 3 days. The mixture was cooled to RT and was partitioned between water (50 mL) and EtOAc (100 mL). The organic phase was separated and was washed with water (4\u00d750 mL) and then dried and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 120 g, 0-50% EtOAc in isohexane, gradient elution) to afford the title compound, Intermediate A16, as a black gum (1.64 g, 30%); Rt 1.43 min (Method 2, acidic); m/z 313 (M+H)+, (ES+).",
    "reference_string": "{\"inputs\": {\"m1_m5_m2_m3_m4_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(3-iodobenzyl)pyrrolidin-2-one\"}], \"amount\": {\"mass\": {\"value\": 5.49, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N1,N2-dimethylcyclohexane-1,2-diamine\"}], \"amount\": {\"volume\": {\"value\": 530.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(tert-butyl)-1H-pyrazol-5-amine\"}], \"amount\": {\"mass\": {\"value\": 2.57, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 4.64, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"copper(I) iodide\"}], \"amount\": {\"mass\": {\"value\": 160.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 110.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The mixture was cooled to RT\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"was partitioned between water (50 mL) and EtOAc (100 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The organic phase was separated\"}, {\"type\": \"WASH\", \"details\": \"was washed with water (4\\u00d750 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by flash column chromatography (SiO2, 120 g, 0-50% EtOAc in isohexane, gradient elution)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"mass\": {\"value\": 120.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isohexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-63693c7948bb4a5c9127d8fc249a2861",
    "procedure_text": "The title compound (0.52 g), was prepared similarly to the procedure of Example 1(C) from methanesulphonyl chloride (0.44 g), 1-(4-amino-2-chlorophenyl)-4-(4-aminophenethyl)piperazine (0.55 g), and pyridine (10 ml).",
    "reference_string": "{\"inputs\": {\"m0_m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanesulphonyl chloride\"}], \"amount\": {\"mass\": {\"value\": 0.44, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(4-amino-2-chlorophenyl)-4-(4-aminophenethyl)piperazine\"}], \"amount\": {\"mass\": {\"value\": 0.55, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.52, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-441e5bff938143ee983436cbe5c61689",
    "procedure_text": "To a solution of N-(4-(6-nitroquinolin-4-ylthio)phenyl)-4-phenylphthalazin-1-amine (228 mg, 455 \u03bcmol) in 1 mL of DMF, was added tin (II) chloride (431 mg, 2273 \u03bcmol) and 115 uL of water. After 15 minutes of sonication, the reaction was stirred at rt. After 2 days, water was removed under vacuum azeotropically with benzene. DCM was added to the suspension. Yellow solids precipitated out of the solution and were filtered off with DCM. The filtrate was concentrated and purified by RPLC on an acidic Gilson column system. Fractions containing the product were washed with sat. NaHCO3. The product was extracted with DCM. The organic was washed with brine, dried over MgSO4, filtered, and concentrated. The product was purified further by performing a column chromatography using 60:40 DCM:(90:10:1 DCM:MeOH:NH4OH). Yellow solid, N-(4-(6-aminoquinolin-4-ylthio)phenyl)-4-phenylphthalazin-1-amine was obtained.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(4-(6-nitroquinolin-4-ylthio)phenyl)-4-phenylphthalazin-1-amine\"}], \"amount\": {\"mass\": {\"value\": 228.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tin (II) chloride\"}], \"amount\": {\"mass\": {\"value\": 431.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 115.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction was stirred at rt\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"After 15 minutes of sonication\", \"duration\": {\"value\": 15.0, \"units\": \"MINUTE\"}}, {\"type\": \"CUSTOM\", \"details\": \"water was removed under vacuum azeotropically with benzene\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzene\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"DCM was added to the suspension\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Yellow solids precipitated out of the solution\"}, {\"type\": \"FILTRATION\", \"details\": \"were filtered off with DCM\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"The filtrate was concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"purified by RPLC on an acidic Gilson column system\"}, {\"type\": \"ADDITION\", \"details\": \"Fractions containing the product\"}, {\"type\": \"WASH\", \"details\": \"were washed with sat. NaHCO3\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The product was extracted with DCM\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic was washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The product was purified further\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"DAY\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(4-(6-aminoquinolin-4-ylthio)phenyl)-4-phenylphthalazin-1-amine\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-7feb1e1ae89d41ef890a92d8d916f4d9",
    "procedure_text": "Performance of the reaction with ethyl bromoacetate: 200 g of 5-bromo-2-hydroxybenzaldehyde are dissolved in 2000 ml of NMP with stirring, and 144 g of potassium carbonate and 175 g of ethyl bromoacetate are added. The mixture is stirred at 105\u00b0 under nitrogen for 15 hours. The resultant orange solution dotted with crystals is cooled to 25\u00b0, 135 g of formamide are added, and the mixture is stirred for a further 30 minutes. 557 ml of sodium methoxide (30% in MeOH) are then allowed to run in over the course of 15 minutes without cooling. After 3 hours, a brownish solution dotted with crystals is present. It is poured into 6 litres of demineralized water (10\u00b0), and the mixture is stirred for a further 30 minutes. The crystals are filtered off with suction, washed with 1 litre of demineralized water, re-suspended in 4 litres of demineralized water, filtered off with suction and re-washed with 1 litre of demineralized water. The crystals are dried overnight to constant weight under reduced pressure at 60\u00b0 C. (product weight: 113 g of pale beige crystals; m.p. 210-213\u00b0; CAS 35351-21-4).",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium methoxide\"}], \"amount\": {\"volume\": {\"value\": 557.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-bromo-2-hydroxybenzaldehyde\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NMP\"}], \"amount\": {\"volume\": {\"value\": 2000.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl bromoacetate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 6.0, \"units\": \"LITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 144.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl bromoacetate\"}], \"amount\": {\"mass\": {\"value\": 175.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"formamide\"}], \"amount\": {\"mass\": {\"value\": 135.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"with stirring\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"The mixture is stirred at 105\\u00b0 under nitrogen for 15 hours\", \"duration\": {\"value\": 15.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"is cooled to 25\\u00b0\"}, {\"type\": \"STIRRING\", \"details\": \"the mixture is stirred for a further 30 minutes\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}}, {\"type\": \"CUSTOM\", \"details\": \"to run in over the course of 15 minutes\", \"duration\": {\"value\": 15.0, \"units\": \"MINUTE\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"without cooling\"}, {\"type\": \"STIRRING\", \"details\": \"the mixture is stirred for a further 30 minutes\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}}, {\"type\": \"FILTRATION\", \"details\": \"The crystals are filtered off with suction\"}, {\"type\": \"WASH\", \"details\": \"washed with 1 litre of demineralized water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered off with suction\"}, {\"type\": \"WASH\", \"details\": \"re-washed with 1 litre of demineralized water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The crystals are dried overnight to constant weight under reduced pressure at 60\\u00b0 C. (product weight: 113 g of pale beige crystals; m.p. 210-213\\u00b0; CAS 35351-21-4)\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pale beige crystals\"}], \"amount\": {\"mass\": {\"value\": 113.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}]}, \"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-ca2131b576614b1797b46a615aa70d4e",
    "procedure_text": "To a solution of (6-Chloro-pyridin-3-yl)-(4-methyl-piperazin-1-yl)-methanone (2.00 g, 7.46 mmol) in 10 mL dimethylformamide was added 3-Amino-5-bromo-1-methyl-1H-pyridin-2-one (1.80 g, 8.95 mmol) and sodium hydride (537 mg, 22.4 mmol). After stirring for 18 hours, this was quenched with water. This was extracted with ethylacetate. The ethylacetate layer was dried over anhydrous sodium sulfate, concentrated in vacuo, and purified by flash chromatography (gradient elution 0 to 5% methanol/dichloromethane) to yield 5-Bromo-1-methyl-3-[5-(4-methyl-piperazine-1-carbonyl)-pyridin-2-ylamino]-1H-pyridin-2-one (900 mg, 1.94 mmol). MS (ESI) 406.0 (M+H)+.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(6-Chloro-pyridin-3-yl)-(4-methyl-piperazin-1-yl)-methanone\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-Amino-5-bromo-1-methyl-1H-pyridin-2-one\"}], \"amount\": {\"mass\": {\"value\": 1.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydride\"}], \"amount\": {\"mass\": {\"value\": 537.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring for 18 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"this was quenched with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"This was extracted with ethylacetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethylacetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The ethylacetate layer was dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethylacetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"purified by flash chromatography (gradient elution 0 to 5% methanol/dichloromethane)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 18.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-Bromo-1-methyl-3-[5-(4-methyl-piperazine-1-carbonyl)-pyridin-2-ylamino]-1H-pyridin-2-one\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 1.94, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 900.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d8e99cc22ae9474396133de3b0e872aa",
    "procedure_text": "4,5-Dibromomethyl-2-oxo-1,3-dioxolene (150 mg, 0.55 mmol) was dissolved in acetonitrile (4.0 mL). Potassium formate (46 mg, 0.55 mmol) was added thereto. This mixture was stirred at 25\u00b0 C. for 5 hours. Through the ordinary post-treatment, crude Compound S-30 (85 mg, yield 65%) was obtained.",
    "reference_string": "{\"inputs\": {\"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4,5-Dibromomethyl-2-oxo-1,3-dioxolene\"}], \"amount\": {\"mass\": {\"value\": 150.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Potassium formate\"}], \"amount\": {\"mass\": {\"value\": 46.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 25.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"This mixture was stirred at 25\\u00b0 C. for 5 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"(85 mg, yield 65%) was obtained\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 5.0, \"units\": \"HOUR\"}, \"products\": [{\"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 65.0}}]}]}]}"
  },
  {
    "reaction_id": "ord-3f91bdc7769a4fb0b03aae8373ddf179",
    "procedure_text": "The title compound was prepared from 1,4-Diethyl-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-8-ylamine and (2,5-Dichloro-pyrimidin-4-yl)-[2-(propane-2-sulfonyl)-phenyl]-amine in an analogous manner to example 724. Product was isolated as a tan solid (0.024 g, 12%). Mp 90-94\u00b0 C.; LCMS (m/e) 529 (M); 1H-NMR (DMSO, 400 MHz) \u03b4 9.47 (s, 1H), 9.43 (s, 1H), 8.59 (m, 1H), 8.29 (s, 1H), 7.86-7.84 (d, 1H, J=7.83 Hz), 7.72 (t, 1H, J=8.08 Hz), 7.40-7.36 (t, 1H, J=7.83 Hz), 7.15 (s, 1H), 7.01-6.95 (d, 1H, J=8.33 Hz), 3.61-3.52 (m, 2H), 3.47-3.45 (q, 2H, J=6.32 Hz), 2.96-2.90 (m, 5H), 2.80-2.70 (m, 2H), 1.23-1.17 (d, 6H, J=6.82 Hz), 1.08-0.98 (t, 6H, J=6.82 Hz).",
    "reference_string": "{\"inputs\": {\"m0_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,4-Diethyl-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-8-ylamine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2,5-Dichloro-pyrimidin-4-yl)-[2-(propane-2-sulfonyl)-phenyl]-amine\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.024, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 12.0}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-959adbca2a5c4868b911760aa7df0ec7",
    "procedure_text": "The product from Example 1B and 2-(3,5-dimethyl-1-adamantyl)acetic acid were processed using the method described in Example 17C to afford the title compound. 1H NMR (500 MHz, DMSO-d6) \u03b4 ppm 0.81 (s, 6H) 0.98-1.20 (m, 2H) 1.20-1.42 (m, 14H) 1.52 (s, 2H) 1.98-2.14 (m, 3H) 3.49-3.73 (m, 1H) 7.89 (t, J=7.48 Hz, 1H) 7.95-8.04 (m, 1H) 8.11 (d, J=8.24 Hz, 1H) 8.34 (d, J=6.71 Hz, 1H) 11.12 (s, 1H); MS (ESI) m/z 408 (M+H)+.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(3,5-dimethyl-1-adamantyl)acetic acid\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2acb18e40ebf43ebbfb726bb5426dade",
    "procedure_text": "Using (3aR*,10aS*)-9-(3-aminobenzyl)-4-(phthalimidoacetyl)-2,3,3a,4,9,10a-hexahydrobenzo[b]cyclopenta[e][1,4]diazepin-10(1H)-one hydrobromide and benzoyl chloride, the title compound was synthesized in otherwise the same manner as Example 20. Yield 56%, m.p. 244\u00b0-246\u00b0 C. (diethyl ether).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(3aR*,10aS*)-9-(3-aminobenzyl)-4-(phthalimidoacetyl)-2,3,3a,4,9,10a-hexahydrobenzo[b]cyclopenta[e][1,4]diazepin-10(1H)-one hydrobromide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzoyl chloride\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 56.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-8dac580a1c1042abb1711bdc36ef2bde",
    "procedure_text": "A mixture of 2.25 g (5 mmoles) of 1-(1-methoxycarbonyl-2-methylprop-2-enyl)-3-phenylacetamido-4-succinimidothio-azetidin-2-one (prepared as described in Example 2) and 1.4 ml (10 mmoles) of triethylamine in 100 ml of tetrahydrofuran was stirred at 65\u00b0 C. for 25 minutes. The reaction mixture was evaporated, treated with 25 ml of ethyl acetate and evaporated once more. The residual foam was dissolved in 50 ml of ethyl acetate, treated with charcoal and concentrated to a small volume. The desired product crystallized upon cooling. There was obtained 1-(1-methoxycarbonyl-2-methylpropenyl)-3-phenylacetamido-4-succinimidothio-azetidin-2-one.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(1-methoxycarbonyl-2-methylprop-2-enyl)-3-phenylacetamido-4-succinimidothio-azetidin-2-one\"}], \"amount\": {\"mass\": {\"value\": 2.25, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 1.4, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 65.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at 65\\u00b0 C. for 25 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was evaporated\"}, {\"type\": \"ADDITION\", \"details\": \"treated with 25 ml of ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated once more\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residual foam was dissolved in 50 ml of ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"treated with charcoal\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"charcoal\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated to a small volume\"}, {\"type\": \"CUSTOM\", \"details\": \"The desired product crystallized\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"upon cooling\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 25.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(1-methoxycarbonyl-2-methylpropenyl)-3-phenylacetamido-4-succinimidothio-azetidin-2-one\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-834e58427fc7400bbc3830cc5ccb4ceb",
    "procedure_text": "To a solution of 50.58 g (289 mmol) of (4-[1,2,3]triazol-2-yl-phenyl)-methanol in 2000 ml of CH2Cl2, 31.59 ml (433 mmol) of thionyl chloride is added dropwise at 0\u20135\u00b0 C. and the reaction mixture is allowed to warm to r.t. After stirring for 16 h, the reaction mixture is basified with sat. NaHCO3 at 0\u20135\u00b0 C. and extracted with CH2Cl2. The combined extracts are washed with brine, dried over MgSO4 and concentrated under reduced pressure to provide the title compound.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(4-[1,2,3]triazol-2-yl-phenyl)-methanol\"}], \"amount\": {\"mass\": {\"value\": 50.58, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"thionyl chloride\"}], \"amount\": {\"volume\": {\"value\": 31.59, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"amount\": {\"volume\": {\"value\": 2000.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring for 16 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted with CH2Cl2\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined extracts are washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2efdb5ca3fd34309bd27df8a9862c990",
    "procedure_text": "118.2 g (5.1 mol) sodium are slowly added to 2.5 liters ethanol. 350.0 g (5.1 mol) imidazole are then added and 570 ml (858.6 g, 5.1 mol) ethyl bromoacetate are added dropwise at an internal temperature of 20-25\u00b0 C. The mixture is stirred at RT for 24 h. The solid which has precipitated out is filtered off, the ethanol is removed in vacuo and the mixture is filtered again. The residue is purified by column chromatography over silica gel (mobile phase: ethyl acetate).",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium\"}], \"amount\": {\"mass\": {\"value\": 118.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 2.5, \"units\": \"LITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"imidazole\"}], \"amount\": {\"mass\": {\"value\": 350.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl bromoacetate\"}], \"amount\": {\"volume\": {\"value\": 570.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture is stirred at RT for 24 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The solid which has precipitated out\"}, {\"type\": \"FILTRATION\", \"details\": \"is filtered off\"}, {\"type\": \"CUSTOM\", \"details\": \"the ethanol is removed in vacuo\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"the mixture is filtered again\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue is purified by column chromatography over silica gel (mobile phase: ethyl acetate)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 24.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-ca30a92c657741658d74282e8b1d155f",
    "procedure_text": "As described for example 1b, 2-methyl-5-[5-methyl-3-(tetrahydro-pyran-4-yl)-isoxazol-4-ylmethoxy]-2H-pyrazole-3-carboxylic acid methyl ester (200 mg, 0.6 mmol), instead of 5-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-2H-pyrazole-3-carboxylic acid methyl ester, was converted, using 4-aminotetrahydropyran instead of morpholine, to the title compound (183 mg, 76%) which was obtained as a colorless gum. MS: m/e=403.1 [M\u2212H]\u2212.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-methyl-5-[5-methyl-3-(tetrahydro-pyran-4-yl)-isoxazol-4-ylmethoxy]-2H-pyrazole-3-carboxylic acid methyl ester\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-2H-pyrazole-3-carboxylic acid methyl ester\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-aminotetrahydropyran\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 183.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 76.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0dfbc301decd47dfa19e832982097f22",
    "procedure_text": "108 g of L-glutamine was dissolved in 343 g of water and 102 g of aqueous 27% sodium hydroxide solution, and cooled to 10\u00b0 C. 138 g of acetone was added to it, and 152 g of lauroyl chloride and 108 g of aqueous 27% sodium hydroxide solution were dropwise added thereto. The acylation liquid was diluted with 300 g of water, then neutralized with 35 g of 75% sulfuric acid and filtered to obtain a white powdery substance, N-lauroyl-L-glutamine. 72.4 g of thionyl chloride was dropwise added to 424 g of isopropyl alcohol, then 100 g of N-lauroyl-L-glutamine was added thereto and reacted at room temperature for 8.5 hours. The reaction liquid was added to 2.0 L of water to precipitate the intended product, and this was taken out by filtration to obtain a crude product. This was recrystallized repeatedly three times with acetone to obtain 59.1 g of N-lauroyl-L-glutamine isopropyl ester.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"LITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"thionyl chloride\"}], \"amount\": {\"mass\": {\"value\": 72.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isopropyl alcohol\"}], \"amount\": {\"mass\": {\"value\": 424.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-lauroyl-L-glutamine\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"reacted at room temperature for 8.5 hours\", \"duration\": {\"value\": 8.5, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The reaction liquid\"}, {\"type\": \"CUSTOM\", \"details\": \"to precipitate the intended product\"}, {\"type\": \"FILTRATION\", \"details\": \"this was taken out by filtration\"}, {\"type\": \"CUSTOM\", \"details\": \"to obtain a crude product\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"This was recrystallized repeatedly three times with acetone\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-lauroyl-L-glutamine isopropyl ester\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 59.1, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 52.4}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-db8543f3b1cf400ca142ce2f4f82afad",
    "procedure_text": "To a 50 mL round bottom flask, 5-(2-chloro-4-morpholino-pyrido[3,2-d]pyrimidin-7-yl)furan-2-carbaldehyde (0.4 g, 0.0012 mol) and THF (15 mL) were added and cooled to 0-5\u00b0 C. To the flask was slowly added 3.0 M methyl magnesium bromide in diethyl ether (0.6 mL, 0.0036 mol). The resulting reaction mixture was stirred at room temperature for 2 h. To the reaction mass, water was added and extracted with DCM. The organic layer was dried over anhydrous sodium sulfate and evaporated under reduced to get the crude product. The crude product was purified by column chromatography using 1% MeOH in chloroform [0.17 g, 40%]. LC-MS (ESI): Calculated mass: 360.1; Observed mass: 361.1(RT: 1.29 min).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"amount\": {\"volume\": {\"value\": 0.6, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-(2-chloro-4-morpholino-pyrido[3,2-d]pyrimidin-7-yl)furan-2-carbaldehyde\"}], \"amount\": {\"mass\": {\"value\": 0.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl magnesium bromide\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 2.5, \"precision\": 2.5, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at room temperature for 2 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The resulting reaction mixture\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with DCM\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layer was dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4361350d343a49b997087a736f033ea0",
    "procedure_text": "To a solution of 2 bromo-5-methyl pyridine (1.81 g, 10.53 mmol) and barium hydroxide (4.97 g, 15.78 mmol) in water (15 mL) was added DME (80 mL). This mixture was treated sequentially with 2-(trifluoromethyl)phenylboronic acid (2.00 g, 10.53 mmol) and palladium tetrakis(triphenylphosphine) (553 mg, 0.48 mmol) and the mixture warmed to 80\u00b0 C. for 48 hours. Water (100 mL) was added and the pH of the solution was adjusted to 10 and extracted with EtOAc (3\u00d7200 mL).",
    "reference_string": "{\"inputs\": {\"m1_m2_m5_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"bromo-5-methyl pyridine\"}], \"amount\": {\"mass\": {\"value\": 1.81, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"barium hydroxide\"}], \"amount\": {\"mass\": {\"value\": 4.97, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DME\"}], \"amount\": {\"volume\": {\"value\": 80.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Water\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(trifluoromethyl)phenylboronic acid\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"palladium tetrakis(triphenylphosphine)\"}], \"amount\": {\"mass\": {\"value\": 553.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 80.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted with EtOAc (3\\u00d7200 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-69c00f963c234f92aadbdf892edab5fc",
    "procedure_text": "To a suspension of 1-(tert-butoxycarbonylamino)cyclopentanecarboxylic acid (500 mg, 2.181 mmol), (2R,5S)-2,5-dimethylpyrrolidine, HCl (296 mg, 2.181 mmol), and triethylamine (0.912 mL, 6.54 mmol) in DMF (5 mL) was added HATU (829 mg, 2.181 mmol). The mixture was stirred at 23\u00b0 C. for 4 h then concentrated. The residue was taken up in EtOAc (25 mL) then washed successively with 0.5 M HCl (2\u00d725 mL), saturated NaHCO3 (2\u00d725 mL), and brine (2\u00d725 mL). The combined organic layers were dried (MgSO4), filtered, then concentrated under reduced pressure. The residue was purified by silica gel flash chromatography to give the title compound (0.47 g) as a white solid. LCMS m/z=311.3 [M+H]+.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HATU\"}], \"amount\": {\"mass\": {\"value\": 829.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(tert-butoxycarbonylamino)cyclopentanecarboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 500.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2R,5S)-2,5-dimethylpyrrolidine, HCl\"}], \"amount\": {\"mass\": {\"value\": 296.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 0.912, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 23.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at 23\\u00b0 C. for 4 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"then concentrated\"}, {\"type\": \"WASH\", \"details\": \"then washed successively with 0.5 M HCl (2\\u00d725 mL), saturated NaHCO3 (2\\u00d725 mL), and brine (2\\u00d725 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic layers were dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by silica gel flash chromatography\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.47, \"units\": \"GRAM\"}}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-759aba803be240b1864ad99e6c50b428",
    "procedure_text": "In an analogous manner to Example 1B, the product from step A is reacted with half-concentrated hydrochloric acid to give 7-(1-aminomethyl-2-oxa-7-aza-bicyclo[3.3.0]-oct-7-yl)-1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid hydrochloride with a melting point of 175\u00b0-177\u00b0 C. (with decomposition).",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-(1-aminomethyl-2-oxa-7-aza-bicyclo[3.3.0]-oct-7-yl)-1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid hydrochloride\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0c0fb65c8a904de180c7476dae37dfe3",
    "procedure_text": "A solution of N-trifluoroacetyl-2-iodo-5-methoxyphenethylamine (23.8 g, 63.8 mmol) in toluene (425 mL) was sequentially treated with K2CO3 (12.4 g, 89.8 mmol), KOH (11.6 g, 207 mmol), n-Bu4NBr (2.2 g, 6.9 mmol) and allyl bromide (10.7 g, 89.8 mmol). The mixture was stirred at 80 C for 3.5 hours, cooled to 20 C, acidified with 10% aqueous HCl, separated and the aqueous phase extracted with ether (500 mL). The combined organic phases were washed with brine (200 mL), dried with Na2SO4 and concentrated to give 20.5 g of a brown oil. 1H NMR (400 MHz, CDCl3), mixture of rotamers d 7.67 (m, 1H), 6.80 (m, 1H), 6.57 (m, 1H), 5.9-5.6 (bm, 1H), 5.27 (m, 2H), 4.11 (d, J=6 Hz, 0.5H), 3.85 (d, J=6 Hz, 0.5H), 3.77 (m, 3H), 3.55 (m, 2H), 3.00 (m, 2H). MS calculated for C14H15F3INO2+H: 414, observed: 414.",
    "reference_string": "{\"inputs\": {\"m1_m6_m2_m3_m7_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-trifluoroacetyl-2-iodo-5-methoxyphenethylamine\"}], \"amount\": {\"mass\": {\"value\": 23.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"K2CO3\"}], \"amount\": {\"mass\": {\"value\": 12.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"KOH\"}], \"amount\": {\"mass\": {\"value\": 11.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"allyl bromide\"}], \"amount\": {\"mass\": {\"value\": 10.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 425.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-Bu4NBr\"}], \"amount\": {\"mass\": {\"value\": 2.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at 80 C for 3.5 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooled to 20 C\"}, {\"type\": \"CUSTOM\", \"details\": \"separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"the aqueous phase extracted with ether (500 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined organic phases were washed with brine (200 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried with Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.5, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brown oil\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 20.5, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 77.8}}], \"isolated_color\": \"brown\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-5df15d82b100491892bb4059c52276de",
    "procedure_text": "3.0 g of 2-n-butoxyphenylglyoxal hydrate (crude oil) are dissolved in 9 ml of dimethylsulfoxide, and 2.8 g of \u03b1-methyl-3,4-dimethoxyphenethylamine are added thereto. The mixture is stirred at room temperature for 30 minutes, whereby a solution of \u03b1-(\u03b1-methyl-3,4-dimethoxyphenylethylimino)-2-n-butoxyacetophenone in dimethylsulfoxide is obtained.",
    "reference_string": "{\"inputs\": {\"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-n-butoxyphenylglyoxal hydrate\"}], \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylsulfoxide\"}], \"amount\": {\"volume\": {\"value\": 9.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"\\u03b1-methyl-3,4-dimethoxyphenethylamine\"}], \"amount\": {\"mass\": {\"value\": 2.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m0_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylsulfoxide\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture is stirred at room temperature for 30 minutes\"}, \"conditions_are_dynamic\": true}, \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"\\u03b1-(\\u03b1-methyl-3,4-dimethoxyphenylethylimino)-2-n-butoxyacetophenone\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-846072823ca34f178a6b2f156873c755",
    "procedure_text": "The title compound was prepared according to the procedure described in Example 11 using 2-ethoxybenzaldehyde and N-isopropylhydroxylamine. The title compound was isolated in 48.8% yield as a solid, m.p. 59.4\u00b0 C. (Rf =0.48 on a silica gel plate using ethyl acetate as the eluant).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-ethoxybenzaldehyde\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-isopropylhydroxylamine\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The title compound was prepared\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-9f60d5c7a383418895395ffe7d11e22f",
    "procedure_text": "A solution of 4-[(2-chloro-\u03b1,\u03b1,\u03b1,6-tetrafluoro-p-tolyl)oxy]-2-(p-methoxyphenoxy)-1-nitrobenzene (12.4 g, 0.027 mol) in methylene chloride is cooled to -78\u00b0 C., treated with boron tribromide (68 mL of a 1M solution in methylene chloride, 0.068 mol), stirred at -78\u00b0 C. for two hours, warmed to room temperature and poured onto cracked ice. After the ice has melted, the phases are separated and the aqueous phase is extracted with methylene chloride. The organic phase is combined with the organic extracts and the resultant organic solution is washed with brine and dried over anhydrous sodium sulfate. Silica gel (5 g) is added to the dried organic solution and the mixture is concentrated in vacuo to obtain a brown powder. The powder is placed on top of silica gel in a flash chromatography column and eluted with a (1:1) ether/hexanes solution to give the title product as a brown oil (7.5 g) which is identified by 1HNMR and 13CNMR spectral analyses.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2_m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"boron tribromide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-[(2-chloro-\\u03b1,\\u03b1,\\u03b1,6-tetrafluoro-p-tolyl)oxy]-2-(p-methoxyphenoxy)-1-nitrobenzene\"}], \"amount\": {\"mass\": {\"value\": 12.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -78.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred at -78\\u00b0 C. for two hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"warmed to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"ADDITION\", \"details\": \"poured\"}, {\"type\": \"CUSTOM\", \"details\": \"the phases are separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"the aqueous phase is extracted with methylene chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"the resultant organic solution is washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"Silica gel (5 g) is added to the dried organic solution\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the mixture is concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"to obtain a brown powder\"}, {\"type\": \"WASH\", \"details\": \"eluted with a (1:1) ether/hexanes solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 7.5, \"units\": \"GRAM\"}}}], \"isolated_color\": \"brown\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e70e6895532d4a47ac160de81e9c793d",
    "procedure_text": "Alliquat 336 (methyltrioctylammonium chloride (0.63 g, 0.0016 mol), dibromomethane (40.7 g, 234.2 mmol), and water (31 mL) were placed in a 500 mL 3-necked flask equipped with an addition funnel, condenser and a stir bar. The addition funnel was charged with a solution of 3-fluorocatechol (20.0 g, 6.1 mmol) in 5M sodium hydroxide (80 mL). The mixture in the flask was heated to reflux and the solution of the catechol was added dropwise with good stirring over 1.5 hours. The resulting dark mixture was heated an additional 2 hours at reflux. After cooling to room temperature, the reaction was diluted with methylene chloride and water. The aqueous layer was extracted with methylene chloride and the combined organic layers were dried and concentrated to give 1-fluoro-2,3-methylenedioxybenzene (14.6 g, 104.2 mmol) as a dark yellow oil: 1H NMR (CDCl3): \u03b4 6.80 (m, 1H), 6.68 (m, 2H), 6.04 (s, 2H).",
    "reference_string": "{\"inputs\": {\"m6_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"catechol\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-fluorocatechol\"}], \"amount\": {\"mass\": {\"value\": 20.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"volume\": {\"value\": 80.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4_m1_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dibromomethane\"}], \"amount\": {\"mass\": {\"value\": 40.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyltrioctylammonium chloride\"}], \"amount\": {\"mass\": {\"value\": 0.63, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 31.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"with good stirring over 1.5 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"equipped with an addition funnel, condenser and a stir bar\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The mixture in the flask was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to reflux\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The resulting dark mixture was heated an additional 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"at reflux\"}, {\"type\": \"EXTRACTION\", \"details\": \"The aqueous layer was extracted with methylene chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the combined organic layers were dried\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.5, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-fluoro-2,3-methylenedioxybenzene\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 104.2, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 14.6, \"units\": \"GRAM\"}}}], \"isolated_color\": \"dark yellow\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2dc38d04f59047c0b83ee12d15b2743d",
    "procedure_text": "A suspension of 5.39 g of H-Lys(Boc)-OtBu hydrochloride (15.9 mmol, 1.0 eq) and 7.1 ml of triethylamine (50.9 mmol, 3.2 eq) in dichloromethane (70 ml) was added to the solution obtained in Example 143d), in such a way that the temperatures did not exceed 10\u00b0 C. After the addition was complete, the mixture was allowed to reach RT and was stirred for a further 2 h. The reaction mixture was then mixed with 200 ml of 0.2 M hydrochloride acid, and the organic phase was separated off and washed with 100 ml of 0.2 M hydrochloric acid and concentrated. 5.5 g of the desired material were obtained as a colorless oil, which crystallized on standing.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloride\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H-Lys(Boc)-OtBu hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 5.39, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 7.1, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 70.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred for a further 2 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"did not exceed 10\\u00b0 C\", \"temperature\": {\"setpoint\": {\"value\": 10.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"ADDITION\", \"details\": \"After the addition\"}, {\"type\": \"CUSTOM\", \"details\": \"to reach RT\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"the organic phase was separated off\"}, {\"type\": \"WASH\", \"details\": \"washed with 100 ml of 0.2 M hydrochloric acid\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired material\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 5.5, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e66cabcabd284aa084b928003f27a520",
    "procedure_text": "N-Bromosuccinimide (0.5 g, 2.8 mmol) was added to a solution of 4-isopropylpyrimidin-2-amine (0.39 g, 2.81 mmol) in chloroform. The resultant yellow solution was stirred at ambient temperature for 1 h and concentrated in vacuo. The residue was purified by column chromatography (3-10% 9:1 methanol:ammonium hydroxide in chloroform) to afford 5-bromo-4-isopropylpyrimidin-2-amine (0.69 g, 3.18 mmol, 113%) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) \u03b4 ppm 8.21 (1H, s), 6.75 (2H, s), 3.10-3.23 (1H, m), 1.14 (6H, d, J=6.80 Hz). MS (LC/MS) R.T.=2.58; [M]+=216.09.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-Bromosuccinimide\"}], \"amount\": {\"mass\": {\"value\": 0.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-isopropylpyrimidin-2-amine\"}], \"amount\": {\"mass\": {\"value\": 0.39, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The resultant yellow solution was stirred at ambient temperature for 1 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by column chromatography (3-10% 9:1 methanol:ammonium hydroxide in chloroform)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium hydroxide\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-bromo-4-isopropylpyrimidin-2-amine\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 3.18, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.69, \"units\": \"GRAM\"}}}], \"isolated_color\": \"pale yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-80f45811703841a69bfaf397ebf8c03b",
    "procedure_text": "By using procedure as described in Example 45 and by reacting (S)-N-{3-[3-fluoro-4-(4-oxo-3,3-dimethylpiperidin-1-yl)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide with sodium cyanide and 3-aminopyridine the compound was obtained in 48% yield.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(S)-N-{3-[3-fluoro-4-(4-oxo-3,3-dimethylpiperidin-1-yl)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium cyanide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-aminopyridine\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"was obtained in 48% yield\"}], \"outcomes\": [{\"products\": [{\"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 48.0}}]}]}]}"
  },
  {
    "reaction_id": "ord-0e706b6a75124728b578aee21d06f168",
    "procedure_text": "1,1\u2032-Bis (diphenylphosphino)ferrocenedichloro palladium(II) (8 mg, 0.09 mmol) was added to a suspension of the product of example 87 (100 mg, 0.19 mmol), 3-hydroxyphenylboronic acid (52 mg, 0.038 mmol) and sodium carbonate (40 mg, 0.038 mmol) in tetrahydrofuran (5 mL) and water (1 mL) and the mixture was heated at 60\u00b0 C. for 12 hours. The suspension was allowed to cool to room temperature and then evaporated to dryness under reduced pressure. The residue was purified by chromatography on silica gel, eluting with dichloromethane:methanol:0.88 ammonia, 99:1:0 to 98:2:0.2, to give the title compound as a gum in 72% yield.",
    "reference_string": "{\"inputs\": {\"m7_m2_m3_m4_m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-hydroxyphenylboronic acid\"}], \"amount\": {\"mass\": {\"value\": 52.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium carbonate\"}], \"amount\": {\"mass\": {\"value\": 40.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,1\\u2032-Bis (diphenylphosphino)ferrocenedichloro palladium(II)\"}], \"amount\": {\"mass\": {\"value\": 8.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"to cool to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated to dryness under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by chromatography on silica gel\"}, {\"type\": \"WASH\", \"details\": \"eluting with dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonia\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"gum\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-44b01532e130439fb79140173460168f",
    "procedure_text": "To a reaction vial was added 5,8-dichloropyrido[2,3-d]pyridazine 78 (165 mg, 825 \u03bcmol) and (R)-(3-methylpiperazin-1-yl)(phenyl)methanone (337 mg, 1.65 mmol). The mixture was heated to 100\u00b0 C. for 2 h. After cooling to room temperature, the resultant glassy product was dissolved in dichloromethane (40 mL) and washed with 1\u00d75 mL NaHCO3 and 1\u00d75 mL of brine. The organic layer was dried over MgSO4, filtered and concentrated. Purification by silica gel column chromatography using a gradient of 70% ethyl acetate in hexanes to 90% EtOAc in hexanes afforded the regioisomeric products. The first eluting product (R)-(4-(5-chloropyrido[2,3-d]pyridazin-8-yl)-3-methylpiperazin-1-yl)(phenyl)methanone 79 (132 mg, 44% yield) was the major product, the second eluting product (R)-(4-(8-chloropyrido[3,2-d]pyridazin-5-yl)-3-methylpiperazin-1-yl)(phenyl)methanone 80 (74 mg, 24% yield) was the minor product. Data for 79: 1H-NMR (400 MHz, CDCl3): \u03b4 9.10 (brs, 1H), 8.47 (dd, J=8.2, 1.6 Hz, 1H), 7.83 (dd, J=8.2, 4.3 Hz, 1H), 5.46 (br m, 1H), 4.97-4.40 (series of m, 2H), 3.99-3.20 (series of m, 4H), 1.40 (br m, 3H). MS 367.1 (calc'd) 368.0 (M+H, found). Data for (R)-(4-(8-chloropyrido[3,2-d]pyridazin-5-yl)-3-methylpiperazin-1-yl)(phenyl)methanone: 1H-NMR (400 MHz, CDCl3): \u03b4 9.27 (dd, J=4.3, 1.6, 1H), 8.39 (J=8.6, 1.6 Hz, 1H), 7.83 (dd, J=8.2, 4.3 Hz, 1H), 7.45 (s, 5H), 4.31 (br s, 1H), 4.11 (br s, 1H), 2.68 (m, 5H), 1.27 (br s, 3H). MS 367.1 (calc'd) 368.0 (M+H, found).",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5,8-dichloropyrido[2,3-d]pyridazine\"}], \"amount\": {\"mass\": {\"value\": 165.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-(3-methylpiperazin-1-yl)(phenyl)methanone\"}], \"amount\": {\"mass\": {\"value\": 337.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"After cooling to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"WASH\", \"details\": \"washed with 1\\u00d75 mL NaHCO3 and 1\\u00d75 mL of brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layer was dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification by silica gel column chromatography\"}, {\"type\": \"CUSTOM\", \"details\": \"afforded the regioisomeric products\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-(4-(5-chloropyrido[2,3-d]pyridazin-8-yl)-3-methylpiperazin-1-yl)(phenyl)methanone\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 132.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 44.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-7d41bb556b24467fb5db54ab3a41d640",
    "procedure_text": "A mixture of 4-(7-bromo-3,4-dihydroisoquinolin-2(1H)-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine (40 mg, 0.1 mmol), piperidine-4-carbonitrile (22 mg, 0.20 mmol, Oakwood, Cat. No. 024547), sodium tert-butoxide (23 mg, 0.24 mmol), 2-(2\u2032-di-tert-butylphosphine)biphenyl palladium(II) acetate (2.8 mg, 0.0060 mmol, Aldrich, Cat. No. 655414) in 1,4-dioxane (1 mL) was degassed with nitrogen and then heated at 120\u00b0 C. overnight. The reaction mixture was cooled to r.t. and concentrated under reduced pressure. The residue was dissolved in MeOH and purified by RP-HPLC (pH=10) to afford the desired compound. LCMS (M+H)+: m/z=433.3.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(2\\u2032-di-tert-butylphosphine)biphenyl palladium(II) acetate\"}], \"reaction_role\": \"CATALYST\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(7-bromo-3,4-dihydroisoquinolin-2(1H)-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine\"}], \"amount\": {\"mass\": {\"value\": 40.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"piperidine-4-carbonitrile\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium tert-butoxide\"}], \"amount\": {\"mass\": {\"value\": 23.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 120.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"655414) in 1,4-dioxane (1 mL) was degassed with nitrogen\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,4-dioxane\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"The reaction mixture was cooled to r.t.\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue was dissolved in MeOH\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"purified by RP-HPLC (pH=10)\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-35e09b6c0aaa448c97897603bb4514c5",
    "procedure_text": "A mixture of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (50 mg, 0.2 mmol), 3-bromobutanenitrile (46 mg, 0.31 mmol, TCI America, Cat. No. B 1452), and cesium carbonate (250 mg, 0.77 mmol) in acetonitrile (1 mL) was stirred at 90\u00b0 C. for 3 hours. After cooling it was quenched with water, extracted with ethyl acetate. The extract was washed with water twice, brine once; dried over Na2SO4. After filtration the filtrate was concentrated to yield 60 mg product. It was directly used in the next step reaction without further purification.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole\"}], \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-bromobutanenitrile\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cesium carbonate\"}], \"amount\": {\"mass\": {\"value\": 250.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"After cooling it\"}, {\"type\": \"CUSTOM\", \"details\": \"was quenched with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The extract was washed with water twice\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"After filtration the filtrate\"}, {\"type\": \"CONCENTRATION\", \"details\": \"was concentrated\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 60.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c20c665e15a74266a85bce98cb2d5f34",
    "procedure_text": "To a solution of the compound of Example 1 (3.0 g, 4.2 mmol) and butyl sulfide (18 mL) in acetonitrile (24 mL) at 0\u00b0 C. was added benzoyl peroxide (2.0 g) in three portions over 3 hours, and the reaction was stirred at 0\u00b0 C. for 1 hour and then at room temperature for 1 hour. Additional benzoyl peroxide (4.0 g) was added in two portions over 2 hours at room temperature. The reaction was diluted with ethyl acetate and washed with 10% Na2CO3 and brine. The organic phase was dried over MgSO4, filtered and evaporated. The concentrate was chromatographed on silica gel eluting with a gradient starting with 50% ethyl acetate in chloroform and ending with ethyl acetate to give the title compound (2.43 g, 68% yield).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzoyl peroxide\"}], \"amount\": {\"mass\": {\"value\": 4.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m5_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound\"}], \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"butyl sulfide\"}], \"amount\": {\"volume\": {\"value\": 18.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzoyl peroxide\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 24.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction was stirred at 0\\u00b0 C. for 1 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WAIT\", \"details\": \"at room temperature for 1 hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"WASH\", \"details\": \"washed with 10% Na2CO3 and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2CO3\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic phase was dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"The concentrate was chromatographed on silica gel eluting with a gradient\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.43, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 68.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-5cb9508c42464895bb9e9610cbdd0ae8",
    "procedure_text": "To 600 mg of N,N-dimethylformamide were added 210 mg of 1-(3-amino-2,4-difluorophenyl)-7-[(3S)-3-aminopyrrolidin-1-yl]-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid and 40 mg of formic acid. The solution was stirred at 120\u00b0 C. for 1 hour. After 8 ml of diisopropyl ether was added and stirred, the solution was allowed to stand. The supernatant was decanted off. Then 2 ml of ethanol was added, and the solution was heated at reflux for 20 minutes and allowed to cool down. The precipitate was collected by filtration and washed with ethanol and then diisopropyl ether to give 180 mg of the title compound.",
    "reference_string": "{\"inputs\": {\"m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"mass\": {\"value\": 600.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(3-amino-2,4-difluorophenyl)-7-[(3S)-3-aminopyrrolidin-1-yl]-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 210.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"formic acid\"}], \"amount\": {\"mass\": {\"value\": 40.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropyl ether\"}], \"amount\": {\"volume\": {\"value\": 8.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 120.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The solution was stirred at 120\\u00b0 C. for 1 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"stirred\"}, {\"type\": \"CUSTOM\", \"details\": \"The supernatant was decanted off\"}, {\"type\": \"ADDITION\", \"details\": \"Then 2 ml of ethanol was added\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"the solution was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"at reflux for 20 minutes\", \"duration\": {\"value\": 20.0, \"units\": \"MINUTE\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"to cool down\"}, {\"type\": \"FILTRATION\", \"details\": \"The precipitate was collected by filtration\"}, {\"type\": \"WASH\", \"details\": \"washed with ethanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropyl ether\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 180.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-efeca2dbc8294417bf15836d54fa7292",
    "procedure_text": "To a solution of ethyl 1-[(3,4-dichlorophenyl)methyl]-1H-1,2,3-triazole-4-carboxylate (Intermediate 10) (0.33 g, 1.09 mmol) in THF was added a 1M solution of DIBAL-H in toluene (2.3 mL, 2.1 eq) and the reaction was stirred at room temperature for 2 hours. The reaction was not completed. Two more equivalents of a 1M solution of DIBAL-H in toluene were added and the reaction was stirred for a further 18 hours. Solid NH4Cl was added followed by water and the aqueous phase was extracted with ether, ethyl acetate, dried over sodium sulphate and evaporated. The title compound was obtained as a white powder after recrystallisation from isopropyl ether (170 mg, 60%). LC/MS: m/z 258 (M+H)+ Rt: 2.45 min.",
    "reference_string": "{\"inputs\": {\"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH4Cl\"}], \"reaction_role\": \"REACTANT\"}]}, \"m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m9_m3_m4_m11\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 1-[(3,4-dichlorophenyl)methyl]-1H-1,2,3-triazole-4-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 0.33, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Intermediate 10\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DIBAL-H\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 2.3, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5_m6_m10\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DIBAL-H\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction was stirred at room temperature for 2 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"the reaction was stirred for a further 18 hours\", \"duration\": {\"value\": 18.0, \"units\": \"HOUR\"}}, {\"type\": \"EXTRACTION\", \"details\": \"the aqueous phase was extracted with ether, ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulphate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulphate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-dab71275069d4627b1a6a16ece283808",
    "procedure_text": "A mixture of (R)-3-(5-acetoxyhexyl)-1,7-dimethylpyrido[2,3-d]pyrimidine-2,4,5(1H,3H,8H)-trione (1.84 g, 5.27 mmol), acetonitrile (20 ml), benzyl bromide (0.95 ml, 7.91 mmol) and potassium carbonate (2.19 g, 15.8 mmol) was stirred at 50\u00b0 C. for 2 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure. The residue was treated with water (50 ml) and extracted with ethyl acetate (50 ml). The organic extract was concentrated under reduced pressure to afford crude (R)-3-(5-acetoxyhexyl)-8-benzyl-1,7-dimethylpyrido[2,3-d]pyrimidine-2,4,5(1H,3H,8H)-trione.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-3-(5-acetoxyhexyl)-1,7-dimethylpyrido[2,3-d]pyrimidine-2,4,5(1H,3H,8H)-trione\"}], \"amount\": {\"mass\": {\"value\": 1.84, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzyl bromide\"}], \"amount\": {\"volume\": {\"value\": 0.95, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 2.19, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 50.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at 50\\u00b0 C. for 2 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"After cooling to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CONCENTRATION\", \"details\": \"the mixture was concentrated under reduced pressure\"}, {\"type\": \"ADDITION\", \"details\": \"The residue was treated with water (50 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate (50 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The organic extract\"}, {\"type\": \"CONCENTRATION\", \"details\": \"was concentrated under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-3-(5-acetoxyhexyl)-8-benzyl-1,7-dimethylpyrido[2,3-d]pyrimidine-2,4,5(1H,3H,8H)-trione\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f68c85ff5c044cf085dd197010cccbbd",
    "procedure_text": "To a solution of 3-cyclohexyl-4-(4-cyclohexyloxy-phenyl)-6-(piperidin-4-yloxy)-pyridazine dihydrochloride (0.079 mmol, 0.04 g) and aqueous formaldehyde (37%, 0.39 mmol, 0.035 mL) in dry DCM (1 mL) was added macroporous resin-bound triacetoxyborohydride (loading 2.36 mmol/gram, 0.47 mmol, 0.20 g). The mixture was shaken for 2 hours. The reaction was placed directly onto a 4 g SiO2 cartridge and the column was eluted with 4-6% (2N NH3 in MeOH) in DCM to give 3-cyclohexyl-4-(4-cyclohexyloxy-phenyl)-6-(1-methyl-piperidin-4-yloxy)-pyridazine. The neutral amine was treated with 2N HCl in diethyl ether (0.5 mL) and DCM (0.5 mL). The volatiles were removed under reduced pressure and the salt was triturated with diethyl ether and filtered to provide the title compound (0.04 g). LCMS: m/z 451 [M+1]. 1H NMR (400 MHz, CD3OD) \u03b4 7.63-7.79 (1H, m), 7.38-7.43 (2H, m), 7.10-7.14 (2H, m), 5.33-5.57 (1H, m), 4.40-4.51 (1H, m), 3.66-3.69 (1H, m), 3.11-3.54 (3H, m), 2.94 (3H, s), 2.37-2.62 (2H, m), 2.20-2.30 (1H, m), 1.20-2.17 (22H, m).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"amine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"amount\": {\"volume\": {\"value\": 0.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"amount\": {\"volume\": {\"value\": 0.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The volatiles were removed under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"the salt was triturated with diethyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.04, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-93491fc306284707b31733b7d3201c83",
    "procedure_text": "Ethyl trans-4-{2-fluoro-1-hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)-pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}cyclohexanecarboxylate (72 mg, 0.130 mmol) was dissolved in HCl (10 M in water, 2 ml, 20.0 mmol) and heated to reflux for 20 min. The reaction was diluted with DMSO and purified on reverse phase HPLC (acetonitrile/water with a 0.1% TFA modifier) to afford racemic trans-4-{2-fluoro-1-hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}cyclohexanecarboxylic acid. MS ESI calc'd. for C24H24F4N4O3S [M+H]+ 525. found 525.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ethyl trans-4-{2-fluoro-1-hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)-pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}cyclohexanecarboxylate\"}], \"amount\": {\"mass\": {\"value\": 72.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMSO\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to reflux for 20 min\", \"duration\": {\"value\": 20.0, \"units\": \"MINUTE\"}}, {\"type\": \"CUSTOM\", \"details\": \"purified on reverse phase HPLC (acetonitrile/water with a 0.1% TFA modifier)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TFA\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"racemic trans-4-{2-fluoro-1-hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}cyclohexanecarboxylic acid\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-7528fce5a4714f8ca751035ef772bb26",
    "procedure_text": "A warm solution of 1 g of 3-[(acetyloxy)methyl]-7-[[2-[4-(chloromethyl)phenyl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid and 2 g of sodium azide in 80 ml of methanol was refluxed for 4 hours after which the solvent was removed under high vacuum at room temperature. The residue was triturated with 80 ml of benzeneacetone (2:1) to give 3-[(Acetyloxy)methyl]-7-[[2-[4-(azidomethyl)phenyl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]-oct-2-ene-2-carboxylic acid. M.P. 135\u00b0-136\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-[(acetyloxy)methyl]-7-[[2-[4-(chloromethyl)phenyl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium azide\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 80.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"was removed under high vacuum at room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The residue was triturated with 80 ml of benzeneacetone (2:1)\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-[(Acetyloxy)methyl]-7-[[2-[4-(azidomethyl)phenyl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]-oct-2-ene-2-carboxylic acid\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-57acb4105cee464aa6ed4e5a8c7b16d7",
    "procedure_text": "The reaction is carried out in a nitrogen atmosphere. 15,4 g p-toluenesulphonic acid is dissolved into 200 ml acetonitrile. To the solution 50,0 g 16\u03b1-hydroxyprednisolone and 17.6 ml butanal are added. The temperature rises to 25\u00b0 C. After 30 min most of the material is dissolved. Shortly thereafter the product starts to crystallize. After 3 hours the reaction is stopped by the addition of 75 ml aqueous saturated sodium hydrogen carbonate solution, whereupon the product crystallizes. The dried product is dissolved in methylene chloride and methanol and is crystallized by the addition of ligroine (b.p. 40-65) giving crude budesonide.",
    "reference_string": "{\"inputs\": {\"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"p-toluenesulphonic acid\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"16\\u03b1-hydroxyprednisolone\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"butanal\"}], \"amount\": {\"volume\": {\"value\": 17.6, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"rises to 25\\u00b0 C\", \"temperature\": {\"setpoint\": {\"value\": 25.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"DISSOLUTION\", \"details\": \"After 30 min most of the material is dissolved\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}}, {\"type\": \"CUSTOM\", \"details\": \"to crystallize\"}, {\"type\": \"ADDITION\", \"details\": \"After 3 hours the reaction is stopped by the addition of 75 ml aqueous saturated sodium hydrogen carbonate solution, whereupon the product\", \"duration\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydrogen carbonate\"}], \"amount\": {\"volume\": {\"value\": 75.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"crystallizes\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The dried product is dissolved in methylene chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"methanol and is crystallized by the addition of ligroine (b.p. 40-65)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"budesonide\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-81184351643c4f218a6de3830b53bef7",
    "procedure_text": "15.2 g of methoxyacetyl chloride are added dropwise at room temperature to 32 g of N-(1'methoxycarbonylethyl)-2,6-dimethyl-3-nitroaniline. After the weakly exothermic reaction has subsided, the reaction solution is stirred for 20 hours at room temperature. The solvent is then removed and the dark red oily residue is distilled in a high vacuum. Compound 28 distills at a temperature of 170\u00b0-174\u00b0 C. and a pressure of 0.07 mbar as a pale yellow oil.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methoxyacetyl chloride\"}], \"amount\": {\"mass\": {\"value\": 15.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(1'methoxycarbonylethyl)-2,6-dimethyl-3-nitroaniline\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction solution is stirred for 20 hours at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"After the weakly exothermic reaction\"}, {\"type\": \"CUSTOM\", \"details\": \"The solvent is then removed\"}, {\"type\": \"DISTILLATION\", \"details\": \"the dark red oily residue is distilled in a high vacuum\"}, {\"type\": \"DISTILLATION\", \"details\": \"Compound 28 distills at a temperature of 170\\u00b0-174\\u00b0 C.\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Compound 28\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 20.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-1420c02aa40d4bfdb249761e407ebb5c",
    "procedure_text": "To a solution of tert-butyl 3-{4-(2-aminopyrimidin-5-yl)-2-[(3S)-3-methylmorpholin-4-yl]-5,6-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl}azetidine-1-carboxylate (760 mg, 1.62 mmol) in methanol (8 mL), was added 4 N HCl in 1,4-dioxane (8 mL, 32 mmol). The reaction was stirred at room temperature for 1 h. The mixture was diluted with toluene and the solvent was removed under reduced pressure to give a foamy residue. The residue was triturated in acetone to get a free flowing tan solid which was collected by filtration to give the title compound in quantitative yield. The material was taken directly in the next step without purification. 1H NMR (400 MHz, CD3OD) \u03b4 8.78 (br s, 2 H), 5.32 (br s, 1 H), 4.62 (br s, 3 H), 4.34 (br s, 2 H), 4.19-3.99 (m, 4 H), 3.85-3.72 (m, 2 H), 3.64-3.46 (m, 2 H), 3.23 (br s, 2 H), 1.41 (d, J=5.5 Hz, 3 H).",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl 3-{4-(2-aminopyrimidin-5-yl)-2-[(3S)-3-methylmorpholin-4-yl]-5,6-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl}azetidine-1-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 760.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,4-dioxane\"}], \"amount\": {\"volume\": {\"value\": 8.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 8.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction was stirred at room temperature for 1 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the solvent was removed under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a foamy residue\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was triturated in acetone\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"to get\"}, {\"type\": \"FILTRATION\", \"details\": \"was collected by filtration\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-6f1f6e73e2fc4e46b090e0eba055da6d",
    "procedure_text": "In 25 mL of dimethylformamide was dissolved 2.5 g of 3,6-dichloro-2-pyrazinecarbonitrile. After adding 3.2 g of 4-(benzyloxy)phenol and 3.0 g of potassium carbonate, the mixture was stirred at room temperature for one hour. A mixture of 25 ml of ethyl acetate and 100 mL of water was added to the reaction mixture, and the organic layer was separated. The organic layer thus obtained was washed successively with water and saturated aqueous solution of sodium chloride and dried on anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. Diisopropyl ether was added to the residue, the insoluble matter was filtered off, and the filtrate was concentrated. The residue thus obtained was washed with n-hexane to obtain 3.84 g of 3-[(4-(benzyloxy)phenoxy)]-6-chloro-2-pyrazinecarbonitrile as a light brown-colored solid product.",
    "reference_string": "{\"inputs\": {\"m5_m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,6-dichloro-2-pyrazinecarbonitrile\"}], \"amount\": {\"mass\": {\"value\": 2.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(benzyloxy)phenol\"}], \"amount\": {\"mass\": {\"value\": 3.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m4_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at room temperature for one hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added to the reaction mixture\"}, {\"type\": \"CUSTOM\", \"details\": \"the organic layer was separated\"}, {\"type\": \"CUSTOM\", \"details\": \"The organic layer thus obtained\"}, {\"type\": \"WASH\", \"details\": \"was washed successively with water and saturated aqueous solution of sodium chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried on anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was removed under reduced pressure\"}, {\"type\": \"ADDITION\", \"details\": \"Diisopropyl ether was added to the residue\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Diisopropyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"the insoluble matter was filtered off\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate was concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue thus obtained\"}, {\"type\": \"WASH\", \"details\": \"was washed with n-hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-[(4-(benzyloxy)phenoxy)]-6-chloro-2-pyrazinecarbonitrile\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 3.84, \"units\": \"GRAM\"}}}], \"isolated_color\": \"light brown-colored\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fdf1c3ca47ac47df888987eea8bda755",
    "procedure_text": "2-(1-((2-chloro-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-ol from Example 8 (88 mg) was reacted with 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole via General Procedure A to produce 29.6 mg of 110 following reverse phase hplc purification. MS (Q1) 488.3 (M)+",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(1-((2-chloro-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-ol\"}], \"amount\": {\"mass\": {\"value\": 88.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"to produce\"}, {\"type\": \"CUSTOM\", \"details\": \"29.6 mg of 110 following reverse phase hplc purification\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"110\"}], \"amount\": {\"mass\": {\"value\": 29.6, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-d56810f074cf4a13b98050696d49342e",
    "procedure_text": "To a stirred solution of 2-(3,4-dihydro-2H-1-benzopyran-4-yl)ethanal (875 mg, 5 mmol) and 4-(2-benzofurancarboxamido)piperidine hydrochloride (1.4 g, 5 mmol)under a nitrogen atmosphere, borane/pyridine complex (0.5 ml, excess) was added. The reaction was stirred overnight (ca 15 h) and evaporated to an oily gum which was neutralized by careful addition of 10% hydrochloric acid. The acidic solution was extracted with diethyl ether. The diethyl ether extracts were discarded. The acidic aqueous layer was basified by dropwise addition of 50% sodium hydroxide. The ethyl acetate layer was washed with distilled water, dried (Na2SO4), filtered and evaporated to afford an oily gum (520 mg). The resulting gum was purified by chromatography on silica (eluant: chloroform/ethanol/ammonium hydroxide; 85/14/1) to afford an oil (260 mg) which was crystallized from diethyl ether to afford the title compound (150 mg, 7%), mp=146\u00b0-8\u00b0. Anal: C25H28N2O3 0.5 H2O, Calc. C, 72.62; H, 7.07; N, 6.77; Found C,72.40; H, 6.94; N, 6.83.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(3,4-dihydro-2H-1-benzopyran-4-yl)ethanal\"}], \"amount\": {\"mass\": {\"value\": 875.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(2-benzofurancarboxamido)piperidine hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 1.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction was stirred overnight (ca 15 h)\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"evaporated to an oily gum which\"}, {\"type\": \"ADDITION\", \"details\": \"was neutralized by careful addition of 10% hydrochloric acid\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The acidic solution was extracted with diethyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"The acidic aqueous layer was basified by dropwise addition of 50% sodium hydroxide\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The ethyl acetate layer was washed with distilled water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"gum\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 520.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 25.7}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"gum\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4e676fcbd6684caaaadff071dec477f8",
    "procedure_text": "The title compound was generated from commercially available nicotinic acid ethyl ester and (2-fluoro-phenyl)-acetonitrile according to the general procedure D described above. The intermediates 2-(2-fluoro-phenyl)-1-pyridin-3-yl-ethanone and 2-(2-fluoro-phenyl)-1-pyridin-3-yl-ethylamine were isolated and characterized.",
    "reference_string": "{\"inputs\": {\"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"nicotinic acid ethyl ester\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2-fluoro-phenyl)-acetonitrile\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(2-fluoro-phenyl)-1-pyridin-3-yl-ethanone\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(2-fluoro-phenyl)-1-pyridin-3-yl-ethylamine\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e7f50f8584194cb7ac89d88c68684af6",
    "procedure_text": "From 2-fluorobenzyl alcohol (5.7 g; 45 mmol) and 5-amino-4-oxopentanoic acid hydrochloride (1.0 g; 6.0 mmol). The reaction was complete after 27 h at 100\u00b0 C. The yield was 0.64 g (44%). Mp 91\u201394\u00b0 C. (dec.)",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-fluorobenzyl alcohol\"}], \"amount\": {\"mass\": {\"value\": 5.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-amino-4-oxopentanoic acid hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"reaction_time\": {\"value\": 27.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-1f731b292c2146df91d1e9222ac71496",
    "procedure_text": "To a solution of 2-(tert-butoxycarbonylamino)-2-(3-fluorophenyl)acetic acid (I52) (1.10 g, 4.09 mmol) in THF (50 ml), were added N,N\u2032-methanediylidenedicyclohexanamine (1.01 g, 4.90 mmol), 1H-benzo[d][1,2,3]triazol-1-ol (0.66 g, 4.90 mmol), and (R)-quinuclidin-3-ol (0.62 g, 4.90 mmol). The reaction was stirred at RT for hours, and the solvent was evaporated. The residue was taken up with DCM, the insoluble solid was filtered off, and the organic solution was washed twice with aq. Na2CO3 and then brine, dried over Na2SO4 and evaporated to obtain (R)-quinuclidin-3-yl 2-(tert-butoxycarbonylamino)-2-(3-fluorophenyl)acetate (1.55 g; quantitative yield).",
    "reference_string": "{\"inputs\": {\"m1_m5_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(tert-butoxycarbonylamino)-2-(3-fluorophenyl)acetic acid\"}], \"amount\": {\"mass\": {\"value\": 1.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N\\u2032-methanediylidenedicyclohexanamine\"}], \"amount\": {\"mass\": {\"value\": 1.01, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1H-benzo[d][1,2,3]triazol-1-ol\"}], \"amount\": {\"mass\": {\"value\": 0.66, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-quinuclidin-3-ol\"}], \"amount\": {\"mass\": {\"value\": 0.62, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction was stirred at RT for hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the solvent was evaporated\"}, {\"type\": \"FILTRATION\", \"details\": \"the insoluble solid was filtered off\"}, {\"type\": \"WASH\", \"details\": \"the organic solution was washed twice with aq. Na2CO3\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2CO3\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"brine, dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-quinuclidin-3-yl 2-(tert-butoxycarbonylamino)-2-(3-fluorophenyl)acetate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.55, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-8e6c5982b70541e08379b36f1e2d6e9d",
    "procedure_text": "A solution of the compound of formula VI, 3,4-dihydro-3,3-dimethylfuro[3,4-b]quinolin-9(1H)-one (6.5 g, described in Example 8), in phosphorus oxychloride (26 ml) is stirred vigorously at room temperature for one hour. The solution is added to 340 ml of crushed ice. The mixture is stirred and the precipitate is removed by filtration. The filtrate is diluted with ice-water (600 ml) and made alkaline with 30% sodium hydroxide solution (75 ml). The precipitate is collected and crystallized from petroleum ether to give the title compound, mp 108\u00b0-110\u00b0 C. The hydrochloride salt of the title compound melts at 189\u00b0-194\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"formula VI\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,4-dihydro-3,3-dimethylfuro[3,4-b]quinolin-9(1H)-one\"}], \"amount\": {\"mass\": {\"value\": 6.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"phosphorus oxychloride\"}], \"amount\": {\"volume\": {\"value\": 26.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice\"}], \"amount\": {\"volume\": {\"value\": 340.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture is stirred\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the precipitate is removed by filtration\"}, {\"type\": \"ADDITION\", \"details\": \"The filtrate is diluted with ice-water (600 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"amount\": {\"volume\": {\"value\": 600.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The precipitate is collected\"}, {\"type\": \"CUSTOM\", \"details\": \"crystallized from petroleum ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"petroleum ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2820ec199cc6448c9ba76796df1d9bb3",
    "procedure_text": "The title compound was synthesized from 1-methyl-7-hydroxy-\u03b2-carboline (0.5 g, 1.587 mmol) in presence of 1-bromomethylcyclohexane (1.240 g, 3.173 mmol) as described here above.",
    "reference_string": "{\"inputs\": {\"m0_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-methyl-7-hydroxy-\\u03b2-carboline\"}], \"amount\": {\"mass\": {\"value\": 0.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-bromomethylcyclohexane\"}], \"amount\": {\"mass\": {\"value\": 1.24, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-444ef3a4d4a34159ba514961f4fdf438",
    "procedure_text": "3,4-Pyridinedicarboxylic acid (1 g; 6.0 mmol) is slurried in DMF (50 mL) at ambient temperature. To this reaction mixture is added sequentially 1-hydroxybenzotriazole hydrate (2.43 g; 18.0 mmol), 4-phenylbutylamine (2.08 mL; 13.2 mmol), triethylamine (1.67 mL; 12.0 mmol), and N-(3-dimethylaminopropyl)-N\u2032-ethylcarbodiimide hydrochloride (2.87 g; 15.0 mmol). The reaction mixture is stirred for 18 hours at ambient temperature. The batch is poured onto ethyl acetate (300 mL), then extracted sequentially with water (100 mL), 1N HCl (100 mL), saturated aqueous sodium bicarbonate (50 mL), and brine (50 mL). The organic phase is dried over MgSO4, filtered, and concentrated in vacuo affording the desired product (2.65 g) as a semi-solid. ESMS: MH+ 430.0.",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-hydroxybenzotriazole hydrate\"}], \"amount\": {\"mass\": {\"value\": 2.43, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-phenylbutylamine\"}], \"amount\": {\"volume\": {\"value\": 2.08, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 1.67, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(3-dimethylaminopropyl)-N\\u2032-ethylcarbodiimide hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 2.87, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,4-Pyridinedicarboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture is stirred for 18 hours at ambient temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"The batch is poured onto ethyl acetate (300 mL)\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted sequentially with water (100 mL), 1N HCl (100 mL), saturated aqueous sodium bicarbonate (50 mL), and brine (50 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic phase is dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 18.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.65, \"units\": \"GRAM\"}}}], \"texture\": {\"type\": \"SEMI_SOLID\", \"details\": \"semi-solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-71ac59d3527e486c810f7ddf29d012d0",
    "procedure_text": "1 3-Benzyloxy-2-methylpyrid-4-one (4 g) is dissolved in dry acetone (100 ml). Acetylbromide (3 g) and triethylamine (2.7 g) are added and the resulting mixture is mechanically stirred overnight. The mixture is then filtered and the filtrate is rotary evaporated to dryness. The residue is dissolved in methylene chloride and washed with dilute hydrochloric acid (pH 3.0), then twice with water, and is dried over Na2SO4 and rotary evaporated to yield a solid residue. Recrystallisation of this residue from an ethylacetate/hexane mixture gives 1-acetyl-3-benzyloxy-2-methylpyrid-4-one as an oil (3.1 g).",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-Benzyloxy-2-methylpyrid-4-one\"}], \"amount\": {\"mass\": {\"value\": 4.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Acetylbromide\"}], \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"mass\": {\"value\": 2.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The mixture is then filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"the filtrate is rotary evaporated to dryness\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue is dissolved in methylene chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with dilute hydrochloric acid (pH 3.0)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"twice with water, and is dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"rotary evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"to yield a solid residue\"}, {\"type\": \"CUSTOM\", \"details\": \"Recrystallisation of this residue from an ethylacetate/hexane mixture\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethylacetate hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-acetyl-3-benzyloxy-2-methylpyrid-4-one\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 3.1, \"units\": \"GRAM\"}}}], \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e0fa568a1c8741549783490a99ffcecd",
    "procedure_text": "In step 16-3, 2-fluoropyridin-4-ylboronic acid (97%) (9.6 g, 66 mmol), Pd(dppf)Cl2 (1.3 g, 1.65 mmol) and 2N Na2CO3 (50 mL, 99 mmol) were added to a suspension of (R)-3-(6-bromopyridin-2-yl)-6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine (16-2) (14.5 g, 33 mmol) in 1,4-dioane (250 mL). The mixture was degassed for 15 minute using N2 and then heated at 110\u00b0 C. for 3 hours. The mixture was filtered through a celite pad and rinsed with ethyl acetate (EtOAc). The filtrate was washed with brine, dried over Na2SO4, and concentrated to give (R)-3-(2\u2032-fluoro-2,4\u2032-bipyridin-6-yl)-6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine (16-3) as a dark oil, which was used in the next step without further purification. LC/MS: 455.2 (M+H+).",
    "reference_string": "{\"inputs\": {\"m1_m5_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-fluoropyridin-4-ylboronic acid\"}], \"amount\": {\"mass\": {\"value\": 9.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2CO3\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-3-(6-bromopyridin-2-yl)-6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine\"}], \"amount\": {\"mass\": {\"value\": 14.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,4-dioane\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd(dppf)Cl2\"}], \"amount\": {\"mass\": {\"value\": 1.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 110.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The mixture was degassed for 15 minute\", \"duration\": {\"value\": 15.0, \"units\": \"MINUTE\"}}, {\"type\": \"FILTRATION\", \"details\": \"The mixture was filtered through a celite pad\"}, {\"type\": \"WASH\", \"details\": \"rinsed with ethyl acetate (EtOAc)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The filtrate was washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-3-(2\\u2032-fluoro-2,4\\u2032-bipyridin-6-yl)-6-(2-(3-fluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine\"}], \"isolated_color\": \"dark\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c6a3263cd24a4d6c83e12346200e9bed",
    "procedure_text": "A solution of 1-[3-(cyclopentyloxy)-4-methoxyphenyl]ethanone oxime (15.3 g) in methanol/ammonia (350 ml) was hydrogenated for 3 hours with Raney nickel (3 g) as a catalyst. After uptake of H2, the catalyst was filtered off, washed with methanol and the filtrate was evaporated. Toluene was added and azeotroped on the rotary evaporator, yielding 14.45 g (100%) of (\u00b1)-3-(cyclopentyloxy)-4-methoxy-\u03b1-methylbenzene-methanamine (interm. 5).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-[3-(cyclopentyloxy)-4-methoxyphenyl]ethanone oxime\"}], \"amount\": {\"mass\": {\"value\": 15.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol ammonia\"}], \"amount\": {\"volume\": {\"value\": 350.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Raney nickel\"}], \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"After uptake of H2, the catalyst was filtered off\"}, {\"type\": \"WASH\", \"details\": \"washed with methanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the filtrate was evaporated\"}, {\"type\": \"ADDITION\", \"details\": \"Toluene was added\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Toluene\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"azeotroped on the rotary evaporator\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(\\u00b1)-3-(cyclopentyloxy)-4-methoxy-\\u03b1-methylbenzene-methanamine\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 14.45, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 100.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-392855616cfa4a6780a51f366183d291",
    "procedure_text": "A mixture of 2,4-dihydroxy-3-methyl-benzaldehyde (3.31 g, 21.8 mmol), benzylbromide (4.09 g, 23.9 mmol), NaHCO3 (5.49 g, 65.4 mmol), 1,4-dioxane (30 mL) and water (12 mL) was stirred at 60\u00b0 C. for overnight. Then the reaction mixture was cooled to RT, water (100 mL) was added, extracted with EtOAc (2\u00d7200 mL). The extract was dried over Na2SO4, evaporated. The residue was purified on SiO2 (25 g) column, hexane-EtOAc (0 to 5%). Yield 1.57 g (6.48 mmol, 29%) as off-white solid.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,4-dihydroxy-3-methyl-benzaldehyde\"}], \"amount\": {\"mass\": {\"value\": 3.31, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzylbromide\"}], \"amount\": {\"mass\": {\"value\": 4.09, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"amount\": {\"mass\": {\"value\": 5.49, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,4-dioxane\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 12.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at 60\\u00b0 C. for overnight\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"Then the reaction mixture was cooled to RT\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with EtOAc (2\\u00d7200 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The extract was dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified on SiO2 (25 g) column, hexane-EtOAc (0 to 5%)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-1532af5266514ae0be2b76d755b10545",
    "procedure_text": "Tert-butyl 4-(2-morpholino-2-oxoethoxy)piperidine-1-carboxylate (75) (8.84 g, 26.92 mmol) was dissolved in dry THF (50 mL), to this was added borane-methyl sulfide complex (20.19 mL, 40.38 mmol) and the reaction was stirred at 40\u00b0 C. for 3 hours then at ambient temperature overnight. The gummy mixture was evaporated and was quenched with 2.0 N sodium carbonate (50 mL), extracted with EtOAc (3\u00d775 mL), the organic layer was dried over MgSO4, filtered and evaporated to afford The desired material as a colourless liquid (6.50 g, 77% yield); 1H NMR (400.132 MHz, CDCl3) \u03b4 1.45 (9H, s), 1.54-1.45 (2H, m), 1.84-1.79 (2H, m), 2.90-2.84 (2H, m), 3.16-3.03 (6H, m), 3.79-3.67 (5H, m), 3.97 (2H, t), 4.15-4.10 (2H, m).",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Tert-butyl 4-(2-morpholino-2-oxoethoxy)piperidine-1-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 8.84, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 40.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction was stirred at 40\\u00b0 C. for 3 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"to this was added borane-methyl sulfide complex (20.19 mL, 40.38 mmol)\"}, {\"type\": \"CUSTOM\", \"details\": \"at ambient temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The gummy mixture was evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"was quenched with 2.0 N sodium carbonate (50 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium carbonate\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with EtOAc (3\\u00d775 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 75.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"the organic layer was dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired material\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 6.5, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 77.0}}], \"isolated_color\": \"colourless\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"liquid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-043c0f46d0a242ee9fa78391287e62b8",
    "procedure_text": "To a stirred solution of 4,7-dichloroquinoline-2-carbonitrile (6 g, 26.9 mmol), (2-fluoro-4-methoxyphenyl)boronic acid (5.03 g, 29.6 mmol), 2M sodium carbonate (29.6 ml, 59.2 mmol) in 10:1 toluene (48.9 ml) ethanol (4.89 ml) was added tetrakis(triphenylphosphine)palladium(0) (0.777 g, 0.672 mmol). The mixture was stirred at 75\u00b0 C. under N2 for 18 hours. The reaction was allowed to cool to ambient temperature. The cooled reaction mixture was diluted with EtOAc and then washed with H2O, brine, dried (MgSO4) and concentrated. The residue was mostly dissolved in warm EtOAc (100 ml), added 100 ml of Et2O, allowed to stand at ambient temperature for 1 hour. The solid was collected and washed with cold Et2O (50 ml) to give 7-chloro-4-(2-fluoro-4-methoxyphenyl)quinoline-2-carbonitrile (4.4 g, 14.07 mmol, 52.3% yield) as a yellow solid.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4,7-dichloroquinoline-2-carbonitrile\"}], \"amount\": {\"mass\": {\"value\": 6.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2-fluoro-4-methoxyphenyl)boronic acid\"}], \"amount\": {\"mass\": {\"value\": 5.03, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium carbonate\"}], \"amount\": {\"volume\": {\"value\": 29.6, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 48.9, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrakis(triphenylphosphine)palladium(0)\"}], \"amount\": {\"mass\": {\"value\": 0.777, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 75.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at 75\\u00b0 C. under N2 for 18 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"to cool to ambient temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The cooled reaction mixture\"}, {\"type\": \"WASH\", \"details\": \"washed with H2O, brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue was mostly dissolved in warm EtOAc (100 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"added 100 ml of Et2O\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Et2O\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WAIT\", \"details\": \"to stand at ambient temperature for 1 hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The solid was collected\"}, {\"type\": \"WASH\", \"details\": \"washed with cold Et2O (50 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Et2O\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 18.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-chloro-4-(2-fluoro-4-methoxyphenyl)quinoline-2-carbonitrile\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 14.07, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 4.4, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 52.3}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 52.3}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-114996d09f9b49b2af9135ab0fe57d8c",
    "procedure_text": "5,6-Difluoro-N-(1-methylethyl)1H-benzimidazol-2-amine (0.24 g, 1.1 mmol), N,O-bis(trimethylsilyl) acetamide (Aldrich, 0.30 mL, 1.2 mmol), and acetonitrile (Aldrich Sure Seal, 40 mL) were combined and refluxed under nitrogen for 15 min. The solution was cooled to room temperature and trimethylsilyl triflate (Aldrich, 0.13 mL, 0.7 mmol) was added. After 10 min, 1,2,3-tri-O-acetyl-5-deoxy-D-ribofuranose (0.38 g, 1.5 mmol) dissolved in acetonitrile (Aldrich Sure Seal, 15 mL) was added. The solution was stirred under nitrogen at rt for 4.5 h and then heated in an 80\u00b0 C. oil bath for 2 h. The solution was then poured into 5% aqueous sodium bicarbonate (50 mL) and extracted with ethyl acetate (3\u00d7100 mL). The organic layers were dried with magnesium sulfate (anhyd), filtered, and evaporated. The crude residue was purified on a silica gel column (2.5\u00d720 cm, 230-400 mesh) with 95:5 dichloromethane-methanol to give the title compound (0.32 g, 0.8 mmol, 71%); 1H NMR (DMSO-d6) \u03b47.40-7.46 (m 1H, Ar\u2014H), 7.21-7.28 (m, 1H, Ar\u2014H), 6.74 (d, 1H, NH, J=7.5 Hz), 6.05 (d, 1H, H-1\u2032, J=6.6 Hz), 5.55-5.59 (m, 1H, CH), 5.21-5.25 (m, 1H, CH), 4.00-4.24 (m, 2H, CH), 2.14 (s, 3H, OAc), 2.01 (s, 3H, OAc), 1.49 (d, 3H, 5\u2032-CH3, J=6.3 Hz), 1.20-1.24 (m, 6H, CH3).",
    "reference_string": "{\"inputs\": {\"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5,6-Difluoro-N-(1-methylethyl)1H-benzimidazol-2-amine\"}], \"amount\": {\"mass\": {\"value\": 0.24, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,O-bis(trimethylsilyl) acetamide\"}], \"amount\": {\"volume\": {\"value\": 0.3, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m4_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,2,3-tri-O-acetyl-5-deoxy-D-ribofuranose\"}], \"amount\": {\"mass\": {\"value\": 0.38, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trimethylsilyl triflate\"}], \"amount\": {\"volume\": {\"value\": 0.13, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The solution was stirred under nitrogen at rt for 4.5 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"refluxed under nitrogen for 15 min\", \"duration\": {\"value\": 15.0, \"units\": \"MINUTE\"}}, {\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"TEMPERATURE\", \"details\": \"heated in an 80\\u00b0 C. oil bath for 2 h\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 80.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate (3\\u00d7100 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layers were dried with magnesium sulfate (anhyd)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude residue was purified on a silica gel column (2.5\\u00d720 cm, 230-400 mesh) with 95:5 dichloromethane-methanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude residue\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 10.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 0.8, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.32, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 71.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-dff22bb4b9684790b62dc3b7881c24d9",
    "procedure_text": "A suspension of 2-chloro-7-(1-methyl-1H-pyrazol-4-yl)pyrido[2,3-d]pyrimidine (Preparation 55, 7.5 mg, 0.03 mmol), 4-(1,2-dimethyl-1H-imidazol-5-yl)-2-methoxyaniline (Preparation 74, 10 mg, 0.05 mmol), R-(+)BINAP (2 mg, 3 umol), Pd(OAc)2 (0.69 mg, 3 umol), K2CO3 (42 mg, 0.31 mmol) in DMF (3 mL) was stirred at 160\u00b0 C. under microwave irradiation for 2 hours. The reaction mixture was filtered, diluted with NaCl solution and extracted with EtOAc. The organic layer was purified by SCX-2 column eluting with 2M NH3 in MeOH and concentrated in vacuo. The residue was purified by Biotage silica gel column chromatography eluting with 0-10% MeOH in EtOAc followed by preparative HPLC to afford the title compound (4 mg, 31%).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m6_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloro-7-(1-methyl-1H-pyrazol-4-yl)pyrido[2,3-d]pyrimidine\"}], \"amount\": {\"mass\": {\"value\": 7.5, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(1,2-dimethyl-1H-imidazol-5-yl)-2-methoxyaniline\"}], \"amount\": {\"mass\": {\"value\": 10.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"R-(+)BINAP\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"K2CO3\"}], \"amount\": {\"mass\": {\"value\": 42.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd(OAc)2\"}], \"amount\": {\"mass\": {\"value\": 0.69, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 160.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at 160\\u00b0 C. under microwave irradiation for 2 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The reaction mixture was filtered\"}, {\"type\": \"ADDITION\", \"details\": \"diluted with NaCl solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaCl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The organic layer was purified by SCX-2 column\"}, {\"type\": \"WASH\", \"details\": \"eluting with 2M NH3 in MeOH\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH3\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by Biotage silica gel column chromatography\"}, {\"type\": \"WASH\", \"details\": \"eluting with 0-10% MeOH in EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 4.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 31.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 31.3}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a099b9b5adda408796e9cb3c2a911cdb",
    "procedure_text": "A mixture of 1-chloro-5-nitroisoquinoline (450 mg, 0.0022 mol), stannous chloride dihydrate (2.4 g, 0.011 mol), and EtOAc (50 mL) was stirred under reflux under an atmosphere of nitrogen for 3 h. After cooling, the mixture was poured into ice-water and basified to pH 10.0 with aq. Na2CO3. The organic phase was separated and the aqueous phase was extracted with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4) and concentrated under vacuum. The residue was purified by column chromatography on silica gel to give the product as a light yellow solid. LC-MS: 3.17 min, 179.2 & 181.2 (M+1).",
    "reference_string": "{\"inputs\": {\"m1_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-chloro-5-nitroisoquinoline\"}], \"amount\": {\"mass\": {\"value\": 450.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"stannous chloride dihydrate\"}], \"amount\": {\"mass\": {\"value\": 2.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2CO3\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"under reflux under an atmosphere of nitrogen for 3 h\", \"duration\": {\"value\": 3.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"After cooling\"}, {\"type\": \"CUSTOM\", \"details\": \"The organic phase was separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"the aqueous phase was extracted with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined organic layers were washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under vacuum\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by column chromatography on silica gel\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"isolated_color\": \"light yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-45bfc47eb8e6418fa6e915e5d58166d9",
    "procedure_text": "A mixture of 4-(4-acetylpiperazin-1-yl)benzaldehyde (1.34 g, 5.77 mmol) and 2-amino-4,6-dimethoxybenzamide (1.03 g, 5.24 mmol) in DMA (30 mL) was treated with p-TsOH (0.100 g, 0.524 mmol) and NaHSO3 (0.578 g, 5.55 mmol). The mixture was heated at 155\u00b0 C. for 6 hours, cooled to room temperature, diluted with water (400 mL), and filtered to give brown solids. The filtrate was extracted with EtOAc (3\u00d7100 mL), concentrated, and combined with the brown solids from the filter cake. The combined solids were purified by silica gel chromatography, eluting with 92:7:1 CHCl3/MeOH/concentrated NH4OH to afford 2-(4-(4-acetylpiperazin-1-yl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one as a yellow solid (1.9 g, 90%).",
    "reference_string": "{\"inputs\": {\"m1_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(4-acetylpiperazin-1-yl)benzaldehyde\"}], \"amount\": {\"mass\": {\"value\": 1.34, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-amino-4,6-dimethoxybenzamide\"}], \"amount\": {\"mass\": {\"value\": 1.03, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMA\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 400.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"p-TsOH\"}], \"amount\": {\"mass\": {\"value\": 0.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHSO3\"}], \"amount\": {\"mass\": {\"value\": 0.578, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 155.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooled to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"to give brown solids\"}, {\"type\": \"EXTRACTION\", \"details\": \"The filtrate was extracted with EtOAc (3\\u00d7100 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The combined solids were purified by silica gel chromatography\"}, {\"type\": \"WASH\", \"details\": \"eluting with 92:7:1 CHCl3/MeOH/concentrated NH4OH\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CHCl3 MeOH\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(4-(4-acetylpiperazin-1-yl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.9, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 90.0}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4753dd608021437cbef4bd0acca1c201",
    "procedure_text": "A solution of compound 78A from the preceding step (8.6 g, 32 mmol) in 30 mL of dichloromethane was added dropwise to 30 mL of methanesulfonic acid stirred under N2 at icebath temperature. The mixture was allowed to warn gradually to room temperature. After an hour 200 mL of icewater was cautiously added (vigorous reaction!), then the mixture was partitioned between a total of 300 mL of water and 350\u2013400 mL of dichloro-methane. The organic layer was drawn off and washed with water, then 0.5M aq NaHCO3, and dried over MgSO4. The solvent was removed in vacuo, and the residue dissolved in a minimum of CHCl3/EtOAc (24:1) and passed slowly through a column of silica gel, eluting with several column volumes of the same solvent. The effluent was stripped of solvent in vacuo to leave the title compound as a clear amber syrup, contaminated with the other possible regio-isomer, but of sufficient purity for the next step.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound 78A\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanesulfonic acid\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred under N2 at icebath temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"to warn gradually to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"ADDITION\", \"details\": \"After an hour 200 mL of icewater was cautiously added\"}, {\"type\": \"CUSTOM\", \"details\": \"(vigorous reaction!)\"}, {\"type\": \"CUSTOM\", \"details\": \"the mixture was partitioned between a total of 300 mL of water and 350\\u2013400 mL of dichloro-methane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 300.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloro-methane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"0.5M aq NaHCO3, and dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The solvent was removed in vacuo\"}, {\"type\": \"DISSOLUTION\", \"details\": \"the residue dissolved in a minimum of CHCl3/EtOAc (24:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CHCl3 EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"eluting with several column volumes of the same solvent\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"isolated_color\": \"clear amber\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"syrup\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3e20dda27f7145ecaac4dc28a09030f1",
    "procedure_text": "Trimethylsilylcyanide (1.63 g, 2 ml) was added to a solution of 2-formylbenzofuran (2.0 g), (prepared as described in French Pat. No. 1.537.206) and a trace of zinc iodide in dry ether (50 ml) at 0\u00b0 under nitrogen. The reaction mixture was stirred under nitrogen at ambient temperature for 10 h. This solution was then added dropwise to a suspension of lithium aluminium hydride (0.63 g) in dry ether under nitrogen. The mixture was heated under reflux for 1 h at the end of the addition. The reaction mixture was cooled; water (0.63 ml), 2 M sodium hydroxide (0.63 ml) and more water (1.89 ml) added, the reaction mixture filtered, the residue washed with chloroform and the combined solvents evaporated to give 2-(2-benzofuranyl)-2-hydroxyethanamine, (1.58 g).",
    "reference_string": "{\"inputs\": {\"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"zinc iodide\"}], \"reaction_role\": \"CATALYST\"}]}, \"m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium aluminium hydride\"}], \"amount\": {\"mass\": {\"value\": 0.63, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m9_m4_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"volume\": {\"value\": 0.63, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 1.89, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 0.63, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Trimethylsilylcyanide\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-formylbenzofuran\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred under nitrogen at ambient temperature for 10 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"(prepared\"}, {\"type\": \"CUSTOM\", \"details\": \"at 0\\u00b0\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The mixture was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"under reflux for 1 h at the end of the addition\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"The reaction mixture was cooled\"}, {\"type\": \"FILTRATION\", \"details\": \"the reaction mixture filtered\"}, {\"type\": \"WASH\", \"details\": \"the residue washed with chloroform\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the combined solvents evaporated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 10.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(2-benzofuranyl)-2-hydroxyethanamine\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.58, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-318321fac2044e15add962df60581aec",
    "procedure_text": "Prepared by the same method as described in example 1 except that (i) in step 82-A step 2-chloro-1,4-diiodo-benzene was used in place of 2-fluoro-1,4-diiodo-benzene; (ii) in step 82-E (S)-2-tert-butoxycarbonylamino-4-methyl-pentanoic acid was used in place of (2S,3S)-2-tert-butoxycarbonylamino-3-phenyl-butyric acid, and (ii) chlorination of the 5-position of the imidazole ring with N-chlorosuccinimide in step 82-F was omitted. HR-MS: calcd for C25H26ClIN4O4 [M+H+] 609.0760. Found 609.0757.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(S)-2-tert-butoxycarbonylamino-4-methyl-pentanoic acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-chlorosuccinimide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"( i )\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloro-1,4-diiodo-benzene\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"( ii )\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"( ii )\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Prepared by the same method\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-a0a0d8966cd64f768f450299f11628fa",
    "procedure_text": "To a solution of 3-hydroxycyclobutanecarboxylic acid (100 mg, 0.86 mmol) in DCM (10 mL) was added DMAP (1.0 mg, 0.086 mmol). The solution was cooled to 0\u00b0 C., followed by the addition of acetyl chloride (0.14 mL, 2.6 mmol). The reaction was heated at 45\u00b0 C. for 4 hours, then cooled to rt and diluted with DCM (20 mL). The mixture was washed with water (10 mL), followed by washing with brine (10 mL), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to obtained the crude product which was used in the next step without further purification.",
    "reference_string": "{\"inputs\": {\"m1_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-hydroxycyclobutanecarboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMAP\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetyl chloride\"}], \"amount\": {\"volume\": {\"value\": 0.14, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The reaction was heated at 45\\u00b0 C. for 4 hours\", \"duration\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 45.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"cooled to rt\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"WASH\", \"details\": \"The mixture was washed with water (10 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"by washing with brine (10 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a7a32108c97f47a8a1c69004790f904a",
    "procedure_text": "To a stirred solution of ethyl 5-(2-formyl-3-methoxyphenoxy)-2,2-dimethylpentanoate (6.46 g, 0.021 M) in dry tetrahydrofuran (60 ml) was added dropwise a solution of magnesium iodide (8.67 g, 0.031 M) in dry ether (130 ml). The mixture was then stirred under reflux (51/2 hr). The cooled mixture, containing ethyl 5-(2-formyl-3-hydroxyphenoxy)-2,2-dimethylpentanonate, was poured into 10% hydrochloric acid (110 ml). The organic layer was separated and the aqueous phase extracted with ethyl acetate. The combined organic solutions were washed with water, dried (sodium sulphate) and evaporated. The residue was dissolved in 95% ethanol (50 ml) and 2 N sodium hydroxide solution (100 ml) and stirred at room temperature (20 hr). The solution was then evaporated and the residue diluted with water and extracted with ether. The aqueous phase was acidified with concentrated hydrochloric acid with cooling and the solid produced filtered off and washed with water to give 5-(2-formyl-3-hydroxyphenoxy)-2,2-dimethylpentanoic acid, m.p. 76\u00b0-77\u00b0 C. from benzene/petrol.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 5-(2-formyl-3-hydroxyphenoxy)-2,2-dimethylpentanonate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2_m6_m3_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 5-(2-formyl-3-methoxyphenoxy)-2,2-dimethylpentanoate\"}], \"amount\": {\"mass\": {\"value\": 6.46, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium iodide\"}], \"amount\": {\"mass\": {\"value\": 8.67, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"amount\": {\"volume\": {\"value\": 130.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 110.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was then stirred\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"under reflux (51/2 hr)\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The organic layer was separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"the aqueous phase extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined organic solutions were washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (sodium sulphate)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulphate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue was dissolved in 95% ethanol (50 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"STIRRING\", \"details\": \"2 N sodium hydroxide solution (100 ml) and stirred at room temperature (20 hr)\", \"duration\": {\"value\": 20.0, \"units\": \"HOUR\"}, \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The solution was then evaporated\"}, {\"type\": \"ADDITION\", \"details\": \"the residue diluted with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"with cooling\"}, {\"type\": \"CUSTOM\", \"details\": \"the solid produced\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered off\"}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-(2-formyl-3-hydroxyphenoxy)-2,2-dimethylpentanoic acid\"}], \"reaction_role\": \"PRODUCT\"}, {\"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-aebf2600940247c2ba98b71cb7809372",
    "procedure_text": "3-Ethylphenol (24.4 g) and 4-fluorobenzoyl chloride (34.9 g) were reacted together as in Example 2 giving three main fractions: B (11.4 g) 126\u00b0-129\u00b0 C. at 0.07 mmHg; C (7.9 g), 129\u00b0-132\u00b0 C. at 0.06 mmHg; D (5.9 g), 132\u00b0-150\u00b0 C. at 0.06 mmHg, all containing ~ 80% of the required isomer. B (4.0 g) was separated by preparative thin layer chromatography to give the title compound (2.6 g), m.p. 44\u00b0-48\u00b0 C. The same compound was obtained using the method of Example 4.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-Ethylphenol\"}], \"amount\": {\"mass\": {\"value\": 24.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-fluorobenzoyl chloride\"}], \"amount\": {\"mass\": {\"value\": 34.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"B (11.4 g) 126\\u00b0-129\\u00b0 C.\"}, {\"type\": \"CUSTOM\", \"details\": \"C (7.9 g), 129\\u00b0-132\\u00b0 C.\"}, {\"type\": \"CUSTOM\", \"details\": \"D (5.9 g), 132\\u00b0-150\\u00b0 C.\"}, {\"type\": \"CUSTOM\", \"details\": \"B (4.0 g) was separated by preparative thin layer chromatography\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.6, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 5.3}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-38a5b1b5afe74d2c923d876b098c4cdb",
    "procedure_text": "A solution of 2-bromobenzaldehyde (18.50 g) in dry ether (20 ml) was added dropwise to a stirred solution of benzylmagnesium chloride [prepared from benzyl chloride (12.64 g) and magnesium (2.68 g)] in dry ether (120 ml), a thick precipitate forming during the addition. The mixture was stirred for 1 hour at room temperature then poured into water, acidified with 2M hydrochloric acid, and extracted with ether. The extracts were washed with water, dried, concentrated and chromatographed using dichloromethane and petrol (1:1) as eluant to give 1-(2-bromophenyl)-2-phenylethan-1-ol (10.95 g, 40%) as a white solid, melting point 84-85\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m5_m2_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-bromobenzaldehyde\"}], \"amount\": {\"mass\": {\"value\": 18.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzylmagnesium chloride\"}], \"amount\": {\"mass\": {\"value\": 12.64, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"amount\": {\"volume\": {\"value\": 120.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred for 1 hour at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"a thick precipitate forming during the addition\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The extracts were washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"chromatographed\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(2-bromophenyl)-2-phenylethan-1-ol\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 10.95, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 40.0}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-7adfae702a1d4db09f6679d56254f0f7",
    "procedure_text": "The title compound (18 g, 88.6%) was prepared as a syrupy liquid from isonipecotic acid (10 g) and benzyl chloroformate (17 ml) in a similar manner to that described in preparation 1.",
    "reference_string": "{\"inputs\": {\"m0_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isonipecotic acid\"}], \"amount\": {\"mass\": {\"value\": 10.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzyl chloroformate\"}], \"amount\": {\"volume\": {\"value\": 17.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"described in preparation 1\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 18.0, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 88.6}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a293aec94fe945f3a188ae43621de17a",
    "procedure_text": "Prepared analogous to Example 5 from 6-chloro-2-ethoxy-benzothiazole and concentrated hydrochloric acid with a yield of 56% of theory. M.p.: 212\u00b0-213\u00b0 C. (toluene)",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-chloro-2-ethoxy-benzothiazole\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 56.0}}]}]}]}"
  },
  {
    "reaction_id": "ord-817cc96b6c454e0689a059affc04ea97",
    "procedure_text": "The title compound was prepared by a method analogous to that described for Example 20 using methyl 4-(1-(4-(2H-indazol-2-yl)phenoxy)butyl)benzoate. Column: Waters Atlantis C18 4.6\u00d750 mm, 5 \u03bcm; Modifier: TFA 0.05%; Gradient: 95% H20/5% acetonitrile linear to 5% H20/95% acetonitrile over 4.0 min, hold at 5% H20/95% acetonitrile to 5.0 min. Flow: 2.0 mL/min.; Retention time: 3.23 minutes. MS (M+1): 458.2.",
    "reference_string": "{\"inputs\": {\"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 4-(1-(4-(2H-indazol-2-yl)phenoxy)butyl)benzoate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TFA\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"to 5.0 min\", \"duration\": {\"value\": 5.0, \"units\": \"MINUTE\"}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2e04fa339a894fbbaef1d8d3fe7f8d1d",
    "procedure_text": "5-chloro-2-[2-(morpholin-4-yl)-4-oxo-5,6-dihydro-4H-[1,3]thiazolo[5,4-c]azepin-8-yl]benzoic acid (0.0500 g, 0.123 mmol) was dissolved in acetonitrile (0.50 mL) and saturated aqueous sodium bicarbonate solution (2.5 mL), then added a solution of potassium iodide (0.102 g, 0.616 mmol) and iodine (0.0406 g, 0.160 mmol) in water (1.0 mL) dropwise and the solution was stirred at room temperature for 16 hours. The reaction mixture was diluted with EA and 15% aqueous sodium thiosulfate solution and the mixture was stirred for 20 minutes. The layers were separated and the aqueous layer was extracted twice more with EA. The combined organic layer was then washed with water and brine then dried over anhydrous sodium sulfate and concentrated. The residue was purified using column chromatography on silica gel (12 gr Analogix column, gradient DCM to 60% EA in DCM over 15 minutes) to give the product (0.0540 g, 82%). LCMS: (AA) ES+ 532, 534. 1H NMR (400 MHz, d6-DMSO) \u03b4: 8.44 (t, J=4.8 Hz, 1H), 8.07-7.90 (m, 1H), 7.92-7.72 (m, 2H), 5.12-4.91 (m, 1H), 3.93-3.81 (m, 1H), 3.77-3.65 (m, 1H), 3.61-3.48 (m, 4H), 3.23-3.08 (m, 4H).",
    "reference_string": "{\"inputs\": {\"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-chloro-2-[2-(morpholin-4-yl)-4-oxo-5,6-dihydro-4H-[1,3]thiazolo[5,4-c]azepin-8-yl]benzoic acid\"}], \"amount\": {\"mass\": {\"value\": 0.05, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 0.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m7_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EA\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium thiosulfate\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3_m4_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"amount\": {\"volume\": {\"value\": 2.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium iodide\"}], \"amount\": {\"mass\": {\"value\": 0.102, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"iodine\"}], \"amount\": {\"mass\": {\"value\": 0.0406, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the solution was stirred at room temperature for 16 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"the mixture was stirred for 20 minutes\", \"duration\": {\"value\": 20.0, \"units\": \"MINUTE\"}}, {\"type\": \"CUSTOM\", \"details\": \"The layers were separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"the aqueous layer was extracted twice more with EA\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EA\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined organic layer was then washed with water and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"then dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified\"}, {\"type\": \"CUSTOM\", \"details\": \"on silica gel (12 gr Analogix column, gradient DCM to 60% EA in DCM over 15 minutes)\", \"duration\": {\"value\": 15.0, \"units\": \"MINUTE\"}}], \"outcomes\": [{\"reaction_time\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.054, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 82.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 82.6}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-86734078989d44ef9dd037485b1756fb",
    "procedure_text": "To a solution of 6-(2-methoxyethoxy)-4-oxo-1,4-dihydro-1,5-naphthyridine-3-carboxylic acid (106 mg, 0.4 mmol) and triethylamine (117 mL, 0.84 mmol) in 4:1 tetrahydrofuran: N,N-dimethylformamide (2 mL) at 0\u00b0 C. was added ethyl chloroformate (66 mL, 0.82 mmol). After stirring at 0\u00b0 C. for 1.25 h, 4-[(N-tert-butoxycarbonyl)-methylaminomethyl)benzylamine hydrochloride (120 mg, 0.42 mmol) and triethylamine (59 mL, 0.42 mmol) was added. The reaction mixture was stirred at 0\u00b0 C. for 0.75 h, then allowed to ambient temperature and stirred for 20 h. N,N-Dimethylethylenediamine (132 mL, 1.2 mmol) was added, the reaction mixture stirred for 1 h, then concentrated in vacuo. The residue was cooled in an ice bath, saturated aqueous ammonium chloride was added and the mixture extracted with dichloromethane. The organic layer was washed with saturated aqueous sodium chloride, dried over sodium sulfate, filtered, and concentrated to give 177 mg of crude N-[4-(N-tert butoxycarbonyl)-methylaminomethyl)benzyl] 6-(2-methoxyethoxy)-4-oxo-1,4-dihydro-1,5-naphthyridine-3-carboxamide.",
    "reference_string": "{\"inputs\": {\"m1_m2_m8_m7_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-(2-methoxyethoxy)-4-oxo-1,4-dihydro-1,5-naphthyridine-3-carboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 106.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 117.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl chloroformate\"}], \"amount\": {\"volume\": {\"value\": 66.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-Dimethylethylenediamine\"}], \"amount\": {\"volume\": {\"value\": 132.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-[(N-tert-butoxycarbonyl)-methylaminomethyl)benzylamine hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 120.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 59.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring at 0\\u00b0 C. for 1.25 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"The reaction mixture was stirred at 0\\u00b0 C. for 0.75 h\", \"duration\": {\"value\": 0.75, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"allowed to ambient temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"STIRRING\", \"details\": \"stirred for 20 h\", \"duration\": {\"value\": 20.0, \"units\": \"HOUR\"}}, {\"type\": \"STIRRING\", \"details\": \"the reaction mixture stirred for 1 h\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The residue was cooled in an ice bath\"}, {\"type\": \"ADDITION\", \"details\": \"saturated aqueous ammonium chloride was added\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"the mixture extracted with dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with saturated aqueous sodium chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.25, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-(2-methoxyethoxy)-4-oxo-1,4-dihydro-1,5-naphthyridine-3-carboxamide\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-bdf7857f58974594b5c8b9ae1693b323",
    "procedure_text": "A mixture of 5.00 g (22.2 mmol) tert-butyl 3-oxo-8-aza-bicyclo[3.2.1]octan-8-carboxylate and benzyl piperazine-1-carboxylate in 60 mL THF was adjusted with AcOH to a pH of 5 and stirred for 1 h at RT. The mixture was combined batchwise with 5.64 g (26.6 mmol) sodium triacetoxyborohydride while cooling with ice and the reaction mixture was stirred overnight at RT. It was combined with 150 mL 15% K2CO3 solution, the organic phase was separated off, the aqueous phase was exhaustively extracted with EtOAc and the combined organic phases were dried over Na2SO4. After elimination of the desiccant and solvent the residue was purified by chromatography (silica gel, EtOAc).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"K2CO3\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl 3-oxo-8-aza-bicyclo[3.2.1]octan-8-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 5.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzyl piperazine-1-carboxylate\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"AcOH\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium triacetoxyborohydride\"}], \"amount\": {\"mass\": {\"value\": 5.64, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred for 1 h at RT\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"while cooling with ice\"}, {\"type\": \"STIRRING\", \"details\": \"the reaction mixture was stirred overnight at RT\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"the organic phase was separated off\"}, {\"type\": \"EXTRACTION\", \"details\": \"the aqueous phase was exhaustively extracted with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"the combined organic phases were dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"After elimination of the desiccant and solvent the residue was purified by chromatography (silica gel, EtOAc)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-a0798f33254e49d4856614cee3bd6850",
    "procedure_text": "A solution of 6-chloro-4-oxo-1-propionyl-1,2,3,4-tetrahydroquinoline (2 g), N,N-dimethylformamide dimethyl acetal (7.009 g), and triethylamine (0.87 g) in benzene (50 m) was refluxed with stirring for 1 hour and then about three-fourths of the solvent was distilled slowly at atmospheric pressure over a period ximately 1 hour. To the residue was added benzene (100 ml) and the solvent was distilled again. The resulting solid was collected by filtration, washed with diethyl ether, and dried to give 6-chloro-3-methylaminomethylene-4-oxo-1-propionyl-1,2,3,4-tetrahydroquinoline (2.02 g).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-chloro-4-oxo-1-propionyl-1,2,3,4-tetrahydroquinoline\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide dimethyl acetal\"}], \"amount\": {\"mass\": {\"value\": 7.009, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"mass\": {\"value\": 0.87, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzene\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"with stirring for 1 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"DISTILLATION\", \"details\": \"about three-fourths of the solvent was distilled slowly at atmospheric pressure over a period ximately 1 hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"ADDITION\", \"details\": \"To the residue was added benzene (100 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzene\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"the solvent was distilled again\"}, {\"type\": \"FILTRATION\", \"details\": \"The resulting solid was collected by filtration\"}, {\"type\": \"WASH\", \"details\": \"washed with diethyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-chloro-3-methylaminomethylene-4-oxo-1-propionyl-1,2,3,4-tetrahydroquinoline\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.02, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d56c5b2b22de4731a6d947cd325624b1",
    "procedure_text": "A solution of 18.1 ml of methanesulphonic acid in 45 ml of ethyl acetate was added dropwise within 2 hours under argon to a solution, cooled to 0-5\u00b0 C., of 7.96 g of S-1,2,4-butanetriol and 33.5 ml of triethylamine in 90 ml of ethyl acetate. The white suspension was stirred at 0-5\u00b0 C. for a further 2 hours and thereafter the suspension was filtered and the yellow filtrate was washed in succession with 75 ml of 1N hydrochloric acid, 75 ml of saturated NaHCO3 solution and 75ml of saturated NaCl solution. The organic phase was dried over Na2SO4, filtered and the filtrate was concentrated. 21.79 g of yellow oil were obtained.",
    "reference_string": "{\"inputs\": {\"m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"S-1,2,4-butanetriol\"}], \"amount\": {\"mass\": {\"value\": 7.96, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 33.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 90.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanesulphonic acid\"}], \"amount\": {\"volume\": {\"value\": 18.1, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 45.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 2.5, \"precision\": 2.5, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The white suspension was stirred at 0-5\\u00b0 C. for a further 2 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"the suspension was filtered\"}, {\"type\": \"WASH\", \"details\": \"the yellow filtrate was washed in succession with 75 ml of 1N hydrochloric acid, 75 ml of saturated NaHCO3 solution and 75ml of saturated NaCl solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 75.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"amount\": {\"volume\": {\"value\": 75.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaCl\"}], \"amount\": {\"volume\": {\"value\": 75.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic phase was dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate was concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"yellow oil\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 21.79, \"units\": \"GRAM\"}}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c277c6b241404fae86005725c479e7c1",
    "procedure_text": "4-Iodo-N-1,3-thiazol-2-ylbenzenesulfonamide Preparation 98, 200 mg, 0.5 mmol), thiophene-2-methanamine (280 uL, 2.7 mmol), hexacarbonylmolybdenum (70 mg, 0.3 mmol), palladium(II) acetate (6 mg, 0.03 mmol), and sodium carbonate (170 mg, 1.6 mmol) in water (1.1 mL, 61 mmol) was heated 30 min at 110\u00b0 C. in the microwave. The reaction mixture was diluted with 1 N HCl and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was dissolved in methylene chloride/MeOH and MP-Carbonate (2.73 mmol/g loading; 1.0 g, 2.73 mmol) was added. After stirring 1 h, LC/MS analysis indicated complete capture of the target compound. The resin was washed with methylene chloride then stirred in 8:1 methylene chloride/AcOH. LC/MS analysis indicated the target compound was released from the resin (not quantified). The material was further purified on the Isco (12 g SiO2, ethyl acetate to 4:1 ethyl acetate-MeOH).",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m7_m8_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-Iodo-N-1,3-thiazol-2-ylbenzenesulfonamide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"thiophene-2-methanamine\"}], \"amount\": {\"volume\": {\"value\": 280.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium carbonate\"}], \"amount\": {\"mass\": {\"value\": 170.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 1.1, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexacarbonylmolybdenum\"}], \"amount\": {\"mass\": {\"value\": 70.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"palladium(II) acetate\"}], \"amount\": {\"mass\": {\"value\": 6.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Carbonate\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 110.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring 1 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined organic layers were washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue was dissolved in methylene chloride/MeOH\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride MeOH\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The resin was washed with methylene chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"STIRRING\", \"details\": \"then stirred in 8:1 methylene chloride/AcOH\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride AcOH\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The material was further purified on the Isco (12 g SiO2, ethyl acetate to 4:1 ethyl acetate-MeOH)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"SiO2\"}], \"amount\": {\"mass\": {\"value\": 12.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate MeOH\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-cd5d5abb3d7d4067acf955a23a372970",
    "procedure_text": "To a solution of the azaindole 25 (18.30 g, 63.9 mmol) in DMF (100 mL) was added KOH (13.27 g, 236.5 mmol) in a single portion. After 0.5 h, iodine (16.18 g, 63.9 mmol) was added in portions over a 3 min. period. After a further 1 h the reaction was quenched by the addition of a solution of sodium thiosulfate (70 g) in H2O (400 mL). The semisolid was filtered off, dissolved in dichloromethane. The solution and washed with saturated brine (1\u00d7), dried (MgSO4), and concentrated to afford the iodide 26, which was used directly in the next step without further purification. 1H NMR (400 MHz; CDCl3) \u03b46.92-6.95 (m, 2H), 7.01 (tt, J=7.3, 1.0 Hz, 1H), 7.08 (dd, J=8.1, 1.3 Hz, 1H), 7.23-7.30 (m, 3H), 7.36 (dt, J=7.3, 1.8 Hz, 1H), 7.40 (s, H), 7.54 (dd, J=7.6, 1.8 Hz, 1H), 7.93 (d, J=2.0 Hz, 1H), 8.54 (d, J=2.0 Hz, 1H) and 11.06 (bs, 1H).",
    "reference_string": "{\"inputs\": {\"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"azaindole\"}], \"amount\": {\"mass\": {\"value\": 18.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"KOH\"}], \"amount\": {\"mass\": {\"value\": 13.27, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"iodine\"}], \"amount\": {\"mass\": {\"value\": 16.18, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"After a further 1 h the reaction was quenched by the addition of a solution of sodium thiosulfate (70 g) in H2O (400 mL)\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium thiosulfate\"}], \"amount\": {\"mass\": {\"value\": 70.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"amount\": {\"volume\": {\"value\": 400.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"The semisolid was filtered off\"}, {\"type\": \"DISSOLUTION\", \"details\": \"dissolved in dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The solution and washed with saturated brine (1\\u00d7)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 0.5, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"iodide\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-abb4a61318c548419bfd5713e8d7a43a",
    "procedure_text": "In a manner similar to that described in Example 207, 3-{[4-(4-Iodo-butoxy)-phenylamino]-methylene}-1,3-dihydro-indol-2-one and piperidine are converted to the named compound.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-{[4-(4-Iodo-butoxy)-phenylamino]-methylene}-1,3-dihydro-indol-2-one\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"piperidine\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-a1dcdd14b4794693bddd5929abe77e02",
    "procedure_text": "A mixture of ethyl 7-allylamino-1H-pyrazolo[4,3-b]-pyridine-6-carboxylate (3.69 g, 15 mmol), 2,2-dimethoxypropane (9.2 ml, 75 mmol) and 4-toluenesulphonic acid (142 mg, 0.75 mmol) in acetone (200 ml) was heated under reflux for 48 h. The solution was cooled and stirred with solid potassium carbonate, then filtered and evaporated in vacuo. Column chromatography of the residue on basic alumina (100 g), eluting with ethyl acetate, gave the title compound as a white solid (3.07 g, 64%), m.p. 102\u00b0-103\u00b0 C. Found: C, 60.31; H, 6.78; N, 17.60; C16H22N4O3 requires C, 60.36; H, 6.97; N, 17.60%",
    "reference_string": "{\"inputs\": {\"m1_m2_m5_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 7-allylamino-1H-pyrazolo[4,3-b]-pyridine-6-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 3.69, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,2-dimethoxypropane\"}], \"amount\": {\"volume\": {\"value\": 9.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-toluenesulphonic acid\"}], \"amount\": {\"mass\": {\"value\": 142.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"under reflux for 48 h\", \"duration\": {\"value\": 48.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"The solution was cooled\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated in vacuo\"}, {\"type\": \"WASH\", \"details\": \"Column chromatography of the residue on basic alumina (100 g), eluting with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 3.07, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 64.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 64.3}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-62746ab6ad93468881bf2fe29ba60212",
    "procedure_text": "To a flask fitted with overhead stirrer, condenser, thermometer and nitrogen line was added 3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-[(1S)-2-methoxy-1-methylethoxy]benzoic acid (1.0 eq), and acetonitrile (10 vols) followed by pyridine (3 eq) under a nitrogen atmosphere. Thionyl chloride (1.2 eq) as a solution in acetonitrile (0.225 vols) was added slowly, drop-wise via syringe pump over at least 2 hours. 5-Methylpyrazin-2-amine (1.2 eq) was added to the mixture as a solid. After 2.5 hours the reaction was quenched by adding toluene (10 vols) and 1.0M sodium carbonate solution (2.5 eq). The layers were separated. The organic layer was retained in the flask, then 1.0M hydrochloric acid (1.94 eq) was added. The mixture was agitated for 15 minutes then separated. The organic layer was washed with two aliquots of water (5 vols) then the solvent was removed on the rotary evaporator. Toluene (5 vols) was added to the residue, and warmed to 45\u00b0 C. Isohexane (1.7 vols) was added, the mixture was seeded, and allowed to cool to ambient temperature overnight. The mixture was cooled to 0\u00b0 C. for 4 hours, and then cooled to \u221210\u00b0 C. for 3 hours. The solid was isolated by filtration then washed with iso-hexane (2.5 vols). After drying in the vacuum oven at 40\u00b0 C. overnight, the desired product was obtained as a solid (corrected yield 85%).",
    "reference_string": "{\"inputs\": {\"m3_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Thionyl chloride\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m10_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium carbonate\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-Methylpyrazin-2-amine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"mixture\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m9\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-[(1S)-2-methoxy-1-methylethoxy]benzoic acid\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 45.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was agitated for 15 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"To a flask fitted with overhead stirrer, condenser\"}, {\"type\": \"CUSTOM\", \"details\": \"drop-wise via syringe\"}, {\"type\": \"WAIT\", \"details\": \"pump over at least 2 hours\"}, {\"type\": \"CUSTOM\", \"details\": \"After 2.5 hours the reaction was quenched\", \"duration\": {\"value\": 2.5, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The layers were separated\"}, {\"type\": \"CUSTOM\", \"details\": \"then separated\"}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with two aliquots of water (5 vols)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was removed on the rotary evaporator\"}, {\"type\": \"ADDITION\", \"details\": \"Toluene (5 vols) was added to the residue\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Toluene\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"Isohexane (1.7 vols) was added\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Isohexane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"to cool to ambient temperature overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"The mixture was cooled to 0\\u00b0 C. for 4 hours\", \"duration\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"cooled to \\u221210\\u00b0 C. for 3 hours\", \"duration\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": -10.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The solid was isolated by filtration\"}, {\"type\": \"WASH\", \"details\": \"then washed with iso-hexane (2.5 vols)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"iso-hexane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"After drying in the vacuum oven at 40\\u00b0 C. overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 40.0, \"units\": \"CELSIUS\"}}}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 85.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0fb4f76975d849eca0b4dd5ad8fb5eb0",
    "procedure_text": "A suspension of 4-[3-(4-acetylaminophenyl)phenyl]-2-benzyl-3-oxo-3,4-dihydropyrido[2,3-b]pyrazine (963 mg) in 3N hydrochloric acid (25 ml) was stirred under reflux for 3 hours. Then the mixture was poured into ice-water and alkalinized with sodium bicarbonate. The resultant solid was collected and washed with water to give 4-[3-(4-aminophenyl)phenyl]-2-benzyl-3-oxo-3,4-dihydropyrido[2,3-b]pyrazine (577 mg).",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-[3-(4-acetylaminophenyl)phenyl]-2-benzyl-3-oxo-3,4-dihydropyrido[2,3-b]pyrazine\"}], \"amount\": {\"mass\": {\"value\": 963.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"under reflux for 3 hours\", \"duration\": {\"value\": 3.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The resultant solid was collected\"}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-[3-(4-aminophenyl)phenyl]-2-benzyl-3-oxo-3,4-dihydropyrido[2,3-b]pyrazine\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 577.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-9db5acc6fc684c5ba3d4f224708eddfc",
    "procedure_text": "To a stirred solution of 1,4-diazabicyclo[3.2.2]nonan-3-one (1.0 g, 7.2 mmol) in 1,4-dioxane (7.2 mL) at room temperature was added lithium aluminum hydride [2.0M/THF] (4.1 mL, 8.2 mmol). The reaction mixture was then heated at reflux for 6 hours before cooling to room temperature. The reaction was quenched by the stepwise addition of 200 L of H2O, 200 L of 15% aqueous NaOH, and 600 L of H2O. The mixture was filtered through Celite which was subsequently washed with EtOAc. The combined filtrate was concentrated in vacuo to afford the product (0.82 g, 90%) which was used without further purification. 1H NMR (400 MHz, CDCl3) \u03b4 3.28-3.25 (m, 1H), 2.99-2.95 (m, 8H), 1.86-1.80 (m, 3H), 1.69-1.64 (m, 2H) ppm.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,4-diazabicyclo[3.2.2]nonan-3-one\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium aluminum hydride\"}], \"amount\": {\"volume\": {\"value\": 4.1, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,4-dioxane\"}], \"amount\": {\"volume\": {\"value\": 7.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The reaction mixture was then heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"at reflux for 6 hours\", \"duration\": {\"value\": 6.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The reaction was quenched by the stepwise addition of 200 L of H2O, 200 L of 15% aqueous NaOH, and 600 L of H2O\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"LITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"LITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"amount\": {\"volume\": {\"value\": 600.0, \"units\": \"LITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"The mixture was filtered through Celite which\"}, {\"type\": \"WASH\", \"details\": \"was subsequently washed with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"The combined filtrate was concentrated in vacuo\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.82, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 90.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 90.2}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b6b2fdde38bf49c48b78d8644be4ed69",
    "procedure_text": "3.90 g of 1-[(2-methoxy-3-pyridyl)methyl]-4-piperidinecarboxaldehyde, 8.92 g of (2-methylsulfonylbenzyl)triphenylphosphonium chloride and 1.96 g of potassium tert-butoxide were suspended in 80 ml of N,N-dimethylformamide, and the mixture was stirred for 3 hours at room temperature. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the crude product was purified by NH form silica gel column chromatography (ethyl acetate:hexane=1:4). The resulting product and 440 mg of 10% palladium-carbon powder (water-containing product) were suspended in 80 ml of ethanol. After replacing the atmosphere of a container with hydrogen, the mixture was stirred at room temperature under normal pressure for 30 minutes. The reaction solution was filtered, and the filtrate was evaporated, to give 4.05 g of the title compound as a colorless oil.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-[(2-methoxy-3-pyridyl)methyl]-4-piperidinecarboxaldehyde\"}], \"amount\": {\"mass\": {\"value\": 3.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 80.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium tert-butoxide\"}], \"amount\": {\"mass\": {\"value\": 1.96, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrogen\"}], \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 80.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"palladium-carbon\"}], \"amount\": {\"mass\": {\"value\": 440.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2-methylsulfonylbenzyl)triphenylphosphonium chloride\"}], \"amount\": {\"mass\": {\"value\": 8.92, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred for 3 hours at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"the mixture was extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The solvent was evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"the crude product was purified by NH\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"form silica gel column chromatography (ethyl acetate:hexane=1:4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"STIRRING\", \"details\": \"the mixture was stirred at room temperature under normal pressure for 30 minutes\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"The reaction solution was filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"the filtrate was evaporated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 4.05, \"units\": \"GRAM\"}}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c82de5be4a37489e8a78f7b2cd97ac4c",
    "procedure_text": "5-tert-Butylazocan-2-one (30 mg) was dissolved in 2 mL methylene chloride and stirred at room temperature under nitrogen. 31.3 g Trimethyloxonium tetrafluoroborate was added and the reaction stirred overnight. The mixture was added to saturated aqueous sodium bicarbonate and extracted with methylene chloride (2\u00d7). The combined organic layers were washed with brine, dried over magnesium sulfate, and the solvent evaporated to provide crude 5-tert-butyl-8-methoxy-2,3,4,5,6,7-hexahydroazocine.",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-tert-Butylazocan-2-one\"}], \"amount\": {\"mass\": {\"value\": 30.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Trimethyloxonium tetrafluoroborate\"}], \"amount\": {\"mass\": {\"value\": 31.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred at room temperature under nitrogen\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"the reaction stirred overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with methylene chloride (2\\u00d7)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined organic layers were washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent evaporated\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-tert-butyl-8-methoxy-2,3,4,5,6,7-hexahydroazocine\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4c422421c7e54962b8df2ba921dc3a26",
    "procedure_text": "To a suspension of 2-(4-methoxy-7-(pyrimidin-5-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetic acid (50 mg, 0.168 mmol), 1-(1-phenyl-1H-tetrazol-5-yl)piperazine hydrochloride (40.2 mg, 0.151 mmol) and 2-(1H-Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (59.2 mg, 0.184 mmol) in DMF (1 ml) was added N,N-Diisopropylethylamine (0.146 ml, 0.838 mmol). The mixture was stirred at room temperature for 4 hours. The mixture was diluted with 150 ml of CH2Cl2 and washed with 5% NaHCO3 (30 ml), brine (30 ml). The organic layer was dried over Na2SO4 and concentrated to give a residue, which was purified by prep. HPLC to give 1-(4-methoxy-7-(pyrimidin-5-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)ethane-1,2-dione (10 mg, 0.020 mmol, 11.68% yield) (light tan solid). LCMS: m/e 511.4 (M+H)+, ret time 1.25 min. 1H NMR (500 MHz, MeOD) \u03b4 ppm 9.30 (s, 1H) 9.17 (s, 2H) 8.38 (s, 1H) 8.16 (s, 1H) 7.58-7.65 (m, 5H) 4.09 (s, 3H) 3.80-3.83 (m, 2H) 3.57-3.60 (m, 2H) 3.38-3.42 (m, 2H) 3.31-3.33 (m, 2H).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-Diisopropylethylamine\"}], \"amount\": {\"volume\": {\"value\": 0.146, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(4-methoxy-7-(pyrimidin-5-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetic acid\"}], \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(1-phenyl-1H-tetrazol-5-yl)piperazine hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 40.2, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(1H-Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate\"}], \"amount\": {\"mass\": {\"value\": 59.2, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at room temperature for 4 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WASH\", \"details\": \"washed with 5% NaHCO3 (30 ml), brine (30 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layer was dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a residue, which\"}, {\"type\": \"CUSTOM\", \"details\": \"was purified by prep\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(4-methoxy-7-(pyrimidin-5-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)ethane-1,2-dione\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 0.02, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 10.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 11.68}}], \"isolated_color\": \"tan\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4e21b58b9de94cb09388838c4be510f1",
    "procedure_text": "Prepared as in Example 112c from 2,6-dinitrobenzonitrile and 4-methoxybenzyl alcohol to provide 2-nitro-6-(4-methoxybenzyloxy)benzonitrile (2.40 g, 81%). 1H NMR (400 MHz, CDCl3) \u03b4 3.82 (s, 3H), 5.26 (s, 2H), 6.93 (m, 2H), 7.35 (dd, J=8.6, 0.7 Hz, 1H), 7.38 (m, 2H), 7.65 (t, J=8.6 Hz, 1H), 7.83 (dd, J=8.2, 0.8 Hz, 1H).",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,6-dinitrobenzonitrile\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-methoxybenzyl alcohol\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-nitro-6-(4-methoxybenzyloxy)benzonitrile\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.4, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 81.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-04d4ebe63e3d4e0f925de11bc81a33e7",
    "procedure_text": "To a solution of m-anisic acid (0.5 g; 3.29 mmol) and HATU (1.4 g; 3.68 mmol) in DMF (5 mL) was added N,N-diisopropylethylamine (2 mL; 11.48 mmol). The reaction was stirred at room temperature for 30 min. Diethylamine (0.377 mL; 3.62 mmol) was added to the reaction. The mixture was stirred at room temperature for 1.5 d, diluted with H2O (5 mL), and extracted with EtOAc (2\u00d75 mL). The organic layer was dried over MgSO4 and concentrated to afford Compound 15a. The crude product was used in the next reaction without further purification. MS: m/z 208.2 (M+H)+.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Diethylamine\"}], \"amount\": {\"volume\": {\"value\": 0.377, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m5_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"m-anisic acid\"}], \"amount\": {\"mass\": {\"value\": 0.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HATU\"}], \"amount\": {\"mass\": {\"value\": 1.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-diisopropylethylamine\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction was stirred at room temperature for 30 min\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"The mixture was stirred at room temperature for 1.5 d\", \"duration\": {\"value\": 1.5, \"units\": \"DAY\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with EtOAc (2\\u00d75 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layer was dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Compound 15a\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-84c305df3f97412688529f1b6ff4a299",
    "procedure_text": "Cesium carbonate [534-17-8] (150 mg, 0.5 mmol) was added to a solution of 1-[5-(6-fluoro-imidazo[1,2-b]pyridazin-3-yl)-thiophen-2-yl]-ethanone (60 mg, 0.2 mmol) and ethanolamine [141-43-5] (29 mg, 0.5 mmol) in N,N-dimethylformamide (3 mL). The mixture was stirred at 40\u00b0 C. for 1 h then partitioned between ethyl acetate and water. Analysis of the organic extract revealed preparation ratio of the desired arylamine product to the ether to be approximately 2:1. Preparative RP-HPLC isolated 22 mg of 1-{5-[6-(2-hydroxy-ethylamino)-imidazo[1,2-b]pyridazin-3-yl]-thiophen-2-yl}-ethanone as a yellow solid. 1H NMR (400 MHz, DMSO-d6) \u03b4 ppm 1.83 (s, 3H) 2.57 (s, 2H) 3.04 (t, J=5.68 Hz, 1H) 4.43 (t, J=5.68 Hz, 1H) 7.04 (d, J=9.60 Hz, 1H) 7.91 (d, J=4.04 Hz, 1H) 8.03 (d, J=4.04 Hz, 1H) 8.16 (d, J=9.60 Hz, 1H) 8.36 (s, 1H). LRMS (ESI) m/z 303.1 [(M+H)]+, calc'd for C14H14N4O2S: 302.36.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Cesium carbonate\"}], \"amount\": {\"mass\": {\"value\": 150.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-[5-(6-fluoro-imidazo[1,2-b]pyridazin-3-yl)-thiophen-2-yl]-ethanone\"}], \"amount\": {\"mass\": {\"value\": 60.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanolamine\"}], \"amount\": {\"mass\": {\"value\": 29.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 40.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at 40\\u00b0 C. for 1 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"then partitioned between ethyl acetate and water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"Analysis of the organic extract\"}, {\"type\": \"CUSTOM\", \"details\": \"preparation ratio of the desired arylamine product to the ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"arylamine\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-{5-[6-(2-hydroxy-ethylamino)-imidazo[1,2-b]pyridazin-3-yl]-thiophen-2-yl}-ethanone\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 22.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 36.4}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-59eaba29f00c43f593b321d34aca87a4",
    "procedure_text": "Prepared using General Procedure 17: To a stirred solution of (R)-methyl 2-(N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)sulfamoyl)acetate (0.40 g, 0.8 mmol) in MeOH (4 mL) was added 6N NaOH (0.27 mL). After 24 h, the crude reaction was concentrated then partitioned between DCM/IPA and 1N HCl. The organic layer was dried over MgSO4 and concentrated to give 0.35 g (91%) of (R)-2-(N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)sulfamoyl)acetic acid 184. An analytically pure sample was prepared by preparative HPLC purification. LCMS-ESI (m/z) calculated for C23H22N4O6S: 482.1; found 505.1 [M+Na]+, tR=8.72 min (Method 2). (S)-2-(N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)sulfamoyl)acetic acid was synthesized in an analogous fashion from (S)-methyl 2-(N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)sulfamoyl)acetate.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-methyl 2-(N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)sulfamoyl)acetate\"}], \"amount\": {\"mass\": {\"value\": 0.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"amount\": {\"volume\": {\"value\": 0.27, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Prepared\"}, {\"type\": \"CUSTOM\", \"details\": \"the crude reaction\"}, {\"type\": \"CONCENTRATION\", \"details\": \"was concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"then partitioned between DCM/IPA and 1N HCl\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM IPA\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layer was dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 24.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-2-(N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)sulfamoyl)acetic acid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.35, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 91.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-ca2fdbd3cfa04b9db071205cd19d7277",
    "procedure_text": "A solution of (2S)-1-[(1-ethoxycarbonylmethoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-6-yl)amino]-3-phenoxy-2-propanol (103 mg) in methanol (5.0 ml) and 0.1N sodium hydroxide aqueous solution (2.5 ml) was stirred for 22 hours and evaporated in vacuo. The residue was triturated in diethyl ether and the precipitated powder was collected by filtration to afford sodium [6,7,8,9-tetrahydro-6-[((2S)-2-hydroxy-3-phenoxypropyl)amino]-5H-benzocyclohepten-1-yloxy]acetate (98 mg) as a pale yellow powder.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2S)-1-[(1-ethoxycarbonylmethoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-6-yl)amino]-3-phenoxy-2-propanol\"}], \"amount\": {\"mass\": {\"value\": 103.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"volume\": {\"value\": 2.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"evaporated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was triturated in diethyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"the precipitated powder was collected by filtration\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium [6,7,8,9-tetrahydro-6-[((2S)-2-hydroxy-3-phenoxypropyl)amino]-5H-benzocyclohepten-1-yloxy]acetate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 98.0, \"units\": \"MILLIGRAM\"}}}], \"isolated_color\": \"pale yellow\", \"texture\": {\"type\": \"POWDER\", \"details\": \"powder\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-75b34d99b7414989a1a25f56e77fc52c",
    "procedure_text": "Step 2 To a stirred solution of 1-tert-butyl 1-ethyl cyclopropane-1,1-dicarboxylate (0.5 g, 2.33 mmol) in THF (11.7 mL) at \u221278\u00b0 C. was added lithium tri-tert-butoxyaluminum hydride solution (11.7 mL, 11.7 mmol) dropwise. The mixture was warmed to room temperature and stirred overnight before it was quenched at 0\u00b0 C. by the addition of a saturated solution of potassium sodium tartrate. EtOAc was added the phases were separated and the aqueous phase was extracted into EtOAc (\u00d72). Combined organic extracts were dried (Na2SO4), filtered and concentrated providing tert-butyl 1-(hydroxymethyl)-cyclopropane-1-carboxylate which was used without further purification, 0.438 g.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-tert-butyl 1-ethyl cyclopropane-1,1-dicarboxylate\"}], \"amount\": {\"mass\": {\"value\": 0.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium tri-tert-butoxyaluminum hydride\"}], \"amount\": {\"volume\": {\"value\": 11.7, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 11.7, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred overnight before it\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"was quenched at 0\\u00b0 C. by the addition of a saturated solution of potassium sodium tartrate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium sodium tartrate\"}], \"reaction_role\": \"WORKUP\"}]}, \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"ADDITION\", \"details\": \"EtOAc was added the phases\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"were separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"the aqueous phase was extracted into EtOAc (\\u00d72)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"Combined organic extracts were dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl 1-(hydroxymethyl)-cyclopropane-1-carboxylate\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3ebba8eb355a4fbfbfd79ac9bd43a382",
    "procedure_text": "170 mg (0.68 mmole) of 5-(3,4-dihydroxy-1-butynyl)-2,2-bithiophene was dissolved in a mixture of 10 ml of dichloromethane and 0.2 ml of pyridine. 0.7 g of stearoyl chloride dissolved in 10 ml of dichloromethane was then dropped into the reaction mixture in ice bath. This reaction solution was stirred for 2 days. It was monitored by thin layer chromatography to determine if there were 3 products obtained, i.e. a mixture of 1 diester and 2 monoesters.",
    "reference_string": "{\"inputs\": {\"m1_m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-(3,4-dihydroxy-1-butynyl)-2,2-bithiophene\"}], \"amount\": {\"mass\": {\"value\": 170.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"amount\": {\"volume\": {\"value\": 0.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"stearoyl chloride\"}], \"amount\": {\"mass\": {\"value\": 0.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diester\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"monoesters\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"This reaction solution was stirred for 2 days\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was then dropped into the reaction mixture in ice bath\"}, {\"type\": \"CUSTOM\", \"details\": \"obtained\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"DAY\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-21aaccbc0b8c43e69d46ca71f2eb029c",
    "procedure_text": "1.72 g (3 mmols) of diphenylmethyl 3-(methoxycarbonylmethyl)-7\u03b2-phenoxyacetylamino-3-cephem-4-carboxylate in 21 ml of methylene chloride are stirred with 1.62 ml (5 equivalents) of anisole and 9.3 ml (40 equivalents) of trifluoroacetic acid for 30 minutes in an ice bath, 100 ml of cold toluene are added and the mixture is evaporated in a rotary evaporator. The residue is digested with ether and the precipitate which has formed is filtered off, washed with ether and dried. A crude product is obtained and is chromatographed on 10 g of silica gel, which had been deactivated by the addition of 5% of water. Elution with methylene chloride and 20-30% of ethyl acetate gives amorphous 3-(methoxycarbonylmethyl-7\u03b2-phenoxyacetylamino-3-cephem-4-carboxylic acid, which according to thin layer chromatography is a single compound; Rf 0.38 (on silica gel; using n-butanol:acetic acid:water, 67:10:23); UV spectrum (in ethanol): \u03bbmax =262, 267 and 274; IR spectrum (in methylene chloride): bands at 2.94, 5.58,5.74, 5.88, 6.11, 6.24, 6.59 and 6.69\u03bc.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diphenylmethyl 3-(methoxycarbonylmethyl)-7\\u03b2-phenoxyacetylamino-3-cephem-4-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 1.72, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"anisole\"}], \"amount\": {\"volume\": {\"value\": 1.62, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trifluoroacetic acid\"}], \"amount\": {\"volume\": {\"value\": 9.3, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 21.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the mixture is evaporated in a rotary evaporator\"}, {\"type\": \"CUSTOM\", \"details\": \"the precipitate which has formed\"}, {\"type\": \"FILTRATION\", \"details\": \"is filtered off\"}, {\"type\": \"WASH\", \"details\": \"washed with ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"CUSTOM\", \"details\": \"A crude product is obtained\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"is chromatographed on 10 g of silica gel, which\"}, {\"type\": \"ADDITION\", \"details\": \"had been deactivated by the addition of 5% of water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"Elution with methylene chloride and 20-30% of ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methoxycarbonylmethyl-7\\u03b2-phenoxyacetylamino-3-cephem-4-carboxylic acid\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-9855f7fc64d740588ae60fe1844b48ff",
    "procedure_text": "To a THF (4 mL) solution of 3-[(3-phenoxyphenyl)[[3-bromophenyl]methyl]amino]-1,1,1-trifluoro-2-propanol (0.60 g, 1.3 mmol) from EX-595B was added benzyl-magnesium bromide in THF (2.0 mL, 2.0 M, 4.0 mmol) and Pd(PPh3)4. The resulting yellow solution was refluxed under N2 for 18 h. The cooled solution was poured into saturated aq. NH4Cl, extracted with ethyl acetate, dried (MgSO4) and evaporated to an oil. Purification by flash chromatography on silica gel eluting with 15% ethyl acetate in hexane gave an oil which was dissolved in EtOH, stripped and dried in vacuo to give 0.39 g (62%) of the desired 3-[(3-phenoxyphenyl)[[3-(phenylmethyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol product as a colorless oil. Anal. calcd. for C29H26NO2F3\u00b70.4 EtOH: C, 72.17; H, 5.77; N, 2.82. Found: C, 72.17; H, 5.42; N, 2.83. HRMS calcd. 478.1994 ([M+H]+, found: 478.1984. 1H NMR (C6D6) \u03b41.58 (d, 1H), 3.22 (dd, 1H), 3.46 (dd, 1H), 3.69 (s, 2H), 3.73 (m, 1H), 4.18 (s, 2H), 6.34 (dd, 1H), 6.47 (dd, 1H), 6.53 (t, 1H), 6.8-7.1 (m 15H).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-[(3-phenoxyphenyl)[[3-bromophenyl]methyl]amino]-1,1,1-trifluoro-2-propanol\"}], \"amount\": {\"mass\": {\"value\": 0.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzyl-magnesium bromide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd(PPh3)4\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOH\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH4Cl\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The resulting yellow solution was refluxed under N2 for 18 h\", \"duration\": {\"value\": 18.0, \"units\": \"HOUR\"}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated to an oil\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification by flash chromatography on silica gel eluting with 15% ethyl acetate in hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"gave an oil which\"}, {\"type\": \"CUSTOM\", \"details\": \"dried in vacuo\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-[(3-phenoxyphenyl)[[3-(phenylmethyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.39, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 62.0}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-6fe51444eb834021a14c70493beacaaf",
    "procedure_text": "To a solution of 5-benzyloxy-6-hydroxy-2-(1-naphthalen-1-yl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid cyclopropyl-(2-hydroxyethyl)-amide (355) (120 mg, 0.22 mmol) and diisopropyl azodicarboxylate (0.22 mL, 1.12 mmol) in dichloromethane (30 mL) was added triphenyl phosphine (351 mg, 1.34 mmol) at room temperature and the reaction mixture was stirred for 15 min at the same temperature. The yellow color disappeared (silica TLC 5% methanol in ethyl acetate, Rf=0.2). The dichloromethane was removed in vacuo and the crude mass was purified by silica gel (normal, 100-200 mesh) column chromatography using a gradient eluent mixture of 1% to 5% methanol in dichloromethane to get pure 9-benzyloxy-2-cyclopropyl-6-(1-naphthalen-1-yl-cyclopentylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (356) (106 mg, 92%) as a white solid.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-benzyloxy-6-hydroxy-2-(1-naphthalen-1-yl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid cyclopropyl-(2-hydroxyethyl)-amide\"}], \"amount\": {\"mass\": {\"value\": 120.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropyl azodicarboxylate\"}], \"amount\": {\"volume\": {\"value\": 0.22, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triphenyl phosphine\"}], \"amount\": {\"mass\": {\"value\": 351.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture was stirred for 15 min at the same temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The dichloromethane was removed in vacuo\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the crude mass was purified by silica gel (normal, 100-200 mesh) column chromatography\"}, {\"type\": \"ADDITION\", \"details\": \"a gradient eluent mixture of 1% to 5% methanol in dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"9-benzyloxy-2-cyclopropyl-6-(1-naphthalen-1-yl-cyclopentylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 106.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 92.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 92.7}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-461d3d1f3b7a4aafb6a74d689355eaa6",
    "procedure_text": "6-(5-Nitropyridin-2-yloxy)-2-phenylchromen-4-one was prepared as described for 5-nitro-2-(2-phenylchroman-6-yloxy)pyridine in Example 1(b) starting from 500 mg of 6-hydroxyflavone. The product was recrystallised from a mixture of 2-propanol and acetone. 1H NMR (300 MHz, d6-DMSO) \u03b4: 9.04 (d, 1H, J 2.9 Hz), 8.67 (dd, 1H, J 9.0, 2.9 Hz), 8.16-8.13 (m, 2H), 7.95 (d, 1H, J 9.0 Hz), 7.82 (d, 1H, J 2.9 Hz), 7.63 (dd, 1H, J 9.1, 2.9 Hz), 7.64-7.61 (m, 3H), 7.38 (d, 1H, J 9.1 Hz), 7.09 (s, 1H).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-nitro-2-(2-phenylchroman-6-yloxy)pyridine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-hydroxyflavone\"}], \"amount\": {\"mass\": {\"value\": 500.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The product was recrystallised from a mixture of 2-propanol and acetone\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-propanol\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-(5-Nitropyridin-2-yloxy)-2-phenylchromen-4-one\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fa8dca432e6a43c4927af002bbe69501",
    "procedure_text": "8-Oxo-9-phenyl-2-(pyridin-3-yl)-8,9-dihydro-7H-purine-6-carboxylic acid. 8-Oxo-9-phenyl-2-(pyridin-3-yl)-8,9-dihydro-7H-purine-6-carboxamide (0.2 g, 0.55 mmol) was dissolved in a mixture of DMSO (3 mL) and aqueous 6N hydrochloric acid solution (1.2 mL). The mixture was heated to 90\u00b0 C. for 24 h and then poured into an ice/water slurry. The pH was adjusted to 5 and the resulting precipitate was filtered and dried to afford the title compound as a solid (0.108 g, 0.323 mmol, 54% yield), which was used directly in the next step. MS (ESI) m/z 334.1 [M+1]+.",
    "reference_string": "{\"inputs\": {\"m2_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"8-Oxo-9-phenyl-2-(pyridin-3-yl)-8,9-dihydro-7H-purine-6-carboxamide\"}], \"amount\": {\"mass\": {\"value\": 0.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMSO\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 1.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"8-Oxo-9-phenyl-2-(pyridin-3-yl)-8,9-dihydro-7H-purine-6-carboxylic acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 90.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"the resulting precipitate was filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 0.323, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.108, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 54.0}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-130e6b76e4c144f3a7794073a6c46351",
    "procedure_text": "The acylated compound (8.20)(1.00 g, 3.75 mmol) was oximated with ethoxyamine hydrochloride (0.39 g, 4.0 mmol) in the presence of triethylamine as described in Part (c) of the general procedure above, to afford the title compound (4.9)(1.00 g, 86%) as a mobile pale yellow oil. (Found: M, 309.196. C17H27NO4 requires 309.194.) 1H n.m.r. \u03b4(CDCl3) 14.80, very broad s, 1H; 4.08, q, J 7 Hz, OCH2CH3 ; 3.00, t, J 7.5 Hz, CH2CH2CH3 ; 2.68, s, 2H5; 2.2-1.2 complex, 11H; 1.30, t, J 7.5 Hz, OCH2CH3 ; 1.15-0.7, m, CH2CH2CH3 and CH3.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound ( 8.20 )\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethoxyamine hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 0.39, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"( c )\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 86.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 86.2}}], \"isolated_color\": \"mobile pale yellow\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a2c0c1dda0404ba6acbb3a7f73fc8562",
    "procedure_text": "2-Amino-6-fluorophenol (95MF2085) (0.256 g, 2.0 mmol), 2-chloroacetyl chloride (0.25 g, 2.2 mmol) and K2CO3 (0.583 g, 4.2 mmol) were mixed according to GP1 to give the title compound as a crude (95MF45) (0.29 g)",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-Amino-6-fluorophenol\"}], \"amount\": {\"mass\": {\"value\": 0.256, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloroacetyl chloride\"}], \"amount\": {\"mass\": {\"value\": 0.25, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"K2CO3\"}], \"amount\": {\"mass\": {\"value\": 0.583, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.29, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-36da02b22ed345d3bdeb04fa171e114b",
    "procedure_text": "To a solution of 6-chloro-7-trifluoromethyl-1,4-dihydro-2,3-quinoxalinedione (31 mg, 0.12 mmol) in concentrated H2SO4 (0.3 mL) at 0\u00b0 C. was added KNO3 (14 mg, 0.141 mmol, Baker). The mixture was stirred at 0\u00b0 C. for 0.5 h and then at room temperature for 20 h and it was poured into ice water (2 g). The precipitate was collected by filtration, giving 31 mg of crude title compound. The sample was dissolved in 1N KOH (1 mL) and filtered. The filtrate was acidified to pH=2 with 4N HCl to give a yellow precipitate which was collected by filtration and then dried in air at 50\u00b0 C. for 4 h to give the title compound (29 mg, 80%) as a yellow powder. Crystallization from DMSO/H2O gave pure compound (18 mg) as yellow microcrystals. mp: 342\u00b0-5\u00b0 C., IR (KBr, cm-1): 3394, 3301, 3248, 3209, 1761, 1701, 1628, 1542. 1H NMR (DMSO-d6): \u03b4 7.618 (s, 1H), 12.351 (s, 1H), 12.552 (s, 1H). HRMS: calcd for C9H3ClF3N3O4 (M+) m/z: 308.9763, found: 308.9759.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-chloro-7-trifluoromethyl-1,4-dihydro-2,3-quinoxalinedione\"}], \"amount\": {\"mass\": {\"value\": 31.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"KNO3\"}], \"amount\": {\"mass\": {\"value\": 14.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2SO4\"}], \"amount\": {\"volume\": {\"value\": 0.3, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"KOH\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at 0\\u00b0 C. for 0.5 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WAIT\", \"details\": \"at room temperature for 20 h\", \"duration\": {\"value\": 20.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"The precipitate was collected by filtration\"}, {\"type\": \"CUSTOM\", \"details\": \"giving 31 mg of crude title compound\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude title compound\"}], \"amount\": {\"mass\": {\"value\": 31.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a yellow precipitate which\"}, {\"type\": \"FILTRATION\", \"details\": \"was collected by filtration\"}, {\"type\": \"CUSTOM\", \"details\": \"dried in air at 50\\u00b0 C. for 4 h\", \"duration\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 50.0, \"units\": \"CELSIUS\"}}}], \"outcomes\": [{\"reaction_time\": {\"value\": 0.5, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 29.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 80.0}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"POWDER\", \"details\": \"powder\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a2d8d691167f4b948cba2b264986dece",
    "procedure_text": "A solution of 5.58 g (29 mmol) 1-(4-aminophenyl)-4-methylpiperazine and 3.77 g (29 mmol) N-ethyldiisopropylamine in 30 ml tetrahydrofuran was cooled in an ice bath and 3.518 g (29 mmol) pivaloyl chloride were added dropwise. The suspension was stirred for 18 h at room temperature. Water (30 ml) and dichloromethane (50 ml) were added and the organic layer was separated. The aqueous phase was re-extracted with dichloromethane. The combined organic layers were dried (magnesium sulfate) and evaporated to give a white solid. Washing with a mixture of hexane and ethyl acetate (4:1) yielded 6.69 g (83%) of a white crystalline compound.",
    "reference_string": "{\"inputs\": {\"m1_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(4-aminophenyl)-4-methylpiperazine\"}], \"amount\": {\"mass\": {\"value\": 5.58, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-ethyldiisopropylamine\"}], \"amount\": {\"mass\": {\"value\": 3.77, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Water\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pivaloyl chloride\"}], \"amount\": {\"mass\": {\"value\": 3.518, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The suspension was stirred for 18 h at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the organic layer was separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"The aqueous phase was re-extracted with dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic layers were dried (magnesium sulfate)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a white solid\"}, {\"type\": \"WASH\", \"details\": \"Washing with a mixture of hexane and ethyl acetate (4:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 18.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"white crystalline compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 6.69, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 83.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 83.8}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-db2a0bc00f7e4894bf66ba889d77f634",
    "procedure_text": "Using procedure 49, 2-(dipropylamino)-2,3-dihydro-1H-indene-5,6-dicarboxylate (92, 0.3 g, 1.0 mmol) was treated with 4-aminobenzamide (1.4 g, 10.0 mmol). Purification on silica gel, eluting with 9:1 CH2Cl2 /MeOH sat'd w/ NH3, afforded a solid that was converted to an HCl salt and recrystallized from EtOAc/MeOH to give 122 as a white solid (m.p. 275-276\u00b0 C.).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(dipropylamino)-2,3-dihydro-1H-indene-5,6-dicarboxylate\"}], \"amount\": {\"mass\": {\"value\": 0.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-aminobenzamide\"}], \"amount\": {\"mass\": {\"value\": 1.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Purification on silica gel\"}, {\"type\": \"WASH\", \"details\": \"eluting with 9:1 CH2Cl2 /MeOH\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2 MeOH\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"afforded a solid\"}, {\"type\": \"CUSTOM\", \"details\": \"recrystallized from EtOAc/MeOH\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc MeOH\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"122\"}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-815b06e463124c968ea2ab30398fc261",
    "procedure_text": "In a similar manner to Example 63, (2S,4S)-1-[[N-(4-carboxybicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (50.3 mg) and 3-fluoro-4-morpholinylaniline (62.0 mg) were used to obtain (2S,4S)-4-fluoro-1-[[N-[4-[N-(3-fluoro-4-morpholinylphenyl)amino]carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]pyrrolidine-2-carbonitrile (28.6 mg).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2S,4S)-1-[[N-(4-carboxybicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile\"}], \"amount\": {\"mass\": {\"value\": 50.3, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-fluoro-4-morpholinylaniline\"}], \"amount\": {\"mass\": {\"value\": 62.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2S,4S)-4-fluoro-1-[[N-[4-[N-(3-fluoro-4-morpholinylphenyl)amino]carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]pyrrolidine-2-carbonitrile\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 28.6, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-062b05b58d5c416ea8ee5f2abff199eb",
    "procedure_text": "2-Oxo-2,3-dihydro-1H-indole-5-carboxylic acid was condensed with 5-(2-pyrrolidin-1-yl-ethoxy)-1H-indole-2-carbaldehyde to give the title compound.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-Oxo-2,3-dihydro-1H-indole-5-carboxylic acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-(2-pyrrolidin-1-yl-ethoxy)-1H-indole-2-carbaldehyde\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fdcc156692e6443a99dc186f2ab6ed98",
    "procedure_text": "Intermediate 21 was coupled with tyramine following procedure F. LC-MS showed the product had the expected M+H+ of 504. 1H NMR (Varian 300 MHz, CDCl3, shifts relative to the solvent peak at 7.24 ppm) \u03b4 8.4 (d, 2H) 8.3 (d, 1H) 8.0 (s, 1H) 7.9 (m, 1H) 7.5 (m, 2H) 7.0 (m, 4H) 6.9 (d, 1H) 6.7 (d, 2H) 5.5 (m, 1H) 4.4 (s, 2H) 3.7 (m, 2H) 3.5 (, 2H) 2.8 (m, 7H).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Intermediate 21\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tyramine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"504\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-3bbe94ba33af4d1f842df36677700530",
    "procedure_text": "To a solution of (2S)-2-(4-bromophenyl)-4-((1R)-1-phenylethyl)morpholine (intermediate 13, 63.3 g, 183 mmol) in tetrahydrofuran (450 ml) was added n-butyllithium (1.57 M in hexane solution, 175 ml, 275 mmol) at \u221278\u00b0 C. and the mixture was stirred for 20 minutes. N,N-dimethylformamide (28.3 ml 365 mmol) was added and the mixture was stirred for 2 hours at \u221278\u00b0 C. and then allowed to be warmed to \u221210\u00b0 C. The reaction was quenched with aqueous ammonium chloride, and the resulting solution was partitioned between water and ethyl acetate. The organic layer was washed with water and brine and dried over sodium sulfate. The solvent was evaporated under reduced pressure to afford crude 4-((2S)-4((1R)-1-phenylethyl) morpholin-2-yl)benzaldehyde (intermediate 14, 55.1 g). This compound was used without further purification.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 28.3, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m5_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2S)-2-(4-bromophenyl)-4-((1R)-1-phenylethyl)morpholine\"}], \"amount\": {\"mass\": {\"value\": 63.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"intermediate 13\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-butyllithium\"}], \"amount\": {\"volume\": {\"value\": 175.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 450.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -10.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred for 20 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"the mixture was stirred for 2 hours at \\u221278\\u00b0 C.\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": -78.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The reaction was quenched with aqueous ammonium chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the resulting solution was partitioned between water and ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with water and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The solvent was evaporated under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 20.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-((2S)-4((1R)-1-phenylethyl) morpholin-2-yl)benzaldehyde\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 55.1, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4d5b65c86c6645749f65d224fc9fcb58",
    "procedure_text": "The title compound (0.41 g, 80% yield) was prepared from (E)-3-[1,1\u2032;3\u2032,1\u2033]terphenyl-4\u2033-yl-but-2-en-1-ol (0.30 g, 1.0 mmol) and (S)-ethyl 2-ethoxy-3-(4-hydroxyphenyl)-propionate (0.25 g, 1.05 mmol) by a procedure analogous to that described in example 52c.",
    "reference_string": "{\"inputs\": {\"m0_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(E)-3-[1,1\\u2032;3\\u2032,1\\u2033]terphenyl-4\\u2033-yl-but-2-en-1-ol\"}], \"amount\": {\"mass\": {\"value\": 0.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(S)-ethyl 2-ethoxy-3-(4-hydroxyphenyl)-propionate\"}], \"amount\": {\"mass\": {\"value\": 0.25, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.41, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 80.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-526f0f308ba44dc7b4ea19f0051a3e75",
    "procedure_text": "A mixture of 1.5 g (6.8 mmol) of ethyl \u03b1-(3-pyridylcarbonyl)isobutyrate and 0.88 g (12 mmol) of phenyl hydrazine was dissolved in 50 ml of toluene, and the solution was dehydrated and heated under reflux in the presence of p-toluenesulfonic acid monohydrate (catalytic amount) for 18 hours. The reaction solution was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=3/2 (v/v)) to give 1.5 g of the object compound as white crystals (yield 83%).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl \\u03b1-(3-pyridylcarbonyl)isobutyrate\"}], \"amount\": {\"mass\": {\"value\": 1.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"phenyl hydrazine\"}], \"amount\": {\"mass\": {\"value\": 0.88, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"p-toluenesulfonic acid monohydrate\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"heated\"}, {\"type\": \"CONCENTRATION\", \"details\": \"The reaction solution was concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=3/2 (v/v))\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-hexane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"object compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.5, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 83.0}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2051d1ebae29408aac813d31e5c3710d",
    "procedure_text": "The compound of Example 16 (340 mg, 1.53 mmol), ethyl 3,4-dihydro-7-(3-iodopropoxy)-8-propyl-2H-I-benzopyran-2propanoate (685 mg, 1.53 mmol), and potassium carbonate (276 mg, 2.00 mmol) were added to 2.0 ml of DMF, and the reaction mixture was stirred at room temperature overnight. Water (50 ml) was added to the reaction mixture and it was extracted four times with 30 ml aliquots of ethyl acetate. The combined ethyl acetate extracts were washed with water, then dried over magnesium sulfate, filtered and concentrated in vacuo to give a brown oil. Chromatography of the oil on silica gel with 30/70 ethyl acetate/hexane as eluant gave the product as a white solid (200 mg).",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Water\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound\"}], \"amount\": {\"mass\": {\"value\": 340.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 3,4-dihydro-7-(3-iodopropoxy)-8-propyl-2H-I-benzopyran-2propanoate\"}], \"amount\": {\"mass\": {\"value\": 685.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 276.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5_m0\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate hexane\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture was stirred at room temperature overnight\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"was extracted four times with 30 ml aliquots of ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined ethyl acetate extracts were washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a brown oil\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"MILLIGRAM\"}}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-8d32d059b743444ab6f3961eb26bc22b",
    "procedure_text": "A solution of dimethyl-2-oxotridecylphosphonate (984 mg, 3.21 mmol) in tetrahydrofuran (25 ml) was added dropwise to a suspension of sodium hydride (128 mg; a 60% suspension in mineral oil) in tetrahydrofuran (5 ml) at 0\u00b0 under argon. After 1.5 hours at room temperature, the mixture was cooled to 0\u00b0 and a solution of 5-trimethylsilyl-3-furaldehyde (450 mg, 2.68 mmol) in tetrahydrofuran (15 ml) was added. Stirring was continued for 14 hours, while the cooling bath attained room temperature. The mixture was quenched with 5% ammonium chloride and washed with 5% sodium bicarbonate and water. Evaporation of the dried (magnesium sulfate) organic phase gave a residue, which was purified by a silica column using 5% ethyl acetate/hexane to give the titled ketone.",
    "reference_string": "{\"inputs\": {\"m1_m5_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethyl-2-oxotridecylphosphonate\"}], \"amount\": {\"mass\": {\"value\": 984.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydride\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-trimethylsilyl-3-furaldehyde\"}], \"amount\": {\"mass\": {\"value\": 450.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"suspension\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"Stirring\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"at 0\\u00b0\"}, {\"type\": \"TEMPERATURE\", \"details\": \"the mixture was cooled to 0\\u00b0\"}, {\"type\": \"WAIT\", \"details\": \"was continued for 14 hours, while the cooling bath attained room temperature\", \"duration\": {\"value\": 14.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The mixture was quenched with 5% ammonium chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with 5% sodium bicarbonate and water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Evaporation of the\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (magnesium sulfate) organic phase\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"gave a residue, which\"}, {\"type\": \"CUSTOM\", \"details\": \"was purified by a silica column\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.5, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ketone\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-26a2143ce3824a61982725e197f07b57",
    "procedure_text": "A mixture of 5-(3-bromopropylidene)-10,11-dihydro-5H-dibenzo[a,d]cycloheptene (5.8 g, 19.8 mmol), ethyl 4-(piperidin-4-yl)butyrate (6.1 g, 29 mmol), potassium carbonate (2.9 g, 21 mmol) and N,N-dimethylformamide (10 ml) was heated at 120\u00b0 C. for 5 h. After cooling, benzene (50 ml) and water (50 ml) were added and the phases were separated. The organic phase was dried and the solvent was evaporated in vacuo. The residue was purified by column chromatography on silica gel (50 g) using mixtures of benzene and chloroform as eluents to give 6.9 g (83%) of 4-(1-(3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-propyl)piperidin-4-yl)butyric acid ethyl ester as an oil.",
    "reference_string": "{\"inputs\": {\"m6_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzene\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-(3-bromopropylidene)-10,11-dihydro-5H-dibenzo[a,d]cycloheptene\"}], \"amount\": {\"mass\": {\"value\": 5.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 4-(piperidin-4-yl)butyrate\"}], \"amount\": {\"mass\": {\"value\": 6.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 2.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 120.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"After cooling\"}, {\"type\": \"CUSTOM\", \"details\": \"the phases were separated\"}, {\"type\": \"CUSTOM\", \"details\": \"The organic phase was dried\"}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was evaporated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by column chromatography on silica gel (50 g)\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(1-(3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-propyl)piperidin-4-yl)butyric acid ethyl ester\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 6.9, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 83.0}}], \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a5cf592e2d004aaa848de6478e32082a",
    "procedure_text": "A 1-L three-neck round-bottomed flask equipped with a mechanical stirrer and reflux condenser was purged with nitrogen and charged with 41 (21.7 g, 93.3 mmol), ethanol (305 mL), iron powder (\u2212325 mesh, 52.1 g, 933 mmol) and 2N hydrochloric acid (50 mL, 100 mmol), and the mixture was heated for 2 h at 60\u00b0 C. After this time, the reaction was cooled to room temperature, and potassium carbonate was added to pH 8 as determined by a pH paper. The resulting suspension was filtered and the filter cake washed with ethanol (4\u00d7100 mL). The filtrate was concentrated under reduced pressure to yield a brown solid. This solid was purified by column chromatography on silica gel to afford 42 in 77% yield (14.5 g) as an off-white powder: mp 104-105\u00b0 C.; 1H NMR (500 MHz, DMSO-d6) \u03b4 7.15 (d, 1H, J=2.5 Hz), 6.46 (d, 1H, J=2.5 Hz), 5.45 (bs, 2H), 3.40 (s, 3H); MS (ESI+) m/z 203 (M+H).",
    "reference_string": "{\"inputs\": {\"m1_m5_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"41\"}], \"amount\": {\"mass\": {\"value\": 21.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"iron\"}], \"amount\": {\"mass\": {\"value\": 52.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 305.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"A 1-L three-neck round-bottomed flask equipped with a mechanical stirrer\"}, {\"type\": \"TEMPERATURE\", \"details\": \"reflux condenser\"}, {\"type\": \"CUSTOM\", \"details\": \"was purged with nitrogen\"}, {\"type\": \"TEMPERATURE\", \"details\": \"After this time, the reaction was cooled to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"The resulting suspension was filtered\"}, {\"type\": \"WASH\", \"details\": \"the filter cake washed with ethanol (4\\u00d7100 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"The filtrate was concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"to yield a brown solid\"}, {\"type\": \"CUSTOM\", \"details\": \"This solid was purified by column chromatography on silica gel\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"42\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 77.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fda91eff74874479a9f700e8925673a9",
    "procedure_text": "L-(-)-proline (7.50 g., 65.1 mmol) and sodium borohydride (2.46 g., 65.1 mmol) were stirred in tetrahydrofuran under nitrogen for sixteen hours. Recrystallized o-nitrophenylpyruvic acid (14.17 g., 76.5 mmol) in tetrahydrofuran (50 ml.) was added dropwise, and the resulting solution was stirred at room temperature for six days. The solvent was evaporated and the resulting gum was stirred with 10% aqueous HCl (200 ml.) for 4.5 hours. A small amount of solid was filtered to provide nearly racemic \u03b1-hydroxy-2-nitrobenzenepropanoic acid, 1.25 g., m.p. 98\u00b0-102\u00b0 C., [\u03b1]D25 -4.21\u00b0 (c 2.045, EtOH).",
    "reference_string": "{\"inputs\": {\"m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"o-nitrophenylpyruvic acid\"}], \"amount\": {\"mass\": {\"value\": 14.17, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"L-(-)-proline\"}], \"amount\": {\"mass\": {\"value\": 7.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium borohydride\"}], \"amount\": {\"mass\": {\"value\": 2.46, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the resulting solution was stirred at room temperature for six days\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The solvent was evaporated\"}, {\"type\": \"STIRRING\", \"details\": \"the resulting gum was stirred with 10% aqueous HCl (200 ml.) for 4.5 hours\", \"duration\": {\"value\": 4.5, \"units\": \"HOUR\"}, \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"A small amount of solid was filtered\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 6.0, \"units\": \"DAY\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"racemic \\u03b1-hydroxy-2-nitrobenzenepropanoic acid\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-10d26f1ffbe34b4fb3ec4cb27f04a2ea",
    "procedure_text": "As the urea granules continued to roll a thin layer of the MDI-isocyanuric acid liquid was sprayed onto the urea, amounting to 40.0 grams. One minute time was allowed for the reaction of the MDI with the urea, and then polyol-melamine amounting to 40.0 grams was sprayed on top of the MDI-isocyanuric layer. The layers were allowed 1 minute at 95\u00b0 C. to react. The melamine and isocyanuric acid reacted to form very fine particles of melamine cyanurate and the MDI and polyol reacted and polymerized to form very strong water insoluble polyurethane resin. The sprays of the MDI-isocyanuric acid, and the polyol-melamine layers were repeated until a total of 240.0 grams coatings were applied. After a final 2 minutes reaction time, the coated urea was cooled to ambient temperature and evaluated.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"urea\"}], \"reaction_role\": \"REACTANT\"}]}, \"m6_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"melamine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isocyanuric acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"urea\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isocyanuric acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"polyol-melamine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"urea\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"to react\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"melamine cyanurate\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-32eb7c4fb7f94725acb9b48ad9d55bd0",
    "procedure_text": "The condensation of (2\u2032R,4R)-5,5-difluoro-5,5\u2033,6,6\u2033-tetrahydro-4\u2033H-dispiro[1,3-oxazine-4,4\u2032-chromene-2\u2032,3\u2033-pyran]-2,6\u2032-diamine (intermediate B7.5) and 5-cyanopicolinic acid yielded the title compound (64% yield) as a yellow solid. MS (ISP): m/z=470.3 [M+H]+.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2\\u2032R,4R)-5,5-difluoro-5,5\\u2033,6,6\\u2033-tetrahydro-4\\u2033H-dispiro[1,3-oxazine-4,4\\u2032-chromene-2\\u2032,3\\u2033-pyran]-2,6\\u2032-diamine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"intermediate B7.5\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-cyanopicolinic acid\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 64.0}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-005cc5e19563402bbd74cb51b5c65018",
    "procedure_text": "To a solution of 4-methyl-2-oxo-2H-chromene-7-carbonitrile (670 mg, 3.6 mmol) in dry THF (30 mL) at \u221220\u00b0 C. was added drop wise 1.0 M LiHMDS solution in THF (5.4 mL). After 30 minutes 2-chloro-1-isocyanato-benzene (221 mg) was added into the reaction mixture and the reaction mixture was stirred for 1 hour. The reaction mixture was then quenched with saturated aqueous ammonium chloride (25 mL) and extracted with ethyl acetate (50 mL). The organic layer was separated and dried over sodium sulfate, then concentrated and purified on silica gel eluted with 30%-100% ethyl acetate in hexanes to yield 2-(7-cyano-2-oxo-2H-chromen-4-yl)-N-(2-chloro-phenyl)-acetamide as a foam.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-methyl-2-oxo-2H-chromene-7-carbonitrile\"}], \"amount\": {\"mass\": {\"value\": 670.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"LiHMDS\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 5.4, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloro-1-isocyanato-benzene\"}], \"amount\": {\"mass\": {\"value\": 221.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture was stirred for 1 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was then quenched with saturated aqueous ammonium chloride (25 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium chloride\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate (50 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The organic layer was separated\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"purified on silica gel\"}, {\"type\": \"WASH\", \"details\": \"eluted with 30%-100% ethyl acetate in hexanes\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(7-cyano-2-oxo-2H-chromen-4-yl)-N-(2-chloro-phenyl)-acetamide\"}], \"texture\": {\"type\": \"FOAM\", \"details\": \"foam\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b2fce8e7a7ca448ebb616344ced82de4",
    "procedure_text": "Followed general procedure using: the corresponding peptidomimetic epoxide ethyl ester 45 (27 mg, 0.05 mmol); LiOH (1.2 mg, 0.05 mmol); after extraction afforded the desired product as a white solid (20 mg, 78.3%). 1H NMR (DMSO-d6, 400 MHz): \u03b4 9.00-8.99 (d, 1H, J=1.79 Hz); 8.74-8.71 (t, 1H); 8.59 (s, 1H); 8.48-8.47 (d, 1H, J=8.42 Hz); 8.47-8.45 (d, 2H, J=9.15 Hz); 8.21-8.19 (d, 2H, J=9.15 Hz); 7.34-7.33 (d, 1H, J=1.78 Hz); 4.69-4.66 (q, 1H); 4.42-4.41 (d, 2H, J=5.60 Hz); 3.60-3.59 (d, 1H, J=1.79 Hz); 3.50-3.10 (m, 3H). 13C NMR (DMSO-d6, 100 MHz): 170.68, 169.07, 165.75, 154.10, 153.25, 147.11, 147.05, 141.26, 126.08, 121.95, 120.94, 116.23, 53.24, 52.95, 51.85, 34.69, 33.44. HRMS-ESI: m/z [M+H+] calculated for C19H17N7O7S: 488.4543, observed: m/z 488.0986 (M+H+); m/z 486.0864 (M\u2212H+). HPLC Method 2: Rt=20.4 min; 93.4%.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"epoxide ethyl ester\"}], \"amount\": {\"mass\": {\"value\": 27.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"LiOH\"}], \"amount\": {\"mass\": {\"value\": 1.2, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"after extraction\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 20.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 78.3}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-96b9fa93e03f4ce4bafc8366aa31db51",
    "procedure_text": "To cyclohexanone (1.0 mL, 10 mmol) in dichloroethane (30 mL) was added cyclopropylamine (0.70 mL, 10 mmol), NaBH(OAc)3 (3.18 g, 15 mmol) and AcOH (0.57 mL, 10 mmol). The reaction was stirred at room temperature for 10 h. The reaction mixture was poured into water (60 mL) and acidified to pH 2 with 5 N HCl followed by removal of the organic portion. The aqueous portion was brought to pH>12 with 5 N NaOH and extracted with CH2Cl2 (3\u00d730 mL). The collected organic extracts were dried with Na2SO4 and the volatile organics were removed in vacuo to afford the desired intermediate.",
    "reference_string": "{\"inputs\": {\"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m6_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cyclohexanone\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cyclopropylamine\"}], \"amount\": {\"volume\": {\"value\": 0.7, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaBH(OAc)3\"}], \"amount\": {\"mass\": {\"value\": 3.18, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"AcOH\"}], \"amount\": {\"volume\": {\"value\": 0.57, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloroethane\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction was stirred at room temperature for 10 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"followed by removal of the organic portion\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with CH2Cl2 (3\\u00d730 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The collected organic extracts were dried with Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the volatile organics were removed in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 10.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired intermediate\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a98e33f216a9467f98b1069e9dbb14ab",
    "procedure_text": "The title compound was prepared from 8-Amino-4-ethyl-7-methoxy-1-methyl-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-one and 1-[5-(2,5-Dichloro-pyrimidin-4-ylamino)-2-methoxy-benzyl]-3-ethyl-1-(2-hydroxy-ethyl)-urea in an analogous manner to example 730 (0.010 g, 9%). Mp 65-70\u00b0 C.; LCMS (m/e) 556 (M); 1H-NMR (DMSO, 400 MHz) \u03b4 8.87 (s, 1H), 8.12 (s, 1H), 7.99 (s, 1H), 7.76 (s, 1H), 7.41 (m, 2H), 7.01 (s, 1H), 6.86-6.84 (d, 1H, J=9.35 Hz), 4.54 (m, 1H), 4.34-4.43 (d, 1H, J=4.04 Hz), 3.86 (s, 3H), 3.78 (s, 4H), 3.68 (s, 2H), 3.45 (s, 4H), 2.97 (s, 2H), 2.80 (s, 2H), 2.63-2.58 (m, 2H), 1.07-1.05 (t, 3H, J=7.07 Hz).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"( M )\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"8-Amino-4-ethyl-7-methoxy-1-methyl-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-one\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-[5-(2,5-Dichloro-pyrimidin-4-ylamino)-2-methoxy-benzyl]-3-ethyl-1-(2-hydroxy-ethyl)-urea\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"example 730\"}], \"amount\": {\"mass\": {\"value\": 0.01, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fbd6b0aedee046f19b1c3bdb954f0b31",
    "procedure_text": "Using the general method of Example 232, 1-(4-aminobutyl)-2-methyl-1H-imidazo[4,5-c]quinolin-4-amine (1.00 g, 3.7 mmol) was reacted with ethanesulfonyl chloride (2.11 mL, 22.3 mmol) to provide 85 mg of N-[4-(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]ethanesulfonamide as an off-white solid, m.p. 210.7\u2013211.6\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(4-aminobutyl)-2-methyl-1H-imidazo[4,5-c]quinolin-4-amine\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanesulfonyl chloride\"}], \"amount\": {\"volume\": {\"value\": 2.11, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-[4-(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]ethanesulfonamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 85.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 6.4}}], \"isolated_color\": \"off-white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-89f1736cad8144088ca459b784a0fb4a",
    "procedure_text": "13 mg of compound (33) was mixed with 200 \u03bcl of tetrahydrofuran and 14.8 \u03bcl of 1M tetrabutylammonium fluoride-tetrahydrofuran solution, and the reaction was conducted at room temperature under stirring for 15 hours. The reaction solution was charged onto a silica gel column (Kieselgel 60, Merck, 1.0\u03c6\u00d730 cm) and eluted with n-hexane-ethyl acetate (2:1). The fraction containing the desired product was concentrated to dryness to give 9.0 mg of compound (34).",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound ( 33 )\"}], \"amount\": {\"mass\": {\"value\": 13.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrabutylammonium fluoride tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 14.8, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"under stirring for 15 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"was conducted at room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"ADDITION\", \"details\": \"The reaction solution was charged onto a silica gel column (Kieselgel 60, Merck, 1.0\\u03c6\\u00d730 cm)\"}, {\"type\": \"WASH\", \"details\": \"eluted with n-hexane-ethyl acetate (2:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-hexane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"The fraction containing the desired product\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"was concentrated to dryness\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"HOUR\"}, \"products\": [{\"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 9.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c37ae6ebcdfb4438bca4ec9d069cae98",
    "procedure_text": "In a 100 ml apparatus, there were combined 30.5 g (0.1 mol) of 92% D3D', 9.1 g (0.1 mol) of methallyl chloride, and 9.5 g (0.1 mol) of Me2SiHCl. Heat was applied to 43\u00b0 C. and 0.05 ml Pt catalyst solution added, causing an exothermic reaction to 95.5\u00b0 C. in 26 min, with the heat source removed. Vacuum distillation of the complete reaction yielded 7.82 g (42.3%) of Me2SiClCH2CHMeCH2Cl and 16.89 g (45.3%) of D3D'CH2CHMeCH2Cl. This example shows that neither Me2SiHCl nor D3D' is an effective promoter for reaction of the other with methallyl chloride when used at the equimolar level.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pt\"}], \"amount\": {\"volume\": {\"value\": 0.05, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methallyl chloride\"}], \"amount\": {\"mass\": {\"value\": 9.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Me2SiHCl\"}], \"amount\": {\"mass\": {\"value\": 9.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"Heat\"}, {\"type\": \"CUSTOM\", \"details\": \"was applied to 43\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 43.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"an exothermic reaction to 95.5\\u00b0 C. in 26 min\", \"duration\": {\"value\": 26.0, \"units\": \"MINUTE\"}, \"temperature\": {\"setpoint\": {\"value\": 95.5, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"with the heat source removed\"}, {\"type\": \"DISTILLATION\", \"details\": \"Vacuum distillation of the complete reaction\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Me2SiClCH2CHMeCH2Cl\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 7.82, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 42.3}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 42.2}}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"D3D'CH2CHMeCH2Cl\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 16.89, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 45.3}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-47a26b8c668e47b399d4a48eceb17c40",
    "procedure_text": "To a solution of the product from Step A (630 mg, 1.0 mmol) in CH2Cl2 (20 mL) at \u221278\u00b0 C. was added boron trichloride (1M in CH2Cl2) (10 mL, 10 mmol). The mixture was stirred at \u221278\u00b0 C. for 2 h, then at \u221220\u00b0 C. for 2.5 h. The reaction was quenched with CH2Cl2/MeOH (1:1) (10 mL), stirred at \u221220\u00b0 C. for 0.5 h, and neutralized at 0\u00b0 C. with aqueous ammonia. The solid was filtered, washed with CH2Cl2/MeOH (1:1) and the combined filtrate evaporated in vacuo. The residue was purified on a silica gel column with CH2Cl2/MeOH, 50/1 and 20/1 as eluent to give the title compound as a colorless foam (250 mg).",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"amount\": {\"mass\": {\"value\": 630.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"boron trichloride\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -78.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at \\u221278\\u00b0 C. for 2 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WAIT\", \"details\": \"at \\u221220\\u00b0 C. for 2.5 h\", \"duration\": {\"value\": 2.5, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": -20.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The reaction was quenched with CH2Cl2/MeOH (1:1) (10 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2 MeOH\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"STIRRING\", \"details\": \"stirred at \\u221220\\u00b0 C. for 0.5 h\", \"duration\": {\"value\": 0.5, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": -20.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"neutralized at 0\\u00b0 C. with aqueous ammonia\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonia\"}], \"reaction_role\": \"WORKUP\"}]}, \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"FILTRATION\", \"details\": \"The solid was filtered\"}, {\"type\": \"WASH\", \"details\": \"washed with CH2Cl2/MeOH (1:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2 MeOH\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the combined filtrate evaporated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified on a silica gel column with CH2Cl2/MeOH, 50/1 and 20/1 as eluent\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2 MeOH\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 250.0, \"units\": \"MILLIGRAM\"}}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"FOAM\", \"details\": \"foam\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e151ef35c16b46b1aebe9eeb5ff99b2b",
    "procedure_text": "A solution of 41.7 ml of chloroformic acid benzyl ester (90%) in toluene is added to 25 g of 3-amino-2(R,S)-methylpropionic acid in 533 ml of 1N sodium hydroxide at 0\u00b0 C. The reaction mixture is then stirred for 30 minutes at 0\u00b0 C. After the addition of 400 ml of diethyl ether, the aqueous phase is removed and 140 ml of 4N hydrochloric acid are added. The crude title compound is obtained from the organic phase by extraction with diethyl ether: Rf (dichloromethane/methanol=8:2)=0.41.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroformic acid benzyl ester\"}], \"amount\": {\"volume\": {\"value\": 41.7, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-amino-2(R,S)-methylpropionic acid\"}], \"amount\": {\"mass\": {\"value\": 25.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"volume\": {\"value\": 533.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"amount\": {\"volume\": {\"value\": 400.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture is then stirred for 30 minutes at 0\\u00b0 C\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the aqueous phase is removed\"}, {\"type\": \"ADDITION\", \"details\": \"140 ml of 4N hydrochloric acid are added\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 140.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-762dd763ee104b21830661a0cc457235",
    "procedure_text": "Potassium carbonate (4.6 g, 33 mmol), potassium iodide (0.25 g, 1.5 mmol) and tert-butylbromoacetate (2.5 ml, 16.5 mmol) were added to a solution of 4-hydroxy-3-methyl-benzoic acid methyl ester from Example E29 (2.5 g, 15 mmol) in acetone (150 ml) and the mixture was heated at reflux for 20 h. The solid was filtered off and the filtrate concentrated in vacuo. The residue was dissolved in EtOAc, washed with 1N KHSO4, water then brine, dried and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; 15% EtOAc:85% hexane) to yield the title compound (3.8 g, 90%).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-hydroxy-3-methyl-benzoic acid methyl ester\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 4.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium iodide\"}], \"amount\": {\"mass\": {\"value\": 0.25, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butylbromoacetate\"}], \"amount\": {\"volume\": {\"value\": 2.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"the mixture was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"at reflux for 20 h\", \"duration\": {\"value\": 20.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"The solid was filtered off\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate concentrated in vacuo\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue was dissolved in EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with 1N KHSO4, water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"KHSO4\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"brine, dried\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by flash chromatography on silica gel (eluant; 15% EtOAc:85% hexane)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 3.8, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 90.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-15ea4bcac9384411bb9a9dade0ebb434",
    "procedure_text": "Reaction of 80% THPC (23.82 g, 0.1 mol) with urea (24.02 g, 0.4 mol), following Example 3, gave 36.18 g (100.8%) of tetrakis(ureidomethyl)phosphonium chloride (I, R=R'=R\"=H, X=Cl) as a colorless, brittle glass, identical (31P NMR) to the product of Example 11.",
    "reference_string": "{\"inputs\": {\"m0_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THPC\"}], \"amount\": {\"mass\": {\"value\": 23.82, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"urea\"}], \"amount\": {\"mass\": {\"value\": 24.02, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrakis(ureidomethyl)phosphonium chloride\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 36.18, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-33ca3d74cbba43e99cdd2e225912df57",
    "procedure_text": "To a stirred solution of 4-bromo-2-(trifluoromethoxy)benzoic acid (1 g, 3.67 mmol) in DMSO (20 mL) was added potassium vinyltrifluoroborate (1.47 g, 11.02 mmol) and potassium carbonate (1.52 g, 11.02 mmol). The reaction mixture was degassed with argon for 30 min Bistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride (0.13 g, 0.18 mmol) was added and the reaction mixture was heated to 80\u00b0 C. for 1 h. The reaction mixture was diluted with water (100 mL), extracted with ethyl acetate (2\u00d750 mL), washed with brine, and dried over Na2SO4. Concentration under reduced pressure furnished the crude compound which was purified by flash column chromatography to afford the product as pale yellow gummy material (0.4 g, 47%): 1H NMR (400 MHz, CDCl3) \u03b4 8.05 (d, J=8.1 Hz, 1H), 7.44 (d, J=1.8 Hz, 1H), 7.35 (s, 1H), 6.78 (dd, J=17.4.1, 11.1 Hz, 1H), 5.92 (d, J=17.4 Hz, 1H), 5.51 (d, J=10.8 Hz, 1H); ESIMS m/z 232.97 ([M+H]E).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Bistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride\"}], \"amount\": {\"mass\": {\"value\": 0.13, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m5_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-bromo-2-(trifluoromethoxy)benzoic acid\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium vinyltrifluoroborate\"}], \"amount\": {\"mass\": {\"value\": 1.47, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 1.52, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMSO\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 80.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate (2\\u00d750 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"Concentration under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"furnished the crude compound which\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude compound\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"was purified by flash column chromatography\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"material\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.4, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 47.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-12f74237b50847df8bf19b828761819c",
    "procedure_text": "To a solution of hydroxy-{2-[2-(4-trifluoromethyl-phenoxymethyl)-1H-benzoimidazol-5-yl]-phenyl}-acetic acid methyl ester (0.312 g, 0.684 mmol) in mixed solvent (14 mL, MeOH: H2O=3:1) at rt was added lithium hydroxide (LiOH) (0.098 g, 4.10 mmol). After stirring for 12 hours, the reaction mixture was diluted with EtOAc and acidified with aqueous 3N HCl. The organic layer was washed with brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to afford the title compound as a white solid (0.296 g, 98%).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m6_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydroxy-{2-[2-(4-trifluoromethyl-phenoxymethyl)-1H-benzoimidazol-5-yl]-phenyl}-acetic acid methyl ester\"}], \"amount\": {\"mass\": {\"value\": 0.312, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium hydroxide\"}], \"amount\": {\"mass\": {\"value\": 0.098, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring for 12 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WASH\", \"details\": \"The organic layer was washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate was concentrated under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 12.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.296, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 98.0}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-869327628c2440739ab17c5d97fd63c3",
    "procedure_text": "A mixture of 2-(4-methoxy-5-nitro-pyridin-2-ylmethyl)-isoindole-1,3-dione (0.24 g, 7.7 mmole) and 48% hydrobromic acid (3 mL), is refluxed for 3 hours. The reaction mixture is cooled, evaporated to dryness in vacuo, dissolved in absolute ethanol (25 mL) and 10% Palladium on carbon (100 mg) is added under an inert atmosphere. This is then hydrogenated on a Par apparatus at 45 psi for 2 hours. The reaction mixture is filtered and evaporated to give a brown solid, 60 mg, (23%), MS (ES+): m/z 140.2 (M+H). Used as is for the next step.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(4-methoxy-5-nitro-pyridin-2-ylmethyl)-isoindole-1,3-dione\"}], \"amount\": {\"mass\": {\"value\": 0.24, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrobromic acid\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"is refluxed for 3 hours\", \"duration\": {\"value\": 3.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"The reaction mixture is cooled\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated to dryness in vacuo\"}, {\"type\": \"DISSOLUTION\", \"details\": \"dissolved in absolute ethanol (25 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"10% Palladium on carbon (100 mg) is added under an inert atmosphere\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Palladium on carbon\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"The reaction mixture is filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a brown solid, 60 mg, (23%), MS (ES+)\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-2a168cc71e1c4471a47f592ea97049ed",
    "procedure_text": "1-Chloro-3-fluoro-2-(trifluoromethyl)benzene (10 g, 50 mmol) was dissolved in tetrahydrofuran (100 ml), cooled to \u221270\u00b0 C. under argon, and treated with a 1.4M solution of sec-butyl lithium in cyclohexane (37.5 ml, 52.5 mmol). Stirring was continued for 2 hrs and then trimethylsilyl chloride (6.7 ml, 52.5 mmol) was added and stirring continued, still at \u221270\u00b0 C., for a further 1 hr. The mixture was allowed to warm to room temperature and the tetrahydrofuran was then removed in vacuo. The residue was partitioned between diethyl ether and water and then the organic layer was separated and washed with 2N aqueous hydrogen chloride. The organic phase was separated and concentrated to give the crude product which was purified by flash silica-gel column chromatography, eluting with hexane, to give pure [4-chloro-2-fluoro-3-(trifluoromethyl)phenyl](trimethyl)silane as a clear oil (10.35 g).",
    "reference_string": "{\"inputs\": {\"m1_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-Chloro-3-fluoro-2-(trifluoromethyl)benzene\"}], \"amount\": {\"mass\": {\"value\": 10.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trimethylsilyl chloride\"}], \"amount\": {\"volume\": {\"value\": 6.7, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sec-butyl lithium\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cyclohexane\"}], \"amount\": {\"volume\": {\"value\": 37.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -70.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"Stirring\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"stirring\"}, {\"type\": \"WAIT\", \"details\": \"continued, still at \\u221270\\u00b0 C., for a further 1 hr\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": -70.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"to warm to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"the tetrahydrofuran was then removed in vacuo\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The residue was partitioned between diethyl ether and water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the organic layer was separated\"}, {\"type\": \"WASH\", \"details\": \"washed with 2N aqueous hydrogen chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrogen chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The organic phase was separated\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"to give the crude product which\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"was purified by flash silica-gel column chromatography\"}, {\"type\": \"WASH\", \"details\": \"eluting with hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"[4-chloro-2-fluoro-3-(trifluoromethyl)phenyl](trimethyl)silane\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 10.35, \"units\": \"GRAM\"}}}], \"isolated_color\": \"clear\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-18d098081dc9423f9bfd9a61c6bc4bec",
    "procedure_text": "Add 3 mg (0.01 mmol) trans-bis(dicyclohexylamin)palladium(II) acetate [T. Bin, J. Org. Chem. 2004, 69, 4330-4335] to a mixture of 100 mg (0.22 mmol) 6-{[6-bromo-5-(4-methoxyphenyl)furo[2,3-d]pyrimidin-4-yl]amino}hexanoic acid methyl ester, 37 mg (0.27 mmol) 4-fluorophenylboronic acid and 95 mg (0.45 mmol) potassium phosphate in 5 ml ethanol, and stir, firstly for 16 h at RT and then for 3 h at 80\u00b0 C. After filtering off the solid, concentrate the filtrate by vacuum evaporation. Purify the residue by preparative RP-HPLC (gradient: water/acetonitrile). 28 mg (26% of theor.) of the desired product is obtained.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-{[6-bromo-5-(4-methoxyphenyl)furo[2,3-d]pyrimidin-4-yl]amino}hexanoic acid methyl ester\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-fluorophenylboronic acid\"}], \"amount\": {\"mass\": {\"value\": 37.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium phosphate\"}], \"amount\": {\"mass\": {\"value\": 95.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trans-bis(dicyclohexylamin)palladium(II) acetate\"}], \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stir, firstly for 16 h at RT\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WAIT\", \"details\": \"for 3 h at 80\\u00b0 C\", \"duration\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 80.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"FILTRATION\", \"details\": \"After filtering off the solid\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrate the filtrate\"}, {\"type\": \"CUSTOM\", \"details\": \"by vacuum evaporation\"}, {\"type\": \"CUSTOM\", \"details\": \"Purify the residue by preparative RP-HPLC (gradient: water/acetonitrile)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water acetonitrile\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0628d4ad640142948598e0c736c1464b",
    "procedure_text": "Lithium thioethoxide was prepared by the dropwise addition of n-butyllithium (4 ml. of 1.53 molar solution in hexane) to a stirred solution of ethyl mercaptan (0.5 ml.) in dry N,N'-dimethylpropylene urea (DMPU) (9 ml.), under a nitrogen atmosphere. A solution of methyl 4-(6-hexanamido-2,3-dihydrobenz-1,4-oxazin-4-ylmethyl)-3-methoxybenzoate (prepared as described in Example 26) (0.35 g.) in DMPU (3 ml.) was added, the mixture stirred at ambient temperature for 15 minutes, then heated to, and maintained at, 130\u00b0 C. for 4 hours. The cooled mixture was diluted with water, acidified with acetic acid, extracted with ethyl acetate, the extracts washed with water, dried (MgSO4) and evaporated. The product was purified by flash chromatography on silica gel, eluting with 80:20:2 v/v/v toluene:ethyl acetate:acetic acid, giving a white solid which was washed with hexane and dried, to give the title compound (0.114 g., 36%) as a white solid, m.p. 183\u00b0-184\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m4_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 4-(6-hexanamido-2,3-dihydrobenz-1,4-oxazin-4-ylmethyl)-3-methoxybenzoate\"}], \"amount\": {\"mass\": {\"value\": 0.35, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMPU\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m0_m2_m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-butyllithium\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl mercaptan\"}], \"amount\": {\"volume\": {\"value\": 0.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N'-dimethylpropylene urea\"}], \"amount\": {\"volume\": {\"value\": 9.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture stirred at ambient temperature for 15 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"heated to, and\"}, {\"type\": \"TEMPERATURE\", \"details\": \"maintained at, 130\\u00b0 C. for 4 hours\", \"duration\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 130.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"the extracts washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"The product was purified by flash chromatography on silica gel\"}, {\"type\": \"WASH\", \"details\": \"eluting with 80:20:2 v/v/v toluene\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"ethyl acetate:acetic acid, giving a white solid which\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"was washed with hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Lithium thioethoxide\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.114, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 36.0}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-63d912cd8e574637aed728ad30d1abb6",
    "procedure_text": "As a result of analysis by gaschromatography, it was found that the yield of 1,4-bis(aminomethyl)cyclohexane was 95.9 mol % and as other products 3.4 mol % of 4-aminomethyl-1-methylcyclohexane, 0.3 mol % of 4-methyl-benzylamine and 0.2 mol % of paraxylene were obtained.",
    "reference_string": "{\"inputs\": {\"m0_m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"paraxylene\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,4-bis(aminomethyl)cyclohexane\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"As a result of analysis by gaschromatography, it\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-aminomethyl-1-methylcyclohexane\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-methyl-benzylamine\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-eb7df7c669f04e7cb5e7cb9f237386b2",
    "procedure_text": "Potassium carbonate (0.915 g, 6.62 mmol) and 2-fluoro-5-ethylphenylboronic acid (0.742 g, 4.14 mmol) were added at room temperature to a solution 331a) (0.8 g, 2.2 mmol) in 2-methyl-2-butanol 1/water (44 mL, 10:1). The reaction apparatus was set under an argon atmosphere and (Ataphos)2PdCl2 (0.156 g, 0.22 mmol) was introduced. The reaction mixture was stirred at 100\u00b0 C. for 4 h, cooled to room temperature and filtered through a pad of celite. The filtrate was concentrated and the remnant purified by flash column chromatography [silica; dichloromethane with 1-2% methanol]. White solid. Yield: 0.5 g (56% of theory)",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m5_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 0.915, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-fluoro-5-ethylphenylboronic acid\"}], \"amount\": {\"mass\": {\"value\": 0.742, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution 331a\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 44.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-methyl-2-butanol\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred at 100\\u00b0 C. for 4 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"(Ataphos)2PdCl2 (0.156 g, 0.22 mmol) was introduced\"}, {\"type\": \"TEMPERATURE\", \"details\": \"cooled to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"filtered through a pad of celite\"}, {\"type\": \"CONCENTRATION\", \"details\": \"The filtrate was concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"the remnant purified by flash column chromatography [silica; dichloromethane with 1-2% methanol]\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-83eb26e9272c43958eb32cb66b52f3ac",
    "procedure_text": "Methyl 3-(3,4-Dimethoxyphenyl)-3-phenylacrylate was prepared analogously to methyl 3,3-bis-(3,4-dimethoxyphenyl)acrylate using 3,4-dimethoxybenzophenone (4.8 g, 20 mmol), trimethylphosphonoacetate (4.1 g, 22 mmol) and lithium hexamethyldisilazide (22 mL, 22 mmol, 1 M) with a reaction time of 138 hours at reflux. The crude mixture was purified by flash column chromatography (silica gel, 1% ethyl acetate/methylene chloride) to afford 14.39 g (73%) of a mixture of the E and Z isomers as an oil. The isomers were separated by additional purification (silica gel, 1% ethyl acetate/methylene chloride) to afford pure samples of each of the isomers.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trimethylphosphonoacetate\"}], \"amount\": {\"mass\": {\"value\": 4.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m0_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 3,3-bis-(3,4-dimethoxyphenyl)acrylate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium hexamethyldisilazide\"}], \"amount\": {\"volume\": {\"value\": 22.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,4-dimethoxybenzophenone\"}], \"amount\": {\"mass\": {\"value\": 4.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"with a reaction time of 138 hours\", \"duration\": {\"value\": 138.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"at reflux\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude mixture was purified by flash column chromatography (silica gel, 1% ethyl acetate/methylene chloride)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude mixture\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Methyl 3-(3,4-Dimethoxyphenyl)-3-phenylacrylate\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"mixture\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 14.39, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 73.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-cba2053e67e34362bcc5567ab35ee0e6",
    "procedure_text": "A mixture of 5-(trans-3-aminocyclobutyl)-7,7-dimethyl-5H-pyrrolo[2,3-b]pyrazin-6(7H)-one dihydrochloride (Intermediate 83, 51 mg, 0.167 mmol), N-ethyl-N-isopropylpropan-2-amine (102 \u03bcl, 0.585 mmol), and 2-(methylsulfonyl)thiazolo[5,4-b]pyridine (Intermediate 76) (43.0 mg, 0.201 mmol) in DMSO (0.3 ml) was stirred at 100\u00b0 C. for 3 h. The mixture was diluted with EtOAc and water in a separatory funnel. The aqueous layer was extracted with EtOAc twice. The combined organic layer was dried over Na2SO4 and concentrated in vacuo. The crude solution was purified by silica gel chromatography (ISCO 12 g, 0-70% EtOAc-hexane) to give 7,7-dimethyl-5-(trans-3-(thiazolo[5,4-b]pyridin-2-ylamino)cyclobutyl)-5H-pyrrolo[2,3-b]pyrazin-6(7H)-one (37 mg, 0.101 mmol, 60.4% yield) as off-white solid. 1H NMR (300 MHz, CHLOROFORM-d) \u03b4 ppm 1.46 (s, 6 H) 2.50 (ddd, J=14.03, 9.35, 3.51 Hz, 2 H) 3.37-3.55 (m, 2 H) 5.30 (t, J=8.48 Hz, 1 H) 5.73 (br. s., 1 H) 7.17-7.25 (m, 1 H) 7.74 (dd, J=8.04, 1.46 Hz, 1 H) 8.05-8.16 (m, 2 H) 8.22 (dd, J=4.75, 1.53 Hz, 1 H).",
    "reference_string": "{\"inputs\": {\"m7_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3_m4_m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-(trans-3-aminocyclobutyl)-7,7-dimethyl-5H-pyrrolo[2,3-b]pyrazin-6(7H)-one dihydrochloride\"}], \"amount\": {\"mass\": {\"value\": 51.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Intermediate 83\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-ethyl-N-isopropylpropan-2-amine\"}], \"amount\": {\"volume\": {\"value\": 102.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(methylsulfonyl)thiazolo[5,4-b]pyridine\"}], \"amount\": {\"mass\": {\"value\": 43.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Intermediate 76\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMSO\"}], \"amount\": {\"volume\": {\"value\": 0.3, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at 100\\u00b0 C. for 3 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"The aqueous layer was extracted with EtOAc twice\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic layer was dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude solution was purified by silica gel chromatography (ISCO 12 g, 0-70% EtOAc-hexane)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude solution\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc hexane\"}], \"amount\": {\"mass\": {\"value\": 12.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7,7-dimethyl-5-(trans-3-(thiazolo[5,4-b]pyridin-2-ylamino)cyclobutyl)-5H-pyrrolo[2,3-b]pyrazin-6(7H)-one\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 0.101, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 37.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 60.4}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 60.5}}], \"isolated_color\": \"off-white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-ca9b3fdba3864890873b407a1113a4c5",
    "procedure_text": "The methyl ester of the compound of Example 1 step 5 (1.00 g, prepared by treating the corresponding acid with excess diazomethane) in 10 mL of a 9:1 THF/H2O solution was treated with 2.52 g of DDQ. The reaction mixture was allowed to stir at room temperature overnight. The reaction mixture at this time was poured into a separatory funnel containing EtOAc and brine. The combined organic layers were washed with water, brine, dried over anhydrous MgSO4 and concentrated. The resulting material was further purified by flash chromatography eluting with 30% EtOAc/hexane. The chromatography procedure was repeated an additional two times. 350 mg of the above ketone was obtained as a grey solid.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DDQ\"}], \"amount\": {\"mass\": {\"value\": 2.52, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diazomethane\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF H2O\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl ester\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"to stir at room temperature overnight\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"The reaction mixture at this time was poured into a separatory funnel\"}, {\"type\": \"WASH\", \"details\": \"The combined organic layers were washed with water, brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The resulting material was further purified by flash chromatography\"}, {\"type\": \"WASH\", \"details\": \"eluting with 30% EtOAc/hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ketone\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 350.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b37846dea5ad4e33841e0847aa2430b4",
    "procedure_text": "To 5.0 g of dimethyl-1,3-dioxolane-2,4-dicarboxylate (Example 5b)) in 100 ml methanol was added a solution of 4.6 g of 50% aqueous sodium hydroxide in 50 ml methanol. After stirring overnight the salt was isolated by filtration and washed with methanol and vacuum dried yielding 2.5 g (42%) of the title compound as a white hygroscopic solid. An additional 1.8 g (30%) could be isolated by addition of ether to the filtrate of the first sample.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethyl-1,3-dioxolane-2,4-dicarboxylate\"}], \"amount\": {\"mass\": {\"value\": 5.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"mass\": {\"value\": 4.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring overnight the salt\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"was isolated by filtration\"}, {\"type\": \"WASH\", \"details\": \"washed with methanol and vacuum\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.5, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 42.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f4368d62d6a347cc92d61658b2bd96e9",
    "procedure_text": "4-{[(4-Benzofuran-2-yl-phenylcarbamoyl)-(4-tert-butyl-phenyl)-methyl]-methyl-amino}-benzoic acid tert-butyl ester (\u02dc140 mg, 0.19 mmol) was taken up in 5 mL of dichloromethane followed by addition of 0.5 mL of TFA and stirred for 16 h at RT. Removal of the organic layer and water was added to give a precipitate, which was filtered to give 110 mg (100%) of pinkish solids. LCMS (M\u22121=531.1).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-{[(4-Benzofuran-2-yl-phenylcarbamoyl)-(4-tert-butyl-phenyl)-methyl]-methyl-amino}-benzoic acid tert-butyl ester\"}], \"amount\": {\"mass\": {\"value\": 140.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TFA\"}], \"amount\": {\"volume\": {\"value\": 0.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred for 16 h at RT\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Removal of the organic layer and water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a precipitate, which\"}, {\"type\": \"FILTRATION\", \"details\": \"was filtered\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pinkish solids\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 110.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 100.0}}], \"isolated_color\": \"pinkish\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solids\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-603b9bf1ee6d4252bccdcb11098269ad",
    "procedure_text": "Potassium carbonate (85.7 g, 0.62 mol) was added to 2-cyano-2-hydroxyiminoacetamide (35.0 g, 0.31 mol) in dimethylsulfoxide (150 ml) under ice-cooling, and the mixture was stirred for 20 mins. On the other hand, a solution of fluoromethyl bromide (27.8 g, 0.31 mol) in dimethylformamide (27 ml) was added dropwise to the reaction mixture under ice-cooling, and the resultant mixture was stirred at a room temperature for 1.5 hrs. The mixture was dispersed in ice water (1 kg), and it was extracted three times with ethyl acetate (500 ml, 400 ml, and 300 ml, respectively). The combined extracts were washed twice with saturated brine (150 ml) and dried over magnesium sulfate (100 g). The ethyl acetate was distilled off under reduced pressure until the residue weighed 65.5 g. The residue was cooled, filtered, and dried to give 2-cyano-2-fluoromethoxyimino-acetamide (32.8 g, yield: 72.6%).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"resultant mixture\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 85.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-cyano-2-hydroxyiminoacetamide\"}], \"amount\": {\"mass\": {\"value\": 35.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylsulfoxide\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"KILOGRAM\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"fluoromethyl bromide\"}], \"amount\": {\"mass\": {\"value\": 27.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 27.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred for 20 mins\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooling\"}, {\"type\": \"TEMPERATURE\", \"details\": \"cooling\"}, {\"type\": \"EXTRACTION\", \"details\": \"it was extracted three times with ethyl acetate (500 ml, 400 ml, and 300 ml\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined extracts were washed twice with saturated brine (150 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over magnesium sulfate (100 g)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"The ethyl acetate was distilled off under reduced pressure until the residue\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"The residue was cooled\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 20.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-cyano-2-fluoromethoxyimino-acetamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 32.8, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 72.6}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 72.9}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3eb63ff252b24af0806e7c079b527d31",
    "procedure_text": "from ethyl 2-[4-(2-aminoethyl)-phenoxy]-2-methylpropionate and benzenesulphonyl chloride;",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 2-[4-(2-aminoethyl)-phenoxy]-2-methylpropionate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzenesulphonyl chloride\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-37724ab1656547ecbe4ee241eb8c5182",
    "procedure_text": "A mixture of 3-formyl-2-methyl-7-nitrobenzo[b]furan (1.83 g) and sodium borohydride (200 mg) in methanol (40 ml) was stirred at ambient temperature for 2 hours. The reaction mixture was poured into cold water. The separated oil was extracted with dichloromethane. The extract was washed with brine, dried and evaporated in vacuo. The residue was purified by column chromatography on silica gel to give 3-hydroxymethyl-2-methyl-7-nitrobenzo[b]furan (1.38 g) as a solid.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-formyl-2-methyl-7-nitrobenzo[b]furan\"}], \"amount\": {\"mass\": {\"value\": 1.83, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium borohydride\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at ambient temperature for 2 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"The separated oil was extracted with dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The extract was washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by column chromatography on silica gel\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-hydroxymethyl-2-methyl-7-nitrobenzo[b]furan\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.38, \"units\": \"GRAM\"}}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-df90ec1d48dd4c80b2823f6af1065953",
    "procedure_text": "Into a 25 mL round-bottomed flask were added 4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)aniline (200 mg, 0.624 mmol), O-4-fluorophenyl carbonochloridothioate (238 mg, 1.249 mmol), and triethylamine (0.348 mL, 2.498 mmol) in THF (5 mL). The solution was stirred under ambient conditions for 2 h before the solvent was removed under reduced pressure. The crude product was added to a silica gel column and was eluted with EtOAc/hexanes gradient to afford the title compound (50 mg, 0.105 mmol, 17%) as a yellow solid: mp 164-169\u00b0 C.; 1H NMR (400 MHz, DMSO-d6) \u03b4 9.42 (s, 1H), 8.19-8.04 (m, 6H), 7.97 (br s, 1H), 7.66-7.57 (d, J=8.24 Hz, 2H), 7.33-7.19 (m, 4H); ESIMS m/z 475 (M+1).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)aniline\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"O-4-fluorophenyl carbonochloridothioate\"}], \"amount\": {\"mass\": {\"value\": 238.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 0.348, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The solution was stirred under ambient conditions for 2 h before the solvent\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"was removed under reduced pressure\"}, {\"type\": \"ADDITION\", \"details\": \"The crude product was added to a silica gel column\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"was eluted with EtOAc/hexanes gradient\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 0.105, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 17.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 16.8}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-6065b7190dfa4a3fb2f8de5f83fec3a0",
    "procedure_text": "A solution of aluminum trichloride (34.8 g, 261.4 mmol) in chloroform (120 mL) under argon and cooled to 0\u00b0 C. and was then treated dropwise with a solution of ethyl chlorooxoacetate (18.7 mL, 167.5 mmol) in chloroform (120 mL). The mixture was then stirred at 0\u00b0 C. for 30 min. After this time a solution of 2-chlorothioanisole (25.0 g, 156.5 mmol) in chloroform (120 mL) was added dropwise to the above mixture at 0\u00b0 C. and it turned red in color. It was allowed to warm to 25\u00b0 C. and stirred for an additional 3.5 h. The reaction was quenched by slowly adding water (500 mL). The solution turned yellow in color and was then transferred to a separatory funnel and extracted with chloroform (3\u00d750 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 80/20 hexanes/ethyl acetate) afforded (3-chloro-4-methylsulfanyl-phenyl)-oxo-acetic acid ethyl ester (31.37 g, 77%) as a yellow oil.",
    "reference_string": "{\"inputs\": {\"m4_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chlorothioanisole\"}], \"amount\": {\"mass\": {\"value\": 25.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"amount\": {\"volume\": {\"value\": 120.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl chlorooxoacetate\"}], \"amount\": {\"volume\": {\"value\": 18.7, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"amount\": {\"volume\": {\"value\": 120.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aluminum trichloride\"}], \"amount\": {\"mass\": {\"value\": 34.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"amount\": {\"volume\": {\"value\": 120.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was then stirred at 0\\u00b0 C. for 30 min\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"to warm to 25\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 25.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"STIRRING\", \"details\": \"stirred for an additional 3.5 h\", \"duration\": {\"value\": 3.5, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The reaction was quenched by slowly adding water (500 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"was then transferred to a separatory funnel\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with chloroform (3\\u00d750 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic phase was dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(3-chloro-4-methylsulfanyl-phenyl)-oxo-acetic acid ethyl ester\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 31.37, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 77.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 77.5}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2aa5e69dbf024cbc8d9fae16f00b1e3e",
    "procedure_text": "A solution of 8.70 g (49.4 mmol) of 3(R)-amino-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (Step E) in 100 mL of methylene chloride was treated with 10.73 g (49.4 mmol) of 3-t-butoxycarbonylamino-3-methylbutanoic acid (Step H) and 13.8 mL of triethylamine (10.0 g, 99 mmol, 2 eq). The reaction flask was immersed in an ambient temperature water bath then 26 g of benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (59 mmol, 1.2 eq) was added all at once and the mixture stirred at room temperature for 2 hours. The reaction mixture was added to 300 mL of ethyl acetate and washed three times with 5% aqueous citric acid, twice with saturated aqueous sodium bicarbonate and once with saturated aqueous sodium chloride. The organic layer was removed, dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The residue was purified by preparative high pressure liquid chromatography on silica, eluting with ethyl acetate/hexane (4:1), to afford 17.42 g (46.4 mmol, 94%) of the product as a white solid. 1H NMR (200 MHz, CDCl3): 1.37 (s, 6H), 1.44 (s, 9H), 1.95 (m, 1H), 2.46 (d, 15 Hz, 1H), 2.59 (d, 15 Hz, 1H), 2.6-3.0, (m, 3H), 4.53 (m, 1H), 5.30 (br s, 1H), 6.72 (d, 7 Hz, 1H), 6.98 (d, 8 Hz, 1H), 7.1-7.3 (m, 3H), 7.82 (br s, 1H). FAB-MS: calculated for C20H29N3O4 375; found 376 (M+H, 70%).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate\"}], \"amount\": {\"mass\": {\"value\": 26.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 300.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m5_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3(R)-amino-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one\"}], \"amount\": {\"mass\": {\"value\": 8.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-t-butoxycarbonylamino-3-methylbutanoic acid\"}], \"amount\": {\"mass\": {\"value\": 10.73, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 13.8, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred at room temperature for 2 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"was immersed in an ambient temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"WASH\", \"details\": \"washed three times with 5% aqueous citric acid\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"citric acid\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The organic layer was removed\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate concentrated under vacuum\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by preparative high pressure liquid chromatography on silica\"}, {\"type\": \"WASH\", \"details\": \"eluting with ethyl acetate/hexane (4:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 46.4, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 17.42, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 94.0}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-8ff1763dee7448c89d898807d294e7ea",
    "procedure_text": "Ethyl 2,2-bis(4-chlorophenyl)acetate (5.50 g, 17.8 mmol) was dissolved in 100 mL of dry tetrahydrofuran and cooled to \u221278\u00b0 C. Lithium bis(trimethylsilyl)amide (1.0 M in hexane, 18.0 mL, 18.0 mmol) was added dropwise via syringe under nitrogen. The reaction was brought to 0\u00b0 C., stirred for 1 hour, and then cooled to \u221278\u00b0 C. A solution of bromoacetonitrile (1.24 mL, 17.8 mmol) dissolved in tetrahydrofuran was added, and the reaction was stirred for 2 hours while warming to room temperature. The reaction was quenched with saturated NH4Cl solution and extracted with diethyl ether. The organic phase was washed with brine, dried over MgSO4, filtered, and concentrated. Chromatography on silica gel (Analogix Intelliflash 280; 10% ethyl acetate/hexane) yielded the title compound: 1H NMR (300 MHz, CDCl3) \u03b4 ppm 7.38-7.32 (m, 4H), 7.22-7.17 (m, 4H), 4.25 (q, J=7.2, 2H), 3.32 (s, 2H), 1.23 (t, J=7.2, 3H); MS (DCI+) m/z 365 (M+NH4)+.",
    "reference_string": "{\"inputs\": {\"m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"bromoacetonitrile\"}], \"amount\": {\"volume\": {\"value\": 1.24, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ethyl 2,2-bis(4-chlorophenyl)acetate\"}], \"amount\": {\"mass\": {\"value\": 5.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Lithium bis(trimethylsilyl)amide\"}], \"amount\": {\"volume\": {\"value\": 18.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -78.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred for 1 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"was brought to 0\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"cooled to \\u221278\\u00b0 C\", \"temperature\": {\"setpoint\": {\"value\": -78.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"STIRRING\", \"details\": \"the reaction was stirred for 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"while warming to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The reaction was quenched with saturated NH4Cl solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH4Cl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with diethyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic phase was washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d29bbf1d91834a47a541397da628a72c",
    "procedure_text": "To a suspension of 0.25 g (0.93 mmol) of ethyl 7-bromoimidazo[1,2-a]pyridine-2-carboxylate, prepared according to the protocol described in step 8.1, in 4 mL of anhydrous dichloromethane, stirred at \u221219\u00b0 C. under an inert atmosphere, are added dropwise 2.09 mL (2.09 mmol) of a molar solution of DIBAL-H in toluene. The reaction mixture is stirred at \u221219\u00b0 C. for 3 hours and then hydrolysed at \u221240\u00b0 C. by successive addition of 0.1 mL of methanol, 0.1 mL of water and 10 mL of 5N HCl. The reaction mixture is then basified with aqueous sodium hydroxide solution (24%) and then extracted with three times 100 mL of dichloromethane. The combined organic phases are dried over sodium sulfate and then concentrated under reduced pressure. The crude reaction product is then purified by chromatography on a column of silica gel, eluting with a mixture of dichloromethane and methanol. 110 mg of the expected product are thus obtained.",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 7-bromoimidazo[1,2-a]pyridine-2-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 0.25, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2_m3_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"molar solution\"}], \"amount\": {\"volume\": {\"value\": 2.09, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DIBAL-H\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m9_m8_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 0.1, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 0.1, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -19.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred at \\u221219\\u00b0 C. under an inert atmosphere\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"prepared\"}, {\"type\": \"STIRRING\", \"details\": \"The reaction mixture is stirred at \\u221219\\u00b0 C. for 3 hours\", \"duration\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": -19.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with three times 100 mL of dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic phases are dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude reaction product\"}, {\"type\": \"CUSTOM\", \"details\": \"is then purified by chromatography on a column of silica gel\"}, {\"type\": \"WASH\", \"details\": \"eluting with a mixture of dichloromethane and methanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"expected product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 110.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-00c6fba4a1004e69b3b84a3a4da22489",
    "procedure_text": "30 mg of sodium-tert-butoxide and 12 mg of bis(tert-butylphosphino)palladium(0) were placed in a Smith\u00ae vial and the vial flushed with nitrogen. 100 mg (0.22 mmol) of 5-bromo-3-(2-methoxy-phenyl)-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine in 1 ml of anhydrous 1,4-dioxane and 35 \u03bcl of N-methylaniline were added and the resulting mixture heated to 130\u00b0 C. for 15 h. The reaction mixture was then cooled to ambient temperature and 0.4 ml of a 1 M solution of tetra-n-butylammonium fluoride in THF added. The mixture was stirred at room temperature for 2 h. 2 ml of methanol and amberlyst strongly acidic ion exchange resin loaded with sodium was added. After shaking at room temperature for 2 h the crude material is directly adsorbed onto silica gel and purified by flash chromatorgraphy on silica gel using a gradient of ethyl acetate in hexanes to afford 42 mg (0.14 mmol; 64% yield) of [3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridine-5-yl]-methyl-phenyl-amine as a brown residue. 1H-NMR (d6-DMSO): \u03b4 11.88 (s, 1H), 8.11 (d, J=2.5 Hz, 1H), 7.75 (d, J=2.4 Hz, 1H), 7.70 (d, J=2.5 Hz, 1H), 7.48 (dd, J=1.5 Hz, 7.3 Hz, 1H), 7.26 (ddd, J=1.5 Hz, 8.3 Hz, 1H), 7.16 (t, J=7.9 Hz, 2H), 7.08 (d, J=8.3 Hz, 1H), 7.00 (t(d), J=0.9 Hz, 8.3 Hz, 1H), 6.72-6.68 (m, 3H), 3.76 (s, 3H), 3.29 (s, 3H); MS: m/z 330 [MH+].",
    "reference_string": "{\"inputs\": {\"m11\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m7_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-bromo-3-(2-methoxy-phenyl)-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,4-dioxane\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-methylaniline\"}], \"amount\": {\"volume\": {\"value\": 35.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium-tert-butoxide\"}], \"amount\": {\"mass\": {\"value\": 30.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m10\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"bis(tert-butylphosphino)palladium(0)\"}], \"amount\": {\"mass\": {\"value\": 12.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium\"}], \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude material\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3_m4_m9\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetra-n-butylammonium fluoride\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 130.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at room temperature for 2 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the vial flushed with nitrogen\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The reaction mixture was then cooled to ambient temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"CUSTOM\", \"details\": \"purified by flash chromatorgraphy on silica gel using a gradient of ethyl acetate in hexanes\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridine-5-yl]-methyl-phenyl-amine\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 0.14, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 42.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 64.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-62b431b4f4414fe89e0bd4a145eaf880",
    "procedure_text": "Isobutyl chloroformate (0.788 g, 5.75 mmol) and N-methylmorpholine (0.581 g, 5.75 mmol) were added to an ice cold solution of 0.485 g (5.75 mmol) of 2-butynoic acid in 20 mL of tetrahydrofuran under N2. After stirring for 10 min, a solution of 1.50 g (4.42 mmol) of 6-amino-4-[(3-bromophenyl)amino]-3-quinolinecarbonitrile in 10 mL of tetrahydrofuran was added and the mixture was stirred overnight at 25\u00b0 C. A second equivalent of preformed mixed anhydride was then added. After 6 h, the reaction was poured into saturated sodium bicarbonate and brine. The product was collected and washed with hot ethyl acetate and ethanol and dried in vacuo to give 0.638 g of yellow solid; mp 283-285\u00b0 C. (dec).",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"anhydride\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m3_m4_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Isobutyl chloroformate\"}], \"amount\": {\"mass\": {\"value\": 0.788, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-methylmorpholine\"}], \"amount\": {\"mass\": {\"value\": 0.581, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-butynoic acid\"}], \"amount\": {\"mass\": {\"value\": 0.485, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5_m9\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-amino-4-[(3-bromophenyl)amino]-3-quinolinecarbonitrile\"}], \"amount\": {\"mass\": {\"value\": 1.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m7_m10\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring for 10 min\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"the mixture was stirred overnight at 25\\u00b0 C\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 25.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"ADDITION\", \"details\": \"was then added\"}, {\"type\": \"WAIT\", \"details\": \"After 6 h\", \"duration\": {\"value\": 6.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The product was collected\"}, {\"type\": \"WASH\", \"details\": \"washed with hot ethyl acetate and ethanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 10.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"yellow solid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.638, \"units\": \"GRAM\"}}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c42a332915334c999a9cb26668b38db1",
    "procedure_text": "To 5 ml of a DMF solution containing 200 mg (0.5181 mmol) of 2,2'-dihydroxy-5,5'-bis (2-ethoxycarbonylethyl) biphenyl and 644.5 \u03bcl (5.181 mmol) of cyclohexyl bromide, there were added 85.8 mg (0.6217 mmol) of anhydrous potassium carbonate and a small amount of copper powder and the resulting mixture was agitated for 41 hours at room temperature, for a further 5 hours at 70\u00b0 C. and for 8 hours at 100\u00b0 C. The reaction mixture was filtered by suction through Celite to remove the solid matter and the filtrate was washed with ethyl acetate. After the solvent in the filtrate was evaporated off under reduced pressure, the evaporated residue was dissolved in chloroform. This solution was washed with dilute hydrochloric acid, dilute aqueous sodium bicarbonate, water and aqueous sodium chloride solution in this sequence and was dried by adding anhydrous sodium sulfate. The residue obtained after the solvent had been evaporated off was purified by silica gel column chromatography (with 20 g of WAKO-gel C-200, eluent: toluene and toluene/ethyl acetate of 1000/1 and 500/1) and further purified by silica-gel column chromatography (with 15 g of WAKO-gel C-200, eluent: hexane and hexane/ethyl acetate 50/1, 30/1, 15/1 and 12/1) to obtain 28.3 mg (0.0605 mmol, 12%) of 2-cyclohexyloxy-2'-hydroxy-5,5'-bis (2-ethoxycarbonylethyl) biphenyl as an oily product.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"copper\"}], \"reaction_role\": \"CATALYST\"}]}, \"m5_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,2'-dihydroxy-5,5'-bis (2-ethoxycarbonylethyl) biphenyl\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cyclohexyl bromide\"}], \"amount\": {\"volume\": {\"value\": 644.5, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 85.8, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The reaction mixture was filtered by suction through Celite\"}, {\"type\": \"CUSTOM\", \"details\": \"to remove the solid matter\"}, {\"type\": \"WASH\", \"details\": \"the filtrate was washed with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"After the solvent in the filtrate was evaporated off under reduced pressure\"}, {\"type\": \"DISSOLUTION\", \"details\": \"the evaporated residue was dissolved in chloroform\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"This solution was washed with dilute hydrochloric acid, dilute aqueous sodium bicarbonate, water and aqueous sodium chloride solution in this sequence\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"was dried\"}, {\"type\": \"ADDITION\", \"details\": \"by adding anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The residue obtained after the solvent\"}, {\"type\": \"CUSTOM\", \"details\": \"had been evaporated off\"}, {\"type\": \"CUSTOM\", \"details\": \"was purified by silica gel column chromatography (with 20 g of WAKO-gel C-200, eluent: toluene and toluene/ethyl acetate of 1000/1 and 500/1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"further purified by silica-gel column chromatography (with 15 g of WAKO-gel C-200, eluent: hexane and hexane/ethyl acetate 50/1, 30/1, 15/1 and 12/1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-cyclohexyloxy-2'-hydroxy-5,5'-bis (2-ethoxycarbonylethyl) biphenyl\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 0.0605, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 28.3, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 12.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b4392133c08c4c74a3406d694807d85d",
    "procedure_text": "The compound I8 was prepared by the procedure described in Example I3 using appropriate intermediates and reagents (Protocol A). Triethylamine was replaced by morpholine resin (2.1 mmol, 0.61 g, loading 3.47 mmol/g); the mixture of morpholine resin and trans-2-aminocyclohexanol hydrochloride (2.1 mmol, 0.318 g) was stirred in ethanol (3.5 mL) at RT for 5 minutes before the addition of 3-methyl-2-methylthio[1,3,4]thiadiazolium perchlorate (3a) (0.7 mmol, 0.25 g). The residue was subjected to silica gel chromatography (Alltech column, 2 g silica) eluting with dichloromethane containing from 0% to 1% methanol. Yield: 0.050 g, 22%.",
    "reference_string": "{\"inputs\": {\"m6_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-methyl-2-methylthio[1,3,4]thiadiazolium perchlorate\"}], \"amount\": {\"mass\": {\"value\": 0.25, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 3.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Triethylamine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"morpholine\"}], \"amount\": {\"mass\": {\"value\": 0.61, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"morpholine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trans-2-aminocyclohexanol hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 0.318, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The compound I8 was prepared by the procedure\"}, {\"type\": \"WASH\", \"details\": \"eluting with dichloromethane containing from 0% to 1% methanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-0b0b07ab02da4e249559844b934af857",
    "procedure_text": "Acetic acid anhydride (0.132 ml) was added to a solution of 1-(3-amino-4-methoxyphenyl)-3-{1-[2-(2-ethoxyphenoxy) ethyl]-4-piperidinyl}-1-propanone dihydrochloride (300 mg) obtained in Example 327 and triethylamine (0.195 ml) in tetrahydrofuran (10 ml) at room temperature, the mixture was stirred for 12 hours, and the reaction mixture was concentrated under reduced pressure. Water (30 ml) and ethyl acetate (40 ml) were added to the residue, and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel chromatography (eluting solvent; ethyl acetate-methanol (9:1)) to give a free base compound of the title compound as a colorless oil (276 mg), The free base compound (270 mg) was treated with a hydrogen chloride-ethanol solution to give the title compound (277 mg) as colorless crystals having a melting point of 127 to 129\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Acetic acid anhydride\"}], \"amount\": {\"volume\": {\"value\": 0.132, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(3-amino-4-methoxyphenyl)-3-{1-[2-(2-ethoxyphenoxy) ethyl]-4-piperidinyl}-1-propanone dihydrochloride\"}], \"amount\": {\"mass\": {\"value\": 300.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 0.195, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred for 12 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"the reaction mixture was concentrated under reduced pressure\"}, {\"type\": \"ADDITION\", \"details\": \"Water (30 ml) and ethyl acetate (40 ml) were added to the residue\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Water\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was evaporated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The resulting residue was purified by silica gel chromatography (eluting solvent; ethyl acetate-methanol (9:1))\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 12.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 276.0, \"units\": \"MILLIGRAM\"}}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3778194a86ac4477a891906108a33d37",
    "procedure_text": "A solution of (4S)-9-(aminomethyl)-7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2(1H)-one bis(trifluoroacetate) (10.0 mg, 0.0265 mmol) in methylene chloride (1.00 mL) was treated with N,N-diisopropylethylamine (13.8 \u03bcL, 0.0795 mmol) followed by acetyl chloride (2.26 \u03bcL, 0.0318 mmol) and stirred at room temperature for 1 h. The reaction mixture was concentrated to give a crude residue. Purification via preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% trifluoroacetic acid, at a flow rate of 60 mL/min) gave the desired product (9 mg, 81%) as a single enantiomer. 1H NMR (500 MHz, DMSO-d6) \u03b4 10.89 (s, 1H), 8.52 (d, J=4.1 Hz, 1H), 8.31 (dd, J=5.7, 5.7 Hz, 1H), 7.79 (ddd, J=7.7, 7.7, 1.8 Hz, 1H), 7.41-7.27 (m, 1H), 7.14 (d, J=7.9 Hz, 1H), 6.70 (s, 1H), 5.53 (dd, J=2.4, 2.4 Hz, 1H), 4.76 (dd, J=11.5, 2.0 Hz, 1H), 4.41 (dd, J=11.5, 3.1 Hz, 1H), 4.32 (d, J=5.8 Hz, 2H), 2.22 (s, 3H), 2.05 (s, 3H), 1.87 (s, 3H); LCMS calculated for C22H22N5O4 (M+H)+: m/z=420.2. found: 420.0.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(4S)-9-(aminomethyl)-7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2(1H)-one bis(trifluoroacetate)\"}], \"amount\": {\"mass\": {\"value\": 10.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-diisopropylethylamine\"}], \"amount\": {\"volume\": {\"value\": 13.8, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetyl chloride\"}], \"amount\": {\"volume\": {\"value\": 2.26, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred at room temperature for 1 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"The reaction mixture was concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a crude residue\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude residue\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Purification via preparative LCMS (XBridge C18 column\"}, {\"type\": \"WASH\", \"details\": \"eluting with a gradient of acetonitrile/water containing 0.1% trifluoroacetic acid, at a flow rate of 60 mL/min)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile water\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 9.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 81.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f045847b9a1a4321b72b0d41b1b33894",
    "procedure_text": "Oxalyl chloride (10 ml) is added dropwise to a suspension of 2-(6-methoxynaphth-2-yl)-propionic acid (17.4 g, 75.6 mmols) in benzene (200 ml). After refluxing for 2 hours, the benzene is evaporated off under reduced pressure and the residue is taken up in alcohol-free methylene chloride (100 ml). This solution is added dropwise, in the course of 30 minutes, to a cooled suspension (0\u00b0 C.) of thiamorpholine hydrochloride (11.6 g, 83.16 mmols) and N-ethylmorpholine (19.12 g, 166 mmols) in methylene chloride (100 ml). After standing overnight, the reaction medium is washed successively with water, hydrochloric acid (10% strength), water, aqueous sodium bicarbonate solution (saturated) and water and then dried (Na2SO4) and evaporated. This yields a solid which is the intermediate (IV). A solution of this amide (5.60 g, 17.78 mmols) in tetrahydrofuran (50 ml) is added dropwise to a stirred solution of borane (55 mmols) in tetrahydrofuran (50 ml), which has been cooled to 0\u00b0 C. The solution is then heated at the reflux temperature for 2 hours and again cooled to 0\u00b0 C. Water is then added cautiously in order to destroy the excess borane, and dilute hydrochloric acid is added.",
    "reference_string": "{\"inputs\": {\"m6_m10_m7_m11\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"amide\"}], \"amount\": {\"mass\": {\"value\": 5.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"borane\"}], \"amount\": {\"moles\": {\"value\": 55.0, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m4_m9\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"thiamorpholine hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 11.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-ethylmorpholine\"}], \"amount\": {\"mass\": {\"value\": 19.12, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Oxalyl chloride\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(6-methoxynaphth-2-yl)-propionic acid\"}], \"amount\": {\"mass\": {\"value\": 17.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzene\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m12\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"intermediate ( IV )\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"After refluxing for 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"the benzene is evaporated off under reduced pressure\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzene\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"the reaction medium is washed successively with water, hydrochloric acid (10% strength), water, aqueous sodium bicarbonate solution (saturated) and water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"This yields a solid which\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The solution is then heated at the reflux temperature for 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"again cooled to 0\\u00b0 C\", \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"to destroy the excess borane, and dilute hydrochloric acid\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"borane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"is added\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-036d589c325b4c25aeab1d9db578c989",
    "procedure_text": "By reacting 1-(4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6-(4-oxopiperidin-1-yl)-1,3,5-triazin-2-yl)phenyl)-3-(pyridin-4-yl)urea-TFA (50 mg) with 1-(2-aminoethyl)pyrrolidine (0.030 mL) and following the procedure as mentioned in Experimental 118, the title product was isolated as its tri-TFA salt; MS (ES+) 599.8 (M+H)+.",
    "reference_string": "{\"inputs\": {\"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6-(4-oxopiperidin-1-yl)-1,3,5-triazin-2-yl)phenyl)-3-(pyridin-4-yl)urea TFA\"}], \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(2-aminoethyl)pyrrolidine\"}], \"amount\": {\"volume\": {\"value\": 0.03, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title product\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tri-TFA\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-ec23c1bef5b14dc9ab667d7d774b8c13",
    "procedure_text": "0.462 g (3.7 mmol) of 1-methyl-1H-pyrrol-2-carboxylic acid (VII), 1.4 g (9.7 mmol) of O-(7-azabenzotriazol-1-yl-)\u2014N,N,N\u2032-tetramethyluroniumhexafluorophosphate (HATU), and 0.640 mL (3.7 mmol) of diisopropylethylamine are placed in 10 mL of dimethylsulfoxide, then stirred for 0.1 hours at ambient temperature. 0.814 g (3.0 mmol) of (2-chloro-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)piperidin-3-ylamine hydrochloride (VI) and 3.7 mmol of diisopropylethylamine are added, then the mixture is stirred for 16 hours at ambient temperature. Then the reaction mixture is suction filtered through Alox, and the mother liquor is concentrated by evaporation. The residue is combined with 1 N sodium hydroxide solution and extracted with dichloromethane. The organic phase is separated off using a phase separator and evaporated to dryness. The crude product is purified by chromatography through a Biotage silica gel cartridge 40s with petroleum ether/ethyl acetate 1:1. 0.970 g of product VIII (85%) is obtained.",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylsulfoxide\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-methyl-1H-pyrrol-2-carboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 0.462, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"O-(7-azabenzotriazol-1-yl-)\\u2014N,N,N\\u2032-tetramethyluroniumhexafluorophosphate\"}], \"amount\": {\"mass\": {\"value\": 1.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2-chloro-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)piperidin-3-ylamine hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 0.814, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropylethylamine\"}], \"amount\": {\"moles\": {\"value\": 3.7, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropylethylamine\"}], \"amount\": {\"volume\": {\"value\": 0.64, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred for 0.1 hours at ambient temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"the mixture is stirred for 16 hours at ambient temperature\", \"duration\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"filtered through Alox\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the mother liquor is concentrated by evaporation\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The organic phase is separated off\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated to dryness\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude product is purified by chromatography through a Biotage silica gel cartridge 40s with petroleum ether/ethyl acetate 1:1\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"40s\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"petroleum ether ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 0.1, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product VIII\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.97, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 85.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 85.6}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-1e353e4c80954f29af594292661aef39",
    "procedure_text": "To a solution of methylenecyclobutane (2 mL, 21.6 mmol) in ethyl acetate (125 mL) was added (Z)-ethyl 2-chloro-2-(hydroxyimino)acetate (6.55 g, 43.2 mmol) and solid sodium bicarbonate (16.3 g, 194 mmol). The reaction mixture was sealed and stirred at room temperature for 6 hours. More (Z)-ethyl 2-chloro-2-(hydroxyimino)acetate (4 g, 26.4 mmol) and sodium bicarbonate (8 g, 95.2 mmol) were added and the reaction was stirred at room temperature for an additional 12 hours. The reaction was diluted with ethyl acetate and washed successively with water and brine, dried (MgSO4) and concentrated to yield crude 5-oxa-6-aza-spiro[3.4]oct-6-ene-7-carboxylic acid ethyl ester, contaminated with (Z)-Ethyl 2-chloro-2-(hydroxyimino)acetate and related compounds.",
    "reference_string": "{\"inputs\": {\"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m6_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylenecyclobutane\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(Z)-ethyl 2-chloro-2-(hydroxyimino)acetate\"}], \"amount\": {\"mass\": {\"value\": 6.55, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"amount\": {\"mass\": {\"value\": 16.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 125.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(Z)-ethyl 2-chloro-2-(hydroxyimino)acetate\"}], \"amount\": {\"mass\": {\"value\": 4.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"amount\": {\"mass\": {\"value\": 8.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred at room temperature for 6 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was sealed\"}, {\"type\": \"STIRRING\", \"details\": \"the reaction was stirred at room temperature for an additional 12 hours\", \"duration\": {\"value\": 12.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"WASH\", \"details\": \"washed successively with water and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 6.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-oxa-6-aza-spiro[3.4]oct-6-ene-7-carboxylic acid ethyl ester\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c86c24d09fc4419e91a20ae25fd01d90",
    "procedure_text": "Starting from 1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-8-trifluoromethyl-3-quinolinecarboxylic acid (1.05 g, 3.5 mmol) and 4-(3-pyrrolidinyl)pyridine, a procedure analogous to that given in Example 1 provided the title compound (0.93 g, 58%) as a beige solid, mp 244\u00b0-245\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-8-trifluoromethyl-3-quinolinecarboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 1.05, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(3-pyrrolidinyl)pyridine\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.93, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 58.0}}], \"isolated_color\": \"beige\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-04d8465a273e4f0ca57607f174b981a5",
    "procedure_text": "10.3 g of thiomorpholine (27) was added dropwise to a mixture of 47.1 g of sarsasapogenin acrylate (28) and 200 g. of tetrahydrofuran. The mixture was stirred at room temperature for 3 hours, after which tetrahydrofuran was distilled off. Subsequent purification by silica gel column chromatography gave 56.2 g of sarsasapogenin [3-(thiomorpholino)propionate] (Quencher 7). Yield 98%.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"thiomorpholine\"}], \"amount\": {\"mass\": {\"value\": 10.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sarsasapogenin acrylate\"}], \"amount\": {\"mass\": {\"value\": 47.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at room temperature for 3 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"DISTILLATION\", \"details\": \"after which tetrahydrofuran was distilled off\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Subsequent purification by silica gel column chromatography\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sarsasapogenin\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 56.2, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 98.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e35e949f3bf648e59184819b2919a362",
    "procedure_text": "To the compound of Example 124 (0.2 g, 0.55 mmoles) dissolved in MeOH (10 ml) was added 2-3 drops K2CO3 10% w/v in H2O and the reaction mixture was stirred at 25\u00b0 overnight. HCl (0.1N, 20 ml) was added and the mixture was filtered. The solid was air dried to give 0.170 g or 96% of the title compound, m.p. 202\u00b0-204\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"K2CO3\"}], \"reaction_role\": \"CATALYST\"}]}, \"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound\"}], \"amount\": {\"mass\": {\"value\": 0.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture was stirred at 25\\u00b0 overnight\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"the mixture was filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 96.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-26d36988725e4d1dbbb1285d158ddc22",
    "procedure_text": "A solution of tert-butyl 4-[(6-methoxy-3-oxo-2,3-dihydrobenzofuran-7-yl)-ethynyl]piperidine-1-carboxylate (0.0721 g, 0.194 mmol) synthesized in Example B55, Step 1 in ethanol (3 mL) was added with 5% palladium/carbon (wetted with 50% water, 0.0700 g), and the mixture was stirred overnight at room temperature under a hydrogen atmosphere. The reaction mixture was filtered through Celite, and the resulting filtrate was concentrated to obtain tert-butyl 4-[2-(6-methoxy-3-oxo-2,3-dihydrobenzofuran-7-yl)ethyl]piperidine-1-carboxylate (0.0593 g, 81%).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl 4-[(6-methoxy-3-oxo-2,3-dihydrobenzofuran-7-yl)-ethynyl]piperidine-1-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 0.0721, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"palladium/carbon\"}], \"amount\": {\"mass\": {\"value\": 0.07, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred overnight at room temperature under a hydrogen atmosphere\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The reaction mixture was filtered through Celite\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the resulting filtrate was concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl 4-[2-(6-methoxy-3-oxo-2,3-dihydrobenzofuran-7-yl)ethyl]piperidine-1-carboxylate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.0593, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 81.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 81.4}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e3ed45c0b50e4541982e4eefd3634cbd",
    "procedure_text": "5-(tert-Butyl)-3-((tert-butylamino)methyl)-3\u2032,4\u2032-dichloro-[1,1\u2032-biphenyl]-2-ol hydrochloride was prepared as a white solid using the procedure described in Example 9 from 5-(tert-butyl)-3\u2032,4\u2032-dichloro-2-hydroxy-[1,1\u2032-biphenyl]-3-carbaldehyde and tert-butylamine.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-(tert-butyl)-3\\u2032,4\\u2032-dichloro-2-hydroxy-[1,1\\u2032-biphenyl]-3-carbaldehyde\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butylamine\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-(tert-Butyl)-3-((tert-butylamino)methyl)-3\\u2032,4\\u2032-dichloro-[1,1\\u2032-biphenyl]-2-ol hydrochloride\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c148554153674d0f8ff4057c16a1fb90",
    "procedure_text": "To a solution of the cyclopropane-1,1-dicarboxylic acid [4-(7-benzyloxy-6-methoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide (4-fluoro-phenyl)-amide (22.4 g, 37.6 mmol) in EtOH (340 mL) was added 1,4-cyclohexadiene (35 mL, 376 mmol) and 10% Pd/C (2.08 g). The reaction mixture was then heated at 65\u00b0 C. with stirring for 3 h (Caution: H2 gas is released from the reaction). It was then allowed to cool to room temperature, and filtered through celite followed by a MeOH wash. The solution was then concentrated under reduced pressure. The yellow residue was taken into EtOAc (1 L). The EtOAc solution was washed with water (1\u00d7), brine (2\u00d7), dried over MgSO4 and concentrated in vacuo. Cyclopropane-1,1-dicarboxylic acid [3-fluoro-4-(7-hydroxy-6-methoxy-quinolin-4-yloxy)-phenyl]-amide (4-fluoro-phenyl)-amide was obtained as a yellow solid (17.3 g, 91.1% yield), which were carried on to the next reaction without further purification. 1H NMR (400 MHz, DMSO, d6): 10.39 (s, 1H), 10.15 (s, 1H), 10.00 (s, 1H), 8.38 (d, 1H), 7.88 (dd, 1H), 7.63 (m, 2H), 7.50 (m, 2H), 7.40 (t, 1H), 7.27 (s, 1H), 7.14 (m, 2H), 6.33 (d, 1H), 3.95 (s, 3H), 1.47 (m, 4H). LC/MS Calcd for [M+H]+ 506.2, found 506.3. Anal. HPLC: 99.4% pure.",
    "reference_string": "{\"inputs\": {\"m2_m4_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cyclopropane-1,1-dicarboxylic acid [4-(7-benzyloxy-6-methoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide (4-fluoro-phenyl)-amide\"}], \"amount\": {\"mass\": {\"value\": 22.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,4-cyclohexadiene\"}], \"amount\": {\"volume\": {\"value\": 35.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOH\"}], \"amount\": {\"volume\": {\"value\": 340.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd/C\"}], \"amount\": {\"mass\": {\"value\": 2.08, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 65.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"with stirring for 3 h (Caution\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"H2 gas is released from the reaction)\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to cool to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"filtered through celite\"}, {\"type\": \"WASH\", \"details\": \"wash\"}, {\"type\": \"CONCENTRATION\", \"details\": \"The solution was then concentrated under reduced pressure\"}, {\"type\": \"WASH\", \"details\": \"The EtOAc solution was washed with water (1\\u00d7), brine (2\\u00d7)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Cyclopropane-1,1-dicarboxylic acid [3-fluoro-4-(7-hydroxy-6-methoxy-quinolin-4-yloxy)-phenyl]-amide (4-fluoro-phenyl)-amide\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 17.3, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 91.1}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d7868ab3ed5b47a0ad85e9e4bee19ef1",
    "procedure_text": "substituting 1-[4-chloro-2-(2,2,2-trifluoroethoxy)phenyl]piperazine and 3-benzyl-1-(3-chloropropyl)-5-methyl-2,4(1H,3H)-pyrimidinedione gave 3-benzyl-1-(3-{4-[4-chloro-2-(2,2,2-trifluoroethoxy)phenyl]piperazin-1-yl}propyl)-5-methyl-2,4(1H,3H)-pyrimidinedione hydrochloride, m.p. 251\u00b0-252\u00b0 C.; Anal.: Calcd. for C27H30F3ClN4O3.HCl: C, 53.55; H, 5.49; N, 9.25%; Found: C, 53.74; H, 5.26; N, 9.37%;",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-[4-chloro-2-(2,2,2-trifluoroethoxy)phenyl]piperazine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-benzyl-1-(3-chloropropyl)-5-methyl-2,4(1H,3H)-pyrimidinedione\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-benzyl-1-(3-{4-[4-chloro-2-(2,2,2-trifluoroethoxy)phenyl]piperazin-1-yl}propyl)-5-methyl-2,4(1H,3H)-pyrimidinedione hydrochloride\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a35001a2ca2e4f4a9f08929975dd943e",
    "procedure_text": "A solution of 2,4,4\u2032-trichlorobenzhydrol (2) (174 mmol), p-toluenesulfonic acid (174 mmol) and 1-benzhydryl-3-azetidinol (1) (87 mmol) in toluene (700 mL) was heated at reflux under Dean-Stark conditions for 30 minutes. The solution was cooled, washed with sodium hydrogen carbonate (saturated aqueous solution, 700 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography [SiO2; (10% ethyl acetate:isohexane)] to furnish the product as a yellow oil (22.0 g, 50%).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,4,4\\u2032-trichlorobenzhydrol\"}], \"amount\": {\"moles\": {\"value\": 174.0, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"p-toluenesulfonic acid\"}], \"amount\": {\"moles\": {\"value\": 174.0, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-benzhydryl-3-azetidinol\"}], \"amount\": {\"moles\": {\"value\": 87.0, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 700.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"at reflux under Dean-Stark conditions for 30 minutes\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"The solution was cooled\"}, {\"type\": \"WASH\", \"details\": \"washed with sodium hydrogen carbonate (saturated aqueous solution, 700 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydrogen carbonate\"}], \"amount\": {\"volume\": {\"value\": 700.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by column chromatography [SiO2; (10% ethyl acetate:isohexane)]\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isohexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 22.0, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 50.0}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-6fa1a28b9b274ed28d51410c5e5f2272",
    "procedure_text": "Tetrahydrofuran (5 ml, dry) was added to a mixture of 2,2-bis-trifluoromethyl-2-hydroxyacetic acid (0.98 g, 4.6 mmol) and 1,1'-carbonyldiimidazole (0.75 g, 4.6 mmol), while under a nitrogen atmosphere. There was an immediate evolution of carbon dioxide. The reaction was heated at 35\u00b0 C. in an ultra-sound bath for 15 mins. The reaction was treated with a solution of 4-(2-pyridylsulfonyl)benzeneamine (1.08 g, 4.6 mmol) in dimethylformamide (11 ml, dry), heated at 46\u00b0 C. for 18 hr, and then 60\u00b0 C. for 24 hr. The incomplete reaction was treated with a solid mixture of 2,2-bis-trifluoromethyl-2-hydroxyacetic acid (0.22 g, 1.0 mmol) and 1,1'-carbonyldiimidazole (0.20 g, 1.2 mmol), and heated to 52\u00b0 C. in an ultrasound bath for 18 hr. The reaction was evaporated to a viscous gold liquid, which was treated with water (100 ml) and extracted with ethyl acetate (2\u00d7100 ml). The combined organic portions were dried (MgSO4) and evaporated to yield a gold oil. Chromatography of this oil on silica gel eluting with chloroform/methanol (98:2) provided the title compound (0.37 g, 14%) as a white solid; mp 199\u00b0-200\u00b0 C. 1H--NMR (250 MHz, d6 --DMSO): 7.70 (m, 1H, ArH), 8.02 (m, 4H, ArH), 8.19 (m, 2H, ArH), 8.71 (d, J=4.0 Hz, 1H, ArH), 9.88 (s, 1H, OH), 10.94 (s, 1H, NH). MS(CI,CH4) 429 (M+1)",
    "reference_string": "{\"inputs\": {\"m8_m0\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform methanol\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m9_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,2-bis-trifluoromethyl-2-hydroxyacetic acid\"}], \"amount\": {\"mass\": {\"value\": 0.98, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,1'-carbonyldiimidazole\"}], \"amount\": {\"mass\": {\"value\": 0.75, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(2-pyridylsulfonyl)benzeneamine\"}], \"amount\": {\"mass\": {\"value\": 1.08, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 11.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,2-bis-trifluoromethyl-2-hydroxyacetic acid\"}], \"amount\": {\"mass\": {\"value\": 0.22, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,1'-carbonyldiimidazole\"}], \"amount\": {\"mass\": {\"value\": 0.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"carbon dioxide\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 35.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"heated at 46\\u00b0 C. for 18 hr\", \"duration\": {\"value\": 18.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 46.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The incomplete reaction\"}, {\"type\": \"TEMPERATURE\", \"details\": \"heated to 52\\u00b0 C. in an ultrasound bath for 18 hr\", \"duration\": {\"value\": 18.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 52.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The reaction was evaporated to a viscous gold liquid, which\"}, {\"type\": \"ADDITION\", \"details\": \"was treated with water (100 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate (2\\u00d7100 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic portions were dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"to yield a gold oil\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 24.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.37, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 14.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 18.8}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e8fc733fff1c45b195ff1aa521046cc2",
    "procedure_text": "In DMF was dissolved 935 mg of the above ester, and to the resulting solution were added 0.5 g of 10% palladium-carbon (Pd-C) and 0.98 ml of a 2 N hydrochloric acid-dioxane solution, after which hydrogen gas was passed through the resulting mixture with ice-cooling and with stirring for 4 hrs. After the reaction, the Pd-C was removed by filtration, and 300 ml of anhydrous diethyl ether was added dropwise to the filtrate, upon which a powder was precipitated. The powder was collected by filtration to obtain 450 mg (yield 78%) of L-phenylalanyl-L-arginine 1-naphthyl ester dihydrochloride, m.p. 215\u00b0 C. (decomp.).",
    "reference_string": "{\"inputs\": {\"m5_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid dioxane\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"palladium-carbon\"}], \"amount\": {\"mass\": {\"value\": 0.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m4_m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ester\"}], \"amount\": {\"mass\": {\"value\": 935.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrogen\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"with stirring for 4 hrs\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooling\"}, {\"type\": \"CUSTOM\", \"details\": \"After the reaction\"}, {\"type\": \"CUSTOM\", \"details\": \"the Pd-C was removed by filtration, and 300 ml of anhydrous diethyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd-C\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"amount\": {\"volume\": {\"value\": 300.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"was added dropwise to the filtrate, upon which a powder\"}, {\"type\": \"CUSTOM\", \"details\": \"was precipitated\"}, {\"type\": \"FILTRATION\", \"details\": \"The powder was collected by filtration\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"L-phenylalanyl-L-arginine 1-naphthyl ester dihydrochloride\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 450.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 78.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-61f4cd57cd8141e4b1090ed046ea2a44",
    "procedure_text": "Benzyl (1R*,3S*, 4R*)-3,4-epoxycyclohexane-1-carboxylate (52.3 g) was dissolved in N,N-dimethylformamide (1000 ml), ammonium chloride (21.9 g) and sodium azide (18.1 g) were added, and the mixture was heated to 70\u00b0 C. and stirred for 24 hours. The solvent was distilled off under reduced pressure, and water was added to conduct extraction with ethyl acetate. The resultant organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain the title compound (61.8 g) as a colorless oil.",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,4-epoxycyclohexane-1-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 52.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 1000.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium chloride\"}], \"amount\": {\"mass\": {\"value\": 21.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium azide\"}], \"amount\": {\"mass\": {\"value\": 18.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 70.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred for 24 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"DISTILLATION\", \"details\": \"The solvent was distilled off under reduced pressure, and water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"EXTRACTION\", \"details\": \"extraction with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The resultant organic layer was washed with saturated saline\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"The solvent was distilled off under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 24.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 61.8, \"units\": \"GRAM\"}}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-41d119b243374a328c28b7d49ce7087b",
    "procedure_text": "As for Example 6, 3-(2-quinolylcarbonyl)propionic acid (0.01 mole) is coupled to L-proline (0.011 mole) with 1,1'-carbonyldiimidazole (0.01 mole) in tetrahydrofuran to give 1-[3-(2-quinolylcarbonyl)propionyl]-L-proline. Bromination of the preceding compound and reaction of the resulting compound with sodium thioacetate gives the product of the Example.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(2-quinolylcarbonyl)propionic acid\"}], \"amount\": {\"moles\": {\"value\": 0.01, \"units\": \"MOLE\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"L-proline\"}], \"amount\": {\"moles\": {\"value\": 0.011, \"units\": \"MOLE\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,1'-carbonyldiimidazole\"}], \"amount\": {\"moles\": {\"value\": 0.01, \"units\": \"MOLE\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-[3-(2-quinolylcarbonyl)propionyl]-L-proline\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-320476cba14d4ae0ba220099f989b6e7",
    "procedure_text": "To a \u221278\u00b0 C. solution of oxalyl chloride (4.80 g, 37.8 mmol) in DCM (200 mL) was add DMSO (5.91 g, 75.6 mmol) dropwise over 10 minutes. After 25 minutes of additional stirring, a \u221278\u00b0 C. solution of benzyl 5-hydroxy-2,2-dimethylpentanoate (4.06 g, 17.2 mmol, Step B) in DCM (200 mL) was added via cannula over 75 minutes. After stirring for an additional 30 minutes, triethylamine (13.9 g, 137 mmol) was added slowly over 25 minutes. The cooling bath was allowed to warm, while the reaction stirred for an additional 18 hours. Reaction solvent was then removed in vacuo, and the residue was dissolved in a mixture of diethyl ether and water (containing enough HCl to remain acidic). The organics were then dried over sodium sulfated, filtered and concentrated in vacuo to give the title compound (3.67 g), which was used without further purification.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"mass\": {\"value\": 13.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzyl 5-hydroxy-2,2-dimethylpentanoate\"}], \"amount\": {\"mass\": {\"value\": 4.06, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m5_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"oxalyl chloride\"}], \"amount\": {\"mass\": {\"value\": 4.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMSO\"}], \"amount\": {\"mass\": {\"value\": 5.91, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring for an additional 30 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"to warm, while the reaction\"}, {\"type\": \"STIRRING\", \"details\": \"stirred for an additional 18 hours\", \"duration\": {\"value\": 18.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"Reaction solvent\"}, {\"type\": \"CUSTOM\", \"details\": \"was then removed in vacuo\"}, {\"type\": \"DISSOLUTION\", \"details\": \"the residue was dissolved in a mixture of diethyl ether and water (containing enough HCl to remain acidic)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organics were then dried over sodium\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 25.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 3.67, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 91.1}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c0568a80a4ee453bb4cec5db7b36ab17",
    "procedure_text": "5-acetyl-2-bromopyridine 38 (0.656 g, 3.28 mmol), phenylboronic acid (0.800 g, 6.56 mmol), Na2CO3 (0.243 g, 2.29 mmol), Pd(PPh3)2Cl2 (0.115 g, 0.16 mmol, 5% Pd), acetonitrile (26 mL) and H2O (26 mL) were added to 50 mL screw cap pressure vessel. The mixture was stirred, degassed by purging with argon for 15 min, sealed and placed in an 80\u00b0 C. oil bath for 14 h (overnight). The dark colored mixture was cooled and extracted with ether. The organic layer was filtered through a pad of celite, rinsed with ether, washed with brine, dried over MgSO4 and filtered. The filtrate was concentrated and the residue purified by flash column chromatography (SiO2, 20 g, 5% EtOAc/hexanes) to afford the coupled ketone 40 as a white solid (0.33 g, 52%): TLC Rf=0.4 (25% EtOAc/hexanes); mp 124.9126.2\u00b0 C.; 1H NMR (500 MHz, CDCl3) \u03b4 9.22 (d, J=2.0 Hz, 1H), 8.28 (dd, J=8.3, 2.2 Hz, 1H), 8.10-7.99 (m, 2H), 7.83 (d, J=8.3 Hz, 1H), 7.55-7.40 (m, 3H), 2.65 (s, 3H); 13C NMR (125 MHz, CDCl3) \u03b4 196.6, 161.1, 150.2, 138.2, 136.7, 130.9, 130.4, 129.2, 127.6, 120.4, 26.9; IR (neat cm\u22121) 3062, 2999, 2960, 2322, 1673, 1557, 1382, 1016, 736; HRMS (DART, M++H) m/z 198.0906 (calculated for C13H12NO, 198.0919).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m5_m4_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-acetyl-2-bromopyridine\"}], \"amount\": {\"mass\": {\"value\": 0.656, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"phenylboronic acid\"}], \"amount\": {\"mass\": {\"value\": 0.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2CO3\"}], \"amount\": {\"mass\": {\"value\": 0.243, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 26.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd(PPh3)2Cl2\"}], \"amount\": {\"mass\": {\"value\": 0.115, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"amount\": {\"volume\": {\"value\": 26.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"screw cap pressure vessel\"}, {\"type\": \"CUSTOM\", \"details\": \"degassed\"}, {\"type\": \"CUSTOM\", \"details\": \"by purging with argon for 15 min\", \"duration\": {\"value\": 15.0, \"units\": \"MINUTE\"}}, {\"type\": \"CUSTOM\", \"details\": \"sealed\"}, {\"type\": \"CUSTOM\", \"details\": \"placed in an 80\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 80.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"for 14 h\", \"duration\": {\"value\": 14.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"(overnight)\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"The dark colored mixture was cooled\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"The organic layer was filtered through a pad of celite\"}, {\"type\": \"WASH\", \"details\": \"rinsed with ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"The filtrate was concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue purified by flash column chromatography (SiO2, 20 g, 5% EtOAc/hexanes)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc hexanes\"}], \"amount\": {\"mass\": {\"value\": 20.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ketone\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.33, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 52.0}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-cfe7470750084ce7bc83a200a0f73ad1",
    "procedure_text": "A solution of 3-butene-2-ol (8.7 mL, 100 mmol) in THF (50 mL) was added to potassium hydride (KH, 600 mg, 15 mmol) over 15 min. The resulting alkoxide solution was added to a stirred solution of trichloroacetonitrile (10.03 mL, 100 mmol) in ether (100 mL) at \u221210\u00b0 C. The solution was stirred at 0\u00b0 C. for 3 h, followed by removal of solvent under reduced pressure (temperature <25\u00b0 C.); pentane (400 mL) and methanol (1 mL) were added, and the mixture filtered. Concentration afforded a yellow oil (17.4 g). The oil was dissolved in xylene (450 mL) and refluxed for 2.5 h. The solvent was removed to yield 16.8 g of the title compound as a white solid.",
    "reference_string": "{\"inputs\": {\"m3_m4_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"alkoxide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trichloroacetonitrile\"}], \"amount\": {\"volume\": {\"value\": 10.03, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m5_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-butene-2-ol\"}], \"amount\": {\"volume\": {\"value\": 8.7, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium hydride\"}], \"amount\": {\"mass\": {\"value\": 600.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The solution was stirred at 0\\u00b0 C. for 3 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"followed by removal of solvent under reduced pressure (temperature <25\\u00b0 C.)\"}, {\"type\": \"ADDITION\", \"details\": \"pentane (400 mL) and methanol (1 mL) were added\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pentane\"}], \"amount\": {\"volume\": {\"value\": 400.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"the mixture filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"Concentration\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"oil\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 17.4, \"units\": \"GRAM\"}}}], \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-859ea284631c4e34b55afa16fcf3b1c8",
    "procedure_text": "Ethyl alcohol (0.63 mL, 10.8 mmol), 2-benzothiazolethiol (2.0 g, 11.9 mmol) and triphenylphosphine (3.1 g, 11.9 mmol) were dissolved in tetrahydrofuran (50 mL) and cooled to 0\u00b0 C. Then added diisopropylazadicarboxylate (2.3 mL, 11.9 mmol) and continued stirring for 1 hr. Upon completion, the reaction mixture was dried in vacuo, filtered through a plug of silica with 5% ethyl acetate in hexane and dried in vacuo again to yield 2-(ethylthio)-1,3-benzothiazole (2.2 g, HPLC RT=3.05 min.). LC-MS m/z=196.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ethyl alcohol\"}], \"amount\": {\"volume\": {\"value\": 0.63, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-benzothiazolethiol\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triphenylphosphine\"}], \"amount\": {\"mass\": {\"value\": 3.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"continued stirring for 1 hr\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"Then added diisopropylazadicarboxylate (2.3 mL, 11.9 mmol)\"}, {\"type\": \"CUSTOM\", \"details\": \"Upon completion, the reaction mixture was dried in vacuo\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered through a plug of silica with 5% ethyl acetate in hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried in vacuo again\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(ethylthio)-1,3-benzothiazole\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.2, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-109404c252df4d07889f21c5b087c808",
    "procedure_text": "4-Hydroxybenzoic acid (1.1 g, 7.96 mmoL) and aniline (742 mg, 7.23 mmol) were dissolved in 20 mL of dry DMF. To the above solution EDCI (1.53 g, 7.23 mmol) was added in one portion and the resulting mixture was stirred at rt overnight under nitrogen. The reaction mixture was then partitioned between EtOAc (200 mL) and water (200 mL). The organic layer was separated, washed consecutively with 1 N HCl, water, saturated sodium bicarbonate solution, water, and brine, and dried over MgSO4. Solvent was removed under reduced pressure and the crude product was purified by column chromatography using 10% EtOAc in hexane to give 450 mg (29% yield) of 4-Hydroxy-N-phenyl-benzamide. MS (ES) m/z: 214.08 (M+1).",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-Hydroxybenzoic acid\"}], \"amount\": {\"mass\": {\"value\": 1.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aniline\"}], \"amount\": {\"mass\": {\"value\": 742.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EDCI\"}], \"amount\": {\"mass\": {\"value\": 1.53, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the resulting mixture was stirred at rt overnight under nitrogen\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was then partitioned between EtOAc (200 mL) and water (200 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The organic layer was separated\"}, {\"type\": \"WASH\", \"details\": \"washed consecutively with 1 N HCl, water, saturated sodium bicarbonate solution, water, and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Solvent was removed under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"the crude product was purified by column chromatography\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-Hydroxy-N-phenyl-benzamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 450.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 29.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 29.2}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-12ed0ba7967045adb1c54f88299c0e4f",
    "procedure_text": "Ethyl 3-(piperid-4-yl)propionate (7 g) (prepared similarly to Preparation 21 A using ethyl alcohol in place of methyl alcohol) was dissolved in ethanolic methylamine (33%, 50 ml) and heated in a stainless steel bomb for 6 hours at 120\u00b0. The mixture was then evaporated to dryness in vacuo and the residue partitioned between 2 N NaOH (20 ml) and chloroform (40 ml). The chloroform layer was dried (Na2CO3) and evaporated to give N-methyl-3-(piperid-4-yl)propionamide (6 g) as a crude oil.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylamine\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ethyl 3-(piperid-4-yl)propionate\"}], \"amount\": {\"mass\": {\"value\": 7.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl alcohol\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"stainless steel\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The mixture was then evaporated to dryness in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue partitioned between 2 N NaOH (20 ml) and chloroform (40 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The chloroform layer was dried (Na2CO3)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2CO3\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-methyl-3-(piperid-4-yl)propionamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 6.0, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-72548e978d084ba492986da4be059f7b",
    "procedure_text": "A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (3.0 g, 13.6 mmol), 2-chloroethyl morpholine hydrochloride (4.46 g, 29.75mmol) and K2CO3 (7.3 g, 2.2 eq) in acetonitrile (60 ml) was heated at reflux for 24 hours. The crude mixture was diluted with DCM and filtered. The solvent was concentrated to an oil (~7.1 g). Purification on a silica gel column (55 g, SiO2, eluted with MeOH:DCM) yielded a solid product weighing 4 g. Recrystallization from hot ethanol yielded 2.1 g (48%), m.p. =131\u00b0-132\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole\"}], \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloroethyl morpholine hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 4.46, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"K2CO3\"}], \"amount\": {\"mass\": {\"value\": 7.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude mixture\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"at reflux for 24 hours\", \"duration\": {\"value\": 24.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"The solvent was concentrated to an oil (~7.1 g)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"oil\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Purification\"}, {\"type\": \"WASH\", \"details\": \"on a silica gel column (55 g, SiO2, eluted with MeOH:DCM)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"yielded a solid product\"}, {\"type\": \"CUSTOM\", \"details\": \"Recrystallization from hot ethanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"yielded 2.1 g (48%)\"}, {\"type\": \"CUSTOM\", \"details\": \"=131\\u00b0-132\\u00b0 C.\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-7571687ce04749808469b21b46322373",
    "procedure_text": "The title compound was prepared according to general method A as described above in Example 1 by reacting 2-[(R)-2-amino-1-propylthio]benzothiazole hydrochloride [prepared by a Mitsunobu reaction as described in Example 1 using 2-[(R)-N-tert-butyloxycarbonyl]amino-1-propanol (2.5 g, 14 mmol) and 2-mercaptobenzothiazole (2.3 g, 14 mmol) followed by acidic hydrolysis] (1.7 g, 5.7 mmol) with 9-(2,3,5-tri-O-benzoyl-\u03b2-D-ribofuranosyl)-2,6-dichloro-9H-purine (2.8 g, 4.5 mmol), followed by debenzoylation of the purified 2',3',5'-tri-O-benzoyl-2-chloro-N-[(R)-1-(2-benzothiazolyl)thio-2-propyl]adenosine in methanolic ammonia (200 ml) (previously saturated at -10\u00b0 C.) to provide the title 2-chloro-N-[(R)-1-(2-benzothiazolyl)thio-2-propyl]adenosine (1.05 g, 24%) (following column chromatography), 1H NMR (DMSO-d6) \u03b41.38 (3H, d, --CHCH3), 3.50-3.68 (4H, m, H-5'a and H-5'b and --CH2 --), 3.95 (1H, d, H-4'), 4.12 (1H, d, H-3'), 4.51 (1H, q, H-2'), 5.07 (1H, t, 5'-OH), 5.22, 5.50 (2H, 2d, 2'- and 3'-OH), 5.83 (1H, d, H-1'), 7.34, 7.45 (2H, 2t, Ar--H), 7.85, 7.98 (2H, 2d, Ar--H), 8.40 (1H, s, H-8), 8.53 (1H, d, N--H). HPLC retention time 16.6 min [gradient elution, 20-80% acetonitrile/water (containing 0.1% TFA)].",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"9-(2,3,5-tri-O-benzoyl-\\u03b2-D-ribofuranosyl)-2,6-dichloro-9H-purine\"}], \"amount\": {\"mass\": {\"value\": 2.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonia\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-[(R)-2-amino-1-propylthio]benzothiazole hydrochloride\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-[(R)-N-tert-butyloxycarbonyl]amino-1-propanol\"}], \"amount\": {\"mass\": {\"value\": 2.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2',3',5'-tri-O-benzoyl-2-chloro-N-[(R)-1-(2-benzothiazolyl)thio-2-propyl]adenosine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-mercaptobenzothiazole\"}], \"amount\": {\"mass\": {\"value\": 2.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The title compound was prepared\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"prepared by a Mitsunobu reaction\"}, {\"type\": \"CUSTOM\", \"details\": \"previously saturated at -10\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": -10.0, \"units\": \"CELSIUS\"}}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloro-N-[(R)-1-(2-benzothiazolyl)thio-2-propyl]adenosine\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.05, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 24.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4adf311b7b004f5687be3ccffad50731",
    "procedure_text": "To a solution of 5-hydroxy-chromen-4-one (J. Het. Chem, 13, 1976, 211) (2.5 g, 15.4 mmol) and 1 mL HCl(c) in 75 mL de-gassed EtOH/THF (3:1) was added 0.5 g 10% Pd/C. The reaction mixture was stirred at room temperature for 20 h under an atmosphere of 1 atm H2(g). The Pd/C was then filtered off, the filtrate collected and concentrated in vacuo to give 2.1 g (91%) of the title compound pure enough for subsequent use. 400 MHz 1H NMR (DMSO-d6) \u03b4 9.27 (s, 1H), 6.76 (t, 1H, J=8.1 Hz), 6.26 (d, 1H, J=8.1 Hz), 6.12 (d, 1H, J=8.1 Hz), 3.98 (t, 2H, J=5.0 Hz), 2.46 (m, 2H), 1.80 (m, 2H).",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-hydroxy-chromen-4-one\"}], \"amount\": {\"mass\": {\"value\": 2.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl(c)\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOH THF\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd/C\"}], \"amount\": {\"mass\": {\"value\": 0.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred at room temperature for 20 h under an atmosphere of 1 atm H2(g)\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The Pd/C was then filtered off\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd/C\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the filtrate collected\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 20.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.1, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 91.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-66c99dd62a384daf8dc6c9aec32b3be3",
    "procedure_text": "Lithium bis(trimethylsilyl)amide (2.8 ml, 1.0 M in THF, 2.76 mmol) was added to a suspension of 5-fluoro-2-phenylisonicotinic acid (500 mg, 2.30 mmol) in THF (10 ml) at \u221278\u00b0 C. The dark colored suspension was stirred for 30 min. In another flask, 2-fluoro-4-iodoaniline (709.30 mg, 2.99 mmol, 1.30 eq) was dissolved in (15 ml) THF and cooled to \u221278\u00b0 C. To this solution lithium bis(trimethylsilyl)amide (5 ml, 1.00 M, 5.06 mmol, 2.20 eq) was added and the mixture was stirred for 1 h. The reaction mixture became very viscous. To this, the homogeneous solution of acid-LiHMDS mixture was added via syringe. The mixture was warmed to room temperature and stirred overnight. Diluted with EtOAc (300 ml), washed with dilute HCl (20 ml), water (20 ml), and then dried and concentrated. Purified on Flashmaster using 100 g cartridge to obtain 565 mg of 5-[(2-fluoro-4-iodophenyl)amino]-2-phenylisonicotinic acid. LC/MS: [8.59 min; 435 (M+1)]",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium bis(trimethylsilyl)amide\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 300.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Lithium bis(trimethylsilyl)amide\"}], \"amount\": {\"volume\": {\"value\": 2.8, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-fluoro-2-phenylisonicotinic acid\"}], \"amount\": {\"mass\": {\"value\": 500.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-fluoro-4-iodoaniline\"}], \"amount\": {\"mass\": {\"value\": 709.3, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acid-LiHMDS\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -78.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The dark colored suspension was stirred for 30 min\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"the mixture was stirred for 1 h\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"The mixture was warmed to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"STIRRING\", \"details\": \"stirred overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"WASH\", \"details\": \"washed with dilute HCl (20 ml), water (20 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"Purified on Flashmaster\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-[(2-fluoro-4-iodophenyl)amino]-2-phenylisonicotinic acid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 565.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 56.6}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a6418a615a7943ed9742c136567884ba",
    "procedure_text": "2.21 g of potassium carbonate and 2.20 ml of acrolein were added to a solution of 3.50 g (16.4 mmol) of 3-(3\u2032-formyl-4\u2032-hydroxybenzyl)pyridine in 1,4-dioxane (40 ml) and the mixture was heated at 100\u00b0 C. for 30 minutes. Then, the resultant reaction mixture was filtered by using Celite (Trademark) and the filtrate was evaporated in vacuo. The residue was purified by a silica gel column chromatography (i.e., hexane: ethyl acetate=2:1 to 1:2) to obtain 3.88 g (yield=94.3%) of the desired compound as a yellow crystal.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 2.21, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acrolein\"}], \"amount\": {\"volume\": {\"value\": 2.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(3\\u2032-formyl-4\\u2032-hydroxybenzyl)pyridine\"}], \"amount\": {\"mass\": {\"value\": 3.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,4-dioxane\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Then, the resultant reaction mixture\"}, {\"type\": \"FILTRATION\", \"details\": \"was filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"the filtrate was evaporated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by a silica gel column chromatography (i.e., hexane: ethyl acetate=2:1 to 1:2)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 3.88, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 94.3}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystal\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0ec225dc43524ace88ad1df5eb99686d",
    "procedure_text": "A solution of (-)-3-((\u03b1R)-\u03b1-((2R,5S)-4-allyl-2,5-dimethyl-1-piperazinyl)-4-bromobenzyl)phenol (3.00 g, 7.2 mmol), from Example 70, in 80 mL of dry tetrahydrofuran was cooled to -78\u00b0 C. n-Butyllithium (9.9 mL of a 1.6M solution in hexanes) was added at a rate to keep the temperature below -70\u00b0 C. After stirring at -78\u00b0 C. for 30 minutes, the reaction was quenched with 15 mL of saturated aqueous ammonium chloride, warmed to room temperature, diluted with water and extracted with ethyl acetate. The ethyl acetate extracts were combined, dried over sodium sulfate, and the solvent removed under vacuum to give a white solid which was recrystallized from acetonitrile to give 2.11 g (88%) of (-)-3-((\u03b1R)-\u03b1-((2R,5S)-4-allyl-2,5-dimethyl-1-piperazinyl)benzyl)phenol as white crystals, mp 195\u00b0-197\u00b0 C., [\u03b1]D20 =-2.8\u00b0 (tetrahydrofuran, c=1.6). HPLC on \u03b2-cyclodextrin with methanol:0.1M ammonium acetate/1:1 gave one peak at tR =8.4 min. NMR (DMSO-d6, 200 MHz): \u03b40.95 (d, J=6 Hz, 3H); 1.1 (d, J=6 Hz, 3H); 1.8 (dd, J1 =7 Hz, J2 =11Hz, 1H); 2.1 (dd, J1 =7 Hz, J2 =9 Hz, 1H); 2.4-2.8 (m, 4H); 2.9 (dd, J1 =7 Hz, J2 =14 Hz, 1H); 3.15 (dd, J1 =5 Hz, J2 =14 Hz, 1H); 4.95 (s, 1H); 5.1 (d, J=10 Hz, 1H); 5.2 (d, J=18 Hz, 1H); 5.8 (m,1H); 6.6 (d, J=8 Hz, 1H); 6.8 (d, J=8 Hz, 1H); 6.95 (s, 1H); 7.1 (t, J=8 Hz, 1H); 7.3 (m, 5H); 9.3 (s, 1H). Mass spectrum (Cl--CH4) m/z: 337 (M+1, 69%); 336 (M+, 15%); 183 (100%); 153 (92%). Calc. for C22 H28N2O: C, 78.53; H, 8.39; N, 8.33. Found: C, 78.37; H, 8.47; N, 8.38.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(-)-3-((\\u03b1R)-\\u03b1-((2R,5S)-4-allyl-2,5-dimethyl-1-piperazinyl)-4-bromobenzyl)phenol\"}], \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-Butyllithium\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 80.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -78.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring at -78\\u00b0 C. for 30 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added at a rate\"}, {\"type\": \"CUSTOM\", \"details\": \"the temperature below -70\\u00b0 C\"}, {\"type\": \"CUSTOM\", \"details\": \"the reaction was quenched with 15 mL of saturated aqueous ammonium chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium chloride\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"warmed to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"ADDITION\", \"details\": \"diluted with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent removed under vacuum\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a white solid which\"}, {\"type\": \"CUSTOM\", \"details\": \"was recrystallized from acetonitrile\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(-)-3-((\\u03b1R)-\\u03b1-((2R,5S)-4-allyl-2,5-dimethyl-1-piperazinyl)benzyl)phenol\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.11, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 88.0}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-6c5215d9a7f14dca98491ef2f8e13ef5",
    "procedure_text": "As in Example 19, a solution of 4-[3-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl] thio]propoxy]-alpha-oxobenzeneacetic acid ethyl ester (0.32 g) in methanol (15 mL) was treated with 2N sodium hydroxide (0.75 mL) was stirred at room temperature. After 3 hours, most of the methanol was removed in vacuo, then the mixture was acidified with 3N hydrochloric acid and extracted with dichloromethane-tetrahydrofuran (1:1). The dried (MgSO4) extracts were evaporated and the crude product was purified by flash chromatography over silica gel (toluene-ethyl acetate-acetic acid; 80:20:0.25 increasing to 74:25:1) to give 4-[3-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]thio]propoxy]-alpha-oxobenzeneacetic acid as an oil.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-[3-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl] thio]propoxy]-alpha-oxobenzeneacetic acid ethyl ester\"}], \"amount\": {\"mass\": {\"value\": 0.32, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"volume\": {\"value\": 0.75, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"most of the methanol was removed in vacuo\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with dichloromethane-tetrahydrofuran (1:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane tetrahydrofuran\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The dried (MgSO4) extracts\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"were evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"the crude product was purified by flash chromatography over silica gel (toluene-ethyl acetate-acetic acid; 80:20:0.25 increasing to 74:25:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene ethyl acetate acetic acid\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-[3-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]thio]propoxy]-alpha-oxobenzeneacetic acid\"}], \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-78f767efa99446aaa18dd7965196b01a",
    "procedure_text": "To a solution of tert-butyl N-[2-(4-bromophenyl)ethyl]-N-[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]carbamate (435 mg) in 1,2-dimethoxyethane (6 ml) were added 4-methoxycarbonyl-phenyl boronic acid (224 mg), tetrakis(triphenylphosphine)-palladium (55 mg) and aqueous solution of sodium carbonate (2M, 1.0 ml), and the mixture was stirred at 80\u00b0 C. for 2 hours under nitrogen. The mixture was diluted with ethyl acetate and water. The organic layer was separated, washed with brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane/ethyl acetate=3/1) to give methyl 4\u2032-[2-[N-(tert-butoxycarbonyl)-N-[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethyl]-1,1\u2032-biphenyl-4-carboxylate (400 mg).",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m7_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl N-[2-(4-bromophenyl)ethyl]-N-[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]carbamate\"}], \"amount\": {\"mass\": {\"value\": 435.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-methoxycarbonyl-phenyl boronic acid\"}], \"amount\": {\"mass\": {\"value\": 224.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium carbonate\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,2-dimethoxyethane\"}], \"amount\": {\"volume\": {\"value\": 6.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrakis(triphenylphosphine)-palladium\"}], \"amount\": {\"mass\": {\"value\": 55.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 80.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at 80\\u00b0 C. for 2 hours under nitrogen\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The organic layer was separated\"}, {\"type\": \"WASH\", \"details\": \"washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by column chromatography on silica gel (hexane/ethyl acetate=3/1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 4\\u2032-[2-[N-(tert-butoxycarbonyl)-N-[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethyl]-1,1\\u2032-biphenyl-4-carboxylate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 400.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-cc9218e9e2c243d28aed8f2f8111e8a6",
    "procedure_text": "To a solution of 2-amino-4-(4-aminophenylsulfinylmethyl)thiazole (2.8 g) in N,N-dimethylformamide (30 ml) was added portionwise the 3-chloroperbenzoic acid (2.6 g) at 5\u00b0 C. with stirring. The mixture was stirred at room temperature for 2 hours and then the solution was poured into ice-water. The precipitates were collected by filtration, washed with aqueous sodium bicarbonate, washed with water and dried in vacuo to give 2-amino-4-(4-aminophenylsulfonylmethyl)thiazole (2.85 g, yield 95.6%). mp: 204\u00b0-208\u00b0 C. (dec.)",
    "reference_string": "{\"inputs\": {\"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-amino-4-(4-aminophenylsulfinylmethyl)thiazole\"}], \"amount\": {\"mass\": {\"value\": 2.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-chloroperbenzoic acid\"}], \"amount\": {\"mass\": {\"value\": 2.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"with stirring\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"The mixture was stirred at room temperature for 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"The precipitates were collected by filtration\"}, {\"type\": \"WASH\", \"details\": \"washed with aqueous sodium bicarbonate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried in vacuo\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-amino-4-(4-aminophenylsulfonylmethyl)thiazole\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.85, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 95.6}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 95.7}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-9aa77c3d1a5c49379fdfc93f65aff247",
    "procedure_text": "To a solution of 2.24 g of 3,4-dihydro-2-p-toluenesulfonyloxymethyl-2H-(1,3)-thiazino[3,2-a]benzimidazole in chloroform (30 ml) was added 4 ml of n-butylamine. A catalytic amount of sodium hydride was thereafter added under ice-cooling, stirring conditions. After stirring for 15 minutes at room temperature, the mixturewas refluxed for 24 hours. The reaction mixture was cooled and then condensed under reduced pressure. The residue was added with water and extracted with chloroform. The extract was washed with water, dried over anhydrous magnesium sulfate. Chloroform was evaporated under reduced pressure. The residue was chromatographed on silica gel and eluted with chloroform to obtain 0.71 g (yield: 43.3%) of the intended product, m.p. 122\u00b0-124\u00b0 C.; IR \u03bdmaxKBr cm-1 : 3320, 3100-2700, 1430; Anal. Calcd. for C15H21N3S: C, 65.42; N, 7.68; N, 15.26; S, 11.64; Found: C, 65.63; H, 7.61; N, 15.46; S, 11.30.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m5_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,4-dihydro-2-p-toluenesulfonyloxymethyl-2H-(1,3)-thiazino[3,2-a]benzimidazole\"}], \"amount\": {\"mass\": {\"value\": 2.24, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-butylamine\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydride\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirring conditions\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooling\"}, {\"type\": \"STIRRING\", \"details\": \"After stirring for 15 minutes at room temperature\", \"duration\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"the mixturewas refluxed for 24 hours\", \"duration\": {\"value\": 24.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"The reaction mixture was cooled\"}, {\"type\": \"CUSTOM\", \"details\": \"condensed under reduced pressure\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with chloroform\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The extract was washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Chloroform was evaporated under reduced pressure\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The residue was chromatographed on silica gel\"}, {\"type\": \"WASH\", \"details\": \"eluted with chloroform\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"intended product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.71, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 43.3}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-90de99c0f10a42e5893ee2e2ccc47b85",
    "procedure_text": "tert-Butyl(3-cyano-5-pyridin-3-yl-2-thienyl)carbamate (800 mg, 2.07 mmol) was dissolved in 4M hydrochloric acid in dioxane (10.4 ml, 41.6 mmol) and the mixture was stirred at room temperature for 6 h. The mixture was quenched with 1N sodium hydroxide (50 mL) and extracted with ethyl acetate (3\u00d7100 mL). The combined organics were dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to afford the title compound as a solid.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-Butyl(3-cyano-5-pyridin-3-yl-2-thienyl)carbamate\"}], \"amount\": {\"mass\": {\"value\": 800.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dioxane\"}], \"amount\": {\"volume\": {\"value\": 10.4, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at room temperature for 6 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The mixture was quenched with 1N sodium hydroxide (50 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate (3\\u00d7100 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organics were dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 6.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0d040f955bf642e0bcbac00b1c44b05b",
    "procedure_text": "The product of EXAMPLE 211 in MeOH is reacted with ammonium chloride by the method of EXAMPLE 27 to generate the title material.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium chloride\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title material\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-090ce16f32c04f7983ae84473edee969",
    "procedure_text": "A mixture of 6.35 g of 2,3-difluoro-6-nitro-{[2-(tetrahydropyran-2-yl)oxypropyl]oxy}benzene (I, Xa=Xb=F, Rc=THP), 60 ml of anhydrous ethanol and 640 mg of pyridinium tosylate was stirred at room temperature overnight and then heated under refluxing for 1 hour. The solvent was removed under reduced pressure. To the residue were added ethyl acetate and 1 N hydrochloric acid. The mixture was shaken, and the organic layer was separated. The organic layer was washed successively with a saturated sodium bicarbonate aqueous solution and water, then dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to yield the oily titled compound. This product was used in the following reaction without purification.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,3-difluoro-6-nitro-{[2-(tetrahydropyran-2-yl)oxypropyl]oxy}benzene\"}], \"amount\": {\"mass\": {\"value\": 6.35, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridinium tosylate\"}], \"amount\": {\"mass\": {\"value\": 640.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at room temperature overnight\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"under refluxing for 1 hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The solvent was removed under reduced pressure\"}, {\"type\": \"ADDITION\", \"details\": \"To the residue were added ethyl acetate and 1 N hydrochloric acid\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"STIRRING\", \"details\": \"The mixture was shaken\"}, {\"type\": \"CUSTOM\", \"details\": \"the organic layer was separated\"}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed successively with a saturated sodium bicarbonate aqueous solution and water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The solvent was removed under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"titled compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-066b7d85fd61498c917d9ac15c4671bc",
    "procedure_text": "To a cold (\u221278\u00b0 C.) solution of the product of step 1 (1.09 g, 4.63 mmol) in anhydrous tetrahydrofuran (10 mL) was added a solution of n-butyllithium (1.6 M in hexanes, 2.89 mL, 4.63 mmol) and the contents of the reaction were allowed to react for 0.5 h. A solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (922 mg, 4.63 mmol) in tetrahydrofuran (10 mL) was added and the combined contents stirred for 2 h at \u221278\u00b0 C. Reaction was quenched by the addition of saturated aqueous ammonium chloride (30 mL), followed by warming to rt. The biphasic mixture was extracted with ethyl acetate (150 mL); washed with water and brine; dried over magnesium sulfate; filtered and concentrated. 4-[4-Chloro-2-(4,4-dimethyl-4,5-dihydro-oxazol-2-yl)-phenyl]-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester was isolated (412 mg, 22%) following silica gel chromatography (80% hexanes/20% ethyl acetate).",
    "reference_string": "{\"inputs\": {\"m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-oxo-piperidine-1-carboxylic acid tert-butyl ester\"}], \"amount\": {\"mass\": {\"value\": 922.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"amount\": {\"mass\": {\"value\": 1.09, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-butyllithium\"}], \"amount\": {\"volume\": {\"value\": 2.89, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -78.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the combined contents stirred for 2 h at \\u221278\\u00b0 C\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"to react for 0.5 h\", \"duration\": {\"value\": 0.5, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"Reaction\"}, {\"type\": \"CUSTOM\", \"details\": \"was quenched by the addition of saturated aqueous ammonium chloride (30 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium chloride\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"by warming to rt\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"The biphasic mixture was extracted with ethyl acetate (150 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with water and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-[4-Chloro-2-(4,4-dimethyl-4,5-dihydro-oxazol-2-yl)-phenyl]-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-93e4bb74356c4aa0b542bfa5fc9f8b54",
    "procedure_text": "This compound was made in a similar manner to 1-butyl-3-hydroxy-3-(2-oxo-2-(pyridin-2-yl)ethyl)indolin-2-one using 5-methyl-1-propylindoline-2,3-dione and 1-(6-methoxypyridin-2-yl)ethanone (commercially available from Fisher Scientific). 1H-NMR \u03b4 7.74 (m, 2H), 7.19 (s, 1H), 7.11 (d, 1H), 6.98 (d, 1H), 6.77 (d, 1H), 5.27 (bs, 1H), 4.03 (s, 3H), 3.65 (m, 3H), 3.49 (d, 1H), 2.30 (s, 3H), 1.74 (m, 2H), 0.97 (t, 3H).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-butyl-3-hydroxy-3-(2-oxo-2-(pyridin-2-yl)ethyl)indolin-2-one\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-methyl-1-propylindoline-2,3-dione\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(6-methoxypyridin-2-yl)ethanone\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-477d37d146394e5b95cff4b7ea8d5daa",
    "procedure_text": "The title compound was prepared in analogy to Example 1a in Scheme 3 by using methyl (4R)-4-(2-chloro-4-fluoro-phenyl)-6-(bromomethyl)-2-thiazol-2-yl-1,4-dihydropyrimidine-5-carboxylate C (200 mg) and 4,10-Dioxa-5,12-diaza-tricyclo[6.3.1.0*2,6*]dodeca-2,5-diene 104a (100 mg). 15 mg of the title compound was isolated as yellow powder.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl (4R)-4-(2-chloro-4-fluoro-phenyl)-6-(bromomethyl)-2-thiazol-2-yl-1,4-dihydropyrimidine-5-carboxylate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4,10-Dioxa-5,12-diaza-tricyclo[6.3.1.0*2,6*]dodeca-2,5-diene\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The title compound was prepared in analogy to Example 1a in Scheme 3\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 15.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0b7e48de51a641f29183c0eb70b85d07",
    "procedure_text": "Compound 9 was prepared from a mixture of 3-chloropropyl pentyl sulfide, 3-amino-5-mercapto-1,2,4-triazole and pyridine in acetonitrile, as described previously for Compound 12. The reaction mixture was poured into water and extracted with CH2Cl2. The extracts were washed with water and brine, dried over MgSO4, and concentrated under vacuum to provide Compound 9 in 71% yield.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Compound 12\"}], \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-chloropropyl pentyl sulfide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-amino-5-mercapto-1,2,4-triazole\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted with CH2Cl2\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The extracts were washed with water and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under vacuum\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Compound 9\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-9441f2cc386049b9957e09c1d276f13c",
    "procedure_text": "A solution of 4-(4-chlorophenyl)piperidine-4-carbonitrile hydrochloride (0.055 g, 0.2155 mmol), 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (0.033 g, 0.2155 mmol) and triethylamine (0.150 ml, 1.0775 mmol) in n-butanol (2.0 ml) was heated to 100\u00b0 C. for 2 days. Concentration and trituration with methanol (3 ml) gave a white solid (0.058 g, 80%). LC-MS (LCT2) m/z 338 [M+H+], Rt 16.17 min.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(4-chlorophenyl)piperidine-4-carbonitrile hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 0.055, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-chloro-7H-pyrrolo[2,3-d]pyrimidine\"}], \"amount\": {\"mass\": {\"value\": 0.033, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 0.15, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-butanol\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"Concentration and trituration with methanol (3 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.058, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 80.0}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f51fbbafbca743e880e1d200adcdec08",
    "procedure_text": "A solution of Stage 3 (28.6 g; assume 24.7 mmol) in methanol (515 ml) was treated with sodium methoxide (0.44 g, 8.13 mmol) for 90 minutes before being treated with a further portion of sodium methoxide (0.44 g, 8.13 mmol). After 30 minutes Dowex 50 [H+] was added to neutralise the solution. The resin was filtered off and the filtrate was evaporated to leave the title Compound as a foam (24 g).",
    "reference_string": "{\"inputs\": {\"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"amount\": {\"mass\": {\"value\": 28.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium methoxide\"}], \"amount\": {\"mass\": {\"value\": 0.44, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 515.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium methoxide\"}], \"amount\": {\"mass\": {\"value\": 0.44, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"After 30 minutes Dowex 50 [H+] was added\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}}, {\"type\": \"FILTRATION\", \"details\": \"The resin was filtered off\"}, {\"type\": \"CUSTOM\", \"details\": \"the filtrate was evaporated\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title Compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 24.0, \"units\": \"GRAM\"}}}], \"texture\": {\"type\": \"FOAM\", \"details\": \"foam\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-39d4199ca79b4f3f8807a5a215f95118",
    "procedure_text": "To a solution of 1-bromo-4-fluoro-2-methoxybenzene (9.0 g) in N-methylpyrrolidone (100 mL, Sure Seal; Aldrich) was added CuCN (6.6 g, 73.7 mmol, 1.8 eq.; Aldrich), and the mixture stirred at 180\u00b0 C. under anhydrous nitrogen for 5.5 hrs. After cooling, 14% aqueous NH4OH (330 mL) was added and stirring continued for 45 min at room temperature. The mixture was extracted with ether (100 mL\u00d73), and the combined extracts washed sequentially with dilute aqueous NH4OH, dilute HCl and brine, then dried (MgSO4), and concentrated to provide the title compound (5.2 g, Yield 85% in 2 steps) as a white solid: 1H NMR (CDCl3, 500 MHz) \u03b4 ppm: 3.91 (3H, s, OMe), 6.69 (1H, dd, J=2.3 Hz, J=10.5 Hz, Ar\u2014H), 6.72 (1H, dt, J=2.5 Hz, J=J=8.0 Hz, Ar\u2014H), 7.55 (1H, dd, J=6.5 Hz, J=8.5 Hz, Ar\u2014H); 13C NMR (CDCl3, 125.8 Hz) \u03b4 ppm: 56.49, 98.16, 100.06, 100.27, 108.31, 108.50, 115.83 135.37, 135.46, 163.25, 163.34 165.47, 167.50. An analytical sample was obtained by trituration with ether: Anal. calcd for C8H6FNO: C 63.57, H 4.00, N 9.26; found: C 63.36, H 3.91, N 9.16.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-bromo-4-fluoro-2-methoxybenzene\"}], \"amount\": {\"mass\": {\"value\": 9.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CuCN\"}], \"amount\": {\"mass\": {\"value\": 6.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-methylpyrrolidone\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH4OH\"}], \"amount\": {\"volume\": {\"value\": 330.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 180.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture stirred at 180\\u00b0 C. under anhydrous nitrogen for 5.5 hrs\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"After cooling\"}, {\"type\": \"STIRRING\", \"details\": \"stirring\"}, {\"type\": \"WAIT\", \"details\": \"continued for 45 min at room temperature\", \"duration\": {\"value\": 45.0, \"units\": \"MINUTE\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"The mixture was extracted with ether (100 mL\\u00d73)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"the combined extracts washed sequentially with dilute aqueous NH4OH, dilute HCl and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH4OH\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 5.5, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 5.2, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 85.0}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c6ea3e7725a643ce863991d3c5e9e0e0",
    "procedure_text": "To a solution of 5-chloro-6-(4-methoxy-benzyloxy)-2-methyl-3-(2-methyl-5-propynoyl-phenyl)-3H-pyrimidin-4-one from Step H (660 mg, 1.56 mmol) in acetonitrile (3 mL) was added 2-hydroxy-2-methylpropionamidine HCl (324 mg, 2.34 mmol) and potassium carbonate (645 mg, 4.68 mmol) and heated at 75\u00b0 C. for eighteen hours. The reaction was returned to ambient temperature and filtered to remove excess salts. The filtrate was concentrated to provide a dark red oil. Normal phase chromatography (ethyl acetate/heptanes) provided the pyrimidine as a yellow oil (336 mg, 42%). MS (M+H): 507",
    "reference_string": "{\"inputs\": {\"m2_m5_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-chloro-6-(4-methoxy-benzyloxy)-2-methyl-3-(2-methyl-5-propynoyl-phenyl)-3H-pyrimidin-4-one\"}], \"amount\": {\"mass\": {\"value\": 660.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-hydroxy-2-methylpropionamidine HCl\"}], \"amount\": {\"mass\": {\"value\": 324.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 645.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 75.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"was returned to ambient temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"to remove excess salts\"}, {\"type\": \"CONCENTRATION\", \"details\": \"The filtrate was concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"to provide a dark red oil\"}], \"outcomes\": [{\"products\": [{\"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyrimidine\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 336.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 42.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 42.5}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-89fb63812ed54f0bbe96acfee1a5ffd7",
    "procedure_text": "42.0 g (0.13 mole) of 1'-t-butoxycarbonylspiro[benzo[c]thiophene-1(3H),4'-piperidine]-2-oxide [prepared as described in step (b) above] were dissolved in 420 ml of 2-propanol, and 150 ml of a 4 N solution of hydrogen chloride in dioxane was added thereto, whilst ice-cooling. The mixture was then stirred for 4 hours. At the end of this time, 200 ml of diethyl ether were added to the mixture, and the mixture was allowed to stand for 1 hour, whilst ice-cooling. The precipitated crystals were then collected by filtration. The crystals were dissolved in 200 ml of a 5% w/v aqueous solution of sodium hydroxide. The product was extracted with methylene chloride, and the organic extract was dried over anhydrous sodium sulfate. The solvent was then removed by distillation under reduced pressure, to give 21.7 of the title compound as a white amorphous product.",
    "reference_string": "{\"inputs\": {\"m3_m4_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrogen chloride\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dioxane\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m2_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1'-t-butoxycarbonylspiro[benzo[c]thiophene-1(3H),4'-piperidine]-2-oxide\"}], \"amount\": {\"mass\": {\"value\": 42.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-propanol\"}], \"amount\": {\"volume\": {\"value\": 420.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was then stirred for 4 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"whilst ice-cooling\"}, {\"type\": \"WAIT\", \"details\": \"to stand for 1 hour, whilst ice-\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"cooling\"}, {\"type\": \"FILTRATION\", \"details\": \"The precipitated crystals were then collected by filtration\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The crystals were dissolved in 200 ml of a 5% w/v aqueous solution of sodium hydroxide\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The product was extracted with methylene chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"the organic extract\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"was dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The solvent was then removed by distillation under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"21.7\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-260cf7005c60435f94896657e37f3f4a",
    "procedure_text": "A suspension of 7-(3-t-butyl-5-amino-1H-pyrazol-1-yl)-3,4-dihydroisoquinoline-1(2H)-thione (0.150 g, 0.499 mmol) in THF (3 mL) was added to a solution of 2,3-dichlorophenyl isocyanate (0.141 g, 0.749 mmol), pyridine (0.061 mL, 0.059 g, 0.749 mmol) and THF (3 mL). The flask which contained the starting material was again rinsed with THF (4 mL) and the solution was added to the reaction flask. The resulting yellow suspension was briefly heated with a heat gun, causing the reaction mixture to become clear. After 18 h, the solution was concentrated and the residue was purified by column chromatography to yield 1-[3-t-butyl-1-(1-thioxo-1,2,3,4-tetrahydroisoquinolin-7-yl)-1H-pyrazol-5-yl]-3-(2,3-dichlorophenyl)urea as a yellow solid (203 mg, 83% yield). 1H NMR (400 MHz, acetone-d6): \u03b4 9.60 (brs, 1H), 8.66 (d, J=2.0 Hz, 1H), 8.61 (brs, 1H), 8.26 (dd, J=8.4, and 2.0 Hz, 1H), 8.17 (brs, 1H), 7.68 (dd, J=8.0, and 2.0 Hz, 1H), 7.40 (d, J=8.4 Hz, 1H), 7.30 (t, J=8.2 Hz, 1H), 7.23 (dd, J=7.6, and 1.2 Hz, 1H), 6.48 (s, 1H), 3.62-3.58 (m, 2H), 3.07 (t, J=6.6 Hz, 2H), 1.33 (s, 9H); MS (ESI) m/z: 488.0 (M+H+).",
    "reference_string": "{\"inputs\": {\"m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,3-dichlorophenyl isocyanate\"}], \"amount\": {\"mass\": {\"value\": 0.141, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"amount\": {\"volume\": {\"value\": 0.061, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-(3-t-butyl-5-amino-1H-pyrazol-1-yl)-3,4-dihydroisoquinoline-1(2H)-thione\"}], \"amount\": {\"mass\": {\"value\": 0.15, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WASH\", \"details\": \"was again rinsed with THF (4 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"the solution was added to the reaction flask\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The resulting yellow suspension was briefly heated with a heat gun\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the solution was concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was purified by column chromatography\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 18.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-[3-t-butyl-1-(1-thioxo-1,2,3,4-tetrahydroisoquinolin-7-yl)-1H-pyrazol-5-yl]-3-(2,3-dichlorophenyl)urea\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 203.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 83.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 83.3}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-7b6a6342b6da434bbe58b2b32bf1af97",
    "procedure_text": "A solution of methyl [(4R)-2-oxo-4-(1,2,4-trioxolan-3-ylmethyl)azetidin-1-yl]glyoxylate (60 mg) in methanol (5 ml) was heated at 65\u00b0-70\u00b0 for two hours. The yellowish solution was cooled to 0\u00b0 C. and treated with a solution of diazomethane (excess) in diethyl ether. After removal of the solvent, the residue was chromatographed on silica gel (1.5 g) eluting with 20% acetone in dicloromethane to give methyl 2-[(2R)-4-oxoazetidin-2-yl]acetate (6 mg).",
    "reference_string": "{\"inputs\": {\"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl [(4R)-2-oxo-4-(1,2,4-trioxolan-3-ylmethyl)azetidin-1-yl]glyoxylate\"}], \"amount\": {\"mass\": {\"value\": 60.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diazomethane\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"After removal of the solvent\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was chromatographed on silica gel (1.5 g)\"}, {\"type\": \"WASH\", \"details\": \"eluting with 20% acetone in dicloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dicloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 2-[(2R)-4-oxoazetidin-2-yl]acetate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 6.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-1884dcf78ab8472887c0bc26f434d363",
    "procedure_text": "A solution of the amide of step 4 (570 mg, 3.38 mmol) in N,N-dimethylformamide (30 mL) was treated with N,N\u2032-carbonyldiimidazole (658 mg, 4.06 mmol) and the reaction mixture stirred at room temperature for 1 hour and then at 90\u00b0 C. for 18 hours. The reaction mixture was concentrated in vacuo and the crude product suspended in acetone and sonicated for 30 minutes. The solid product was filtered off and dried in vacuo to yield the dione product. 1H NMR (DMSO-D6, 400 MHz) \u03b4: 1.02 (t, 3H), 3.37 (m, 2H), 3.77 (m, 2H), 3.83 (s, 3H), 4.63 (m, 2H), 10.75 (s, 1H), 11.40 (s, 1H). MS ES\u2212 m/z 281 [M-H]\u2212.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"amide\"}], \"amount\": {\"mass\": {\"value\": 570.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N\\u2032-carbonyldiimidazole\"}], \"amount\": {\"mass\": {\"value\": 658.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture stirred at room temperature for 1 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WAIT\", \"details\": \"at 90\\u00b0 C. for 18 hours\", \"duration\": {\"value\": 18.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 90.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CONCENTRATION\", \"details\": \"The reaction mixture was concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"sonicated for 30 minutes\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}}, {\"type\": \"FILTRATION\", \"details\": \"The solid product was filtered off\"}, {\"type\": \"CUSTOM\", \"details\": \"dried in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"to yield the dione product\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-051e71b1bc544da49558a780e708ca6e",
    "procedure_text": "N-(2,4-dimethoxybenzyl)-4-oxo-N-(thiazol-2-yl)-3,4-dihydroquinazoline-7-sulfonamide (0.990 g, 2.159 mmol) was dissolved in toluene (10.80 ml) and POCl3 (0.403 ml, 4.32 mmol) was added. The reaction was stirred for 90 minutes at room temperature, then heated to 90\u00b0 C. and stirred for four hours. The reaction was diluted with ethyl acetate and washed with saturated sodium bicarbonate solution. The aqueous layer was extracted twice with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated to afford a brown oily solid. The solid was triturated in heptane, stirred for 30 minutes, and filtered. The resulting material was vacuum dried to afford crude 4-chloro-N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)quinazoline-7-sulfonamide as a free flowing tan solid. (ESI) 499.1 (M+Na)+.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(2,4-dimethoxybenzyl)-4-oxo-N-(thiazol-2-yl)-3,4-dihydroquinazoline-7-sulfonamide\"}], \"amount\": {\"mass\": {\"value\": 0.99, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 10.8, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"POCl3\"}], \"amount\": {\"volume\": {\"value\": 0.403, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction was stirred for 90 minutes at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"heated to 90\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 90.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"STIRRING\", \"details\": \"stirred for four hours\", \"duration\": {\"value\": 4.0, \"units\": \"HOUR\"}}, {\"type\": \"WASH\", \"details\": \"washed with saturated sodium bicarbonate solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The aqueous layer was extracted twice with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"the combined organic layers were dried with sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"to afford a brown oily solid\"}, {\"type\": \"CUSTOM\", \"details\": \"The solid was triturated in heptane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"heptane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"STIRRING\", \"details\": \"stirred for 30 minutes\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 90.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-chloro-N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)quinazoline-7-sulfonamide\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-6757a9d247104066a3a03254243b6f01",
    "procedure_text": "This material was prepared by the reaction 7-chloro-N,N-dimethylthieno[3,2-b]pyridine-2-carboxamide 33a (0.077 g, 0.32 mmole) and 6-hydroxy-N,1,2-trimethyl-1H-indole-3-carboxamide 16e (0.070 g, 0.32 mmole) and Cs2CO3 (0.104 g, 0.32 mmole) in a manner as previously described for example 1 to give a pale yellow solid (0.098 g, 73%). 1H NMR (300 MHz, CD3OD) \u03b48.38 (1H, d, J=5.5 Hz), 7.75 (1H, d, J=8.7 Hz), 7.66 (1H, s), 7.28 (1H, d, J=2.1 Hz), 6.94 (1H, dd, J=2.1, 8.7 Hz), 6.60 (1H, d, J=5.5 Hz), 3.61 (3H, s), 3.21 (6H, m), 2.87 (3H, s), 2.56 (3H, s). ESIMS (MH+): 423.05.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-chloro-N,N-dimethylthieno[3,2-b]pyridine-2-carboxamide\"}], \"amount\": {\"mass\": {\"value\": 0.077, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-hydroxy-N,1,2-trimethyl-1H-indole-3-carboxamide\"}], \"amount\": {\"mass\": {\"value\": 0.07, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Cs2CO3\"}], \"amount\": {\"mass\": {\"value\": 0.104, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.098, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 73.0}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-bd917dc650ec40149d8330ea22309810",
    "procedure_text": "400 mg (0.0018 mol, 1 eq) of 4-bromo-2-fluoro-1-nitro-benzene, 330 mg (0.0018 mol, 1 eq) of D9, 350 mg (0.0027 mol, 1.5 eq) of diisopropylethylamine, and 5 mL of dimethylformamide were combined, heated to 200\u00b0 C. and held for 1 min in a microwave reactor. 80 mL of water was then added and the reaction extracted with 2\u00d775 mL of dichloromethane. The dichloromethane layers were combined, dried with sodium sulfate, and evaporated to yield N-(5-bromo-2-nitrophenyl)-1-(tetrahydro-2H-pyran-4-yl)-4-piperidinamine which was used without further purification in the next step. MS (ESI): 385 [M+H]+.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-bromo-2-fluoro-1-nitro-benzene\"}], \"amount\": {\"mass\": {\"value\": 400.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"D9\"}], \"amount\": {\"mass\": {\"value\": 330.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 80.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropylethylamine\"}], \"amount\": {\"mass\": {\"value\": 350.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 200.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"the reaction extracted with 2\\u00d775 mL of dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 75.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried with sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(5-bromo-2-nitrophenyl)-1-(tetrahydro-2H-pyran-4-yl)-4-piperidinamine\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-8ecb8f81b0c04c17b53fe80b7692d8c9",
    "procedure_text": "9,10-bis(3-(9-Phenanthryl)phenyl)-9,10-dihydroxy-9,10-dihydroanthracene (5.2 g, 7.3 mmole) was suspended in acetic acid (120 ml). To the resultant suspension, a 57% hydroiodic acid (10 ml, 77 mmole, 10 eq) was added and the obtained mixture was stirred at 100\u00b0 C. for 6 hours. To the reaction mixture, a 50% aqueous solution of hypophosphorous acid (40 ml) was added. The formed solid was separated by filtration and washed with water, methanol and acetone and a white solid (5.0 g, quant.) was obtained.",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 120.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"9,10-bis(3-(9-Phenanthryl)phenyl)-9,10-dihydroxy-9,10-dihydroanthracene\"}], \"amount\": {\"mass\": {\"value\": 5.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"resultant suspension\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydroiodic acid\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aqueous solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hypophosphorous acid\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the obtained mixture was stirred at 100\\u00b0 C. for 6 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The formed solid was separated by filtration\"}, {\"type\": \"WASH\", \"details\": \"washed with water, methanol and acetone\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"a white solid (5.0 g, quant.) was obtained\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 6.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-727ad54a5f6c46758cdbc2deeb37f22e",
    "procedure_text": "2-Ethyl-5-methoxy-1H-indole (5.6 g, 21.5 mmol) was dissolved in 150 mL of DMF and 20 mL of THF and 1.0 g (25 mmol) of 60% sodium hydride was added. After stirring for 0.17 hours, 3.0 mL (25 mmol) of benzyl bromide was added. The mixture was stirred at room temperature for 10 hours, diluted with water and extracted with ethyl acetate. The ethyl acetate solution was washed with water, saturated NaCl solution, and dried (Na2SO4). The EtOAc was evaporated and the residue was chromatographed on silica gel eluting with a gradient, 5% EtOAc/hexane\u2192415% EtOAc/hexane to give 4.6 g (82% yield) of 2-ethyl-5-methoxy-1-(phenylmethyl)-1H-indole.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzyl bromide\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydride\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-Ethyl-5-methoxy-1H-indole\"}], \"amount\": {\"mass\": {\"value\": 5.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring for 0.17 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"The mixture was stirred at room temperature for 10 hours\", \"duration\": {\"value\": 10.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The ethyl acetate solution was washed with water, saturated NaCl solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaCl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The EtOAc was evaporated\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the residue was chromatographed on silica gel eluting with a gradient, 5% EtOAc/hexane\\u2192415% EtOAc/hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 0.17, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-ethyl-5-methoxy-1-(phenylmethyl)-1H-indole\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 4.6, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 82.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-df963e46b8fc4e6f94b8c44472c67877",
    "procedure_text": "(S)-2-({(S)-7-(2-amino-4-methyl-thiazole-5-sulfonyl)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl}-amino)-3-(4\u2032-cyano-biphenyl-4-yl)-propionic acid methyl ester (30 mg) was reacted with isobutyryl chloride according to General Procedure F to give (S)-3-(4\u2032-cyano-biphenyl-4-yl)-2-({(S)-7-[2-(isobutyrylamino)-4-methyl-thiazole-5-sulfonyl]-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl}-amino)-propionic acid methyl ester. This ester, upon hydrolysis according to General Procedure B, gave the title compound. LCMS (m/z): 980.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(S)-2-({(S)-7-(2-amino-4-methyl-thiazole-5-sulfonyl)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl}-amino)-3-(4\\u2032-cyano-biphenyl-4-yl)-propionic acid methyl ester\"}], \"amount\": {\"mass\": {\"value\": 30.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isobutyryl chloride\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(S)-3-(4\\u2032-cyano-biphenyl-4-yl)-2-({(S)-7-[2-(isobutyrylamino)-4-methyl-thiazole-5-sulfonyl]-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl}-amino)-propionic acid methyl ester\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-60b40dc07df24afca246c42268b74f2a",
    "procedure_text": "The title compound was prepared from (2S)-3-[4-(3-Hydroxy-propoxy)-phenyl]-2-methoxy-propionic acid linked to Wang's Resin (Example 94, Step D) via Mitsunobu coupling with 4-trifluoromethylphenol and cleavage from the resin (Standard Procedure G) gave an oily solid.",
    "reference_string": "{\"inputs\": {\"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-trifluoromethylphenol\"}], \"reaction_role\": \"REACTANT\"}]}, \"m0_m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2S)-3-[4-(3-Hydroxy-propoxy)-phenyl]-2-methoxy-propionic acid\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"gave an oily solid\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-9677621b00474baf85c0428f0d2eec6a",
    "procedure_text": "In analogy with Example 1i), 0.50 g of 5(S)-[1(S)-(Boc-amino)-2-phenylethyl]-3(R)-[(p-cyanophenyl)methyl]dihydrofuran-2-(3H)-one in 19 ml of dimethoxyethane and 10 ml of water is hydrolysed with 4.8 ml of a 1 M lithium hydroxide solution to form the title compound: TLC Rf (B)=0.3.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5(S)-[1(S)-(Boc-amino)-2-phenylethyl]-3(R)-[(p-cyanophenyl)methyl]dihydrofuran-2-(3H)-one\"}], \"amount\": {\"mass\": {\"value\": 0.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium hydroxide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethoxyethane\"}], \"amount\": {\"volume\": {\"value\": 19.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-00335d5f2aca490b9cdabe3754c26738",
    "procedure_text": "To a solution of compound 118E (128 mg, 0.33 mmol) in THF (15 mL) was added 0.1 M aqueous LiOH (3.75 mL) and the mixture was stirred at room temperature. After 24 h, the resultant solution was acidified to pH 4 and the mixture was extracted with ethyl acetate (3\u00d750 mL). The combined organic extracts were washed with water (20 mL) and concentrated to give the crude product, which was further purified by chromatography on 70-230 mesh silica gel eluted with CH2Cl2:methanol:water 40:10:1 to afford 104 mg (0.29 mmol, 88%) of the product as a solid, mp 206-207\u00b0 C.; 1H NMR (300 MHz, DMSO-d6) \u03b4 2.05 (s, 3H), 3.81 (s, 2H), 7.65 (m, 4H); 13C NMR (75 MHz, DMSO-d6) \u03b4 24.8, 37.3, 119.0, 127.5, 137.9, 142.6, 153.3, 169.4, 169.5, 170.9; MS (LCQ, ESI+) Calcd for C12H13N4O5S2 357.0. found 357.0 (M+H)+. HRMS (ESI+, m/z) Calcd for C12H13N4O5S2 357.0327. found 357.0326 (M+H)+.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound 118E\"}], \"amount\": {\"mass\": {\"value\": 128.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"LiOH\"}], \"amount\": {\"volume\": {\"value\": 3.75, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"resultant solution\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"the mixture was extracted with ethyl acetate (3\\u00d750 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined organic extracts were washed with water (20 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"to give the crude product, which\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"was further purified by chromatography on 70-230 mesh silica gel\"}, {\"type\": \"WASH\", \"details\": \"eluted with CH2Cl2:methanol:water 40:10:1\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2 methanol water\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 24.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 0.29, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 104.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 88.0}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0277b409438e45d98a090a531d97ffca",
    "procedure_text": "A mixture of 12 g. (0.045 mole) of 2-(3-ethyl-5-methyl-4-isoxazolyl)-3-acetyl indole, 4 g. (0.049 mole) of dimethylamine hydrochloride, and 0.5 ml. concentrated hydrochloric acid in 70 ml. of ethanol is heated to reflux and treated by portionwise addition with 14 g. (0.470 mole) of paraformaldehyde over 5 hours. The resulting mixture is refluxed an additional 24 hours, cooled and evaporated in vacuo. The residue is then dissolved in 300 ml. methylene chloride and washed with 200 ml. 2N hydrochloric acid. The aqueous acid is cooled and made basic with 2N sodium hydroxide and extracted with methylene chloride. The organic layer is dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo. The residue is crystallized from ether to give 3-dimethylamino-1-[2-(3-ethyl-5-methyl-4-isoxazolyl)-1H-indole-3-yl]-1-propanone, m.p. 146\u00b0-148\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"paraformaldehyde\"}], \"amount\": {\"moles\": {\"value\": 0.47, \"units\": \"MOLE\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(3-ethyl-5-methyl-4-isoxazolyl)-3-acetyl indole\"}], \"amount\": {\"moles\": {\"value\": 0.045, \"units\": \"MOLE\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylamine hydrochloride\"}], \"amount\": {\"moles\": {\"value\": 0.049, \"units\": \"MOLE\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"A mixture of 12 g\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to reflux\"}, {\"type\": \"ADDITION\", \"details\": \"treated by portionwise addition with 14 g\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The resulting mixture is refluxed an additional 24 hours\", \"duration\": {\"value\": 24.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"cooled\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated in vacuo\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue is then dissolved in 300 ml\"}, {\"type\": \"WASH\", \"details\": \"methylene chloride and washed with 200 ml\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"The aqueous acid is cooled\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with methylene chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layer is dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue is crystallized from ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-dimethylamino-1-[2-(3-ethyl-5-methyl-4-isoxazolyl)-1H-indole-3-yl]-1-propanone\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e4ab0645ddb7498cb398c74f0f9d61bd",
    "procedure_text": "A solution of 4,7-dibromo-5-aminobenzimidazole (1.5 g, 5.1 mmol) in 10 ml of DMF was transferred into pressure bottle under Ar2. To the solution was added tetramethyltin 3.6 ml, 20 mmol) and bis(triphenylphosphine) palladium(II) chloride (200 mg). The resulting reaction mixture was stirred at 140\u00b0 C. for 24 h and concentrated in vacuo, yielding a dark oil which was subjected to column chromatography (40% EtOAC/CHCl3) to yield 0.34 g (1.5 mmol, 29%) of the desired product as well as 0.75 g of 4,7-dimethyl-5-aminobenzimidazole.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CHCl3\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4,7-dibromo-5-aminobenzimidazole\"}], \"amount\": {\"mass\": {\"value\": 1.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetramethyltin\"}], \"amount\": {\"volume\": {\"value\": 3.6, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"bis(triphenylphosphine) palladium(II) chloride\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 140.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at 140\\u00b0 C. for 24 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The resulting reaction mixture\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"yielding a dark oil which\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 24.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 1.5, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.34, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 29.0}}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4,7-dimethyl-5-aminobenzimidazole\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.75, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a9d9abf345964295afaba69909efd13a",
    "procedure_text": "Compounds of Formula (I), wherein R3 is \u2014C(O)OCH3, A is phenyl, and X and Z are oxygen, D and T are CH, M is C, Q is N(R7)p, either p or q is 1, and the other is 0, can be prepared according to the synthetic sequence shown in Scheme 1 and further detailed in the Examples section following. 4-Acetamidophenol (1) in DMF is reacted with 5-chloro-2-nitroaniline (2) in the presence of 60% NaH to provide 5-(4-acetamidophenoxy)-2-nitroaniline (3). The nitroaniline (3) is then refluxed with Na2S2O4 to provide 4-(4-acetamidophenoxy)phenylene-1,2-diamine (4). (It is understood that reduction of nitro group of (3) can be effected in many ways, for example by use of H2, Pd/C; Raney Nickel with hydrazine; SnCl4 in HCl; etc.) Diamine (4) is refluxed with 1,3-bis(methoxycarbonyl)-2-methyl-2-thiopseudourea in ethanol and the acetylated carbamate (5) is obtained. HCl is added to deacetylate the carbamate (5) to give methyl (5-(4-aminophenoxy)-1H-benzimidazol-2-yl)carbamate (7). Alternatively, carbamate (7) may be prepared by refluxing 3,4,4\u2032-triaminodiphenylether (6) with 1,3-bis(methoxycarbonyl)-2-methyl-2-thiopseudourea and then treating with conc. HCl to give carbamate (7). Carbamate (7) is then reacted with the appropriate phenyl isocyanate (8) to give the resultant benzimidazole (9) of the present invention. It is understood that R1 and R2 are as described above. When X of Formula (I) is sulfur and Z of Formula (I) is oxygen, the final compounds are obtained by following the same procedure using a phenylthiol derivative of 1. When X of Formula (I) is sulfur, the compound thus obtained can be oxidized with MCPBA (metachloroperbenzoic acid) to give compounds containing sulfone (SO2) or sulfine (SO) as X. Also, when 3-(3-substitutedphenyl)aminocarbonylamino)phenoxy derivatives of Formula 1 are prepared, 3-acetamidophenol is utilized instead of 4-acetamidophenol.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"( I )\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"phenyl\"}], \"reaction_role\": \"REACTANT\"}]}, \"m4_m7_m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-Acetamidophenol\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-chloro-2-nitroaniline\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaH\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"oxygen\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"can be prepared\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-(4-acetamidophenoxy)-2-nitroaniline\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-93f32cfd125842b2bdee916822c06e39",
    "procedure_text": "Combine (R)-oxiranemethanol (32.85 g, 443.5 mmol) with 2-chloro-3-hydroxypyridine (52.23 g, 403.18 mmol) in THF (1.34 L). Stir the mixture until the solids dissolve. Cool it to 0\u00b0 C. and slowly add triphenylphosphine (116.33 g, 443.5 mmol). After all the solids dissolve, add diisopropyl azodicarboxylate (87.92 mL, 443.5 mmol) drop-wise over 25 minutes at a sufficiently slow rate to maintain the internal temperature of the reaction below 10\u00b0 C. Stir the mixture while cooling for 30 minutes then allow the mixture to warm to ambient temperature and continue stirring overnight. Add EtOAc, and wash with NaOH (2\u00d71.0 N). Dry the organic layer over Na2SO4; filter; and concentrate the filtrate under reduced pressure. Triturate the residue with a mixture of 2:1 Et2O: hexanes and stir for 5 minutes. Filter and concentrate the filtrate under reduced pressure to provide a residue. Purify the residue via flash column chromatography (2\u00d7330 g SiO2), eluting with a gradient of 0-66% THF/Hexane. Combine the desired fractions, and concentrate under reduced pressure to provide the title compound (32.6 g, 43.6%) as a white solid. MS (m/z): 186 (M+1).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropyl azodicarboxylate\"}], \"amount\": {\"volume\": {\"value\": 87.92, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-oxiranemethanol\"}], \"amount\": {\"mass\": {\"value\": 32.85, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloro-3-hydroxypyridine\"}], \"amount\": {\"mass\": {\"value\": 52.23, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 1.34, \"units\": \"LITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triphenylphosphine\"}], \"amount\": {\"mass\": {\"value\": 116.33, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"Stir the mixture until the solids\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"DISSOLUTION\", \"details\": \"dissolve\"}, {\"type\": \"DISSOLUTION\", \"details\": \"After all the solids dissolve\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to maintain\"}, {\"type\": \"CUSTOM\", \"details\": \"the internal temperature of the reaction below 10\\u00b0 C\"}, {\"type\": \"STIRRING\", \"details\": \"Stir the mixture\"}, {\"type\": \"TEMPERATURE\", \"details\": \"while cooling for 30 minutes\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"to warm to ambient temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"STIRRING\", \"details\": \"continue stirring overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"WASH\", \"details\": \"Add EtOAc, and wash with NaOH (2\\u00d71.0 N)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"Dry the organic layer over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filter\"}, {\"type\": \"CONCENTRATION\", \"details\": \"and concentrate the filtrate under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"Triturate the residue\"}, {\"type\": \"ADDITION\", \"details\": \"with a mixture of 2:1 Et2O\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Et2O\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"STIRRING\", \"details\": \"hexanes and stir for 5 minutes\", \"duration\": {\"value\": 5.0, \"units\": \"MINUTE\"}, \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"Filter\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrate the filtrate under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"to provide a residue\"}, {\"type\": \"CUSTOM\", \"details\": \"Purify the residue via flash column chromatography (2\\u00d7330 g SiO2)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"SiO2\"}], \"amount\": {\"mass\": {\"value\": 330.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"eluting with a gradient of 0-66% THF/Hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF Hexane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrate under reduced pressure\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 32.6, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 43.6}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 43.6}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-07d193c1256449a281f899a18411e461",
    "procedure_text": "Prepared using general procedure 44. A mixture of sulfathiazole (5 gm, 19.5 mmol) and maleic anhydride (1.92 g, 19.5 mmol) was heated under refluxed for 16 hrs. The reaction was cooled to RT and then to 0\u00b0 C. for 4 hrs. The formed precipitate was filtered off and washed with cold water. The crude solid was dissolved in CH2Cl2 and absorbed onto Celite. Purification via silica gel chromatography using 10% MeOH in CH2Cl2 gave (1H-pyrrole-2,5-dione)-N-(thiazol-2-yl)benzene sulfonamide (2 g, 30%). LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=336.2; tR=2.12 min.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sulfathiazole\"}], \"amount\": {\"mass\": {\"value\": 5.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"maleic anhydride\"}], \"amount\": {\"mass\": {\"value\": 1.92, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Prepared\"}, {\"type\": \"TEMPERATURE\", \"details\": \"was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"under refluxed for 16 hrs\", \"duration\": {\"value\": 16.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"The formed precipitate was filtered off\"}, {\"type\": \"WASH\", \"details\": \"washed with cold water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISSOLUTION\", \"details\": \"The crude solid was dissolved in CH2Cl2\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"absorbed onto Celite\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification via silica gel chromatography\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(1H-pyrrole-2,5-dione)-N-(thiazol-2-yl)benzene sulfonamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 30.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 30.4}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4aa3580a8071440eaf1672bb3830ce0a",
    "procedure_text": "To a solution of Z-1-butyl-5-[[2-butyl-3-(triphenylmethyl)-3H-imidazol-5-yl]methylene]-2,4 imidazolidinedione (1.20 g, 2.26 mmol) in DMF (5 mL) was added K2CO3 (1.56 g, 11.3 retool) and then 1-iodobutane (0.344 mL, 3.02 mmol). The mixture was stirred for 16 hours and then diluted with ether and washed with water and brine. After drying over MgSO4 the product was isolated by chromatography on silica eluting with 80 % petroleum ether 20 % ethyl acetate. MS (CI) 588",
    "reference_string": "{\"inputs\": {\"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Z-1-butyl-5-[[2-butyl-3-(triphenylmethyl)-3H-imidazol-5-yl]methylene]-2,4 imidazolidinedione\"}], \"amount\": {\"mass\": {\"value\": 1.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"K2CO3\"}], \"amount\": {\"mass\": {\"value\": 1.56, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-iodobutane\"}], \"amount\": {\"volume\": {\"value\": 0.344, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred for 16 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WASH\", \"details\": \"washed with water and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"After drying over MgSO4 the product\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"was isolated by chromatography on silica eluting with 80 % petroleum ether 20 % ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"petroleum ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-6aba9df3a58e4a90b2c3c5ed9bb97577",
    "procedure_text": "To a cooled (0\u00b0 C.) solution of 2,4-dichloro-6-phenyl-1,3,5-triazine (16.0 g, 70.8 mmol, 1.00 equiv) dissolved in 1:1 CH3CN:H2O (80 mL) was added NH2Me (8.00 g, 27.5% solution in H2O, 70.8 mmol, 1.00 equiv). The solution was treated with 1 N NaOH to maintain a pH of 9-10 and stirred for 15 min. The resulting suspension was diluted with water and filtered to provide 12 g of crude product. A portion of this material (8 g) was purified by reverse-phase HPLC to afford 3.6 g of the title compound. MS (ES+): m/e 221.1 [M+H]+.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH3CN\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,4-dichloro-6-phenyl-1,3,5-triazine\"}], \"amount\": {\"mass\": {\"value\": 16.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m6_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH2Me\"}], \"amount\": {\"mass\": {\"value\": 8.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"amount\": {\"volume\": {\"value\": 80.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred for 15 min\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"to maintain a pH of 9-10\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"to provide 12 g of crude product\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"amount\": {\"mass\": {\"value\": 12.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"A portion of this material (8 g) was purified by reverse-phase HPLC\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"material\"}], \"amount\": {\"mass\": {\"value\": 8.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 3.6, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e39577f6343a4c40baf476ebfc53823d",
    "procedure_text": "3-(R)-(4-(S)-Benzyl-2-oxo-oxazolidine-3-carbonyl)-5-cyclohexyl-pentanoic acid (1.76 g, 4.53 mmol, 1.0 eq.) dissolved in DMF (10 mL) and treated with HATU (1.3 g, 5.0 mmol, 1.1 eq.), morpholine (680 \u03bcL, 7.77 mmol, 1.7 eq.) and DIPEA (870 \u03bcL, 5.0 mmol, 1.1 eq.). Alternatively an additional equivalent of morpholine can be used in the reaction and CH2Cl2 can be used as the reaction solvent. The reaction is monitored by LC/MS. The reaction mixture is diluted with ethyl acetate (50 mL) and extracted with 0.5 M HCl (2\u00d710 mL), saturated NaHCO3, and brine. The organic layer is dried over MgSO4, filtered and evaporated. The crude mixture is used in Step F directly or purified by normal-phase silica chromatography in a 20-50% ethyl acetate in hexanes gradient to provide 1-(4-(S)-Benzyl-2-oxo-oxazolidin-3-yl)-2-(R)-(2-cyclohexyl-ethyl)-4-morpholin-4-yl-butane-1,4-dione as a white solid (1.91 g, 4.18 mmol, 92%): 1H NMR (CDCl3, 400 MHz) \u03b4 0.80-0.91 (m, 2H), 1.09-1.27 (m, 6H), 1.44-1.53 (m, 1H), 1.61-1.73 (m, 6H), 2.12 (s, 2H), 2.35 (dd, 1H, J=17.2, 4.0 Hz), 2.49 (dd, 1H, J=13.6, 9.6 Hz), 2.71 (dd, 1H, J=17.6, 10.8 Hz), 3.03 (dd, 1H, J=13.6, 3.2 Hz), 3.48-3.72 (m, 8H), 3.87-3.97 (m, 3H), 4.43 (m, 1H), 6.90-7.10 (m, 5H), 8.02 (s, 1H).",
    "reference_string": "{\"inputs\": {\"m5_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"morpholine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(R)-(4-(S)-Benzyl-2-oxo-oxazolidine-3-carbonyl)-5-cyclohexyl-pentanoic acid\"}], \"amount\": {\"mass\": {\"value\": 1.76, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HATU\"}], \"amount\": {\"mass\": {\"value\": 1.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"morpholine\"}], \"amount\": {\"volume\": {\"value\": 680.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DIPEA\"}], \"amount\": {\"volume\": {\"value\": 870.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted with 0.5 M HCl (2\\u00d710 mL), saturated NaHCO3, and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layer is dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"purified by normal-phase silica chromatography in a 20-50% ethyl acetate in hexanes gradient\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(4-(S)-Benzyl-2-oxo-oxazolidin-3-yl)-2-(R)-(2-cyclohexyl-ethyl)-4-morpholin-4-yl-butane-1,4-dione\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 4.18, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.91, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 92.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 92.3}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-00d19ad5eb2041dfaabe8e1cb7076b01",
    "procedure_text": "A solution of phthalic dicarboxaldehyde (248 mg; 1.80 mmol) and 2-Amino-3-cycloheptyl-propionic acid (318 mg; 1.72 mmol) in acetonitrile was heated to reflux for 18 h. The mixture was then allowed to cool to room temperature and the mixture stored in the refrigerator for 3 h. The solid was filtered off, rinsed with cold acetonitrile and air dried to give 424 mg (82%) of 3-Cycloheptyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid as a beige solid: EI-HRMS m/e calcd for C18H23NO3 (M+) 301.1678, found 301.1668.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-Amino-3-cycloheptyl-propionic acid\"}], \"amount\": {\"mass\": {\"value\": 318.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"to reflux for 18 h\", \"duration\": {\"value\": 18.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"The solid was filtered off\"}, {\"type\": \"WASH\", \"details\": \"rinsed with cold acetonitrile and air\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-Cycloheptyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 424.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 82.0}}], \"isolated_color\": \"beige\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-9aa5d6b825ee47659f4772d9519f0ba3",
    "procedure_text": "To a solution of ethyl 4-{[5-(biphenyl-4-yl)-4,6-difluoro-1H-benzimidazol-2-yl]oxy}cyclohexanecarboxylate (0.615 g, 1.291 mmol) in THF (5 ml) was added potassium trimethyl silanolate (0.550 g, 4.29 mmol). The reaction was stirred overnight at ambient temperature. Then the volatiles were removed in vacuo and the resulting residue was acidified with 1N aqueous HCl and extracted with EtOAc. The organic phase was washed with water and concentrated in vacuo. Purification of the resulting residue by reverse phase HPLC eluting with 50-100% MeCN: H2O afforded the title compound as a white solid. LC-MS: calculated for C26H22F2N2O3 448.16, observed m/e 449.01 (M+H)+ (Rt 2.32/4 min). 1H NMR (500 MHz, C2D6OS): \u03b4 7.80-7.70 (m, 4H), 7.55-7.45 (m, 4H), 7.40 (m, 1H), 7.15 (d, 1H), 5.00-4.90 (m, 1H), 2.30 (m, 1H), 2.25 (m, 2H), 2.00 (m, 2H), 1.50 (m, 4H).",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 4-{[5-(biphenyl-4-yl)-4,6-difluoro-1H-benzimidazol-2-yl]oxy}cyclohexanecarboxylate\"}], \"amount\": {\"mass\": {\"value\": 0.615, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium trimethyl silanolate\"}], \"amount\": {\"mass\": {\"value\": 0.55, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction was stirred overnight at ambient temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Then the volatiles were removed in vacuo\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic phase was washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification of the resulting residue by reverse phase HPLC\"}, {\"type\": \"WASH\", \"details\": \"eluting with 50-100% MeCN\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeCN\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fcf4cdc5076c4ac088906b41d542d27e",
    "procedure_text": "A solution of 2,2,2-trichloroethyl {4-[acetyl(methyl)amino]phenyl}carbamate (200 mg, 0.589 mmol), 1-(3-phenyl-1,2,4-thiadiazol-5-yl)piperazine (145 mg, 0.589 mmol), diisopropylethylamine (0.103 ml, 0.589 mmol) and dimethylsulfoxide (4 ml) was stirred at 70\u00b0 C. for 12 hours, the reaction mixture was poured into water and the mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate) to obtain the desired product as a solid. This was recrystallized from a mixed solvent of ethyl acetate and hexane to obtain the desired product (47.3 mg, 18.3%) as a solid.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,2,2-trichloroethyl {4-[acetyl(methyl)amino]phenyl}carbamate\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(3-phenyl-1,2,4-thiadiazol-5-yl)piperazine\"}], \"amount\": {\"mass\": {\"value\": 145.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropylethylamine\"}], \"amount\": {\"volume\": {\"value\": 0.103, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylsulfoxide\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"the mixture was extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The extract was washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"The solvent was distilled off under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by silica gel column chromatography (ethyl acetate)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-36d296f61eac49cebe1b2291f4a261c1",
    "procedure_text": "Methanesulfonic acid 4-oxo-5-[5-(quinazolin-4-yloxy)-pentyloxy]-4H-pyran-2-ylmethyl ester 20 (100 mg, 0.23 mmol) was dissolved in dichloromethane (3 mL). Pyrrolidine (48 \u03bcL, 0.575 mmol) was added via syringe. The mixture was stirred at 45\u00b0 C. for 1.5 h. .CH2Cl2 (75 ml) was added and the solution was washed with NaHCO3 10% (3\u00d750 mL), brine (3\u00d750 mL). The organic layer was dried over MgSO4, filtered and evaporated. The crude product was purified by column chromatography on silica using as eluent CH2Cl2:MeOH=90:10. 5-(5-(Quinazolin-4-yloxy)pentyloxy)-2-((pyrrolidin-1-yl)methyl)-4H-pyran-4-one EHT 5317 was obtained (30 mg, 35% yield) as a colourless oil.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"amount\": {\"volume\": {\"value\": 75.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Methanesulfonic acid 4-oxo-5-[5-(quinazolin-4-yloxy)-pentyloxy]-4H-pyran-2-ylmethyl ester\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pyrrolidine\"}], \"amount\": {\"volume\": {\"value\": 48.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 45.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at 45\\u00b0 C. for 1.5 h.\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WASH\", \"details\": \"the solution was washed with NaHCO3 10% (3\\u00d750 mL), brine (3\\u00d750 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layer was dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude product was purified by column chromatography on silica using as eluent CH2Cl2\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.5, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-(5-(Quinazolin-4-yloxy)pentyloxy)-2-((pyrrolidin-1-yl)methyl)-4H-pyran-4-one\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 35.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-918d04a60c2a46588ee12e549cde5bee",
    "procedure_text": "A solution of 10-chloro-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[4,3-f][1,4]oxazepine (80.0 mg, 0.242 mmol), piperazin-2-one (48.4 mg, 0.484 mmol), XPhos (23.0 mg, 0.0484 mmol), and Sodium-tert-butoxide (46.5 mg, 0.484 mmol) in was heated in microwave at 125 C for 30 min. The reaction was filtered thru celite then rinsed with EtOAc. The filtrate was washed water, brine. The organic layer was dried Na2SO4, concentrated to give 307, analyzed by rHPLC. MS: (ESI+)=395.2. 1H NMR (500 MHz, DMSO) \u03b4 8.06 (s, 1H), 8.03 (d, J=5.7 Hz, 2H), 7.93 (s, 1H), 7.59 (s, 1H), 5.72 (dt, J=13.1, 6.6 Hz, 1H), 4.62-4.52 (m, 2H), 4.51-4.39 (m, 2H), 3.94 (s, 2H), 3.73-3.62 (m, 2H), 3.37-3.30 (m, 2H), 1.51 (d, J=6.6 Hz, 6H).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"10-chloro-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[4,3-f][1,4]oxazepine\"}], \"amount\": {\"mass\": {\"value\": 80.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"piperazin-2-one\"}], \"amount\": {\"mass\": {\"value\": 48.4, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"XPhos\"}], \"amount\": {\"mass\": {\"value\": 23.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Sodium-tert-butoxide\"}], \"amount\": {\"mass\": {\"value\": 46.5, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The reaction was filtered thru celite\"}, {\"type\": \"WASH\", \"details\": \"then rinsed with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The filtrate was washed water, brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"307\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0cf02fa20a0f4cb28295c40b36d6faf2",
    "procedure_text": "70.0 g (123 mmol) of 2'-dehydroplectaniaxanthin are dissolved in 2000 ml of methylene chloride and 500 ml of methanol. At 16-18\u00b0 C. 4.70 g (123 mmol) of sodium borohyride are added in portions, and the mixture is stirred for 1.5 hours at room temperature. The resulting solution is then cooled to 10\u00b0 C., and approx. 150 ml of 1N sulphuric acid are added at such a rate that the temperature is maintained between 10\u00b0 and 15\u00b0 C. until a pH between 7 and 8 is obtained. The resulting mixture is then extracted three times with 500 ml of methylene chloride in each case. The organic layer is washed several times with 500 ml of ice-water, then dried over anhydrous sodium sulphate and evaporated at 35\u00b0 C. using a water jet vacuum. The resulting crystalline mass is stirred with 1500 ml of diethyl ether and the resulting suspension filtered. In this way there are obtained 12.2 g (HPLC purity 97%) of racemic plectaniaxanthin crystals.",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2'-dehydroplectaniaxanthin\"}], \"amount\": {\"mass\": {\"value\": 70.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 2000.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium\"}], \"amount\": {\"mass\": {\"value\": 4.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sulphuric acid\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture is stirred for 1.5 hours at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"At 16-18\\u00b0 C\", \"temperature\": {\"setpoint\": {\"value\": 17.0, \"precision\": 1.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"The resulting solution is then cooled to 10\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 10.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"is maintained between 10\\u00b0 and 15\\u00b0 C. until a pH between 7 and 8\"}, {\"type\": \"CUSTOM\", \"details\": \"is obtained\"}, {\"type\": \"EXTRACTION\", \"details\": \"The resulting mixture is then extracted three times with 500 ml of methylene chloride in each case\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer is washed several times with 500 ml of ice-water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous sodium sulphate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulphate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated at 35\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 35.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"STIRRING\", \"details\": \"The resulting crystalline mass is stirred with 1500 ml of diethyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"amount\": {\"volume\": {\"value\": 1500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"the resulting suspension filtered\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.5, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"plectaniaxanthin\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 12.2, \"units\": \"GRAM\"}}}], \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-8a6e9e4489b8485a9039ddebfc823b31",
    "procedure_text": "To a solution of 3-(5-Cyano-2-nitro-phenylamino)-propionic acid ethyl ester (1.53 g, 5.8 mmol) in MeOH (10 mL) was added a slurry of Pd/C (0.3 g) in MeOH. The reaction mixture was saturated with H2 and stirred for 2 h. When the reaction was complete, the reaction mixture was filtered and the filtrate was concentrated to afford 0.65 g (48%) of the desired product as a brown solid. The resulting residue was used for the next reaction without further purification. LCMS (ESMS): m/z 233.66 (M+H+).",
    "reference_string": "{\"inputs\": {\"m1_m2_m4_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(5-Cyano-2-nitro-phenylamino)-propionic acid ethyl ester\"}], \"amount\": {\"mass\": {\"value\": 1.53, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd/C\"}], \"amount\": {\"mass\": {\"value\": 0.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred for 2 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"the reaction mixture was filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate was concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.65, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 48.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 48.0}}], \"isolated_color\": \"brown\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d1d2d4bbb79644d4a492a41958a56b38",
    "procedure_text": "To a stirred solution of 8.8 g (0.022 mol) sodium hydroxide in 500 ml methanol was added 20 g (0.22 mol) acetamidine hydrochloride. After stirring for an additional 1/4 hour, 37.7 g (0.2 mol) alpha-(2,6-dimethylphenylamino)acethydrazide was added. The reaction mixture was heated under reflux for about 18 hours, cooled and filtered. The filtrate was evaporated under a reduced pressure to give a solid residue. The residue was diluted with dichloromethane, filtered, dried over magnesium sulfate and evaporated under reduced pressure to give a solid residue, which was triturated with ethyl ether/petroleum ether and dried to give 34.3 g of the product, m.p. 125\u00b0-126\u00b0 C. The product is tabulated in Table I as Compound No. 2-A.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"mass\": {\"value\": 8.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetamidine hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 20.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"alpha-(2,6-dimethylphenylamino)acethydrazide\"}], \"amount\": {\"mass\": {\"value\": 37.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring for an additional 1/4 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The reaction mixture was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"under reflux for about 18 hours\", \"duration\": {\"value\": 18.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"cooled\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"The filtrate was evaporated under a reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a solid residue\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a solid residue, which\"}, {\"type\": \"CUSTOM\", \"details\": \"was triturated with ethyl ether/petroleum ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl ether petroleum ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 34.3, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d75cbae2334b4631b422a24ea60d2e4a",
    "procedure_text": "A solution of 22.63 g (0.25 mol) of acryloyl chloride in 250 ml of methylene chloride was added over a period of 35 minutes to a mixture of 46.81 g (0.25 mol) of N-(4-hydroxyphenyl)methanesulfonamide, 25.30 g (0.25 mol) of triethylamine and 750 ml of methylene chloride at 0\u00b0 C. The resultant solution was stirred at reduced temperature for 2.17 hours, washed three times with water and dried over magnesium sulfate. Concentration of the solution in vacuo gave a solid which after two recrystallizations from benzene and drying gave 13.4 g (22.2 percent yield) of N-(4-acryloyloxyphenyl)methanesulfonamide; m.p.=136.5\u00b0 to 139.5\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"resultant solution\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m5_m2_m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acryloyl chloride\"}], \"amount\": {\"mass\": {\"value\": 22.63, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(4-hydroxyphenyl)methanesulfonamide\"}], \"amount\": {\"mass\": {\"value\": 46.81, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"mass\": {\"value\": 25.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 750.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WASH\", \"details\": \"washed three times with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Concentration of the solution in vacuo gave a solid which\"}, {\"type\": \"CUSTOM\", \"details\": \"after two recrystallizations from benzene\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzene\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"drying\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(4-acryloyloxyphenyl)methanesulfonamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 13.4, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 22.2}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 22.2}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fbb1f14df4a344ae97a76f0efd3e86ed",
    "procedure_text": "5-(4-Phenoxyphenyl)-7H-pyrrolo[2,3-d]-pyrimidin-4-ylamine (906 mg) was reacted with 2-chloronicotinonitrile (510 mg) in the presence of sodium hydride (150 mg) in dimethylformamide (30 ml) at 100\u00b0 C. for 5 hours to give 2-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]pyridine-3-carbonitrile, m.p. 242-242.5\u00b0 C., after workup.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-(4-Phenoxyphenyl)-7H-pyrrolo[2,3-d]-pyrimidin-4-ylamine\"}], \"amount\": {\"mass\": {\"value\": 906.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloronicotinonitrile\"}], \"amount\": {\"mass\": {\"value\": 510.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydride\"}], \"amount\": {\"mass\": {\"value\": 150.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]pyridine-3-carbonitrile\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-1027af87488d4f5287903b9277bedd53",
    "procedure_text": "4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methoxyaniline (30 mg) was dissolved in chloroform (1 ml) and triethylamine (0.1 ml) to prepare a solution. A solution of triphosgene (35 mg) in chloroform (0.2 ml) was then added to the solution, and the mixture was stirred at room temperature for one hr. Next, a solution of (1R)-1-(4-fluorophenyl)ethylamine (35 mg) in chloroform (0.2 ml) was added thereto, and the mixture was stirred at room temperature for 10 hr. The stirred mixture was purified by chromatography on silica gel using chloroform/methanol for development to give the title compound (43 mg, yield 95%).",
    "reference_string": "{\"inputs\": {\"m4_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(1R)-1-(4-fluorophenyl)ethylamine\"}], \"amount\": {\"mass\": {\"value\": 35.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"amount\": {\"volume\": {\"value\": 0.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 0.1, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methoxyaniline\"}], \"amount\": {\"mass\": {\"value\": 30.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triphosgene\"}], \"amount\": {\"mass\": {\"value\": 35.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"amount\": {\"volume\": {\"value\": 0.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at room temperature for one hr\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"the mixture was stirred at room temperature for 10 hr\", \"duration\": {\"value\": 10.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The stirred mixture was purified by chromatography on silica gel\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 43.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 95.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 95.2}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a122641fff0b4ee09144ab386dd059fa",
    "procedure_text": "To a solution of (S)-2-chloro-N-(2-hydroxy-1-phenylethyl)acetamide (600 mg, 2.8 mmol) in anhydrous THF solution at 0\u00b0 C. was added NaH mineral oil suspension (247 mg, 6.18 mmol). The resulting mixture was stirred overnight at room temperature. The reaction mixture was concentrated to dryness, and the residue was partitioned between CH2Cl2/brine/H2O (20 mL/18 mL/2 mL). CH2Cl2 layer was dried over anhydrous Na2SO4, filtered off, concentrated in vacuo. The crude product, (S)-5-phenylmorpholin-3-one, was obtained as a white solid (498 mg, 97%). The crude product was used directly in next step without further purification. LCMS (m/z): 178.2 (MH+), 0.47 min.",
    "reference_string": "{\"inputs\": {\"m2_m5_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(S)-2-chloro-N-(2-hydroxy-1-phenylethyl)acetamide\"}], \"amount\": {\"mass\": {\"value\": 600.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaH\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"suspension\"}], \"amount\": {\"mass\": {\"value\": 247.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The resulting mixture was stirred overnight at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"The reaction mixture was concentrated to dryness\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was partitioned between CH2Cl2/brine/H2O (20 mL/18 mL/2 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2 brine H2O\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"CH2Cl2 layer was dried over anhydrous Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered off\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(S)-5-phenylmorpholin-3-one\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 498.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 97.0}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3e194bb5849e4ddca4ab72fa94daab57",
    "procedure_text": "To a suspension of 148 mg (0.20 mmol) of the above 5-chloro-7-[2-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazol-3-yl]-3-methyl-1H-8-oxa-1,2,6-triaza-cyclopenta[a]naphthalen-9-one in 5.92 mL of a mixture acetonitrile: H2O 4:1 (v/v) is added 51 \u03bcL (0.60 mmol) of isopropylamine. The reaction mixture is stirred for 6 hours at ambient temperature. Brine is then added to the mixture and the product is extracted with ethyl acetate (3 times). The regrouped organic phases are dried on Na2SO4, filtrated and evaporated. The purification of the residue by flash chromatography (SiO2, heptane/ethyl acetate 1:1) affords 30 mg (28%) of a white solid; LC/MS:540/542 (M+H)+, m.p.: 235-236\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-chloro-7-[2-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazol-3-yl]-3-methyl-1H-8-oxa-1,2,6-triaza-cyclopenta[a]naphthalen-9-one\"}], \"amount\": {\"mass\": {\"value\": 148.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile H2O\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"mixture\"}], \"amount\": {\"volume\": {\"value\": 5.92, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Brine\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isopropylamine\"}], \"amount\": {\"volume\": {\"value\": 51.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture is stirred for 6 hours at ambient temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"the product is extracted with ethyl acetate (3 times)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The regrouped organic phases are dried on Na2SO4\"}, {\"type\": \"FILTRATION\", \"details\": \"filtrated\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"The purification of the residue by flash chromatography (SiO2, heptane/ethyl acetate 1:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"heptane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 6.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"white solid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 30.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 28.0}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-432dda6871c243b5a9313f3249e8ec40",
    "procedure_text": "To a solution of [2-Chloro-6-(4-fluoro-phenyl)-quinazolin-4-yl]-cyclopropylamine (150 mg, 0.48 mmol) and 1-Methyl-1H-pyrazol-3-ylamine (70 mg, 0.72 mmol) in 1,4-dioxane (5 ml) was added 2,6-lutidine (2 equiv.; 102 mg, 0.96 mmol). The solution was heated to 100\u00b0 C. for 3 hours, then cooled and purified by RP HPLC with a gradient of H2O, 0.1% TFA-acetonitrile, to provide the desired product (140 mg, 0.287 mmol, 60% yield). The product was characterized as follows: MS (m/z): 375 ([M+H]+, 100); HPLC Rt=1.60 minutes (Method B).",
    "reference_string": "{\"inputs\": {\"m1_m2_m4_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"[2-Chloro-6-(4-fluoro-phenyl)-quinazolin-4-yl]-cyclopropylamine\"}], \"amount\": {\"mass\": {\"value\": 150.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-Methyl-1H-pyrazol-3-ylamine\"}], \"amount\": {\"mass\": {\"value\": 70.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,6-lutidine\"}], \"amount\": {\"mass\": {\"value\": 102.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,4-dioxane\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooled\"}, {\"type\": \"CUSTOM\", \"details\": \"purified by RP HPLC with a gradient of H2O, 0.1% TFA-acetonitrile\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TFA acetonitrile\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 0.287, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 140.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 60.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4737dcee7af3481aa69af4c9c05d8908",
    "procedure_text": "In analogy to example 2, (RS)-(1-benzenesulfonyl-aziridin-2-yl)-[4-(2,5-dimethyl-phenyl)-piperazin-1-yl]-methanone (example 2, step 3) was reacted with sodium iodide and ethyl isocyanate to give the title compound as a colorless solid. MS: 471.1 ([M+H]+)",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(RS)-(1-benzenesulfonyl-aziridin-2-yl)-[4-(2,5-dimethyl-phenyl)-piperazin-1-yl]-methanone\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium iodide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl isocyanate\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-cfa8b9df50894377a2779d5199dbe6c5",
    "procedure_text": "Ethyl (2S)-5-oxopyrrolidine-2-carboxylate (0.200 g, 1.27 mmol) was azeotroped three times from toluene (25 mL each), dissolved in tetrahydrofuran (4.4 mL) and cooled to \u221278\u00b0 C. 1 M lithium hexamethyldisilazide in tetrahydrofuran (1 M, 3.75 mL) was added via syringe and the colorless solution was stirred 30 min before addition of 2-[4-(bromomethyl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.4 g, 1.0 mmol) in tetrahydrofuran (2.0 mL). The slightly yellow solution was stirred at \u221278\u00b0 C. for 30 min and then at \u221210\u00b0 C. for 1 h and warmed to rt for an additional 1 h before it was cooled back to \u221278\u00b0 C. and quenched with acetic acid (1.00 mL, 17.6 mmol). Evaporation and purification by preparative LCMS gave the desired product as a colorless glass, (296 mg, 62%). 1H NMR (400 MHz, CD3OD): \u03b4 7.67 (d, J=7.4 Hz, 2H), 7.22 (d, J=7.4 Hz, 2H), 4.20 (q, J=7.2 Hz, 2H), 3.08 (d, J=13.0 Hz, 1H), 3.05 (d, J=13.0 Hz, 1H), 2.35 (m, 1H), 2.23 (m, 1H), 2.15 (m, 1H), 1.79 (m, 1H), 1.35 (s, 12H), 1.25 (t, J=7.0 Hz, 3H); LCMS found for C20H29BNO5 (M+H)+: m/z=374.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium hexamethyldisilazide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 3.75, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-[4-(bromomethyl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane\"}], \"amount\": {\"mass\": {\"value\": 0.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 4.4, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ethyl (2S)-5-oxopyrrolidine-2-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 0.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -78.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The slightly yellow solution was stirred at \\u221278\\u00b0 C. for 30 min\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WAIT\", \"details\": \"at \\u221210\\u00b0 C. for 1 h\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": -10.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"warmed to rt for an additional 1 h before it\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"was cooled back to \\u221278\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": -78.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"Evaporation and purification by preparative LCMS\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 296.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 62.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 79.3}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"glass\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2e145f4613764b27b8eb5bc83a0d1a19",
    "procedure_text": "To a round-bottomed flask equipped with stirring was added Boc-L-Tic-OH (Bachem) (1 g, 3.6 mmol) and CH2Cl2 (20 mL), followed by TEA (0.5 mL, 3.6 mmol) and N,O-dimethylhydroxylamine hydrochloride. The reaction mixture was cooled to 0\u00b0 C., EDC (690 mg, 3.6 mmol) and HOBT (550 mg, 3.6 mmol) were added, and the reaction mixture was stirred at 0\u00b0 C. for 1 h then at RT for 18 h. The organic layer was washed with 0.5 N HCl, satd NaHCO3, and brine. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo to afford a colorless oil. Into a round bottomed flask equipped with magnetic stirring, was added the oil dissolved in Et2O (15 mL), and the flask was cooled to \u221278\u00b0 C. LiAlH4 (1M in Et2O, Aldrich) (3.2 mL, 3.2 mmol) was added, and after 30 min the reaction was warmed to RT. The organic layer was washed with 0.5 N HCl, satd NaHCO3, and brine. After drying the organic layer over Na2SO4, it was filtered and concentrated in vacuo to afford (3S)\u2014N-Boc-1,2,3,4-tetrahydroisoquinoline-3-carbaldehyde as a colorless oil (588 mg).",
    "reference_string": "{\"inputs\": {\"m1_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Boc-L-Tic-OH\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"LiAlH4\"}], \"amount\": {\"volume\": {\"value\": 3.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Et2O\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TEA\"}], \"amount\": {\"volume\": {\"value\": 0.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EDC\"}], \"amount\": {\"mass\": {\"value\": 690.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HOBT\"}], \"amount\": {\"mass\": {\"value\": 550.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,O-dimethylhydroxylamine hydrochloride\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"with stirring\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"To a round-bottomed flask equipped\"}, {\"type\": \"STIRRING\", \"details\": \"the reaction mixture was stirred at 0\\u00b0 C. for 1 h\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with 0.5 N HCl\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layer was dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"to afford a colorless oil\"}, {\"type\": \"CUSTOM\", \"details\": \"Into a round bottomed flask equipped with magnetic stirring\"}, {\"type\": \"ADDITION\", \"details\": \"was added the oil\"}, {\"type\": \"TEMPERATURE\", \"details\": \"the flask was cooled to \\u221278\\u00b0 C\", \"temperature\": {\"setpoint\": {\"value\": -78.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"after 30 min the reaction was warmed to RT\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with 0.5 N HCl\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"After drying the organic layer over Na2SO4, it\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"was filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 18.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(3S)\\u2014N-Boc-1,2,3,4-tetrahydroisoquinoline-3-carbaldehyde\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 588.0, \"units\": \"MILLIGRAM\"}}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-47512f488e744481bc72ecd928172a44",
    "procedure_text": "Following the procedure of Example 13, using the compound obtained in Example 28 in place of 2-(4-(pyridin-2-ylmethylene)piperidine-1-carboxamido)thiazole-5-carboxylic acid and using 2-aminothiazole (30 mg, 290 \u03bcmol) in place of morpholine, the title compound (45 mg, 47%) was obtained as a white solid.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-aminothiazole\"}], \"amount\": {\"mass\": {\"value\": 30.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 45.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 47.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-719546471bed4ee7b47cd57e513c7527",
    "procedure_text": "A methanol (300 ml) solution of o-nitrobenzaldehyde (103.1 g), dimethylmalonate (90.1 g), acetic acid (1.2 ml) and piperidine (12 ml) was heated under reflux for 25 hours. The reaction mixture was concentrated. Water was added to the mixture, which was extracted with ethylacetate. The organic layer was washed with 1N hydrochloric acid, water, a saturated aqueous sodium hydrogencarbonate solution and a saturated aqueous sodium chloride solution, then dried and concentrated. The obtained crude crystals were washed with IPE to give the entitled compound (59.79 g). The mother liquor was further purified by silica gel column chromatography (eluent: ethyl acetate/hexane=1/2). The obtained crude crystals were recrystallized from ethyl acetate-hexane to give the entitled compound (34.13 g).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m5_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 300.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"o-nitrobenzaldehyde\"}], \"amount\": {\"mass\": {\"value\": 103.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylmalonate\"}], \"amount\": {\"mass\": {\"value\": 90.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"piperidine\"}], \"amount\": {\"volume\": {\"value\": 12.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 1.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"under reflux for 25 hours\", \"duration\": {\"value\": 25.0, \"units\": \"HOUR\"}}, {\"type\": \"CONCENTRATION\", \"details\": \"The reaction mixture was concentrated\"}, {\"type\": \"ADDITION\", \"details\": \"Water was added to the mixture, which\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"was extracted with ethylacetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethylacetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with 1N hydrochloric acid, water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"a saturated aqueous sodium hydrogencarbonate solution and a saturated aqueous sodium chloride solution, then dried\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydrogencarbonate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The obtained crude crystals\"}, {\"type\": \"WASH\", \"details\": \"were washed with IPE\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 59.79, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-1b3d176ce95b4fb988d126c645c6cad0",
    "procedure_text": "A solution of 6-[cyclohexyl(cyclopropylmethyl)amino]-N-(4-formylphenyl)pyrimidine-4-carboxamide (Intermediate 24, 80 mg; 0.18 mmol) in DCM (8 ml) was treated with Glycine tert-butyl ester hydrochloride (Sachem, 60.6 mg; 0.36 mmol) and triethylamine (50 \u03bcl; 0.36 mmol). After 2 minutes sodium triacetoxyborohydride (96 mg; 0.45 mmol) and acetic acid (2 \u03bcl; 0.04 mmol) were added and the reaction was stirred at room temperature for 20 hours. The solvent was removed under vacuum and the residue was redissolved in EtOAc. The organic phase was washed twice with an aqueous solution (1N) of NaOH and once with brine, dried (MgSO4) and the solvent removed under vacuum to afford the title compound as a colorless oil (62.7 mg, 70%) after purification by column chromatography (silica) eluting with cyclohexane containing increasing amounts of EtOAc.",
    "reference_string": "{\"inputs\": {\"m1_m2_m7_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-[cyclohexyl(cyclopropylmethyl)amino]-N-(4-formylphenyl)pyrimidine-4-carboxamide\"}], \"amount\": {\"mass\": {\"value\": 80.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Intermediate 24\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Glycine tert-butyl ester hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 60.6, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"amount\": {\"volume\": {\"value\": 8.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium triacetoxyborohydride\"}], \"amount\": {\"mass\": {\"value\": 96.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction was stirred at room temperature for 20 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The solvent was removed under vacuum\"}, {\"type\": \"DISSOLUTION\", \"details\": \"the residue was redissolved in EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic phase was washed twice with an aqueous solution (1N) of NaOH and once with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent removed under vacuum\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 20.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 62.7, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 70.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 70.6}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f80136fb666f4f5da8af342d3cc39c96",
    "procedure_text": "Under a nitrogen atmosphere at 0\u00b0 C., to a solution (21 mL) of the compound (5.4 g, 21 mmol) obtained in Example 64b in tetrahydrofuran were added acetyl chloride (2.0 g, 25 mmol) and triethylamine (3.8 mL, 27 mmol), and the mixture was stirred at room temperature for 30 min. The resulting salt was removed and the solvent was evaporated under reduced pressure to give a crude title compound as a colorless solid.",
    "reference_string": "{\"inputs\": {\"m1_m2_m5_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"amount\": {\"volume\": {\"value\": 21.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound\"}], \"amount\": {\"mass\": {\"value\": 5.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetyl chloride\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 3.8, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at room temperature for 30 min\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The resulting salt was removed\"}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was evaporated under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude title compound\"}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-34dcbf19568849c0b4a90d39bda0a641",
    "procedure_text": "1.96 g. crude 3-(5-nitro-1-methyl-2-imidazolyl)-6-chloro-s-triazolo[4,3-b]pyridazine was dissolved in 35 ml. of a mixture of dioxan and methanol (1:1), 0.84 g. sodium methylate added thereto, the reaction mixture heated under reflux for 1 hour, the solution then evaporated in a vacuum, the residue triturated with water, filtered with suction and dried at 120\u00b0 C. in a vacuum. There was thus obtained 0.64 g. of the desired 3-(5-nitro-1-methyl-2-imidazolyl)-6-methoxy-s-triazolo[4,3-b]pyridazine, which has a melting point of 193\u00b0 - 198\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(5-nitro-1-methyl-2-imidazolyl)-6-chloro-s-triazolo[4,3-b]pyridazine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dioxan\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium methylate\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"the reaction mixture heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"under reflux for 1 hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"the solution then evaporated in a vacuum\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue triturated with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered with suction\"}, {\"type\": \"CUSTOM\", \"details\": \"dried at 120\\u00b0 C. in a vacuum\", \"temperature\": {\"setpoint\": {\"value\": 120.0, \"units\": \"CELSIUS\"}}}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-680e88ba08a9475c82ebd0f90d1dd7cd",
    "procedure_text": "A solution of benzo[b]thiophene-2,6-dicarboxylic acid 2-ethyl ester (1.6 g, 6.4 mmol) in anhydrous THF (40 mL, 25 vol) was cooled to 0\u00b0 C. To this BH3 (1M in THF, 30 mL, 30.0 mmol) was added slowly. The reaction was allowed to warm to r.t. and stirred for 3 h. The solution was then cooled to 0\u00b0 C. and quenched using 1N HCl (7.5 mL). The reaction mixture was concentrated under vacuum to remove all THF and the resulting solid isolated by filtration and dried under vacuum to give 6-hydroxymethyl-benzo[b]thiophene-2-carboxylic acid ethyl ester (1.3 g, 87%). LCMS m/z 237 [M++H]+, 1H NMR (300 MHz, DMSO), \u03b4: 1.34 (3H, t J=6.9 Hz, CH3), 4.35 (2H, q J=7.1 Hz, CH2), 4.65 (2H, s, CH2), 6.53 (1H, br s, OH), 7.42 (1H, d J=9.4 Hz), 7.98 (3H, m, ArH), 8.18 (1H, s, ArH).",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzo[b]thiophene-2,6-dicarboxylic acid 2-ethyl ester\"}], \"amount\": {\"mass\": {\"value\": 1.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred for 3 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The solution was then cooled to 0\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"quenched\"}, {\"type\": \"CONCENTRATION\", \"details\": \"The reaction mixture was concentrated under vacuum\"}, {\"type\": \"CUSTOM\", \"details\": \"to remove all THF\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the resulting solid isolated by filtration\"}, {\"type\": \"CUSTOM\", \"details\": \"dried under vacuum\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-hydroxymethyl-benzo[b]thiophene-2-carboxylic acid ethyl ester\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.3, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 87.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-91b9568a50ca433189a22aee8fe77cad",
    "procedure_text": "N-{2-Chloro-4-[(7-hydroxy-6-methoxy-4-quinazolinyl)oxy]phenyl}-N\u2032-methylurea (2.0 g) was dissolved in N,N-dimethylformamide (50 ml), and triphenylphosphine (2.8 g), piperidinopropanol (0.9 g), and diethyl azodicarboxylate (1.9 g) were added to the solution. The mixture was stirred at room temperature for 2 hr. Triphenylphosphine (2.8 g), piperidinopropanol (0.6 g), and diethyl azodicarboxylate (1.9 g) were then again added to the reaction solution, followed by stirring at room temperature for additional 10 hr. The solvent was removed by distillation under the reduced pressure. The residue was purified by chromatography on silica gel by development with chloroform/methanol (20/1) to give 650 mg (yield 25%) of the title compound.",
    "reference_string": "{\"inputs\": {\"m5_m6_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Triphenylphosphine\"}], \"amount\": {\"mass\": {\"value\": 2.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"piperidinopropanol\"}], \"amount\": {\"mass\": {\"value\": 0.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl azodicarboxylate\"}], \"amount\": {\"mass\": {\"value\": 1.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-{2-Chloro-4-[(7-hydroxy-6-methoxy-4-quinazolinyl)oxy]phenyl}-N\\u2032-methylurea\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triphenylphosphine\"}], \"amount\": {\"mass\": {\"value\": 2.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"piperidinopropanol\"}], \"amount\": {\"mass\": {\"value\": 0.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl azodicarboxylate\"}], \"amount\": {\"mass\": {\"value\": 1.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at room temperature for 2 hr\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"by stirring at room temperature for additional 10 hr\", \"duration\": {\"value\": 10.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The solvent was removed by distillation under the reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by chromatography on silica gel by development with chloroform/methanol (20/1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 650.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 25.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b8945447a3d94694b0452f02a79fbfc5",
    "procedure_text": "Ethyl N-(2-methoxy-6,7-dimethylquinoxalin-3-yl)carbamate (35 mg, 0.13 mmol) and 1-(3-methoxy phenyl)piperazine (50 mg, 0.26 mmol) were dissolved in tetrahydrofuran (2 ml) at room temperature and thereto DBU (40 mg, 0.26 mmol) was added. The resulting mixture was stirred at 70\u00b0 C. for 7 hours and concentrated under the reduced pressure to remove the solvent, and purified by SiO2 column chromatography. Extraction of the residue with a n-hexane:ethyl acetate (2:1) mixture and concentration gave 37 mg of the titled compound (yield, 68%). 1H NMR (300 MHz, CDCl3) \u03b4 2.33 (s, 3H), 2.39 (s, 3H), 3.22-3.30 (m, 4H), 3.75 (m, 4H), 3.80 (s, 3H), 4.13 (s, 3H), 6.46-6.49 (m, 2H), 6.55-6.58 (m, 1H), 7.20-7.23 (m, 1H), 7.52 (s, 1H), 7.60 (s, 1H).",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ethyl N-(2-methoxy-6,7-dimethylquinoxalin-3-yl)carbamate\"}], \"amount\": {\"mass\": {\"value\": 35.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(3-methoxy phenyl)piperazine\"}], \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DBU\"}], \"amount\": {\"mass\": {\"value\": 40.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 70.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The resulting mixture was stirred at 70\\u00b0 C. for 7 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"concentrated under the reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"to remove the solvent\"}, {\"type\": \"CUSTOM\", \"details\": \"purified by SiO2 column chromatography\"}, {\"type\": \"EXTRACTION\", \"details\": \"Extraction of the residue\"}, {\"type\": \"CONCENTRATION\", \"details\": \"with a n-hexane:ethyl acetate (2:1) mixture and concentration\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-hexane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 7.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"titled compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 37.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 68.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c0cea33f55ad4dea92a5c5ccb7e444e4",
    "procedure_text": "Benzyl bromide (0.111 mL, 0.934 mmol) was added to a flask charged with (2S,4R)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-amino-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide (0.330 g, 0.778 mmol), DMF (3 mL) and potassium carbonate (0.429 g, 3.11 mmol). The reaction mixture was stirred at ambient temperature for 1 hour and then diluted with methanol (2 mL). Product was purified by reverse phase HPLC to give Compound 179, (2S,4R)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-(benzylamino)-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide (97 mg, 0.19 mmol, 24%) as an off-white solid. 1H-NMR (400 MHz, DMSO-d6): 10.08 (s, 1H), 8.44 (s, 1H), 7.95 (s, 1H), 7.57 (d, J=9.6 Hz, 2H), 7.38-7.30 (m, 4H), 7.26-7.16 (m, 3H), 7.03-6.93 (m, 4H), 5.24-5.21 (m, 2H), 4.53-4.48 (m, 1H), 3.85-3.79 (m, 1H), 3.75 (s, 2H), 3.51-3.45 (m, 2H), 3.17 (d, J=6.0 Hz, 1H), 2.15-2.00 (m, 2H). MS (EI) for C28H27FN6O3. found 515.2 (MH+).",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2S,4R)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-amino-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide\"}], \"amount\": {\"mass\": {\"value\": 0.33, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 0.429, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Benzyl bromide\"}], \"amount\": {\"volume\": {\"value\": 0.111, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred at ambient temperature for 1 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Product was purified by reverse phase HPLC\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Compound 179\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2S,4R)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-(benzylamino)-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 0.19, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 97.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 24.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 24.4}}], \"isolated_color\": \"off-white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-5a841fbd5485428baff20afcce6f244a",
    "procedure_text": "3-Chloro-8-methoxy-2,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound S1-2, 18.9 mg, 0.0556 mmol) and pyridinium chloride (220 mg, 34 eq.) were stirred at 185\u00b0 C. for 2.5 hr. After cooling, the reaction solution was added with water and ethyl acetate, and the organic layer was washed with water and saturated brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to obtain the title compound as a crude product.",
    "reference_string": "{\"inputs\": {\"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-Chloro-8-methoxy-2,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one\"}], \"amount\": {\"mass\": {\"value\": 18.9, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridinium chloride\"}], \"amount\": {\"mass\": {\"value\": 220.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"After cooling\"}, {\"type\": \"WASH\", \"details\": \"the organic layer was washed with water and saturated brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-bf8005f5c20f4059b1a58cc43d115631",
    "procedure_text": "Sodium isopropylcyclopentadienide is prepared in THF as described in Preparation A. Then dimeric allyl nickel bromide is prepared by reacting 70 g of nickel carbonyl and 50 ml of allyl bromide in 200 ml of THF. The final solution is added dropwise onto the solution of sodium isopropylcyclopentadienide and allowed to stir at room temperature for two hours. The mixture becomes violet immediately and NaBr precipitates. The solution containing isopropylcyclopentadienyl nickel allyl is transferred to another flask and solvent is removed by pumping at or below room temperature. The product is removed by vacuum distillation at 10-2 torr in the range of 30\u00b0-40\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m0_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"nickel carbonyl\"}], \"amount\": {\"mass\": {\"value\": 70.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"final solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium isopropylcyclopentadienide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"allyl bromide\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"to stir at room temperature for two hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"as described in Preparation A\"}, {\"type\": \"CUSTOM\", \"details\": \"NaBr precipitates\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaBr\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"The solution containing isopropylcyclopentadienyl nickel allyl\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isopropylcyclopentadienyl nickel allyl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"is transferred to another flask\"}, {\"type\": \"CUSTOM\", \"details\": \"solvent is removed\"}, {\"type\": \"CUSTOM\", \"details\": \"below room temperature\"}, {\"type\": \"CUSTOM\", \"details\": \"The product is removed by vacuum distillation at 10-2 torr in the range of 30\\u00b0-40\\u00b0 C.\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Sodium isopropylcyclopentadienide\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"allyl nickel bromide\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-8c970c055dde43c78692552106cd5af1",
    "procedure_text": "A mixture of methyl 4-fluoro-3-methoxybenzoate (2.13 g), 4-bromo-1H-imidazole (3.74 g) and potassium carbonate (4.80 g) in DMF (20 mL) was stirred at 100\u00b0 C. overnight, and allowed to cool to room temperature, and ethyl acetate and water were added. The aqueous layer was separated, and acidified with 6N hydrochloric acid (pH=3-4), and the resultant precipitate was collected by filtration to give the title compound (1.92 g).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 4-fluoro-3-methoxybenzoate\"}], \"amount\": {\"mass\": {\"value\": 2.13, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-bromo-1H-imidazole\"}], \"amount\": {\"mass\": {\"value\": 3.74, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 4.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at 100\\u00b0 C. overnight\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"to cool to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The aqueous layer was separated\"}, {\"type\": \"FILTRATION\", \"details\": \"the resultant precipitate was collected by filtration\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"resultant precipitate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.92, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-9eceb86e95c944d285e10f6b7b9fc955",
    "procedure_text": "Under argon, a 1.60 M solution of n-butyllithium in hexane (2.5 mL, 4.1 mmol) was added to anhydrous tetrahydrofuran (7.0 mL) stirred in a dry ice-acetone bath, followed by dropwise addition of a solution of 4-ethoxy-1-iodo-3,5-dimethoxybenzene (570.0 mg, 1.85 mmol) in anhydrous tetrahydrofuran (1.5 mL). After the mixture was stirred for 20 minutes in the dry ice-acetone bath, triisopropyl borate (0.50 mL, 2.2 mmol) was added, and the mixture was additionally stirred for 20 minutes. The reaction mixture was stirred at room temperature for 1 hour, and concentrated under reduced pressure. To the residue, a 0.1 M aqueous sodium hydroxide (4.4 mL) solution was added. The aqueous solution was washed with chloroform, acidified by the addition of concentrated hydrochloric acid, and extracted with chloroform. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Chloroform-hexane was added to the residue and the resulting precipitate was collected by filtration to afford the title compound as a colorless amorphous powder (162.0 mg, yield: 39%).",
    "reference_string": "{\"inputs\": {\"m4_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-ethoxy-1-iodo-3,5-dimethoxybenzene\"}], \"amount\": {\"mass\": {\"value\": 570.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 1.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dry ice acetone\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triisopropyl borate\"}], \"amount\": {\"volume\": {\"value\": 0.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m3_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-butyllithium\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"amount\": {\"volume\": {\"value\": 2.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 7.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred in a dry ice-acetone bath\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"STIRRING\", \"details\": \"the mixture was additionally stirred for 20 minutes\", \"duration\": {\"value\": 20.0, \"units\": \"MINUTE\"}}, {\"type\": \"STIRRING\", \"details\": \"The reaction mixture was stirred at room temperature for 1 hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"ADDITION\", \"details\": \"To the residue, a 0.1 M aqueous sodium hydroxide (4.4 mL) solution was added\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"volume\": {\"value\": 4.4, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The aqueous solution was washed with chloroform\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"acidified by the addition of concentrated hydrochloric acid\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with chloroform\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"ADDITION\", \"details\": \"Chloroform-hexane was added to the residue\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Chloroform hexane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"the resulting precipitate was collected by filtration\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 162.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 39.0}}], \"isolated_color\": \"colorless amorphous\", \"texture\": {\"type\": \"POWDER\", \"details\": \"powder\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b022266247cc4279872de53e1506eb90",
    "procedure_text": "To a solution of 3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acid (4.51 g) in N,N-dimethylacetamide (60 mL) at -20\u00b0 C. was added thionyl chloride (3.39 g) and the mixture was allowed to stir at -10\u00b0 to -15\u00b0 C. for 1 hour. 4-Amino-3-fluorobenzophenone (4.00 g) was added in one portion and the reaction mixture was stirred at room temperature overnight. The mixture was poured into water and the aqueous solution was decanted. The remaining oily precipitate was dissolved in dichloromethane, dried, and evaporated to yield a tan solid. Recrystallization from dichloromethane and hexanes yielded the title compound as a white solid (5.43 g); mp 138\u00b0-139\u00b0 C.; MS: m/z=356(M+1); NMR: 1.62 (s,3), 7.56-7.64 (m,4), 7.70 (d,1, J=6.5), 7.75 (d,2, J=8.0), 7.82 (s,1), 8.01 (t,1, J=7.9), 9.39 (s,1). Analysis for C17H13F4NO3 : Calculated: C, 57.47; H, 3.69; N, 3.94; Found: C, 57.51; H, 3.60; N, 3.93.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m5_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acid\"}], \"amount\": {\"mass\": {\"value\": 4.51, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"thionyl chloride\"}], \"amount\": {\"mass\": {\"value\": 3.39, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylacetamide\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-Amino-3-fluorobenzophenone\"}], \"amount\": {\"mass\": {\"value\": 4.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"to stir at -10\\u00b0 to -15\\u00b0 C. for 1 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"the reaction mixture was stirred at room temperature overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"the aqueous solution was decanted\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The remaining oily precipitate was dissolved in dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"to yield a tan solid\"}, {\"type\": \"CUSTOM\", \"details\": \"Recrystallization from dichloromethane and hexanes\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 5.43, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 82.2}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-5a62234e18af44129d58ca83a2c70384",
    "procedure_text": "Under a nitrogen atmosphere, 1.4 g (8.0 mmol) of N-methoxycarbonyl-(L)-valine, 2.87 g (15 mmol) of EDC and 1.35 g (10 mmol) of HOBT are dissolved in 22 ml of DMF. After 45 min, 4.2 ml (30 mmol) of TEA are added and then a solution of 2.34 g (5.0 mmol) of 1-[4-(thiazol-2-yl)-phenyl]-4(S)-hydroxy-2-(tert-butoxycarbonyl)amino-5(S)-amino-6-phenyl-2-azahexane in 45 ml of DMF is added dropwise. After 1.5 hours, the reaction mixture is concentrated by evaporation; the residue is taken up in methylene chloride and washed with water, sat. NaHCO3 solution, water and brine. The aqueous phases are extracted 2\u00d7 with methylene chloride; the combined organic phases are dried (Na2SO4) and concentrated by evaporation. Column chromatography (SiO2 ; methylene chloride/ethyl acetate 2:1) and crystallisation from ethyl acetate/ether yield the title compound: m.p: 178-179\u00b0 C.; HPLC20-100 : tRet =15.8.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TEA\"}], \"amount\": {\"volume\": {\"value\": 4.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-[4-(thiazol-2-yl)-phenyl]-4(S)-hydroxy-2-(tert-butoxycarbonyl)amino-5(S)-amino-6-phenyl-2-azahexane\"}], \"amount\": {\"mass\": {\"value\": 2.34, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 45.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-methoxycarbonyl-(L)-valine\"}], \"amount\": {\"mass\": {\"value\": 1.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EDC\"}], \"amount\": {\"mass\": {\"value\": 2.87, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HOBT\"}], \"amount\": {\"mass\": {\"value\": 1.35, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 22.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WAIT\", \"details\": \"After 1.5 hours\", \"duration\": {\"value\": 1.5, \"units\": \"HOUR\"}}, {\"type\": \"CONCENTRATION\", \"details\": \"the reaction mixture is concentrated by evaporation\"}, {\"type\": \"WASH\", \"details\": \"washed with water, sat. NaHCO3 solution, water and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The aqueous phases are extracted 2\\u00d7 with methylene chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"the combined organic phases are dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated by evaporation\"}, {\"type\": \"CUSTOM\", \"details\": \"Column chromatography (SiO2 ; methylene chloride/ethyl acetate 2:1) and crystallisation from ethyl acetate/ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 45.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3a360cec7cb9413caaff6e9048d9d51b",
    "procedure_text": "To a solution of 1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-3-vinyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea (200 mg) (0.46 mmol) in tert-butanol:water (1:1) (8.0 mL) was added AD mix 0 (2.0 g) and methanesulfonamide (400 mg). The mixture was stirred overnight. To the reaction was added 10% Na2SO3 solution and extracted three times with EtOAc. Organics were dried (MgSO4) and filtered off and then concentrated in vacuo. to give a white solid 178 mg. MS m/z=468.2 (M+H)",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO3\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"0\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanesulfonamide\"}], \"amount\": {\"mass\": {\"value\": 400.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-{4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-3-vinyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butanol water\"}], \"amount\": {\"volume\": {\"value\": 8.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred overnight\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted three times with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"Organics were dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered off\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 178.0, \"units\": \"MILLIGRAM\"}}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a246ba03b2794938b409a453e2573092",
    "procedure_text": "Scheme 7 shows a general method for substitution at the 2-position of 4,5-dihydrobenzo[b]thieno[2,3-d]oxepine intermediates 74 by acylation with a carboxylic acid such as 2-phenylacetic acid to give 1-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-2-phenylethanone intermediate 81. Bromination gives 2-bromo-1-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-2-phenylethanone intermediate 82. Cyclization with a thioamide compound gives 4-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-5-phenylthiazole 83.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4,5-dihydrobenzo[b]thieno[2,3-d]oxepine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"carboxylic acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-phenylacetic acid\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-2-phenylethanone\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-8ea30533c71f44d4a1ebafe8a1895273",
    "procedure_text": "A solution of 1-hydroxycyclopropanecaboxylic acid (0.66 g, 6.44 mmol) in dry dimethylacetamide (10 ml) was stirred under a nitrogen atmosphere at -15\u00b0 C. Thionyl chloride (0.77 g, 6.44 mmol) was added and the resulting mixture was allowed to stir at -15\u00b0 C. for 1 hour. 4-Phenylsulfonylaniline (1.0 g, 4.29 mmol) was then added and the reaction mixture was stirred at -15\u00b0 C. for a further 15 mins. The solution was then allowed to warm to room temperature where it was stirred overnight. The reaction mixture was poured onto ice, extracted with ethyl acetate, and the combined ethyl acetate portions were washed with 1M HCl. After drying (MgSO4) the ethyl acetate was removed by evaporation to give a buff-colored solid. Crystallization of this material from ethyl acetate/hexane yielded the title tertiary carbinol, (0.82 g, 60%) as a white solid; mp=214.5\u00b0-216\u00b0 C. 1H-NMR (250 MHz, d6 -DMSO): 0.98 (m, 2H, 2 CH2), 1.15 (m, 2H, CH2), 6.63 (s, 1H, OH), 7.65 (m, 3H, ArH), 7.95 (m, 6H, ArH), 10.29 (s, 1H, NH). MS (CI, CH4): 318(M+1, 100). Analysis for C16H15NO4S: Calculated: C, 60.55; H, 4.76; N, 4.41 Found; C, 60.51; H, 4.77; N, 4.40",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH4\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Thionyl chloride\"}], \"amount\": {\"mass\": {\"value\": 0.77, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-hydroxycyclopropanecaboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 0.66, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylacetamide\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-Phenylsulfonylaniline\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -15.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"to stir at -15\\u00b0 C. for 1 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"the reaction mixture was stirred at -15\\u00b0 C. for a further 15 mins\", \"duration\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"temperature\": {\"setpoint\": {\"value\": -15.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"to warm to room temperature where it\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"STIRRING\", \"details\": \"was stirred overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"ADDITION\", \"details\": \"The reaction mixture was poured onto ice\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"the combined ethyl acetate portions were washed with 1M HCl\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"After drying (MgSO4) the ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"was removed by evaporation\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a buff-colored solid\"}, {\"type\": \"CUSTOM\", \"details\": \"Crystallization of this material from ethyl acetate/hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate hexane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"yielded the title tertiary carbinol, (0.82 g, 60%) as a white solid\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"carbinol\"}], \"amount\": {\"mass\": {\"value\": 0.82, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-c977c862da95489f8b2f25084ee884b2",
    "procedure_text": "A solution of 4-(N-(4-chlorophenylcarbonyl)amino)-2-hydroxybutyric acid methyl ester (3 g) in tetrahydrofuran (15 ml) was dropped to a mixture of 60% sodium hydride (2.38 g) in tetrahydrofuran (10 ml) at \u221278\u00b0 C. The mixture was stirred at 0\u00b0 C. for 30 minutes. t-Butyl bromoacetate (0.975 g) was dropped to the mixture at \u221278\u00b0 C. The mixture was stirred at 0\u00b0 C. for 1.5 hours. To the reaction mixture, 1N hydrochloric acid was added and the mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (n-Hexane:Ethyl acetate=1:1) to give the title compound (3.194 g) having the following physical data.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m5_m2_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(N-(4-chlorophenylcarbonyl)amino)-2-hydroxybutyric acid methyl ester\"}], \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydride\"}], \"amount\": {\"mass\": {\"value\": 2.38, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"t-Butyl bromoacetate\"}], \"amount\": {\"mass\": {\"value\": 0.975, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at 0\\u00b0 C. for 30 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"The mixture was stirred at 0\\u00b0 C. for 1.5 hours\", \"duration\": {\"value\": 1.5, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"the mixture was extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The extract was washed with a saturated aqueous solution of sodium hydrogen carbonate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydrogen carbonate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium chloride\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by column chromatography on silica gel (n-Hexane:Ethyl acetate=1:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-Hexane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 3.194, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4132ae36f9d74e539886968456c5848c",
    "procedure_text": "The mixture of regioisomers from step 2 {[(S)-1-(2-amino-4-iodo-phenylcarbamoyl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester and [(S)-1-(2-amino-5-iodo-phenylcarbamoyl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester} (1.0 g, 2.08 mmol) were dissolved in glacial acetic acid (30 mL) and heated to 65\u00b0 C. for 1 hour. The reaction was cooled, concentrated in vacuo, basified with 10% w/v aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate (2\u00d720 mL). The organic extracts were combined, washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by chromatography over silica gel eluted with 20% v/v ethyl acetate/hexanes to give [(S)-1-(5-iodo-1H-benzoimidazol-2-yl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester as a mixture of tautomers (950 mg, 99%).",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"[(S)-1-(2-amino-4-iodo-phenylcarbamoyl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"[(S)-1-(2-amino-5-iodo-phenylcarbamoyl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 65.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The reaction was cooled\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate (2\\u00d720 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude product was purified by chromatography over silica gel\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"eluted with 20% v/v ethyl acetate/hexanes\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"[(S)-1-(5-iodo-1H-benzoimidazol-2-yl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f619e409009c45c5a33bb7c776b6313d",
    "procedure_text": "3,4-Dihydro-2H-1,4-benzoxazine-6-ylmethyl)amine: a solution of 3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-carbonitrile (1.3 g ) in anhydrous TBF (20 mL) was slowly added to a stirred and ice -cooled solution of lithium aluminum hydride (30 mL, 1 M solution in THF). With continued cooling water (5 mmol) and sodium hydroxide (5 mL, 20% solution), water (20 mL) and ethyl acetate (30 mL) were added in succession. The organic solution was decanted from the white residue. The residue was washed twice with ether, all the organic solution were combined then dried over anhydrous sodium sulfate. Filtration and concentration followed by drying in vacuo afforded 3,4-dihydro-2H-1,4-benzoxazine-6-ylmethylamine (0.78 g,): 1H NMR (400 MHz; DMSO-D6): 6.52 (d, 1H); 6.49 (s, 1H); 6.37 (d, 1H); 5.6 (br s, NH); 4.05 (t, 2H); 3.4 (m, 2H).",
    "reference_string": "{\"inputs\": {\"m1_m2_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"amine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-carbonitrile\"}], \"amount\": {\"mass\": {\"value\": 1.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TBF\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4_m5_m6_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"moles\": {\"value\": 5.0, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium aluminum hydride\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"a stirred\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"were added in succession\"}, {\"type\": \"CUSTOM\", \"details\": \"The organic solution was decanted from the white residue\"}, {\"type\": \"WASH\", \"details\": \"The residue was washed twice with ether, all the organic solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"were combined then dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"Filtration and concentration\"}, {\"type\": \"CUSTOM\", \"details\": \"by drying in vacuo\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,4-dihydro-2H-1,4-benzoxazine-6-ylmethylamine\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.78, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-256c0c4f032748399f1026b55b13ea32",
    "procedure_text": "9.4 ml of trifluoroacetic acid and 0.31 ml of trifluoromethanesulfonic acid were added, whilst ice-cooling, to a solution of 940 mg of (2S,4S)-2-(3,4-dimethyl-1-piperazinylcarbonyl)-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (prepared as described in Preparation 13) in 1.88 ml of anisole, and the resulting mixture was stirred at room temperature for 1 hour. At the end of this time, the reaction mixture was treated in a similar manner to that described in Example 13(1), to give 1.2 g of the title compound as a powder.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trifluoroacetic acid\"}], \"amount\": {\"volume\": {\"value\": 9.4, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trifluoromethanesulfonic acid\"}], \"amount\": {\"volume\": {\"value\": 0.31, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2S,4S)-2-(3,4-dimethyl-1-piperazinylcarbonyl)-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)pyrrolidine\"}], \"amount\": {\"mass\": {\"value\": 940.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"anisole\"}], \"amount\": {\"volume\": {\"value\": 1.88, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the resulting mixture was stirred at room temperature for 1 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"At the end of this time, the reaction mixture was treated in a similar manner to that\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.2, \"units\": \"GRAM\"}}}], \"texture\": {\"type\": \"POWDER\", \"details\": \"powder\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-509745c59192416d87415d11a7cf2b1b",
    "procedure_text": "A solution of methyl 2-amino-3-chlorobenzoate (1.7 g, 9.16 mmol) in THF (40 mL) was dropwise added to a suspension of the LAH (521 mg, 13.7 mmol) in THF (15 mL) at room temperature over 10 min under N2, and stirred for 2 hrs. The reaction was carefully quenched with saturated Na2SO4 (10 mL) at 0\u00b0 C., extracted with Et2O (2\u00d750 mL). The combined organic layers were washes with brine (30 mL), dried on MgSO4, and concentrated on rotary vacuum to afford the expected product as a yellow solid (1.08 g, 75%), which was pure enough to be used in the next step without further purification; 1H NMR (400 MHz, CDCl3) \u03b4 ppm 1.65 (s, 1H), 4.59-4.70 (m, 4H), 6.60-6.65 (m, 1H), 6.96 (dd, J=7.55, 1.26 Hz, 1H), 7.19-7.25 (m, 1H); Mass spec. 158.02 (MH+), Calc. for C7H8ClNO2 157.03.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 2-amino-3-chlorobenzoate\"}], \"amount\": {\"mass\": {\"value\": 1.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"LAH\"}], \"amount\": {\"mass\": {\"value\": 521.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred for 2 hrs\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The reaction was carefully quenched with saturated Na2SO4 (10 mL) at 0\\u00b0 C.\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}, \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with Et2O (2\\u00d750 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Et2O\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried on MgSO4\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated on rotary vacuum\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"expected product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.08, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 75.0}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d0ff734280c548898ae943c93ad82861",
    "procedure_text": "A solution of oxalyl chloride (28.8 ml) in dry dichloromethane (100 ml) was cooled to -60\u00b0 C. and a solution of dimethylsulfoxide (8.9 ml) in dichloromethane (30 ml) was added, followed by a slurry of 3-(1-dodecyl)-5-isoxazolemethanol (14.0 g) in dry dichloromethane (200 ml). The mixture was stirred at -60\u00b0 C. for 1 hr, quenched with triethylamine (87 ml) and allowed to warm to room temperature. The solution was poured into water (300 ml) and extracted with dichloromethane. The organic phases were washed with dilute citric acid solution, dried, filtered, and the filtrate was evaporated. The residue was passed through a short pad of silica gel using dichloromethane as the eluent. The solution was evaporated and the residue was recrystallized from ether-hexane to give 11.5 g (78%) of product, mp 53-54\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"oxalyl chloride\"}], \"amount\": {\"volume\": {\"value\": 28.8, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylsulfoxide\"}], \"amount\": {\"volume\": {\"value\": 8.9, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(1-dodecyl)-5-isoxazolemethanol\"}], \"amount\": {\"mass\": {\"value\": 14.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -60.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at -60\\u00b0 C. for 1 hr\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"quenched with triethylamine (87 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 87.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"to warm to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"ADDITION\", \"details\": \"The solution was poured into water (300 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 300.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic phases were washed with dilute citric acid solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"citric acid\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"the filtrate was evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"The solution was evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was recrystallized from ether-hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether-hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 11.5, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 78.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a82b20b84d7a4bd284309a062181d38b",
    "procedure_text": "Chlorodiisopropylphosphine (6.00 g, 39.3 mmol) was dissolved in THF (150 mL) and cooled to \u221278\u00b0 C. Vinylmagnesium bromide (1 M in THF, 43.2 mL, 43.2 mmol) was added dropwise. The dry ice bath was then removed, and the reaction was allowed to warm to room temperature. After 2 h at room temperature, the reaction was quenched with saturated NH4Cl, and 30% H2O2 (75 mL) was added. The mixture was vigorously stirred at room temperature for 2 h. It was then extracted with CH2Cl2 (2\u00d7), dried (MgSO4), and evaporated. Flash chromatography (0-10% MeOH/EtOAc) afforded diisopropyl(vinyl) phosphine oxide as a colorless oil. 1H NMR (CDCl3, 600 MHz) \u03b4 6.31 (td, J=18.6, 2.2 Hz, 1H), 6.24 (ddd, J=34.8, 12.8, 2.3 Hz, 1H), 6.03 (ddd, J=27.3, 18.7, 12.8 Hz, 1H), 2.01-1.92 (m, 2H), 1.15 (dd, J=15.0, 7.0 Hz, 6H), 1.06 (dd, J=15.9, 7.4 Hz, 6H). MS: cal'd 161 (MH+), exp 161 (MH+).",
    "reference_string": "{\"inputs\": {\"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Chlorodiisopropylphosphine\"}], \"amount\": {\"mass\": {\"value\": 6.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Vinylmagnesium bromide\"}], \"amount\": {\"volume\": {\"value\": 43.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -78.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was vigorously stirred at room temperature for 2 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The dry ice bath was then removed\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dry ice\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"to warm to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"the reaction was quenched with saturated NH4Cl, and 30% H2O2 (75 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH4Cl\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O2\"}], \"amount\": {\"volume\": {\"value\": 75.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"EXTRACTION\", \"details\": \"It was then extracted with CH2Cl2 (2\\u00d7)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropyl(vinyl) phosphine oxide\"}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-34d3c4a23f6940a69f4d288b69ba76b6",
    "procedure_text": "690 mg (2.25 mmol) of 7-chloro-8-cyano-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid are stirred with 312 mg (2.47 mmol) of (1S,6S)-2,8-diazabicyclo[4.3.0]nonane and 504 mg (4.50 mmol) of 1,4-diazabicyclo[2.2.2]octane (DABCO) in a mixture of 6.6 ml of dimethylformamide and 6.6 ml of acetonitrile at room temperature overnight. All the volatile components are removed in vacuo, the residue is taken up in water and the resulting solution is brought to pH 7 with dilute hydrochloric acid. The precipitate formed is filtered off with suction, the filtrate is extracted with methylene chloride and the combined organic phases are dried with sodium sulfate and concentrated in vacuo.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-chloro-8-cyano-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 690.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(1S,6S)-2,8-diazabicyclo[4.3.0]nonane\"}], \"amount\": {\"mass\": {\"value\": 312.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,4-diazabicyclo[2.2.2]octane\"}], \"amount\": {\"mass\": {\"value\": 504.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 6.6, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 6.6, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"All the volatile components are removed in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The precipitate formed\"}, {\"type\": \"FILTRATION\", \"details\": \"is filtered off with suction\"}, {\"type\": \"EXTRACTION\", \"details\": \"the filtrate is extracted with methylene chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"the combined organic phases are dried with sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-f22373ef009c4ad394520835f6116971",
    "procedure_text": "A solution of (\u00b1)-7-(2-chloro-5-fluorophenyl)-5-guanidinoimino-4-methyl-5,6,7,8-tetrahydroquinoline (7.1 g) in ethanol (85 ml) was combined with L-pyroglutamic acid (2.72 g) and heated to form a uniform solution. The mixture was allowed to stand to cool gradually, and stirred at room temperature for 14 hours. The crystal precipitated was recovered by a filtration and washed with ethanol to obtain (+)-7-(2-chloro-5-fluorophenyl)-5-guanidinoimino-4-methyl-5,6,7,8-tetrahydroquinoline L-pyroglutamate (4.1 g). This crystal was suspended in methanol (50 ml) and combined with a 28% solution of sodium methoxide in methanol (1.7 g) and then the solvent was distilled off under reduced pressure. The resultant crystal was washed with water and dried to obtain a crystal (3.1 g). This was dissolved in ethanol (20 ml) and combined with methanesulfonic acid (1.8 g). The solvent was distilled off under reduced pressure, and the resultant crystal was recrystallized from ethanol to obtain (+)-7-(2-chloro-5-fluorophenyl)-5-guanidinoimino-4-methyl-5,6,7,8-tetrahydroquinoline methanesulfonate (Compound H)(3.6 g, 99.3% ee).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(\\u00b1)-7-(2-chloro-5-fluorophenyl)-5-guanidinoimino-4-methyl-5,6,7,8-tetrahydroquinoline\"}], \"amount\": {\"mass\": {\"value\": 7.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"L-pyroglutamic acid\"}], \"amount\": {\"mass\": {\"value\": 2.72, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 85.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred at room temperature for 14 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"heated\"}, {\"type\": \"CUSTOM\", \"details\": \"to form a uniform solution\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to cool gradually\"}, {\"type\": \"CUSTOM\", \"details\": \"The crystal precipitated\"}, {\"type\": \"FILTRATION\", \"details\": \"was recovered by a filtration\"}, {\"type\": \"WASH\", \"details\": \"washed with ethanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 14.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(+)-7-(2-chloro-5-fluorophenyl)-5-guanidinoimino-4-methyl-5,6,7,8-tetrahydroquinoline L-pyroglutamate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 4.1, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0511df7feda94f6ca53db344690ef4d4",
    "procedure_text": "Codeinone (300 g) was added to a stirred suspension of potassium tert-butoxide (153 g) in N,N-dimethylformamide (5 ml) at room temperature. After 10 minutes, methyl trifluoromethanasulphonate (164 mg) was added dropwise to the suspension. The solution was stirred for 5 minutes, diluted with ethyl acetate (30 ml), and then poured into water (50 ml). The aqueous phase was removed, and the organic phase was dried with sodium sulphate and evaporated, producing an orange solid. Analysis by HPLC Against pure thebaine gave a thebaine content of 10%.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Codeinone\"}], \"amount\": {\"mass\": {\"value\": 300.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium tert-butoxide\"}], \"amount\": {\"mass\": {\"value\": 153.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The solution was stirred for 5 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"methyl trifluoromethanasulphonate (164 mg) was added dropwise to the suspension\"}, {\"type\": \"CUSTOM\", \"details\": \"The aqueous phase was removed\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"the organic phase was dried with sodium sulphate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulphate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"producing an orange solid\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 10.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"thebaine\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-ff1845f6151d41e5adb35c2e5389c5c9",
    "procedure_text": "Compound 231 was prepared following the procedure outlined in Example 215 using terephthalic acid (11.4 mg, 0.0684 mmol) and 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-(2-(2-(2-hydroxyethoxy)ethoxy)-ethyl)benzenesulfonamide (Compound 175.1, 100 mg, 0.136 mmol). Purification by preparative HPLC gave the title compound (9.8 mg) as a TFA salt. 1H-NMR (400 MHz, CD3OD): \u03b4 7.86-7.85 (m, 9H), 7.83 (s, 2H), 7.50 (s, 1H), 7.41 (d, 4H), 6.80 (s, 1H), 3.68-3.42 (m, 26H), 3.34 (m, 2H), 3.09-3.01 (m, 12H). MS (m/z): 1135.07 [M+H]+.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"terephthalic acid\"}], \"amount\": {\"mass\": {\"value\": 11.4, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-(2-(2-(2-hydroxyethoxy)ethoxy)-ethyl)benzenesulfonamide\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Compound 175.1\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Compound 231 was prepared\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Compound 231\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Purification by preparative HPLC\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 9.8, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 12.7}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-45dd34347ecd432da80163173777b734",
    "procedure_text": "A mixture of 4-(5-amino-6-methylisoquinolin-1-ylamino)benzonitrile (0.150 g, 0.55 mmol) and 4-(2-fluoropyridin-3-yl)-5H-pyrrolo[3,2-d]pyrimidine (0.13 g, 0.60 mmol) in anhydrous THF (10 mL) was stirred at RT and treated dropwise with lithium bis(trimethylsilyl)amide (1.0 M solution in THF; 1.7 mL, 1.7 mmol) to give a dark suspension. After 1 h stirring, the mixture was treated with 1 N aq HCl (10 mL) and stirred at RT for 10 min. The reaction mixture was added to satd NaHCO3 (70 mL) and extracted with 3:1 CHCl3IPA (3\u00d770 mL). The combined organic layers were washed with satd NaCl (50 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep\u00ae pre-packed silica gel column (40 g), eluting with a gradient of 70% to 90% EtOAc in CH2Cl2 to provide 50 mg. The crude product was purified by reverse-phase preparative HPLC using a Phenomenex Gemini column, 10 micron, C18, 110 \u212b, 150\u00d730 mm, 0.1% TFA in CH3CN/H2O, gradient 10% to 100% over 13 min. Fractions containing product were combined, concentrated in vacuo, and lyophilized to give 4-(5-(3-(5H-pyrrolo[3,2-d]pyrimidin-4-yl)pyridin-2-ylamino)-6-methylisoquinolin-1-ylamino)benzonitrile as a bright yellow solid. MS (ESI, pos. ion) m/z: 469.2 [M+H]+",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(5-amino-6-methylisoquinolin-1-ylamino)benzonitrile\"}], \"amount\": {\"mass\": {\"value\": 0.15, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(2-fluoropyridin-3-yl)-5H-pyrrolo[3,2-d]pyrimidine\"}], \"amount\": {\"mass\": {\"value\": 0.13, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"amount\": {\"volume\": {\"value\": 70.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium bis(trimethylsilyl)amide\"}], \"amount\": {\"volume\": {\"value\": 1.7, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at RT\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"to give a dark suspension\"}, {\"type\": \"STIRRING\", \"details\": \"After 1 h stirring\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"STIRRING\", \"details\": \"stirred at RT for 10 min\", \"duration\": {\"value\": 10.0, \"units\": \"MINUTE\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with 3:1 CHCl3IPA (3\\u00d770 mL)\"}, {\"type\": \"WASH\", \"details\": \"The combined organic layers were washed with satd NaCl (50 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaCl\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"chromatographed through a Redi-Sep\\u00ae pre-packed silica gel column (40 g)\"}, {\"type\": \"WASH\", \"details\": \"eluting with a gradient of 70% to 90% EtOAc in CH2Cl2\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"to provide 50 mg\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude product was purified by reverse-phase preparative HPLC\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"over 13 min\", \"duration\": {\"value\": 13.0, \"units\": \"MINUTE\"}}, {\"type\": \"ADDITION\", \"details\": \"Fractions containing product\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(5-(3-(5H-pyrrolo[3,2-d]pyrimidin-4-yl)pyridin-2-ylamino)-6-methylisoquinolin-1-ylamino)benzonitrile\"}], \"isolated_color\": \"bright yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-757d161eaac94406b4d2426d198ede66",
    "procedure_text": "Under a nitrogen atmosphere, to a solution of (6-(2-fluoro-5-methoxyphenyl)-5-isobutoxypyridin-3-yl)methanol (100 mg) and methyl 3-cyclopropyl-3-(3-hydroxyphenyl)propanoate (72 mg) in toluene (4.7 mL) were added 1,1\u2032-(azodicarbonyl)dipiperidine (132 mg) and tributylphosphine (131 \u03bcL), and the mixture was stirred at room temperature for 14 hr. Hexane/ethyl acetate (1:1) was added to the reaction mixture, and the resulting precipitate was filtered off. The solvent in the filtrate was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (132 mg) as a colorless oil.",
    "reference_string": "{\"inputs\": {\"m1_m2_m5_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(6-(2-fluoro-5-methoxyphenyl)-5-isobutoxypyridin-3-yl)methanol\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 3-cyclopropyl-3-(3-hydroxyphenyl)propanoate\"}], \"amount\": {\"mass\": {\"value\": 72.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,1\\u2032-(azodicarbonyl)dipiperidine\"}], \"amount\": {\"mass\": {\"value\": 132.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tributylphosphine\"}], \"amount\": {\"volume\": {\"value\": 131.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 4.7, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Hexane ethyl acetate\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at room temperature for 14 hr\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"the resulting precipitate was filtered off\"}, {\"type\": \"CUSTOM\", \"details\": \"The solvent in the filtrate was evaporated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was purified by silica gel column chromatography (ethyl acetate/hexane)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 14.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 132.0, \"units\": \"MILLIGRAM\"}}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-5628c8cae2a94c10bdc39a7ddb9c562d",
    "procedure_text": "A solution of 4-chloro-6-methoxyisoquinolin-1(2H)-one (1.5 g, 5.90 mmol) in POCl3 (15 ml) was refluxed for overnight. The solvent was evaporated under reduced pressure and the residue was diluted with cold water. The aqueous solution was basified by solid sodium carbonate and extracted with ethyl acetate. The combine organic layer was dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to get crude compound. The crude compound was purified by silica gel chromatography (10% ethyl acetate in pet ether) to get desired compound (1.1 g, 65.0%) as white solid. 1H NMR (400 MHz, DMSO-d6): \u03b4 ppm 8.53(s, 1H), 8.27-8.24 (d, J=12 Hz, 1H), 7.56-7.53 (d, J=12 Hz, 1H), 7.41 (s, 1H), 4.02 (s, 3H); MS: MS m/z 230.03 (M++2).",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-chloro-6-methoxyisoquinolin-1(2H)-one\"}], \"amount\": {\"mass\": {\"value\": 1.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"POCl3\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The solvent was evaporated under reduced pressure\"}, {\"type\": \"ADDITION\", \"details\": \"the residue was diluted with cold water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combine organic layer was dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"to get crude compound\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude compound was purified by silica gel chromatography (10% ethyl acetate in pet ether)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude compound\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pet ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.1, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 65.0}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c1586d1d7c594be29ecb0742d385ab20",
    "procedure_text": "A suspension of 4.54 g (20 mmol) of 3-hydroxy-2-phenyl-7-azabenzo[b]thiophene and 2.75 g (22 mmol) of potassium t-butoxide in 50 mL of tetrahydrofuran was stirred until the solid dissolved. Then 2.0 g (25 mmol) of chloromethyl methyl ether was added and the solution was stirred at room temperature for 2 hours. The solution was partitioned between ether and water and the aqueous layer was washed with two portions of ether. The ether extracts were washed with brine, dried over MgSO4, and concentrated to 4.33 g (80%) of an oil that crystallized upon standing, m.p. 54\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-hydroxy-2-phenyl-7-azabenzo[b]thiophene\"}], \"amount\": {\"mass\": {\"value\": 4.54, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium t-butoxide\"}], \"amount\": {\"mass\": {\"value\": 2.75, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloromethyl methyl ether\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred until the solid\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"DISSOLUTION\", \"details\": \"dissolved\"}, {\"type\": \"STIRRING\", \"details\": \"the solution was stirred at room temperature for 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The solution was partitioned between ether and water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"the aqueous layer was washed with two portions of ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The ether extracts were washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated to 4.33 g (80%) of an oil that\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"oil\"}], \"amount\": {\"mass\": {\"value\": 4.33, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"crystallized\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-4de06b1383524b0abfcdf44bf42290a3",
    "procedure_text": "[Step 2] 60 mg of 1-acetyl-2-methyl-4-[(2-fluorophenyl)imino]-1,2,3,4-tetrahy droquinoline and 28 mg of sodium cyanoborohydride were dissolved in 2 mL of methanol, and the solution was stirred for 18 hours at 50\u00b0 C. After completion of the reaction, 1 N hydrochloric acid was added to the reaction liquid, and the mixture was stirred for 30 minutes. The reaction liquid was neutralized with a saturated aqueous solution of sodium hydrogen carbonate, and then was extracted with chloroform. The organic layer was washed with a saturated solution of sodium hydrogen carbonate and saturated brine, dehydrated over anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by using silica gel chromatography (diethyl ether:hexane=2:1), and thus 53 mg (88%) of the title compound was obtained as a colorless oily substance.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydrogen carbonate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-acetyl-2-methyl-4-[(2-fluorophenyl)imino]-1,2,3,4-tetrahy droquinoline\"}], \"amount\": {\"mass\": {\"value\": 60.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium cyanoborohydride\"}], \"amount\": {\"mass\": {\"value\": 28.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 50.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the solution was stirred for 18 hours at 50\\u00b0 C\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added to the reaction liquid\"}, {\"type\": \"STIRRING\", \"details\": \"the mixture was stirred for 30 minutes\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}}, {\"type\": \"CUSTOM\", \"details\": \"The reaction liquid\"}, {\"type\": \"EXTRACTION\", \"details\": \"was extracted with chloroform\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with a saturated solution of sodium hydrogen carbonate and saturated brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydrogen carbonate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The resulting residue was purified\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 18.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 53.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 88.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-91a85395c02c4e2e9faad6727c7d80db",
    "procedure_text": "Separately, in a 100 mL round-bottomed flask, methyl 4-(3-(4-chloro-2-(phenylamino)phenyl)-3-oxopropyl)benzoate (898 mg, 2.28 mmol) was combined with THF to give a yellow solution. A 1.0 M solution of NaHMDS in THF (5.7 ml, 5.7 mmol) was added. The reaction mixture was stirred at room temperature for 15 minutes. A heterogeneous mixture of oxazole-2-carbonyl chloride from above, THF (5 mL), DMF (500 \u03bcL) was added dropwise to the reaction mixture. The mixture was stirred at room temperature overnight. The reaction flask was cooled to 0\u00b0 C., then the reaction was quenched with water. The resulting heterogeneous mixture was extracted with ethyl acetate, and the organic phase was dried over MgSO4, filtered, then concentrated. The crude product was dissolved in methylene chloride, then concentrated over silica gel. The silica gel supported crude product was loaded onto a 80 gram analogix column. Flash chromatography (15% EtOAc-hexanes\u219255% EtOAc-hexanes) provided 4-(7-Chloro-2-oxazol-2-yl-4-oxo-1-phenyl-1,4-dihydro-quinolin-3-ylmethyl)-benzoic acid methyl ester (28 mg, 2.6%) as a light yellow solid.",
    "reference_string": "{\"inputs\": {\"m7_m8_m9\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"oxazole-2-carbonyl chloride\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 4-(3-(4-chloro-2-(phenylamino)phenyl)-3-oxopropyl)benzoate\"}], \"amount\": {\"mass\": {\"value\": 898.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"reaction_role\": \"REACTANT\"}]}, \"m4_m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHMDS\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 5.7, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred at room temperature for 15 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"to give a yellow solution\"}, {\"type\": \"ADDITION\", \"details\": \"was added dropwise to the reaction mixture\"}, {\"type\": \"STIRRING\", \"details\": \"The mixture was stirred at room temperature overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"The reaction flask was cooled to 0\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"the reaction was quenched with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The resulting heterogeneous mixture was extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"the organic phase was dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The crude product was dissolved in methylene chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated over silica gel\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc-hexanes\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 55.0}}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(7-Chloro-2-oxazol-2-yl-4-oxo-1-phenyl-1,4-dihydro-quinolin-3-ylmethyl)-benzoic acid methyl ester\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 28.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 2.6}}], \"isolated_color\": \"light yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3b881560f7b243a99ea95302fd21773b",
    "procedure_text": "In a manner similar to that described for method I, 1-benzyl-8-chloro-4-dimethylaminomethylene-3,4-dihydro-1H-benzo[b]azepine-2,5-dione (v-N) and 4-guanidinobenzoic acid were converted to I-6 (26%): MS m/z\u2550471 (M+H)HRMS Calcd. for C26H19ClN4O3: 471.1223, Found 471.1310.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-benzyl-8-chloro-4-dimethylaminomethylene-3,4-dihydro-1H-benzo[b]azepine-2,5-dione\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-guanidinobenzoic acid\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-96f0eca424fe491285d6ced19efc7790",
    "procedure_text": "To a solution of (2-chloro-8-methylquinolin-3-yl)methanol (2.0 g, 10 mmol) in DCM (200 mL) were added triphenylphosphine (2.6 g, 10 mmol), iodine (2.6 g, 10 mmol) and imidazole (0.7 g, 10 mmol) and the reaction mixture was stirred for 2 h at r.t. The mixture was washed with water (50 mL) and the organic layer was separated, dried and concentrated in vacuo. Purification by column chromatography (SiO2, 50% Et2O in heptane) gave the title compound as a brown solid (2.2 g, 72%). \u03b4H (CDCl3) 8.17 (s, 1H), 7.62 (d, J 9 Hz, 1H), 7.55 (d, J 9 Hz, 1H), 7.45 (t, J 9 Hz, 1H), 4.68 (s, 2H), 2.75 (s, 3H). LCMS (ES+) 318.0, 320.0 (M+H)+, RT 4.53 minutes (Method 3).",
    "reference_string": "{\"inputs\": {\"m1_m5_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2-chloro-8-methylquinolin-3-yl)methanol\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triphenylphosphine\"}], \"amount\": {\"mass\": {\"value\": 2.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"iodine\"}], \"amount\": {\"mass\": {\"value\": 2.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"imidazole\"}], \"amount\": {\"mass\": {\"value\": 0.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture was stirred for 2 h at r.t\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WASH\", \"details\": \"The mixture was washed with water (50 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the organic layer was separated\"}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification by column chromatography (SiO2, 50% Et2O in heptane)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Et2O\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"heptane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.2, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 72.0}}], \"isolated_color\": \"brown\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b98e08f1c06d4043bedec7b7196bf316",
    "procedure_text": "To a clean and dry 1000 ml round bottom flask equipped with a 250 ml addition funnel, low temperature thermometer and magnetic stir bar was transferred anhydrous tetrahydrofuran (500.0 ml) under nitrogen. 4-bromobenzocyclobutane (25.0 g, 0.1370 mol) was added to this flask by syringe. The reaction vessel was placed into a dry ice/acetone bath until a temperature of <\u221270\u00b0 C. was achieved. The reaction mixture was then allowed to stir for 45 minutes at a stirring speed of 550 rpm in order to verify the integrity of the stirring apparatus at this temperature. Tert-butyllithium solution (161 ml, 0.2730 mol) was transferred to the addition funnel by cannula, then added dropwise to the reaction never allowing the temperature to rise above \u221265\u00b0 C. Following addition, the reaction was allowed to stir for a period of 30 minutes. The vessel was then removed from the dry ice/acetone bath and allowed to warm to a temperature of \u221220\u00b0 C. The vessel was then again placed into the dry ice/acetone bath until a temperature of <\u221270\u00b0 was achieved. 1,4-dibromobutane (64.7 ml, 0.5460 mol) was added to the reaction dropwise via syringe, maintaining the current temperature. The reaction was allowed to stir for 30 minutes at this temperature following addition. The reaction was slowly warmed to room temperature over the following 12 hours. Reaction completion was confirmed by GC-MS. After warming, the reaction was quenched by the addition of isopropanol (25.0 ml) via syringe.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-bromobenzocyclobutane\"}], \"amount\": {\"mass\": {\"value\": 25.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Tert-butyllithium\"}], \"amount\": {\"volume\": {\"value\": 161.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,4-dibromobutane\"}], \"amount\": {\"volume\": {\"value\": 64.7, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -20.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"to stir for 45 minutes at a stirring speed of 550 rpm in order\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"To a clean and dry 1000 ml round bottom flask\"}, {\"type\": \"CUSTOM\", \"details\": \"equipped with a 250 ml addition funnel\"}, {\"type\": \"CUSTOM\", \"details\": \"The reaction vessel was placed into a dry ice/acetone bath until a temperature of <\\u221270\\u00b0 C.\"}, {\"type\": \"ADDITION\", \"details\": \"added dropwise to the reaction\"}, {\"type\": \"CUSTOM\", \"details\": \"to rise above \\u221265\\u00b0 C\"}, {\"type\": \"ADDITION\", \"details\": \"addition\"}, {\"type\": \"STIRRING\", \"details\": \"to stir for a period of 30 minutes\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}}, {\"type\": \"CUSTOM\", \"details\": \"The vessel was then removed from the dry ice/acetone bath\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dry ice acetone\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"was then again placed into the dry ice/acetone bath until a temperature of <\\u221270\\u00b0\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dry ice acetone\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"maintaining the current temperature\"}, {\"type\": \"STIRRING\", \"details\": \"to stir for 30 minutes at this temperature\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}}, {\"type\": \"ADDITION\", \"details\": \"addition\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The reaction was slowly warmed to room temperature over the following 12 hours\", \"duration\": {\"value\": 12.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"Reaction completion\"}, {\"type\": \"TEMPERATURE\", \"details\": \"After warming\"}, {\"type\": \"CUSTOM\", \"details\": \"the reaction was quenched by the addition of isopropanol (25.0 ml) via syringe\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isopropanol\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 45.0, \"units\": \"MINUTE\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-d820d861d00a410fb7a2e4f57cae49eb",
    "procedure_text": "3-(4-Dimethylaminomethyl-2-pyridylmethylthio)propionitrile in a mixture of dry methanol and dry chloroform under nitrogen at 2\u00b0 C. is treated with dried hydrogen chloride gas and allowed to stand at ca. 0\u00b0 C. to give after basification with ice cold potassium carbonate solution methyl-3-(4-dimethylaminomethyl-2-pyridylmethylthio)propionimidate which is reacted in methanol with sulphamide under reflux. Evaporation of the solvent at reduced pressure and purification of the product by chromatography yields N-sulphamoyl-3-(4-dimethylaminomethyl-2-pyridylmethylthio)propionamidine.",
    "reference_string": "{\"inputs\": {\"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrogen chloride\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m6_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(4-Dimethylaminomethyl-2-pyridylmethylthio)propionitrile\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m5_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sulphamide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"to stand at ca. 0\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"to give after basification with ice cold potassium carbonate solution methyl-3-(4-dimethylaminomethyl-2-pyridylmethylthio)propionimidate which\"}, {\"type\": \"TEMPERATURE\", \"details\": \"under reflux\"}, {\"type\": \"CUSTOM\", \"details\": \"Evaporation of the solvent\"}, {\"type\": \"CUSTOM\", \"details\": \"at reduced pressure and purification of the product by chromatography\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-sulphamoyl-3-(4-dimethylaminomethyl-2-pyridylmethylthio)propionamidine\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-06ee06d1617c47dfa039b7b272c245db",
    "procedure_text": "A mixture of o-methoxybenzaldehyde (2.00 g., 14.7 moles) and hydantoin (1.47 g., 1 molar ratio) in water (12ml) was heated to 70\u00b0; monoethanolamine (1.35 g., 1.5 molar ratio) was then added. The mixture was heated in an oil bath (90\u00b0-92\u00b0 ) and stirred magnetically for 4 hours. Usual workup gave the title compound as an orange solid (2.90 g.), m.p. 174\u00b0-179\u00b0.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"o-methoxybenzaldehyde\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydantoin\"}], \"amount\": {\"mass\": {\"value\": 1.47, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 12.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"monoethanolamine\"}], \"amount\": {\"mass\": {\"value\": 1.35, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred magnetically for 4 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"was heated to 70\\u00b0\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The mixture was heated in an oil bath (90\\u00b0-92\\u00b0 )\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.9, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 90.5}}], \"isolated_color\": \"orange\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-406130b63c134689a9c2a0bd5cc10f43",
    "procedure_text": "Tetrachloroterephthalonitrile (26.6 g, 0.1 mol) and ethanol (532 g) were mixed, and the resultant mixture was heated to 79\u00b0 C. with stirring. To the mixture, a 20% aqueous solution of sodium hydroxide (16 g) was added over six hours. Liquid chromatographic analysis revealed the reaction mixture contained 16.5 g of 2,3,5,6-tetrachloro-4-cyanobenzamide (yield 58%).",
    "reference_string": "{\"inputs\": {\"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"resultant mixture\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Tetrachloroterephthalonitrile\"}], \"amount\": {\"mass\": {\"value\": 26.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"mass\": {\"value\": 532.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aqueous solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"mass\": {\"value\": 16.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"with stirring\"}, \"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,3,5,6-tetrachloro-4-cyanobenzamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 16.5, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 58.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 58.1}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-405272e1d190469298d2211149065b43",
    "procedure_text": "The titled amide was prepared from the trans-diamine and 4-nitrobenzoylchloride according to general procedure B using p-nitrobenzoylchloride (1.86 g.; 0.01 mole), the diamine (1.42 g.; 0.01 mole) and triethylamine (1.01 g.; 0.01 mole). The crude oil was crystallized from etherpetroleum ether (30\u00b0-60\u00b0); 2.232 g. (77% yield) of yellow needles, m.p. 103\u00b0-104\u00b0. The analytical sample melted at 102\u00b0-103\u00b0. uv sh 215 nm (\u03b5 2,000); \u03bbmax 266 (11,800). ir NH 3380, 3320; N-alkyl 2780; C=O 1645; C=C 1605, 1595; amide II/NO2 /C=C 1535, 1525, 1485, 1350; aromatic 870, 845, 720, nmr in CDCl3 and 100 MHz was in accord. Mass spectrum M+ 291.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"p-nitrobenzoylchloride\"}], \"amount\": {\"mass\": {\"value\": 1.86, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m0_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trans-diamine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-nitrobenzoylchloride\"}], \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"mass\": {\"value\": 1.01, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diamine\"}], \"amount\": {\"mass\": {\"value\": 1.42, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The crude oil was crystallized from etherpetroleum ether (30\\u00b0-60\\u00b0)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"amide\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"yellow needles\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 77.0}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"needles\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-18f26900838f4a10a131c54d87af47f5",
    "procedure_text": "To a flask containing a bi-phasic mixture of 2-bromo-4-nitroanisole (15.0 g, 64.6 mmol) and 3-chlorophenylboronic acid (12.1 g, 77.6 mmol) in ethylene glycol dimethyl ether (187.5 mL) and 2.0 N aqueous cesium carbonate (97 mL) was added 1-1\u2032-bis(diphenylphosphino)ferrocene)dichloro palladium (II), complex with dichloromethane (1:1) (1.5 g). The mixture was heated at reflux for 4 hours under a nitrogen atmosphere. The crude reaction mixture was partitioned between ethyl acetate (350 mL) and brine (250 mL) and then filtered through a Buchner funnel. Layers were separated and the organic layer was washed with brine (250 mL). The organic phase was dried over Na2SO4, filtered, and concentrated to a dark oil. The crude residue was purified by flash chromatography on silica gel using dichloromethane as the eluent to afford 2-(3-chlorophenyl)-4-nitroanisole as a yellow solid (13.9 g, 59.4 mmol).",
    "reference_string": "{\"inputs\": {\"m3_m7_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-1\\u2032-bis(diphenylphosphino)ferrocene\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"mass\": {\"value\": 1.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloro palladium (II)\"}], \"reaction_role\": \"CATALYST\"}]}, \"m1_m2_m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-bromo-4-nitroanisole\"}], \"amount\": {\"mass\": {\"value\": 15.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-chlorophenylboronic acid\"}], \"amount\": {\"mass\": {\"value\": 12.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethylene glycol dimethyl ether\"}], \"amount\": {\"volume\": {\"value\": 187.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cesium carbonate\"}], \"amount\": {\"volume\": {\"value\": 97.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"To a flask containing\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The mixture was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"at reflux for 4 hours under a nitrogen atmosphere\", \"duration\": {\"value\": 4.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The crude reaction mixture\"}, {\"type\": \"CUSTOM\", \"details\": \"was partitioned between ethyl acetate (350 mL) and brine (250 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 350.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered through a Buchner funnel\"}, {\"type\": \"CUSTOM\", \"details\": \"Layers were separated\"}, {\"type\": \"WASH\", \"details\": \"the organic layer was washed with brine (250 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic phase was dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated to a dark oil\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude residue was purified by flash chromatography on silica gel\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude residue\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(3-chlorophenyl)-4-nitroanisole\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 59.4, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 13.9, \"units\": \"GRAM\"}}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2346e23d79da465d8c18320dfc54e36a",
    "procedure_text": "2-Amino-pentanoic acid [1-(1,1-dimethyl-3-morpholin-4-yl-propyl)-1H-imidazol-4-yl]-amide was reacted with 6,8-Difluoro-3,4-dihydro-1H-naphthalen-2-one to provide the title compound: 13C NMR 14.2, 19.5, 19.6, 28.2, 28.3, 28.5, 28.6, 28.6, 28.7, 28.8, 29.7, 29.8, 30.8, 36.5, 36.6, 39.8, 52.3, 52.7, 54.0, 57.2, 57.3, 60.3, 60.8, 67.1, 100.8, 101.1, 101.3, 104.6, 104.7, 110.5, 110.6, 110.8, 110.9, 130.5, 137.6, 137.7, 139.9, 159.7, 162.3, 172.3, 172.5; MS m/z 504.2 (M+1).",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-Amino-pentanoic acid [1-(1,1-dimethyl-3-morpholin-4-yl-propyl)-1H-imidazol-4-yl]-amide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6,8-Difluoro-3,4-dihydro-1H-naphthalen-2-one\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-663349c3268548c9a8831dc48b484298",
    "procedure_text": "2-Amino-2-[6-(trans-4-tert-butyl-cyclohexyloxy)-5-trifluoromethyl-quinolin-2-yl]-propan-1-ol Enantiomer 1 was synthesized as per 2-amino-2-[6-(trans-4-tert-butyl-cyclohexyloxy)-quinolin-2-yl]-propan-1-ol (Example 18) in 52% yield as bis-TFA salt using 2-amino-2-[6-(trans-4-tert-butyl-cyclohexyloxy)-5-trifluoromethyl-quinolin-2-yl]-propionic acid ethyl ester Enantiomer 1 as starting material. MS: m/z=425.30 [M+H]+. 1NMR (400 MHz, CHLOROFORM-d) \u03b4 ppm: 8.68 (d, J=8.8 Hz, 1H), 8.12 (d, J=9.0 Hz, 1H), 7.47-7.60 (m, 2H), 4.31-4.44 (m, 1H), 4.09-4.26 (m, 2H), 2.13-2.25 (m, 2H), 1.85-1.95 (m, 2H), 1.81 (s, 3H), 1.48-1.62 (m, 2H), 1.03-1.22 (m, 3H), 0.90 (s, 9H).",
    "reference_string": "{\"inputs\": {\"m0_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-amino-2-[6-(trans-4-tert-butyl-cyclohexyloxy)-quinolin-2-yl]-propan-1-ol\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TFA\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-amino-2-[6-(trans-4-tert-butyl-cyclohexyloxy)-5-trifluoromethyl-quinolin-2-yl]-propionic acid ethyl ester\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-Amino-2-[6-(trans-4-tert-butyl-cyclohexyloxy)-5-trifluoromethyl-quinolin-2-yl]-propan-1-ol\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 52.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-61fde83b4d5144c994f4ab48e3e2741b",
    "procedure_text": "tert-Butyl 3-[(11s)-6-amino-10,11-dihydro-8H-[1,4]oxazino[4\u2032,3\u2032:1,2]imidazo[4,5-c]quinolin-11-yl]propylcarbamate (689 mg, 1.74 mmol) was dissolved in 10 mL of ethanol and 2 mL of a 4.0 M solution of HCl in ethanol was added. The reaction mixture was heated to 75\u00b0 C. After 1 hour, the reaction mixture was concentrated under reduced pressure. The resulting residue was treated with 25 mL H2O and 20 mL of CHCl3. The layers were separated and the organic portion was discarded. The aqueous layer was then made basic by addition of 5 mL of concentrated NH4OH solution. The aqueous portion was then extracted with CHCl3 (6\u00d710 mL). The combined organic extracts were concentrated under reduced pressure to give (11S)-11-(3-aminopropyl)-10,11-dihydro-8H-[1,4]oxazino[4\u2032,3\u2032:1,2]imidazo[4,5-c]quinolin-6-amine (469 mg) as a white foam.",
    "reference_string": "{\"inputs\": {\"m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-Butyl 3-[(11s)-6-amino-10,11-dihydro-8H-[1,4]oxazino[4\\u2032,3\\u2032:1,2]imidazo[4,5-c]quinolin-11-yl]propylcarbamate\"}], \"amount\": {\"mass\": {\"value\": 689.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 75.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"the reaction mixture was concentrated under reduced pressure\"}, {\"type\": \"ADDITION\", \"details\": \"The resulting residue was treated with 25 mL H2O and 20 mL of CHCl3\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CHCl3\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The layers were separated\"}, {\"type\": \"ADDITION\", \"details\": \"The aqueous layer was then made basic by addition of 5 mL of concentrated NH4OH solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH4OH\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The aqueous portion was then extracted with CHCl3 (6\\u00d710 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CHCl3\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"The combined organic extracts were concentrated under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(11S)-11-(3-aminopropyl)-10,11-dihydro-8H-[1,4]oxazino[4\\u2032,3\\u2032:1,2]imidazo[4,5-c]quinolin-6-amine\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 469.0, \"units\": \"MILLIGRAM\"}}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"FOAM\", \"details\": \"foam\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0c308f299efd4872858f34fbc6e1f580",
    "procedure_text": "By following serially the procedures of Examples 1 and 2 but replacing 2-mercapto-2,4,6-cycloheptatrien-1-one with an equivalent amount of 5-mercapto-7H-benzocyclohepten-7-one, 9-amino-7H-cyclohepta[c]pyridin-7-one, 5-mercapto-3H,-6,7-dihydrocyclobutacyclohepten-3-one, 1-ethylamino-3H-6,7,8,9,10,11-hexahydrocycloheptacycloocten-3-one and 5-mercapto-3H-6,7,8,9,10,11,12,13-octahydrocycloheptacyclodecen-3-one, the following compounds are obtained respectively: [(7-oxo-7H-benzocyclohepten-5-yl)thio]oxoacetic acid ethyl ester (l; R1, R5, and R6 = H; R2 = S--CO--COOC2H5 ; and R3 and R4 together form a --CH=CH--CH=CH-- chain), [(7-oxo-7H-cyclohepta[c]pyridin-9-yl)-amino]oxo-acetic acid ethyl ester (I; R1, R5 and R6 = H; R2 = NC2H5 --CO--COOC2H5 ; and R3 and R4 together form a --CH=CH--N=CH-- chain). [(3-oxo-3H-6,7-dihydrocyclobutacyclohepten-5-yl)thio]oxo-acetic acid ethyl ester (I; R1, R5 and R6 = H; R2 = S--CO--COOC2H5 ; and R3 and R4 together form a --CH2CH2 -- chain), [N-(3-oxo-3H-6,7,8,9,10,11-hexahydrocycloheptacycloocten-1-yl)ethylamino]oxo-acetic acid ethyl ester (I; R1, R2 and R6 = H; R3 and R4 together form a --(CH2)6 chain; and R5 = NC2H5 --CO--COOC2H 5) and [(3-oxo-3H-6,7,8,9,10,11,12,13-octahydrocycloheptacyclodecen-5-yl)thio]oxo-acetic acid ethyl ester (I; R1, R5 and R6 = H; R2 = S--CO--COOC2H5 ; and R3 and R4 together form a --(CH2)8 -- chain).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"9-amino-7H-cyclohepta[c]pyridin-7-one\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-mercapto-2,4,6-cycloheptatrien-1-one\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-mercapto-7H-benzocyclohepten-7-one\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6,7-dihydrocyclobutacyclohepten-3-one\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-mercapto-3H-6,7,8,9,10,11,12,13-octahydrocycloheptacyclodecen-3-one\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-1a274eb274754d368c893024268328f8",
    "procedure_text": "To a solution of indoline-5-sulfonamide (Intermediate 54A, 100 mg, 0.50 mmol) in MeCN (5.0 mL) was added cyclohexanecarbonyl chloride (0.14 mL, 1.00 mmol) and K2CO3 (174 mg, 1.26 mmol). The resulting reaction mixture was stirred at room temperature overnight and then diluted with EtOAc and sat. aq. NaHCO3 solution. The organic layer was washed with 1 N aq. NaOH solution, followed by 10% aq. LiCl solution. The combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo. The residue was triturated with CH2Cl2 to give the title compound (31 mg, 20%) as a white solid. 1H NMR (DMSO-d6) \u03b4 8.16 (d, J=6.8 Hz, 1H), 7.64-7.60 (m, 2H), 7.19 (m, 2H), 4.22 (t, J=8.5 Hz, 2H), 3.21-3.16 (m, 2H), 2.62-2.55 (m, 1H), 1.91-1.65 (m, 5H), 1.45-1.16 (m, 5H); MS(ESI+) m/z 309.1 (M+H)+.",
    "reference_string": "{\"inputs\": {\"m1_m2_m5_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"indoline-5-sulfonamide\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Intermediate 54A\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cyclohexanecarbonyl chloride\"}], \"amount\": {\"volume\": {\"value\": 0.14, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"K2CO3\"}], \"amount\": {\"mass\": {\"value\": 174.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeCN\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m6_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at room temperature overnight\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The resulting reaction mixture\"}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with 1 N aq. NaOH solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic extracts were dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was triturated with CH2Cl2\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 31.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 20.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 20.1}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-20b3ad675ffe462da4204a4077bd4509",
    "procedure_text": "A solution of tert-butyl 11-[(E)-2-nitroethenyl]-1,2,4,5-tetrahydro-3H-[1,4]diazepino[1,7-a]indole-3-carboxylate (396 mg, 1.1 mmol) in methanol (10 mL) is cooled to 0\u00b0 C. and treated with a saturated solution of hydrochloric acid in methanol (5 mL). After 3 hrs, the volatiles are removed under reduced pressure, diluted with 5M sodium hydroxide (15 mL), and extracted twice with dichloromethane (20 mL). The combined organics are washed once with brine (15 mL), dried over MgSO4, filtered, and concentrated to give a yellow solid. This material is recrystallized from dichloromethane/ethyl acetate to afford 209 mg of 11-[(E)-2-nitroethenyl]-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indole as a light yellow solid, mp 225-226\u00b0 C. IR (drift) 1603, 1488, 1469, 1318, 1301, 1281, 1257, 1251, 1206, 1187, 1062, 976, 946, 763, 745 cm\u22121; OAMS supporting ions at: ESI+ 258.1.",
    "reference_string": "{\"inputs\": {\"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl 11-[(E)-2-nitroethenyl]-1,2,4,5-tetrahydro-3H-[1,4]diazepino[1,7-a]indole-3-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 396.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the volatiles are removed under reduced pressure\"}, {\"type\": \"ADDITION\", \"details\": \"diluted with 5M sodium hydroxide (15 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted twice with dichloromethane (20 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined organics are washed once with brine (15 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a yellow solid\"}, {\"type\": \"CUSTOM\", \"details\": \"This material is recrystallized from dichloromethane/ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"11-[(E)-2-nitroethenyl]-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indole\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 209.0, \"units\": \"MILLIGRAM\"}}}], \"isolated_color\": \"light yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-afd73e13d2bc4c22b2e64f4b00bfdebb",
    "procedure_text": "A stirred mixture of 2-(5-amino-2-propoxyphenyl)-8-azapurin-6-one (2.02 g), ethyl 2-ethoxy-1-cyclopentenecarboxylate (1.43 g) and dry sulpholane (20 ml) was heated at 125\u00b0-130\u00b0 C. for 2 hours. The solution was then cooled and poured into dilute hydrochloric acid (200 ml; 2 N) and the yellow solid obtained was filtered off and recrystallised from a mixture of petroleum ether (b.p. 60\u00b0-80\u00b0 C.) and ethyl acetate to give 2-[5-(2-ethoxycarbonylcyclopent-1-enylamino)-2-propoxyphenyl]-8-azapurin-6-one (0.85 g), m.p. 164\u00b0-165\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(5-amino-2-propoxyphenyl)-8-azapurin-6-one\"}], \"amount\": {\"mass\": {\"value\": 2.02, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 2-ethoxy-1-cyclopentenecarboxylate\"}], \"amount\": {\"mass\": {\"value\": 1.43, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sulpholane\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"was heated at 125\\u00b0-130\\u00b0 C. for 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"The solution was then cooled\"}, {\"type\": \"CUSTOM\", \"details\": \"the yellow solid obtained\"}, {\"type\": \"FILTRATION\", \"details\": \"was filtered off\"}, {\"type\": \"CUSTOM\", \"details\": \"recrystallised from a mixture of petroleum ether (b.p. 60\\u00b0-80\\u00b0 C.) and ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"petroleum ether\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-[5-(2-ethoxycarbonylcyclopent-1-enylamino)-2-propoxyphenyl]-8-azapurin-6-one\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.85, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-5e9234667d8a40c6ac3b222d15b5dedc",
    "procedure_text": "To a stirred suspension of 2-methyl-acrylic acid 2-[3-(4-{[2-(4-cyanobenzyloxy-carbamoyl)-phenylamino]-methyl}-pyridin-2-yl)-ureido]-ethyl ester (Example 533, 500 mg) in methanol (10 ml) was added 2 M aqueous sodium hydroxide (5 ml). The reaction mixture was stirred at room temperature for 20 minutes. The pH of the mixture was adjusted to 5 by addition of 4 M hydrochloric acid and water (15 ml) was added. The resulting precipitated material was isolated by filtration and dried in vacuo, and gave the title compound. 13C-NMR (DMSO-d6) \u03b4 167.4, 154.8, 153.8, 151.1, 148.6, 146.7, 141.8, 132.6, 132.1, 129.1, 128.0, 118.6, 115.1, 114.8, 113.0, 111.6, 110.8, 109.3, 76.0, 60.2, 45.3, 41.8.",
    "reference_string": "{\"inputs\": {\"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-methyl-acrylic acid 2-[3-(4-{[2-(4-cyanobenzyloxy-carbamoyl)-phenylamino]-methyl}-pyridin-2-yl)-ureido]-ethyl ester\"}], \"amount\": {\"mass\": {\"value\": 500.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred at room temperature for 20 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"CUSTOM\", \"details\": \"The resulting precipitated material\"}, {\"type\": \"CUSTOM\", \"details\": \"was isolated by filtration\"}, {\"type\": \"CUSTOM\", \"details\": \"dried in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 20.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-205a7a5781f24176abd4a795644df55f",
    "procedure_text": "A solution of 7-amino-2-methyl-4-(4-oxocyclohexyl)-2,3-dihydro-1H-isoindol-1-one (100.0 mg, 0.3871 mmol) in 1,2-dichloroethane (2.0 mL) was charged with 1-methylpiperazine (58.16 mg, 0.5807 mmol) and sodium triacetoxyborohydride (164.1 mg, 0.7743 mmol). The reaction mixture was stirred at rt for 24 hours. The reaction mixture was quenched with NaHCO3 (10 mL) and extracted with EtOAc (20 mL). The organic layer was washed with brine (10 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to yield a light yellow oil. The crude material was purified and by silica gel chromatography on the combi-flash Rf system using DCM/7M NH3 in MeOH (100:0\u219290:10) as eluent to afford the cis isomer (76.5 mg, 58%, first eluting product) and the trans isomer (30.0 mg, 23%, second eluting product). Cis isomer: 1H NMR (CDCl3, 400 MHz): \u03b4=1.42-1.56 (m, 4 H), 1.82-1.96 (m, 2 H), 2.06 (d, J=11.87 Hz, 2 H), 2.27 (br. s., 1 H), 2.34 (s, 3 H), 2.38-2.78 (m, 9 H), 3.14 (s, 3 H), 4.31 (s, 2 H), 5.08 (s, 2 H), 6.58 (d, J=8.34 Hz, 1 H), 7.18 (d, J=8.34 Hz, 1 H). MS (ES+): m/z 343.25 [MH+]. Trans isomer: 1H NMR (CDCl3, 400 MHz): \u03b4=1.35-1.75 (m, 7 H), 1.91 (d, J=12.13 Hz, 2 H), 2.03-2.13 (m, 2 H), 2.34 (s, 3 H), 2.47-2.82 (m, 7 H), 3.14 (s, 3 H), 4.28 (s, 2 H), 5.09 (s, 2 H), 6.56 (d, J=8.34 Hz, 1 H), 7.09 (d, J=8.34 Hz, 1 H). MS (ES+): m/z 343.26 [MH+].",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-amino-2-methyl-4-(4-oxocyclohexyl)-2,3-dihydro-1H-isoindol-1-one\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-methylpiperazine\"}], \"amount\": {\"mass\": {\"value\": 58.16, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium triacetoxyborohydride\"}], \"amount\": {\"mass\": {\"value\": 164.1, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,2-dichloroethane\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred at rt for 24 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was quenched with NaHCO3 (10 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with EtOAc (20 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with brine (10 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"to yield a light yellow oil\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude material was purified and by silica gel chromatography on the combi-flash Rf system\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude material\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"to afford the cis isomer (76.5 mg, 58%, first eluting product)\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 24.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-383f99465b3f4bbc92ffb34fe7a00415",
    "procedure_text": "(4R-cis)-1-[2-[6-[2-(diphenylamino)-2-oxoethyl]-2,2-dimethyl-1,3-dioxan-4-yl]ethyl]-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1H-pyrrole-3-carboxamide is dissolved in methanol (300 mL) and reacted by adding 1.0N hydrochloric acid (100 mL) and stirring for 12 hours at room temperature. The white crystalline solid [R-(R*,R*)]-5-(4-fluorophenyl)-\u03b2,\u03b3-dihydroxy-2-(1-methylethyl)-N,N,4-triphenyl-3-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanamide is isolated by filtration (mp 228.5\u00b0-232.9\u00b0 C., uncorrected). FTIR (KBr) 3400 (broad), 2850, 1640 cm-1 ;",
    "reference_string": "{\"inputs\": {\"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(4R-cis)-1-[2-[6-[2-(diphenylamino)-2-oxoethyl]-2,2-dimethyl-1,3-dioxan-4-yl]ethyl]-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1H-pyrrole-3-carboxamide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 300.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirring for 12 hours at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"reacted\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 12.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-(4-fluorophenyl)-\\u03b2,\\u03b3-dihydroxy-2-(1-methylethyl)-N,N,4-triphenyl-3-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanamide\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2698af81d9664a2abb556fa3efb019cb",
    "procedure_text": "A solution of 2-(4-amino-phenyl)-3-cyclopentyl-N-thiazol-2-yl-propionamide (prepared in Example 3, 158 mg, 0.5 mmol) in pyridine (5 mL) at 25\u00b0 C. was treated with methanesulfonyl chloride (50 \u03bcL, 0.57 mmol ). The reaction was stirred at 25\u00b0 C. for 7 h and was then concentrated in vacuo. High pressure liquid chromatography (Chromegasphere SI-60, 10 \u03bcM, 60 \u00c5, 25 cm\u00d723 cm ID, 40/60 heptane/ethyl acetate) afforded 3-cyclopentyl-2-(4-methanesulfonylamino-phenyl)-N-thiazol-2-yl-propionamide (98.2 mg, 49.9%) as a tan solid: mp 85-90\u00b0 C.; EI-HRMS m/e calcd for C18H23N3O3S (M+) 393.1180, found 393.1185.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(4-amino-phenyl)-3-cyclopentyl-N-thiazol-2-yl-propionamide\"}], \"amount\": {\"mass\": {\"value\": 158.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanesulfonyl chloride\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 25.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction was stirred at 25\\u00b0 C. for 7 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"was then concentrated in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 7.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-cyclopentyl-2-(4-methanesulfonylamino-phenyl)-N-thiazol-2-yl-propionamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 98.2, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 49.9}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 49.9}}], \"isolated_color\": \"tan\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fe4d7a7ce46d4a9480adc6f27919bf13",
    "procedure_text": "Methyl 5-amino-2,4-dimethylbenzoate (0.752 g, 4.20 mmol) in 5 mL water was cooled with an ice bath. H2SO4 (1.1 mL, 21 mmol) was added followed by a solution of sodium nitrite (0.301 g, 4.4 mmol) in 3 mL of water. The reaction was stirred in an ice bath for 30 min, and then in a 100\u00b0 C. oil bath for 60 min. The reaction was cooled to rt and partitioned between EtOAc and brine. The organic phase was dried (Na2SO4) and concentrated to give the title compound as a yellow oil. 1H NMR (CDCl3) \u03b4 7.48 (s, 1H), 7.00 (s, 1H), 5.95 (bs, 1H), 3.90 (s, 3H), 2.50 (s, 3H), 2.28 (s, 3H).",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Methyl 5-amino-2,4-dimethylbenzoate\"}], \"amount\": {\"mass\": {\"value\": 0.752, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2SO4\"}], \"amount\": {\"volume\": {\"value\": 1.1, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium nitrite\"}], \"amount\": {\"mass\": {\"value\": 0.301, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction was stirred in an ice bath for 30 min\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WAIT\", \"details\": \"in a 100\\u00b0 C. oil bath for 60 min\", \"duration\": {\"value\": 60.0, \"units\": \"MINUTE\"}, \"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"partitioned between EtOAc and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic phase was dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a122f5d4ee1141fe8b1e32748c526b27",
    "procedure_text": "To a suspension of 9.33 g (50 mmol) of 2-amino-3-(3-chloropropyloxy)pyridine and 6.97 g (50 mmol) of thiazolidine-2,4-dione sodium salt in 200 ml of N,N-dimethylformamide, 7.49 g (50 mmol) of sodium iodide was added, followed by refluxing at 80\u00b0 C. for 16 hours. After cooling, the reaction mixture was poured into water, extracted with ethyl acetate, washed with water and dried, after which the solvent was distilled off. The residue was purified by column chromatography (eluent, n-hexane/ethyl acetate=1/4\u2192ethyl acetate) to yield 8.14 g (60.9%, yellow solid) of the desired product.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m5_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-amino-3-(3-chloropropyloxy)pyridine\"}], \"amount\": {\"mass\": {\"value\": 9.33, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"thiazolidine-2,4-dione sodium salt\"}], \"amount\": {\"mass\": {\"value\": 6.97, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium iodide\"}], \"amount\": {\"mass\": {\"value\": 7.49, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 80.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"TEMPERATURE\", \"details\": \"After cooling\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"DISTILLATION\", \"details\": \"after which the solvent was distilled off\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by column chromatography (eluent, n-hexane/ethyl acetate=1/4\\u2192ethyl acetate)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-hexane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-7e4729d3f25b43c7a305fc9f28cfc5f9",
    "procedure_text": "A mixture of potassium phthalimide (1.16 g, 6.29 mmoles) and 40 ml of dried N,N-dimethylformamide was heated up to 110\u00b0 C. To this mixture was added dropwise a solution of methyl 22-tosyloxydocosanoate (2.20 g, 4.19 mmoles) in 70 ml of N,N-dimethylformamide, and the reaction mixture was reacted for 2 hours at 110\u00b0 C. After the completion of reaction, the reaction mixture was subjected to the same after-treatment steps as in Reference Example 2, to give methyl 22-phthalimidodocosanoate (1.57 g, 95%) having the following properties.",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium phthalimide\"}], \"amount\": {\"mass\": {\"value\": 1.16, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 22-tosyloxydocosanoate\"}], \"amount\": {\"mass\": {\"value\": 2.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 70.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 110.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the reaction mixture was reacted for 2 hours at 110\\u00b0 C\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 110.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"After the completion of reaction\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 22-phthalimidodocosanoate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.57, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 95.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-edd58421a098409c89da7fdc5d5a496a",
    "procedure_text": "A reaction tube having an inside diameter of 5 cm was filled with 440 g of a supported catalyst containing 3.85% by weight of boron phosphate (P2O5 /B2O3 mole ratio being 1) deposited on silica pellets having a pore diameter of about 0.05 micron as a carrier. Ethyl p-hydroxybenzoate and ammonia were introduced into the reaction tube at a rate of 39.5 g/hr and 323.7 g/hr respectively, and reacted in the vapor phase at 400\u00b0 C. The ratio of ammonia to ethyl p-hydroxybenzoate in the gaseous mixture was 80:1, and the contact time was 10 seconds. When the reaction was continued for 19 hours, 511.1 g of p-hydroxybenzonitrile was obtained from 750.5 g of ethyl p-hydroxybenzoate. The yield was 95.0%. Gas chromatographic analysis showed that phenol was formed as a by-product in an amount of only 0.2% by weight.",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl p-hydroxybenzoate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"supported catalyst\"}], \"amount\": {\"mass\": {\"value\": 440.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"boron phosphate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ethyl p-hydroxybenzoate\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonia\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonia\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"A reaction tube having\"}, {\"type\": \"CUSTOM\", \"details\": \"reacted in the vapor phase at 400\\u00b0 C\", \"temperature\": {\"setpoint\": {\"value\": 400.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"WAIT\", \"details\": \"When the reaction was continued for 19 hours\", \"duration\": {\"value\": 19.0, \"units\": \"HOUR\"}}], \"outcomes\": [{\"reaction_time\": {\"value\": 10.0, \"units\": \"SECOND\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"p-hydroxybenzonitrile\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 511.1, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl p-hydroxybenzoate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 750.5, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-223be83c87f740759e6483538c22cf73",
    "procedure_text": "To a solution of 3-[4-(1-ethoxycarbonyl-ethyl)-7-fluoro-3-thioxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yloxy]-3-methyl-azetidine-1-carboxylic acid tert-butyl ester (0.080 g, 0.171 mmol) in EtOH (5 mL) was added hydrazine hydrate (0.085 g, 1.707 mmol) and the mixture was heated to reflux for 2 h. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The residue was purified by preparative TLC (eluting with 30% EtOAc in petroleum ether) to give 3-(7-fluoro-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yloxy)-3-methyl-azetidine-1-carboxylic acid tert-butyl ester (0.033 g, 46%) as a white solid. LC/MS (Table 1, Method 2) Rt=1.144 min.; MS m/z: 421 [M+H]+.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-[4-(1-ethoxycarbonyl-ethyl)-7-fluoro-3-thioxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yloxy]-3-methyl-azetidine-1-carboxylic acid tert-butyl ester\"}], \"amount\": {\"mass\": {\"value\": 0.08, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrazine hydrate\"}], \"amount\": {\"mass\": {\"value\": 0.085, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOH\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"the mixture was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to reflux for 2 h\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by preparative TLC (eluting with 30% EtOAc in petroleum ether)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"petroleum ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(7-fluoro-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yloxy)-3-methyl-azetidine-1-carboxylic acid tert-butyl ester\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.033, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 46.0}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-6e3121fea4484fdc864d06acf7e72e71",
    "procedure_text": "Analogously to Example 37, 220 mg (1.08 mmol) of 5-aminoquinoline-2-carboxylic acid-methylamide is reacted with 550 mg (1.78 mmol) of 4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentanal and 3.0 ml of concentrated acetic acid in 30 ml of toluene. After chromatography on silica gel with hexane-ethyl acetate (0-70%), 259 mg (48% of theory) of the product is obtained.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane ethyl acetate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-aminoquinoline-2-carboxylic acid-methylamide\"}], \"amount\": {\"mass\": {\"value\": 220.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentanal\"}], \"amount\": {\"mass\": {\"value\": 550.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-e8e200119d424baf95d6bec17fdad4cf",
    "procedure_text": "A mixture of 0.332 g of 4-(5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-ylcarbonyl)benzoic acid, 0.222 g of triethylamine, 0.157 g of 2,3-dimethylaniline hydrochloride, 0.15 ml of diethylphosphoryl cyanide in 20 ml of dichloromethane is heated on a steam bath for 3 hours. The mixture is washed with H2O, 1M NaHCO3, H2O, 1N HCl, brine and dried (Na2SO4). The solution is filtered through a thin pad of hydrous magnesium silicate and the filter cake washed with dichloromethane. The filtrate is concentrated to dryness under vacuum and the residue crystallized from dichloromethane-hexane to give 0.11 g of crystals, m.p. 239\u00b0-240\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-ylcarbonyl)benzoic acid\"}], \"amount\": {\"mass\": {\"value\": 0.332, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"mass\": {\"value\": 0.222, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,3-dimethylaniline hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 0.157, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethylphosphoryl cyanide\"}], \"amount\": {\"volume\": {\"value\": 0.15, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"is heated on a steam bath for 3 hours\", \"duration\": {\"value\": 3.0, \"units\": \"HOUR\"}}, {\"type\": \"WASH\", \"details\": \"The mixture is washed with H2O, 1M NaHCO3, H2O, 1N HCl, brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"The solution is filtered through a thin pad of hydrous magnesium silicate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium silicate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"the filter cake washed with dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"The filtrate is concentrated to dryness under vacuum\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue crystallized from dichloromethane-hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crystals\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.11, \"units\": \"GRAM\"}}}], \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f32b8dd19c844cdc8a5c470249a37b71",
    "procedure_text": "6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid 10b (22 mg, 0.057 mmol) is dissolved in DMF (1 mL) and HOBt (9 mg, 0.062 mmol) followed by triethyl amine (18 \u03bcl, 0.132 mmol) is added. Cyclopropyl methyl hydroxylamine hydrochloride (8 mg, 0.062 mmol) is added followed by EDCl (14 mg, 0.074 mmol). After 16 hours, the reaction mixture is diluted with ethyl acetate and water and the layers separated. The organic layer is washed with saturated NH4Cl, brine, saturated NaHCO3, water and brine. The organic layer is dried (MgSO4) and concentrated under reduced pressure to give 23 mg (89%) pure desired product. MS APCI (+) m/z 455, 453 (M+Br pattern) detected; MS APCI (\u2212) m/z 453, 451 (M\u2212 Br pattern) detected; 1H NMR (400 MHz, DMSO-d6) \u03b4 11.69 (broad s, 1H), 8.43 (s, 1H), 7.62 (d, 1H), 7.28 (dd, 1H), 6.42 (m, 1H), 3.63 (d, 2H), 1.03 (m, 1H), 0.48 (m, 2H), 0.19 (m, 2H); 19F NMR (376 MHz, DMSO-d6) \u2212132.95 (s).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Cyclopropyl methyl hydroxylamine hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 8.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EDCl\"}], \"amount\": {\"mass\": {\"value\": 14.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 22.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HOBt\"}], \"amount\": {\"mass\": {\"value\": 9.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m7_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethyl amine\"}], \"amount\": {\"volume\": {\"value\": 18.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"is added\"}, {\"type\": \"CUSTOM\", \"details\": \"the layers separated\"}, {\"type\": \"WASH\", \"details\": \"The organic layer is washed with saturated NH4Cl, brine, saturated NaHCO3, water and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH4Cl\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layer is dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pure desired product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 23.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 89.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d9969137f74d4fa0925b8ccaec78fd90",
    "procedure_text": "3-Azetidine carboxylic acid (2.25 g, 22.2 mmol) and acetic anhydride (80 ml) were heated gently until all of the acid had dissolved. The reaction was stirred at room temperature for 18 hours and then the acetic anhydride was removed under reduced pressure. Water was added and evaporated under reduced pressure. The residue was dissolved in hot ethyl acetate and filtered whilst hot and the filtrate was evaporated under reduced pressure to afford the title compound as a white solid, 1.54 g.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-Azetidine carboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 2.25, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic anhydride\"}], \"amount\": {\"volume\": {\"value\": 80.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction was stirred at room temperature for 18 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"DISSOLUTION\", \"details\": \"had dissolved\"}, {\"type\": \"CUSTOM\", \"details\": \"the acetic anhydride was removed under reduced pressure\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic anhydride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"Water was added\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated under reduced pressure\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue was dissolved in hot ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered whilst hot and the filtrate\"}, {\"type\": \"CUSTOM\", \"details\": \"was evaporated under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 18.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e7ffef75693f49bc8d316c29283ef975",
    "procedure_text": "2-Methylthio-4-(3,5-di-t-butyl-4-hydroxybenzoyl)pyrrole (1 g) was added to a cooled, stirred suspension of 0.28 g of sodium hydride (50% in mineral oil) in 20 ml of anhydrous dimethylformamide under nitrogen. After 45 minutes at room temperature, the mixture was cooled to 0\u00b0 C. and 0.25 ml of methyl iodide was added. After 30 minutes, the reaction mixture was poured into a 10% HCl-ice-water mixture, then extracted three times with 100 ml ethyl acetate. The organic layer was washed five times with 100 ml water, dried and evaporated to dryness. Crystallization of the residue from ethyl acetate-hexane gave 0.93 g of the title compound (mp 173\u00b0-175\u00b0 C.).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl ice water\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-Methylthio-4-(3,5-di-t-butyl-4-hydroxybenzoyl)pyrrole\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydride\"}], \"amount\": {\"mass\": {\"value\": 0.28, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl iodide\"}], \"amount\": {\"volume\": {\"value\": 0.25, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WAIT\", \"details\": \"After 30 minutes\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted three times with 100 ml ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed five times with 100 ml water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated to dryness\"}, {\"type\": \"CUSTOM\", \"details\": \"Crystallization of the residue from ethyl acetate-hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 45.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.93, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-686c274e7c9b409d90f64cfef2944c26",
    "procedure_text": "The starting material for the abovementioned synthetic route a), viz. N-benzyl-aminoacetonitrile, is prepared by reaction of benzylamine and formaldehyde with the extremely toxic hydrocyanic acid (see also Tetrahedron Letters [23], 27 (1982), 2741-4). The starting material for the synthetic route b), viz. N-benzylglycine, also firstly has to be prepared by reaction of glycine with benzyl chloride or of chloroacetic acid with benzylamine. The reaction of N-benzylaminoacetonitrile or N-benzylglycine as per a) or b) is carried out either by fusion with urea for a long time or by reaction with the toxic cyanic acid. Both methods give 1-benzyl-hydantoin in only low yields: thus, according to Huaxue Shiji 1993, 15(1) 15-16, the reaction of N-benzylglycine (obtained by reaction of benzylarnine with chloroacetic acid) with cyanic acid gives 1-benzylhydantoin in a yield of only 39.5% and the reaction of N-benzylglycine with urea gives 1-benzylhydantoin in a yield of only 45.6%. The subsequent bromination of the 1-benzylhydantoin and treatment with ethanol again proceeds in only a low yield of 42.7%.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-benzylglycine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"urea\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-benzylhydantoin\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 42.7}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2b9145dc8e4f4810a65a8b60e400f5ed",
    "procedure_text": "In 2 ml of benzene are dissolved 0.5 mmol of (3R,4R)-4-methylsulfonyl-3-tritylamino-2-azetidinone and 0.1 mmol of tetra-n-amylammonium bromide, and a solution of 0.55 mmol of potassium cyanide in 0.55 ml of water is added at 15\u00b0 C. The mixture is stirred vigorously for 15 minutes and treated in the same manner as Example 20 to give (3S,4RS)-4-cyano-3-tritylamino-2-azetidinone with the (3R,4R):(3S,4S) ratio of 1:4.",
    "reference_string": "{\"inputs\": {\"m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium cyanide\"}], \"amount\": {\"moles\": {\"value\": 0.55, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 0.55, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(3R,4R)-4-methylsulfonyl-3-tritylamino-2-azetidinone\"}], \"amount\": {\"moles\": {\"value\": 0.5, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzene\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetra-n-amylammonium bromide\"}], \"amount\": {\"moles\": {\"value\": 0.1, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture is stirred vigorously for 15 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"treated in the same manner as Example 20\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(3S,4RS)-4-cyano-3-tritylamino-2-azetidinone\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fe38a927fc2c4b8f9a11063efa2980bd",
    "procedure_text": "To 0.16 g of 1-(2-(1,4-dioxaspiro(4.5)decan-8-yl)ethyl)-7-methoxyquinoxalin-2(1H)-one, 1.5 mL of an 80% aqueous trifluoroacetic acid solution was added at room temperature, and the mixture was stirred at the same temperature for 15 minutes. Thereto was added ethyl acetate under cooling with ice, and the reaction mixture was adjusted to pH 8.0 with an aqueous saturated sodium hydrogen carbonate solution. The organic layer was separated, washed with an aqueous saturated sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to obtain 0.18 g of a brown oily substance, 7-methoxy-1-(2-(4-oxocyclohexyl)ethyl)quinoxalin-2(1H)-one.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(2-(1,4-dioxaspiro(4.5)decan-8-yl)ethyl)-7-methoxyquinoxalin-2(1H)-one\"}], \"amount\": {\"mass\": {\"value\": 0.16, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trifluoroacetic acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydrogen carbonate\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at the same temperature for 15 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"under cooling with ice\"}, {\"type\": \"CUSTOM\", \"details\": \"The organic layer was separated\"}, {\"type\": \"WASH\", \"details\": \"washed with an aqueous saturated sodium chloride solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was removed under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-methoxy-1-(2-(4-oxocyclohexyl)ethyl)quinoxalin-2(1H)-one\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-229d39f536cc42418c394d4cb62b8ec9",
    "procedure_text": "To a solution of about 50 grams (0.24 mole) of p-methoxyphenylmagnesium bromide in tetrahydrofuran (THF) were added at room temperature 30.2 grams (0.08 mole) of 1-(p-benzyloxybenzoyl)-6-methoxy-2-tetralone dissolved in THF. Upon completion of the addition, the entire mixture was warmed to 45\u00b0 C. Analysis of a sample of the mixture by thin-layer chromatography (TLC) showed the absence of starting material. The mixture then was poured into aqueous ammonium chloride solution, and the resulting mixture was extracted with ethyl acetate. The ethyl acetate extract was washed, dried, and evaporated. The resulting residue was dissolved in benzene, and a catalytic amount of p-toluenesulfonic acid was added. The mixture was stirred at room temperature until a TLC of the mixture indicated the absence of any carbinol intermediate. The mixture then was washed with water, dried, and concentrated. The residue was chromatographed over one kg. of alumina using 6 l. of benzene. The product was eluted with a mixture of 2 percent ethyl acetate in benzene. The product, 3-(4-methoxyphenyl-4-(4-benzyloxybenzoyl)-7-methoxy-1,2-dihydronaphthalene was obtained as an oil.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"p-methoxyphenylmagnesium bromide\"}], \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(p-benzyloxybenzoyl)-6-methoxy-2-tetralone\"}], \"amount\": {\"mass\": {\"value\": 30.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium chloride\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 45.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at room temperature until a TLC of the mixture\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"Upon completion of the addition\"}, {\"type\": \"EXTRACTION\", \"details\": \"the resulting mixture was extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The ethyl acetate extract\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"was washed\"}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The resulting residue was dissolved in benzene\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzene\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"a catalytic amount of p-toluenesulfonic acid was added\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"p-toluenesulfonic acid\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The mixture then was washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was chromatographed over one kg\"}, {\"type\": \"WASH\", \"details\": \"The product was eluted with a mixture of 2 percent ethyl acetate in benzene\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzene\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-methoxyphenyl-4-(4-benzyloxybenzoyl)-7-methoxy-1,2-dihydronaphthalene\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-63eb4457df0e43e4991ecee5b81c8cc3",
    "procedure_text": "To a slurry of 3.0g (0.075 mol) of sodium hydride in 30 mL of DMF at room temperature was added 10g (0.069 mol) of 4-phenyl-1H-pyrazole of example 1. The mixture was stirred 1 hr and 7.8 mL (0.07 mol) of ethyl bromoacetate was added with cooling. The reaction was stirred 3 hr at room temperature, briefly at 100\u00b0 C. and was poured onto ice. The product was filtered off, rinsed with water, dried, and washed with hexane to yield 14.0g of ethyl 4-phenyl-1H-pyrazole-1-acetate.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl bromoacetate\"}], \"amount\": {\"volume\": {\"value\": 7.8, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydride\"}], \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"10g\"}], \"amount\": {\"moles\": {\"value\": 0.069, \"units\": \"MOLE\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-phenyl-1H-pyrazole\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred 1 hr\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"with cooling\"}, {\"type\": \"STIRRING\", \"details\": \"The reaction was stirred 3 hr at room temperature, briefly at 100\\u00b0 C.\", \"duration\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}, \"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"ADDITION\", \"details\": \"was poured onto ice\"}, {\"type\": \"FILTRATION\", \"details\": \"The product was filtered off\"}, {\"type\": \"WASH\", \"details\": \"rinsed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"WASH\", \"details\": \"washed with hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 4-phenyl-1H-pyrazole-1-acetate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 14.0, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e0f33865263b40a3a8a8eb6eb3697abc",
    "procedure_text": "A mixture of 3-thiophenecarboxylic acid (12.81 g), pyridinium bromide perbromide (35.54 g) and acetic acid (50 ml) was stirred at 45\u00b0 C. for 48 hours. The mixture was poured into ice-water and precipitated crystals were collected by filtration. The crystals were dissolved in ethyl acetate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 5-bromo-3-thiophenecarboxylic acid (19.78 g) as crystals.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-thiophenecarboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 12.81, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridinium bromide perbromide\"}], \"amount\": {\"mass\": {\"value\": 35.54, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 45.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at 45\\u00b0 C. for 48 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"precipitated crystals\"}, {\"type\": \"FILTRATION\", \"details\": \"were collected by filtration\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The crystals were dissolved in ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 48.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-bromo-3-thiophenecarboxylic acid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 19.78, \"units\": \"GRAM\"}}}], \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-1cbd60187ba94695bd9229ce46880f8c",
    "procedure_text": "Ethyl 4-(2-fluoro-4-iodoanilino)-1-[2-(2-methoxyethoxy)ethyl]-6-oxo-1,6-dihydro-3-pyridinecarboxylate was dissolved in EtOH and treated with 1 M NaOH, as for example 1, step C, to hydrolyse the ester to give 4-(2-fluoro-4-iodoanilino)-1-[2-(2-methoxyethoxy)ethyl]-6-oxo-1,6-dihydro-3-pyridinecarboxylic acid as a cream solid (99%), used directly in the next step. 1H NMR [(CD3)2SO, 400 MHz] \u03b4 13.00 (v br s, 1H), 9.72 (br s, 1H), 8.41 (s, 1H), 7.75 (dd, J=10.1, 1.9 Hz, 1H), 7.60 (ddd, J=8.3, 1.9, 0.8 Hz, 1H), 7.32 (t, J=8.5 Hz, 1H), 5.47 (d, 1.2 Hz, 1H), 4.05 (t, J=5.2 Hz, 2H), 3.60 (t, J=5.2 Hz, 2H), 3.53-3.50 (m, 2H), 3.42-3.38 (m, 2H), 3.21 (s, 3H). HRMS (EI+) calcd C17H18FIN2O5 (M+) 476.0245, found 476.0236.",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ethyl 4-(2-fluoro-4-iodoanilino)-1-[2-(2-methoxyethoxy)ethyl]-6-oxo-1,6-dihydro-3-pyridinecarboxylate\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOH\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ester\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(2-fluoro-4-iodoanilino)-1-[2-(2-methoxyethoxy)ethyl]-6-oxo-1,6-dihydro-3-pyridinecarboxylic acid\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 99.0}}], \"isolated_color\": \"cream\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-1acd644a37df4694a2fcf243047bf2fb",
    "procedure_text": "Benzylamine (0.3 mL) was added to a solution of 4-(4-chlorosulfonylmethyl-benzyl)-nitrobenzene (100 mg) in tetrahydrofuran (4 mL). The mixture was stirred for 2 hours, poured into dilute aqueous potassium carbonate, and extracted with dichloromethane (3\u00d715 mL). Solvents were evaporated and the residue was chromatographed on silica gel, eluting with 2% acetone in dichloromethane, to give 4-(4-benzylaminosulfonylmethylbenzyl)-nitrobenzene (44 mg) as a solid.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Benzylamine\"}], \"amount\": {\"volume\": {\"value\": 0.3, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(4-chlorosulfonylmethyl-benzyl)-nitrobenzene\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred for 2 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted with dichloromethane (3\\u00d715 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Solvents were evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was chromatographed on silica gel\"}, {\"type\": \"WASH\", \"details\": \"eluting with 2% acetone in dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(4-benzylaminosulfonylmethylbenzyl)-nitrobenzene\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 44.0, \"units\": \"MILLIGRAM\"}}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2018704cc1174aaa8ca8deffb705e67d",
    "procedure_text": "0.23 g (0.78 mmol) (2-chloro-pyridin-4-yl)-(4,5-difluoro-2,3-dihydro-indol-1-yl)-methanone were added to 0.20 g (0.78 mmol) spiro[piperidine-4,4\u2032-pyrido[2,3-d][1,3]oxazin]-2\u2032(1\u2032H)-one-hydrochloride and 0.11 g (0.78 mmol) potassium carbonate in 3.0 mL NMP. The reaction mixture was first of all stirred for 10 h at 130\u00b0 C., then cooled to RT and then stirred overnight at RT. The crude product was combined with water/acetonitrile and purified by preparative HPLC-MS. The product fractions were combined and evaporated down. The residue was triturated with diisopropylether, suction filtered and dried in the air.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2-chloro-pyridin-4-yl)-(4,5-difluoro-2,3-dihydro-indol-1-yl)-methanone\"}], \"amount\": {\"mass\": {\"value\": 0.23, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"spiro[piperidine-4,4\\u2032-pyrido[2,3-d][1,3]oxazin]-2\\u2032(1\\u2032H)-one-hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 0.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 0.11, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NMP\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water acetonitrile\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 130.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"all stirred for 10 h at 130\\u00b0 C.\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooled to RT\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"STIRRING\", \"details\": \"stirred overnight at RT\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"purified by preparative HPLC-MS\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated down\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was triturated with diisopropylether, suction\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropylether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"dried in the air\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 10.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-d454133d54fa47baa5a8285fdc01e4ca",
    "procedure_text": "A mixture of 5-amino-3-(4-fluorophenyl)-4-(pyridin-4-yl)pyrazole (1.016 g), methyl acrylate (10 ml), pyridine (20 ml) and water (5 ml) was refluxed for 8 hours. The mixture was cooled and concentrated in vacuo. The residue was dissolved in a mixture of acetic acid (10 ml) and concentrated hydrochloric acid (1.5 ml). The solution was refluxed for 2 hours, cooled and neutralized with an aqueous saturated sodium bicarbonate solution. The separated solid was collected, washed with water and dried to give 2-(4-fluorophenyl)-5-oxo-3-(pyridin-4-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine (750 mg).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-amino-3-(4-fluorophenyl)-4-(pyridin-4-yl)pyrazole\"}], \"amount\": {\"mass\": {\"value\": 1.016, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl acrylate\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"was refluxed for 8 hours\", \"duration\": {\"value\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"The mixture was cooled\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue was dissolved in a mixture of acetic acid (10 ml) and concentrated hydrochloric acid (1.5 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 1.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"The solution was refluxed for 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"cooled\"}, {\"type\": \"CUSTOM\", \"details\": \"The separated solid was collected\"}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(4-fluorophenyl)-5-oxo-3-(pyridin-4-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 750.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-9bacf8af02d0472988be2abdf86b1363",
    "procedure_text": "A mixture containing ethyl methallyl carbonate (1.44 g, 0.010 mole), cyclohexanone (0.98 g, 0.010 mole), 5 percent palladium on carbon (1.0 g), triphenylphosphine (0.20 g, 0.76 mmole), and tetrahyrofuran (15 ml) was refluxed under N2 for 22 hours. Gas chromatographic quantification by means of an internal standard (ethylbenzene) showed 41.6 percent of the cyclohexanone has been consumed and that the desired product, 2-methallylcyclohexanone was formed in 49.2 yield based on unrecovered cyclohexanone. Preparative gas chromatography of the crude mixture gave a pure sample of the product whose structure was confirmed by infrared and nuclear magnetic resonance spectroscopy.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethylbenzene\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m6_m3_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl methallyl carbonate\"}], \"amount\": {\"mass\": {\"value\": 1.44, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cyclohexanone\"}], \"amount\": {\"mass\": {\"value\": 0.98, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triphenylphosphine\"}], \"amount\": {\"mass\": {\"value\": 0.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"palladium on carbon\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahyrofuran\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cyclohexanone\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"was refluxed under N2 for 22 hours\", \"duration\": {\"value\": 22.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"has been consumed and that the desired product\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-methallylcyclohexanone\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4f4ef74569eb429e8372156b81935597",
    "procedure_text": "To 390 ml of ion-exchanged water were added 30 g of cyanocobalamin, 2.1 g of cobalt chloride hexahydrate, and 22.5 ml of 2-butanone. After replacing the inside atmosphere of the system with nitrogen gas, the mixture was heated in a water bath, to which an aqueous solution of sodium borohydride (12 g/60 ml) was added dropwise under stirring at the internal temperature of 50\u00b0 C. over 2 hours. After stirring for further 30 minutes as it was, an aqueous solution of trimethylsulfoxonium bromide (11.5 g/60 ml) was further added thereto over 30 minutes. The mixture was stirred for further 3 hours as it was, followed by stirring overnight at a bath temperature of 15\u00b0 C. The resulting precipitates were collected by filtration and dried to give a crude product of the title compound. To the crude product was added a 50% acetone aqueous solution. After heating at 35\u00b0 C., the mixture was adjusted to pH 7.0 with concentrated hydrochloric acid. Then, acetone was added dropwise thereinto and the mixture was stirred overnight. The precipitated crystals were collected by filtration and dried, to give the title compound in a yield of 88%.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trimethylsulfoxonium bromide\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m6_m1_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cyanocobalamin\"}], \"amount\": {\"mass\": {\"value\": 30.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cobalt chloride hexahydrate\"}], \"amount\": {\"mass\": {\"value\": 2.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-butanone\"}], \"amount\": {\"volume\": {\"value\": 22.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 390.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium borohydride\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 50.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"under stirring at the internal temperature of 50\\u00b0 C. over 2 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added dropwise\"}, {\"type\": \"STIRRING\", \"details\": \"After stirring for further 30 minutes as it\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}}, {\"type\": \"WAIT\", \"details\": \"over 30 minutes\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}}, {\"type\": \"STIRRING\", \"details\": \"The mixture was stirred for further 3 hours as it\", \"duration\": {\"value\": 3.0, \"units\": \"HOUR\"}}, {\"type\": \"STIRRING\", \"details\": \"by stirring overnight at a bath temperature of 15\\u00b0 C\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 15.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The resulting precipitates\"}, {\"type\": \"FILTRATION\", \"details\": \"were collected by filtration\"}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b2d8249382f743b7b410c08da07f158c",
    "procedure_text": "A solution of diisopropylamine (0.740 mL) in THF (25 mL) was cooled to \u221278\u00b0 C., n-butyllithium-hexane solution (3.26 mL, 1.6 mol/L) was added dropwise and, after the completion of the dropwise addition, the mixture was stirred at \u221278\u00b0 C. for 1 hr. Subsequently, a solution of tert-butyl cyclopropanecarboxylate (0.800 g) in THF (5 mL) was added dropwise, and the mixture was further stirred at \u221278\u00b0 C. for 30 min. A solution of benzyl(4S)-4-methyl-2,5-dioxo-1,3-oxazolidine-3-carboxylate (1.00 g) in THF (10 mL) was added dropwise at \u221278\u00b0 C. over 10 min, and the mixture was further stirred at \u221278\u00b0 C. for 30 min. Acetic acid (2.0 mL) was added to the reaction mixture and, after warming to room temperature, water was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=50/1\u21921/1) to give the title compound as a colorless oil (yield: 401 mg, 29%).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Acetic acid\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzyl(4S)-4-methyl-2,5-dioxo-1,3-oxazolidine-3-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropylamine\"}], \"amount\": {\"volume\": {\"value\": 0.74, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl cyclopropanecarboxylate\"}], \"amount\": {\"mass\": {\"value\": 0.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -78.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at \\u221278\\u00b0 C. for 1 hr\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"n-butyllithium-hexane solution (3.26 mL, 1.6 mol/L) was added dropwise\"}, {\"type\": \"ADDITION\", \"details\": \"after the completion of the dropwise addition\"}, {\"type\": \"STIRRING\", \"details\": \"the mixture was further stirred at \\u221278\\u00b0 C. for 30 min\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"temperature\": {\"setpoint\": {\"value\": -78.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"STIRRING\", \"details\": \"the mixture was further stirred at \\u221278\\u00b0 C. for 30 min\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"temperature\": {\"setpoint\": {\"value\": -78.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"after warming to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"the mixture was extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The extract was washed with saturated brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=50/1\\u21921/1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 401.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 29.0}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-24c2e0bbbf464776a9e97fe23467ad23",
    "procedure_text": "The title compound was prepared from 4-(5-chloro-thiophen-2-yl)-6-trifluoromethyl-1H-pyrimidin-2-one (10.0 g, 35.6 mmol) and phosphoroxychloride (50 ml) according to the general procedure I. Obtained as a brown oil (10.4 g, 98%). MS (EI) 298.0, 299.9 [(M)+].",
    "reference_string": "{\"inputs\": {\"m0_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(5-chloro-thiophen-2-yl)-6-trifluoromethyl-1H-pyrimidin-2-one\"}], \"amount\": {\"mass\": {\"value\": 10.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"phosphoroxychloride\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"oil\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 10.4, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 98.0}}], \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-6e793f5a68084c4b8b73cdbba47ae39f",
    "procedure_text": "Ethyl 6-bromo-3,4-dihydro-2-hydroxy-1-naphthoate (6.0 g, 20.2 mmoles) was reacted with guanidine (6.9 g of hydrochloride salt, 72.2 mmoles) in the same manner as in example 1. The product was precipitated from aqueous sodium hydroxide with acetic acid, filtered, washed with water and dried to give 3-amino-8-bromo-5,6-dihydrobenzo[f]quinazolin-1(2H)-one as an off-white solid. (2.75 g, 46%) 1H NMR (DMSO-d6, 300 MHZ) \u03b4: 2.55(t, J=7.5 Hz, 2H, CH2); 2.79(t, J=7.4 Hz, 2H, CH2); 6.75(br s, 2H, NH2); 7.32(dd, J=8.4, 2.3 Hz, 1H, Ar); 7.34(s, 1H, Ar); 8.40(d, J=8.4 Hz, 1H, Ar); 11.00(br s, 1H, NH).",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ethyl 6-bromo-3,4-dihydro-2-hydroxy-1-naphthoate\"}], \"amount\": {\"mass\": {\"value\": 6.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"guanidine\"}], \"amount\": {\"mass\": {\"value\": 6.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The product was precipitated from aqueous sodium hydroxide with acetic acid\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-amino-8-bromo-5,6-dihydrobenzo[f]quinazolin-1(2H)-one\"}], \"isolated_color\": \"off-white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-5a853d308c2249cc84e153663b48b288",
    "procedure_text": "3-Cyclobutyl-7-[(5-iodo-2-pyridinyl)oxy]-2,3,4,5-tetrahydro-1H-3-benzazepine (E207) (294 mg, 0.7 mmol) 1,10 phenanthroline (38 mg, 0.2 mmol), 5-methyl-2-pyrrolidinone (139 mg 1.4 mmol) were dissolved in dioxane (2 ml). Copper(I) Iodide (39 mg, 0.2 mmol) and caesium carbonate (479 mg, 1.5 mmol) were added and the mixture heated in a microwave reactor at 175\u00b0 C. for 15 minutes. The mixture was cooled and filtered through celite, washing through with dichloromethane. The filtrate was concentrated in vacuo and the crude material purified by column chromatography, eluting with dichloromethane through to a mixture of 0.880 ammonia:methanol:dichloromethane (1:9:90) to afford the title compound (137 mg); MS (ES+) m/e 392 [M+H]+.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-Cyclobutyl-7-[(5-iodo-2-pyridinyl)oxy]-2,3,4,5-tetrahydro-1H-3-benzazepine\"}], \"amount\": {\"mass\": {\"value\": 294.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,10 phenanthroline\"}], \"amount\": {\"mass\": {\"value\": 38.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-methyl-2-pyrrolidinone\"}], \"amount\": {\"mass\": {\"value\": 139.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dioxane\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m6_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"caesium carbonate\"}], \"amount\": {\"mass\": {\"value\": 479.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Copper(I) Iodide\"}], \"amount\": {\"mass\": {\"value\": 39.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 175.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The mixture was cooled\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered through celite\"}, {\"type\": \"WASH\", \"details\": \"washing through with dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"The filtrate was concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"the crude material purified by column chromatography\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude material\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"eluting with dichloromethane through to a mixture of 0.880 ammonia:methanol:dichloromethane (1:9:90)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonia methanol dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 137.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e4d9ce48d6d6442a85e8652ecce26759",
    "procedure_text": "A mixture of 2.8 g. of 4,9-dihydro-4-methyl-10H-thieno[3,4-b][1,5]benzodiazepin-10-one and 620 mg. of 50% sodium hydride in mineral oil in 30 ml. of dry dimethylformamide is stirred for 11/4 hours. A 2.1 g. portion of methyl iodide is added and the mixture is stirred overnight. The mixture is poured onto ice water and the solid is collected and dried. The solid changes to a glass which is dissolved in methylene chloride, washed with water, filtered and concentrated to dryness. The crude oily solid is triturated in hexane and ether. The ether hexane mixture is concentrated to a yellow gum, dissolved in 15 ml. of 30% methylene chloride in hexane and chromatographed on an alumina column, eluting with the same solvent. Four 200 ml. fractions are collected. The solvent is changed to methylene chloride:hexane (50:50) for fractions 5-8 (200 ml.). The solvent is changed to 100% methylene chloride for fractions 8-11 (200 ml.). The solvent is changed to 20% ethyl acetate in benzene for fractions 12-19 (200 ml.). Fractions 11-19 are combined and concentrated to a yellow oil which crystallizes with trituration in hexane, giving the desired product, mp. 101\u00b0-102\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4,9-dihydro-4-methyl-10H-thieno[3,4-b][1,5]benzodiazepin-10-one\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydride\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl iodide\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture is stirred overnight\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"A mixture of 2.8 g\"}, {\"type\": \"ADDITION\", \"details\": \"The mixture is poured onto ice water\"}, {\"type\": \"CUSTOM\", \"details\": \"the solid is collected\"}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The solid changes to a glass which is dissolved in methylene chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated to dryness\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude oily solid is triturated in hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"The ether hexane mixture is concentrated to a yellow gum\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether hexane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISSOLUTION\", \"details\": \"dissolved in 15 ml\"}, {\"type\": \"CUSTOM\", \"details\": \"of 30% methylene chloride in hexane and chromatographed on an alumina column\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"eluting with the same solvent\"}, {\"type\": \"CUSTOM\", \"details\": \"fractions are collected\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated to a yellow oil which\"}, {\"type\": \"CUSTOM\", \"details\": \"crystallizes with trituration in hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3d3d431edfe84994b9de008e04e45793",
    "procedure_text": "To a mixture of Boc-D-Trp(CH3)-OH (1.59 g), HCl.H-D-Phe-OCH3 (1.08 g) and HOBT (0.81 g) in DMF (20 ml) was added WSCD (0.93 g) under ice-bath cooling. After being stirred for 2 hours at room temperature, the mixture was concentrated in vacuo and the residue was dissolved in ethyl acetate (50 ml). The solution was washed with 0.5N hydrochloric acid (20 ml), water (20 ml), saturated sodium bicarbonate (20 ml) and water (20 ml\u00d72) successively, dried over magnesium sulfate and evaporated in vacuo. The residue was triturated with ether to give Boc-D-Trp(CH3)-D-Phe-OCH3 (1.45 g).",
    "reference_string": "{\"inputs\": {\"m3_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H-D-Phe-OCH3\"}], \"amount\": {\"mass\": {\"value\": 1.08, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HOBT\"}], \"amount\": {\"mass\": {\"value\": 0.81, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Boc-D-Trp(CH3)-OH\"}], \"amount\": {\"mass\": {\"value\": 1.59, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After being stirred for 2 hours at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooling\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the mixture was concentrated in vacuo\"}, {\"type\": \"DISSOLUTION\", \"details\": \"the residue was dissolved in ethyl acetate (50 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The solution was washed with 0.5N hydrochloric acid (20 ml), water (20 ml), saturated sodium bicarbonate (20 ml) and water (20 ml\\u00d72) successively\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was triturated with ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Boc-D-Trp(CH3)-D-Phe-OCH3\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.45, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-43f3879cfabd408989adf9b201bbebc7",
    "procedure_text": "Following the example above and beginning with 4-[3-aminobenzoyl]-1-methylpiperidine (25 mg, 0.115 mmol) and 3,4,5-trifluorobenzoyl chloride (30 \u03bcL, 0.229 mmol), 42.5 mg (99%) of the title compound were recovered.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-[3-aminobenzoyl]-1-methylpiperidine\"}], \"amount\": {\"mass\": {\"value\": 25.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,4,5-trifluorobenzoyl chloride\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 42.5, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 99.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-06d1b4ce98814298ad8c33193a70363b",
    "procedure_text": "A mixture of 3-(2-chloroethyl)-9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one hydrochloride (formula-5) (40 grams), acetic acid (200 ml) and palladium carbon (40 grams) was taken in an autoclave. Hydrogen gas with a pressure of 3.0-3.5 Kg/cm2 was applied to the above mixture at 35\u00b0 C. for 6 hrs. The reaction was quenched with water and filtered the resultant mixture through a hyflow bed. The pH of the filtrate was adjusted to 6 using aqueous sodium hydroxide solution The reaction mixture was cooled to 0\u00b0 C. and stirred for 1 hr. The solid formed was filtered, washed with water and dried to yield the title compound.",
    "reference_string": "{\"inputs\": {\"m1_m4_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(2-chloroethyl)-9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 40.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"palladium carbon\"}], \"amount\": {\"mass\": {\"value\": 40.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Hydrogen\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred for 1 hr\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The reaction was quenched with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered the resultant mixture through a hyflow bed\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"resultant mixture\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The solid formed\"}, {\"type\": \"FILTRATION\", \"details\": \"was filtered\"}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-779f2a65a89b4a9198ae62e5b6c57b50",
    "procedure_text": "First. 60 g of tin (11) chloride was dissolved in 60 ml of concentrated hydrochloric acid, and the mixture was cooled to \u221230\u00b0 C., to which a diazonium solution prepared from 19 g of ethyl 5-amino-2-chlorocinnamate and 6.3 g of sodium nitrite was added dropwise at 0\u00b0 C. or lower. The reaction mixture was stirred at room temperature for 1 hour, and the precipitated crystals were collected by filtration. These crystals were added to ice-water, neutralized with 2N aqueous sodium hydroxide, and extracted with chloroform. The chloroform layer was dried and concentrated, which afforded 7.0 g of ethyl 2-chloro-5-hydrazinocinnamate.",
    "reference_string": "{\"inputs\": {\"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diazonium\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tin (11) chloride\"}], \"amount\": {\"mass\": {\"value\": 60.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 5-amino-2-chlorocinnamate\"}], \"amount\": {\"mass\": {\"value\": 19.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium nitrite\"}], \"amount\": {\"mass\": {\"value\": 6.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred at room temperature for 1 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added dropwise at 0\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"FILTRATION\", \"details\": \"the precipitated crystals were collected by filtration\"}, {\"type\": \"ADDITION\", \"details\": \"These crystals were added to ice-water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with chloroform\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The chloroform layer was dried\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 2-chloro-5-hydrazinocinnamate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 7.0, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-be882b54e4974b72bbba61b26b31f860",
    "procedure_text": "In a solvent mixture of 50 ml water and 35 ml tetrahydrofuran were dissolved 1.64 g of 7\u03b2-amino-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid and 1.68 g of sodium hydrogen carbonate. To this solution was added a solution of 2.1 g 4-bromo-2-methoxyimino-3-oxobutyryl chloride in 15 ml tetrahydrofuran and the mixture was stirred at 20\u00b0-25\u00b0 C. for 5 minutes. Then, a solution of 1.52 g thiourea in 20 ml water was added thereto and the mixture was stirred at the same temperature for 1 hour. The reaction mixture was adjusted to pH 7.0 with 20% aqueous sodium carbonate solution and concentrated under reduced pressure. The concentrate was subjected to column chromatography using Diaion HP-40 (Mitsubishi Chemical Industries, Ltd.) and elution was carried out with 400 ml of water-isopropyl alcohol (9:1, v/v). The eluate was lyophilized to give 2.35 g of sodium 7\u03b2-[2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylate. Yield 88.2%. Analysis by high-performance liquid chromatography showed that the proportion of the (E)-isomer was not more than 1% of the (Z)-isomer.",
    "reference_string": "{\"inputs\": {\"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium carbonate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m4_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"thiourea\"}], \"amount\": {\"mass\": {\"value\": 1.52, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-bromo-2-methoxyimino-3-oxobutyryl chloride\"}], \"amount\": {\"mass\": {\"value\": 2.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m9_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 35.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7\\u03b2-amino-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 1.64, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydrogen carbonate\"}], \"amount\": {\"mass\": {\"value\": 1.68, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at 20\\u00b0-25\\u00b0 C. for 5 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"the mixture was stirred at the same temperature for 1 hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"WASH\", \"details\": \"Diaion HP-40 (Mitsubishi Chemical Industries, Ltd.) and elution\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 5.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium 7\\u03b2-[2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.35, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 88.2}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 88.2}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3b66df1ecca8498f97fe08d517b6ba46",
    "procedure_text": "To a solution of methyl 2-(6-methyl-3-phenyl-4-p-tolylthieno[2,3-b]pyridin-5-yl)pentanoate (0.27 g; 0638 mmol) in methanol (6.3 mL) was added a solution of sodium hydroxide 5 N (1.3 mL) and the mixture was heated at 60\u00b0 C. for 18 h. After cooling, the reaction mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate and the mixture was acidified with HCl (1N) until pH 1. The organic layer was washed with brine, water, dried over magnesium sulphate and concentrated under reduced pressure. The crude residue was crystallized from a mixture ethyl acetate-heptane to furnish 0.052 g (20%) of the title compound as a light yellow solid.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 2-(6-methyl-3-phenyl-4-p-tolylthieno[2,3-b]pyridin-5-yl)pentanoate\"}], \"amount\": {\"mass\": {\"value\": 0.27, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"volume\": {\"value\": 1.3, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 6.3, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"After cooling\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the reaction mixture was concentrated under reduced pressure\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue was dissolved in ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with brine, water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over magnesium sulphate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulphate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude residue was crystallized from a mixture ethyl acetate-heptane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude residue\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate heptane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.052, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 20.0}}], \"isolated_color\": \"light yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-96d71262863545a38f6b46505783a1e5",
    "procedure_text": "To a mixture of 0.08 g (0.17 mmole) of 4-(7,7-difluoro-5-methyl-6-oxo-9-phenethyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid (I-275), 0.12 mL (0.64 mmole) of ethyldiisopropyl amine and 0.019 g (0.19 mmole) of N,N-dimethyl-propane-1,3-diamine in 2.0 mL of dimethylformamide was added 0.079 g (0.19 mmole) of 1-(di-1-pyrrolidinylmethylene)-1H-benzotriazolium 3-oxide hexafluorophosphate. The mixture was stirred at room temperature for 1 hour, then diluted with 10 mL of ice water. The mixture was extracted with dichloromethane 3 times. The combined organic layers were washed three times with sodium carbonate, three times with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by silica gel chromatography, eluting with dichloromethane-methanol (gradient, 100:0-70:30) gave 0.045 g of 4-(7,7-difluoro-5-methyl-6-oxo-9-phenethyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(3-dimethylamino-propyl)-3-methoxy-benzamide (I-279) as a white solid.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(di-1-pyrrolidinylmethylene)-1H-benzotriazolium 3-oxide hexafluorophosphate\"}], \"amount\": {\"mass\": {\"value\": 0.079, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(7,7-difluoro-5-methyl-6-oxo-9-phenethyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid\"}], \"amount\": {\"mass\": {\"value\": 0.08, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyldiisopropyl amine\"}], \"amount\": {\"volume\": {\"value\": 0.12, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethyl-propane-1,3-diamine\"}], \"amount\": {\"mass\": {\"value\": 0.019, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at room temperature for 1 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"The mixture was extracted with dichloromethane 3 times\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined organic layers were washed three times with sodium carbonate, three times with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium carbonate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification by silica gel chromatography\"}, {\"type\": \"WASH\", \"details\": \"eluting with dichloromethane-methanol (gradient, 100:0-70:30)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(7,7-difluoro-5-methyl-6-oxo-9-phenethyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(3-dimethylamino-propyl)-3-methoxy-benzamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.045, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-1fb0347b741848aa94bd4771fc3a216f",
    "procedure_text": "2-Hydroxybenzaldehyde was condensed with 2,2-dimethyl-1-iodo octane to yield 2-(2,2-dimethyl octyloxy) benzaldehyde which was reduced to 2-(2,2-dimethyl, octyloxy)benzyl alcohol and then converted to [[2-(2,2-dimethyloctyloxy)phenyl]methyl]triphenylphosphonium bromide as in Example 1. Condensation of this phosphonium bromide with 7-formyl-3-methyl-2,4,6-octatrienoic acid ethyl ester as described in Example 3 followed by hydrolysis, as in Example 5, gave the (All-E)-3,7-Dimethyl-9-[2-[(2,2dimethyl-octyl]phenyl]-2,4,5,8-non-atetraenoic acid mp 113-117\u00b0 (from dichloromethane/hexane mixture).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-Hydroxybenzaldehyde\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,2-dimethyl-1-iodo octane\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(2,2-dimethyl octyloxy) benzaldehyde\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3f46d0ea4e104f86bb514854e60be92b",
    "procedure_text": "To a solution of N-[1-[2-[1-(2-phenyl-1,3-dioxan-5-yl)cyclohexyl]ethyl]piperidin-4-yl]-N-(5-methylpyridin-2-yl)-2-furancarboxamide (110 mg) in methanol (5 mL) was added 4N hydrochloric acid (0.5 mL). After stirring the solution at room temperature for 2 hours, it was concentrated under reduced pressure. Saturated aqueous sodium bicarbonate solution was added to the residue and it was extracted with chloroform. The combined organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the title compound. To a solution of the residue in ethyl acetate (10 mL) was added a 4N hydrochloric acid/ethyl acetate solution (0.15 mL), and the solution was stirred at room temperature for 1 hour. The crystals thus separated out were then filtered to give its hydrochloride (60 mg).",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-[1-[2-[1-(2-phenyl-1,3-dioxan-5-yl)cyclohexyl]ethyl]piperidin-4-yl]-N-(5-methylpyridin-2-yl)-2-furancarboxamide\"}], \"amount\": {\"mass\": {\"value\": 110.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 0.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring the solution at room temperature for 2 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"it was concentrated under reduced pressure\"}, {\"type\": \"ADDITION\", \"details\": \"Saturated aqueous sodium bicarbonate solution was added to the residue and it\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"was extracted with chloroform\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic layer was dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a7433a2daf48467298f16d28adb7de9c",
    "procedure_text": "The compound (S)-4-[3-(tert-Butyldimethylsilanyloxy)-2-methyl-propyl]-7-fluoro-4H-benzo[1,4]oxazin-3-one (111MF14) (3.79 g, 10.7 mmol) and tetrabutylammonium fluoride monohydrate (3.99 g, 14.3 mmol) were mixed according to GP8. CC (SiO2; Heptane/EtOAc 4:1-4) gave the title compound (111MF18) (2.57 g, 100%). 1H NMR (CDCl3) \u03b4 6.99-6.95 (m, 1H), 7.77-7.72 (m, 2H), 4.63 (m, 2H), 4.23-4.16 (m, 1H), 3.58-3.40 (m, 3H), 2.86 (s, 1H), 2.05-1.97 (m, 1H), 1.04 (d, J=6.8 Hz, 3H); 13C NMR (CDCl3) 164.6, 159.2 (d, J=244.5 Hz), 146.4 (d, J=11.6 Hz), 124.9 (d, J=3.1 Hz), 115.9 (d, J=9.6 Hz), 109.4 (d, J=22.7 Hz), 105.3 (d, J=26.1 Hz), 67.5, 63.8, 43.8, 34.0, 15.0.",
    "reference_string": "{\"inputs\": {\"m3_m0\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Heptane EtOAc\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(S)-4-[3-(tert-Butyldimethylsilanyloxy)-2-methyl-propyl]-7-fluoro-4H-benzo[1,4]oxazin-3-one\"}], \"amount\": {\"mass\": {\"value\": 3.79, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrabutylammonium fluoride monohydrate\"}], \"amount\": {\"mass\": {\"value\": 3.99, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.57, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 100.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-8af1cb5a3b074eabadb65b118d9aae2e",
    "procedure_text": "A mixture consisting of 1.9 g of 1-(2-ethylaminopyrimidin-4-yl)ethanone and 1.86 ml of diethyl ketomalonate is heated at 110\u00b0 C. for 18 hours. The mixture is purified by column chromatography (silica gel, mobile phase: methylene chloride:methanol=98:2).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(2-ethylaminopyrimidin-4-yl)ethanone\"}], \"amount\": {\"mass\": {\"value\": 1.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ketomalonate\"}], \"amount\": {\"volume\": {\"value\": 1.86, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 110.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The mixture is purified by column chromatography (silica gel, mobile phase: methylene chloride:methanol=98:2)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-c20fbb4bca5b4114bf251fb42f1137cb",
    "procedure_text": "2.9 g (11 mmole) of ethyl 4-(2-ethoxy-2-oxoethoxy)benzoate, 1.4 g (12 mmole) of 3-picolylamine and 2.1 g (1.3 mmole) of DBU were dissolved in ethanol (12 ml), and reaction was then carried out for 24 hours. After the reaction mixture had been concentrated, partition was carried out between ethyl acetate and water. The organic layer was then treated in an ordinary manner to obtain 3.3 g (yield: 90%) of ethyl 4-{2-oxo-2-[(pyridin-3-ylmethyl)amino]ethoxy}benzoate.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 4-(2-ethoxy-2-oxoethoxy)benzoate\"}], \"amount\": {\"mass\": {\"value\": 2.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-picolylamine\"}], \"amount\": {\"mass\": {\"value\": 1.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DBU\"}], \"amount\": {\"mass\": {\"value\": 2.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 12.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"reaction\"}, {\"type\": \"CONCENTRATION\", \"details\": \"After the reaction mixture had been concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"partition\"}, {\"type\": \"ADDITION\", \"details\": \"The organic layer was then treated in an ordinary manner\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 24.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 4-{2-oxo-2-[(pyridin-3-ylmethyl)amino]ethoxy}benzoate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 3.3, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 90.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f08f5c0ab5e341139d5f0a004898ef11",
    "procedure_text": "{1-[4-(2-Ethyl-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin-3-ylmethyl)-phenyl]-3-methyl-1H-pyrazol-4-yl}-methanol (18) (500 mg, 1.38 mmol) was dissolved in 10 ml of dichloromethane and after addition of manganese dioxide (1.2 g, 13.8 mmol) the reaction mixture was stirred for 3 h at rt. The mixture was filtrated though celite and evaporated under reduced pressure. The product was used in the next step without further purification.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"{1-[4-(2-Ethyl-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin-3-ylmethyl)-phenyl]-3-methyl-1H-pyrazol-4-yl}-methanol\"}], \"amount\": {\"mass\": {\"value\": 500.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"manganese dioxide\"}], \"amount\": {\"mass\": {\"value\": 1.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred for 3 h at rt\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The mixture was filtrated though celite\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The product was used in the next step without further purification\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-691a022e249b4105a906542bf4e6107e",
    "procedure_text": "A slurry of 6-(3-cyclopropyl-3-fluoroazetidin-1-yl)-N-(3-methyl-1H-pyrazol-5-yl)-2-(methylsulfonyl)pyrimidin-4-amine (61 g, 170 mmol) and 3,3,3-trifluoro-N-(4-mercaptophenyl)propanamide (41 g, 175 mmol) in CH3CN (1300 mL) was heated to reflux for 1.5 hours. During this time, the slurry transformed from thin and yellowish to thick and brilliant white. The mixture was then cooled to 0\u00b0 C. and stirred at this temperature for 15 min. The mixture was then filtered and washed with cold CH3CN (650 mL). The resulting solid was dried for 20 hours at 38\u00b0 C. under house vacuum. The white solid was charged to a suitable reactor with EtOAc (1300 mL) and NaHCO3(sat) (1300 mL). The mixture was stirred until no more solid remained. Then, the aqueous and organic layers were separated and the aqueous layer was washed with EtOAc (390 mL). The combined organic layers were dried over MgSO4, filtered, washed with EtOAc (130 mL) and concentrated to a minimal volume on rotavap. The resulting mixture was re-crystallized out of EtOAc and hexane to give the desired product as a white solid (56.2 g, 72%) 1H NMR (MeOD, 400 MHz): 0.40-0.45 (2H, m), 0.60-0.65 (2H, m), 1.3-1.4 (1H, m), 2.05 (2H, s), 3.25-3.40 (2H, m), 3.85-3.40 (4H, m), 5.40-5.50 (2H, m), 7.50-7.55 (2H, d), 7.65-7.70 (2H, d). ES+522.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-(3-cyclopropyl-3-fluoroazetidin-1-yl)-N-(3-methyl-1H-pyrazol-5-yl)-2-(methylsulfonyl)pyrimidin-4-amine\"}], \"amount\": {\"mass\": {\"value\": 61.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,3,3-trifluoro-N-(4-mercaptophenyl)propanamide\"}], \"amount\": {\"mass\": {\"value\": 41.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH3CN\"}], \"amount\": {\"volume\": {\"value\": 1300.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred at this temperature for 15 min\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"to reflux for 1.5 hours\", \"duration\": {\"value\": 1.5, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"The mixture was then filtered\"}, {\"type\": \"WASH\", \"details\": \"washed with cold CH3CN (650 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH3CN\"}], \"amount\": {\"volume\": {\"value\": 650.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The resulting solid was dried for 20 hours at 38\\u00b0 C. under house vacuum\", \"duration\": {\"value\": 20.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 38.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"ADDITION\", \"details\": \"The white solid was charged to a suitable reactor with EtOAc (1300 mL) and NaHCO3(sat) (1300 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 1300.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3(sat)\"}], \"amount\": {\"volume\": {\"value\": 1300.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"STIRRING\", \"details\": \"The mixture was stirred until no more solid\"}, {\"type\": \"CUSTOM\", \"details\": \"Then, the aqueous and organic layers were separated\"}, {\"type\": \"WASH\", \"details\": \"the aqueous layer was washed with EtOAc (390 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 390.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic layers were dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"WASH\", \"details\": \"washed with EtOAc (130 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 130.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated to a minimal volume on rotavap\"}, {\"type\": \"CUSTOM\", \"details\": \"The resulting mixture was re-crystallized out of EtOAc and hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 56.2, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 72.0}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a15d4b8c29c14cc68ed9d4abd4ae92bd",
    "procedure_text": "1,8-Diazabicyclo[5.4.0]-7-undecene (0.750 mL, 5.02 mmol) was added to a suspension of 3-(piperidin-4-yl)-1H-pyrazol-5-amine hydrochloride (0.400 g, 1.67 mmol) produced in Reference Example 33 in dimethyl sulfoxide (4 mL), and the mixture was stirred at room temperature for 10 minutes. Then, 3,6-dichloropyridazine (0.249 g, 1.67 mmol) was added thereto, and the mixture was stirred at room temperature for 1 hour and at 60\u00b0 C. for 4 hours. After cooling to room temperature, water was added to the reaction solution, followed by extraction with ethyl acetate. The obtained organic layer was washed with brine and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography [elute: ethyl acetate/methanol=95/5-90/10 (gradient)] to obtain the title compound (0.330 g, yield: 71%).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,8-Diazabicyclo[5.4.0]-7-undecene\"}], \"amount\": {\"volume\": {\"value\": 0.75, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(piperidin-4-yl)-1H-pyrazol-5-amine hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 0.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethyl sulfoxide\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,6-dichloropyridazine\"}], \"amount\": {\"mass\": {\"value\": 0.249, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at room temperature for 10 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"the mixture was stirred at room temperature for 1 hour and at 60\\u00b0 C. for 4 hours\", \"duration\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}, \"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"After cooling to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"followed by extraction with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The obtained organic layer was washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"the solvent was distilled off under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The obtained residue was purified by silica gel column chromatography [elute: ethyl acetate/methanol=95/5-90/10 (gradient)]\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 10.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.33, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 71.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f9502d79ad3643e58aefc8f36bc005d0",
    "procedure_text": "A solution of 3-benzyloxy-1-cyclopropyl-6-fluoro-7-pyrrolidin-1-yl-1H-quinazoline-2,4-dione (Example F-3, 0.15 g, 0.38 mmol) in trifluoroacetic acid (TFA, 3.0 mL) was reacted with a 1.0 M solution of boron tris(trifluoroacetate) (1.5 mL, 1.5 mmol, Angew. Chem, Internat. Ed., 1973;12:147) in TFA and allowed to stir for 2 hours. The mixture was then concentrated and the residue diluted in methanol and concentrated. This process was repeated two times. The residue was then triturated from diethyl ether/hexanes and filtered to provide 0.073 g of the title compound as solid, mp 248-250\u00b0 C. (dec.).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trifluoroacetic acid\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-benzyloxy-1-cyclopropyl-6-fluoro-7-pyrrolidin-1-yl-1H-quinazoline-2,4-dione\"}], \"amount\": {\"mass\": {\"value\": 0.15, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TFA\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"boron tris(trifluoroacetate)\"}], \"amount\": {\"volume\": {\"value\": 1.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"to stir for 2 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"The mixture was then concentrated\"}, {\"type\": \"ADDITION\", \"details\": \"the residue diluted in methanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was then triturated from diethyl ether/hexanes\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.073, \"units\": \"GRAM\"}}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-ea8219f6f8184ae897806366e57fd5bd",
    "procedure_text": "5-Bromomethylbenzo[b]thiophene was prepared from 5-methylbenzo[b]thiophene and N-bromosuccinimide as in Example 1 except that the reaction was refluxed 15 hours.",
    "reference_string": "{\"inputs\": {\"m0_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-methylbenzo[b]thiophene\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-bromosuccinimide\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"was refluxed 15 hours\", \"duration\": {\"value\": 15.0, \"units\": \"HOUR\"}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-Bromomethylbenzo[b]thiophene\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-847a9db6abed4dd0aa234b477f940c29",
    "procedure_text": "The title compound was prepared from tert-butyl 2-[3-amino-6-methyl-2-oxo-1(2H)-pyridinyl]acetate (EXAMPLE 1, STEP 1-3), and 1-butanesulfonyl chloride using the procedure of EXAMPLE 9 (STEP 2). The product was recrystallized from ethylacetate to give a white crystalline solid compound.",
    "reference_string": "{\"inputs\": {\"m0_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl 2-[3-amino-6-methyl-2-oxo-1(2H)-pyridinyl]acetate\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-butanesulfonyl chloride\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The product was recrystallized from ethylacetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethylacetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"to give a white crystalline solid compound\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3148ca06fb094b389c509dc2d366203e",
    "procedure_text": "Freidel-Crafts acylation is performed on 2\u2032,4\u2032,6\u2032-triiodo-3-nitrobiphenyl-4-carboxylic acid (6) in the presence of AlCl3 and CH3COCl to yield 2\u2032,4\u2032,6\u2032-triiodo-3\u2032-acetyl-3-nitrobiphenyl-4-carboxylic acid (12). C 13 \u2062 H 6 \u2062 I 3 \u2062 N \u2062 \u2003 \u2062 O 4 \u2062 \u2192 C \u2062 \u2003 \u2062 H 3 \u2062 \u2003 \u2062 C \u2062 \u2003 \u2062 O \u2062 \u2003 \u2062 Cl Al \u2062 \u2003 \u2062 Cl 3 \u2062 C 15 \u2062 H 8 \u2062 I 3 \u2062 N \u2062 \u2003 \u2062 O 5 2\u2032,4\u2032,6\u2032-triiodo-3\u2032-acetyl-3-nitrobiphenyl-4-carboxylic acid (12) is then reacted with a zinc mercury amalgam and hydrochloric acid and heated to yield 2\u2032,4\u2032,6\u2032-triiodo-3\u2032-ethyl-3-nitrobiphenyl-4-carboxylic acid (13). C 15 \u2062 H 8 \u2062 I 3 \u2062 N \u2062 \u2003 \u2062 O 5 \u2062 \u2192 \u0394 Zn ( Hg ) , \u2003 \u2062 H \u2062 \u2003 \u2062 Cl \u2062 C 15 \u2062 H 10 \u2062 I 3 \u2062 N \u2062 \u2003 \u2062 O 4 2\u2032,4\u2032,6\u2032-triiodo-3\u2032-ethyl-3-nitrobiphenyl-4-carboxylic acid (13) is reacted with thionyl chloride to yield 2\u2032,4\u2032,6\u2032-triiodo-3\u2032-ethyl-3-nitrobiphenyl-4-carbonyl chloride (14). C 15 \u2062 \u2003 \u2062 H 10 \u2062 I 3 \u2062 N \u2062 \u2003 \u2062 O 4 \u2062 \u2192 S \u2062 \u2003 \u2062 O \u2062 \u2003 \u2062 Cl 2 \u2062 C 15 \u2062 \u2003 \u2062 H 9 \u2062 Cl \u2062 I 3 \u2062 N \u2062 \u2003 \u2062 O 3 1,3,4,6-tetra-O-acetyl-D-glucosamine (9) is reacted with 2\u2032,4\u2032,6\u2032-triiodo-3\u2032-ethyl-3-nitrobiphenyl-4-carbonyl chloride (14) to yield 2-nitro-4-(3\u2032-ethyl-2\u2032,4\u2032,6\u2032-triiodophenyl)-benzoyl-1,3,4,6-tetra-O-acetyl-D-glucosamine (15). C14H21NO9+C15H9ClI3NO3\u2192C29H29I3N2O12 2-nitro-4-(3\u2032-ethyl-2\u2032,4\u2032,6\u2032-triiodophenyl)-benzoyl-1,3,4,6-tetra-O-acetyl-D-glucosamine (15) is treated with stannous chloride and hydrochloric acid to yield 2-amino-4-(3\u2032-ethyl-2\u2032,4\u2032,6\u2032-triiodophenyl)-benzoyl-D-glucosamine (16). C 29 \u2062 \u2003 \u2062 H 29 \u2062 I 3 \u2062 N 2 \u2062 O 12 \u2062 \u2192 Sn \u2062 \u2003 \u2062 Cl 2 , \u2003 \u2062 H \u2062 \u2003 \u2062 Cl \u2062 C 21 \u2062 \u2003 \u2062 H 23 \u2062 I 3 \u2062 N 2 \u2062 \u2003 \u2062 O 6 Example 2 is similar in general structure to Example 1, with the additional presence of a short alkyl chain attached to the radio-opaque tri-iodophenyl moiety at the C-3\u2032 position to further increase lipophilicity of the molecule and enhance cell membrane permeability. The computed logP of Example 2 is 5.31.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"C14H21NO9 C15H9ClI3NO3\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"stannous chloride\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-amino-4-(3\\u2032-ethyl-2\\u2032,4\\u2032,6\\u2032-triiodophenyl)-benzoyl-D-glucosamine\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-50a10d99e6b849369f1b7639f16475a6",
    "procedure_text": "A solution of Example 226 (15 mg, 0.025 mmol) in methanol (0.5 mL) and dichloromethane (2 drops) at 0\u00b0 C. was treated with NaBH4 (24mg, 0.6 mmol), stirred for 1 hour, warmed to room temperature, and stirred for 90 minutes. The mixture was treated with water and filtered. The filter cake was treated with dichloromethane (5 mL) and methanol (1 drop), stirred for 2 hours, and filtered. The filter cake was washed with diethyl ether, and dried under vacuum to provide the desired product. MS(ESI(\u2212)) m/e 597 (M\u2212H)\u2212; 1H NMR (300 MHz, DMSO-d6) \u03b4 8.49 (d, 1H), 8.45 (d, 1H), 7.85 (dd, 1H), 7.71 (d, 2H), 7.40 (m, 2H), 7.30 (m, 2H), 7.20 (m, 2H), 6.95 (d, 1H), 6.90 (d, 2H), 4.34 (t, 1H), 3.75 (m, 2H), 3.60 (m, 2H), 3.39 (m, 2H), 3.25 (m, 2H), 2.65 (m, 2H), 1.71 (m, 2H), 1.45 (m, 2H), 1.25-1.11 (m, 4H).",
    "reference_string": "{\"inputs\": {\"m1_m4_m5_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"amount\": {\"mass\": {\"value\": 15.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaBH4\"}], \"amount\": {\"mass\": {\"value\": 24.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 0.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"CATALYST\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred for 1 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"stirred for 90 minutes\", \"duration\": {\"value\": 90.0, \"units\": \"MINUTE\"}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"ADDITION\", \"details\": \"The filter cake was treated with dichloromethane (5 mL) and methanol (1 drop)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"STIRRING\", \"details\": \"stirred for 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"WASH\", \"details\": \"The filter cake was washed with diethyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried under vacuum\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0bf73639e41044249bff2805ce4195d3",
    "procedure_text": "7 g (50 mmole) of potassium carbonate and 6.5 ml (55 mmole) of benzyl bromide are weighted to the suspension of 6 g (50 mmole) of 2-(cyanoamino)pyridine in 100 ml of acetone, then the reaction mixture is refluxed under vigorous stirring for 2.5 hours. After cooling the inorganic salt is filtered off and the acetone filtrate is evaporated under reduced pressure. The residue is triturated with 10 ml of ether, filtered and washed twice with 5 ml of ether each to obtain 5.55 g (53.1%) of the named compound, m.p.: 142\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 7.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzyl bromide\"}], \"amount\": {\"volume\": {\"value\": 6.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(cyanoamino)pyridine\"}], \"amount\": {\"mass\": {\"value\": 6.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"under vigorous stirring for 2.5 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"the reaction mixture is refluxed\"}, {\"type\": \"TEMPERATURE\", \"details\": \"After cooling the inorganic salt\"}, {\"type\": \"FILTRATION\", \"details\": \"is filtered off\"}, {\"type\": \"CUSTOM\", \"details\": \"the acetone filtrate is evaporated under reduced pressure\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The residue is triturated with 10 ml of ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"WASH\", \"details\": \"washed twice with 5 ml of ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.5, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"named compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 5.55, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 53.1}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 53.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2e00f144eb2a42b98629dc467dee78b7",
    "procedure_text": "(The following reaction is done in an oxygenfree N2 atmosphere.) Add ethanol (0.8 mL), Tetrakis-(triphenylphosphine)-palladium(0) (30 mg, 2.2 mol %) and Na2CO3 decahydrate (944 mg, 3.30 mmol; presolved in 1.2 mL H2O) subsequently to dissolved 2-Amino-benzeneboronic acid (70) (201 mg, 1.30 mmol) in toluene (6.0 mL). Degas the reaction mixture for 5 times and flood with N2 again. Add (3-Bromo-phenyl)-acetic acid methyl ester (69) (270 mg, 1.18 mmol) in toluene (6.0 mL), degas again (5 times) and stir the reaction solution overnight at 100\u00b0 C. Partition the reaction solution between EtOAc and brine (1+1) and extract the separated aqueous layer 3 times with EtOAc. Wash combined organic layer with brine and dry with Na2SO4. Remove solvent under reduced pressure and purify the crude product by preparative radial chromatography (silica gel 60 PF, CyH/EtOAc 3+1) to obtain (2\u2032-Amino-biphenyl-3-yl)-acetic acid methyl ester (71) as an orange oil (304 mg, 81%). 1H NMR (400 MHz, CDCl3): 3.66 (s, 2H); 3.69 (s, 3H); 3.62-3.86 (br.s, 2H); 6.75 (d, 1H, J=8.1 Hz); 6.80 (t, 1H, J=7.3 Hz); 7.11 (d, 1 H, J=7.3 Hz); 7.15 (d, 1H, J=8.1 Hz); 7.22-7.26 (br.m, 1H); 7.32-7.42 (m, 3H).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N2\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(3-Bromo-phenyl)-acetic acid methyl ester\"}], \"amount\": {\"mass\": {\"value\": 270.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 6.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-Amino-benzeneboronic acid\"}], \"amount\": {\"mass\": {\"value\": 201.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 6.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m8_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 0.8, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2CO3 decahydrate\"}], \"amount\": {\"volume\": {\"value\": 1.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Tetrakis-(triphenylphosphine)-palladium(0)\"}], \"amount\": {\"mass\": {\"value\": 30.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stir the reaction solution overnight at 100\\u00b0 C\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"(The following reaction\"}, {\"type\": \"CUSTOM\", \"details\": \"Degas the reaction mixture for 5 times and flood with N2 again\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N2\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Partition the reaction solution between EtOAc and brine (1+1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extract the separated aqueous layer 3 times with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"Wash\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dry with Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Remove solvent under reduced pressure and purify the crude product by preparative radial chromatography (silica gel 60 PF, CyH/EtOAc 3+1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CyH EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2\\u2032-Amino-biphenyl-3-yl)-acetic acid methyl ester\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 304.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 81.0}}], \"isolated_color\": \"orange\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-703b84937ff14d55ba27c71c6f0c3993",
    "procedure_text": "A solution of 5-bromo-1,2-dimethyl-1H-imidazole (0.0183 g, 0.104 mmol), 3-[(S)-1-(2-chloro-3-fluoro-6-methoxy-phenyl)-ethyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (0.030 g, 0.070 mmol), potassium carbonate (0.0289 g, 0.209 mmol) and 1,1\u2032-bis(diphenylphosphino)ferrocenepalladium(II) dichloride, dichloromethane (2.84 mg, 0.00348 mmol) in previously degassed 4:1 dioxane:water (1.50 mL) was evacuated and charged with N2 (2\u00d7) and heated under microwave conditions [Biotage, 100\u00b0 C., 30 min, high absorption]. The reaction mixture was purified by Gilson HPLC resulting in the title compound as a white solid. 1H NMR (400 MHz, CD3OD): \u03b4=1.80 (d, J=7.1 Hz, 3H), 2.58 (s, 3H), 3.47 (s, 3H), 3.67 (s, 3H), 5.12 (q, J=7.1 Hz, 1H), 6.90 (dd, J=4.3, 9.1 Hz, 1H), 7.08 (dd, J=9.0, 9.0 Hz, 1H), 7.22 (s, 1H), 7.46 (d, J=1.0 Hz, 1H), 7.56 (s, 1H), 8.18 (d, J=1.8 Hz, 1H). MS (ES+): m/z 399.12, 401.11 (76/24) [MH+]. HPLC: tR=2.77 min (polar\u20145 min, ZQ3).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m5_m4_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-bromo-1,2-dimethyl-1H-imidazole\"}], \"amount\": {\"mass\": {\"value\": 0.0183, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-[(S)-1-(2-chloro-3-fluoro-6-methoxy-phenyl)-ethyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine\"}], \"amount\": {\"mass\": {\"value\": 0.03, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 0.0289, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"mass\": {\"value\": 2.84, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,1\\u2032-bis(diphenylphosphino)ferrocenepalladium(II) dichloride\"}], \"reaction_role\": \"CATALYST\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dioxane\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"water (1.50 mL) was evacuated\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 1.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"charged with N2 (2\\u00d7)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N2\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was purified by Gilson HPLC\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c7f404e41c8d4d45860f7422efd7efbc",
    "procedure_text": "The reaction and workup procedures of Example 140 were repeated except that 95 mg of 20-(5,5-dimethyl-1,3-dioxan-2-yl)-1\u03b1-(tert-butyldimethylsilyl)oxy-3\u03b2-(N,N-dimethylcarbamoyl)oxy-7\u03b1-(methoxycarbonyl)oxypregna-5-ene was used in lieu of 100 mg of 20-(5,5-dimethyl-1,3-dioxan-2-yl)-1\u03b1,3\u03b2,7\u03b1-tris(methoxycarbonyloxy)pregn-5-ene to give 55 mg of 20-(5,5-dimethyl-1,3-dioxan-2-yl)-1\u03b1-(tert-butyldimethylsilyl)oxypregn-5-ene-3\u03b2,7\u03b1-diol showing the following physical properties.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"20-(5,5-dimethyl-1,3-dioxan-2-yl)-1\\u03b1-(tert-butyldimethylsilyl)oxy-3\\u03b2-(N,N-dimethylcarbamoyl)oxy-7\\u03b1-(methoxycarbonyl)oxypregna-5-ene\"}], \"amount\": {\"mass\": {\"value\": 95.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"20-(5,5-dimethyl-1,3-dioxan-2-yl)-1\\u03b1,3\\u03b2,7\\u03b1-tris(methoxycarbonyloxy)pregn-5-ene\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The reaction and workup procedures of Example 140\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"20-(5,5-dimethyl-1,3-dioxan-2-yl)-1\\u03b1-(tert-butyldimethylsilyl)oxypregn-5-ene-3\\u03b2,7\\u03b1-diol\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 55.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-452765c8caf24e35aef406d7c2ffac82",
    "procedure_text": "A solution of 3-bromo-3-(m-nitrobenzoyl)propionic acid (3.78 g, 0.0125 mole) in methanol (50 ml) was mixed with a suspension of 5-benzyl-3,4,5,6-tetrahydro-s-triazin-2(1H)thione (2.6 g, 0.0125 mole) in the same solvent (150 ml). The mixture was warmed until a clear solution was obtained and allowed to stand for two hours. Evaporation of the solvent gave a yellow solid foam (5.3 g, 83%). 2.5 Grams of this material were dissolved in warm ethanol and a colourless solid gradually crystallised and was collected to give 3-benzyl-7-carboxymethyl-6-hydroxy-6-(m-nitrophenyl)-3,4,6,7-tetrahydro-2H-thiazolo[3,2-a]-s-triazine hydrobromide (1.2 g), m.p. 147\u00b0-148\u00b0 C. (decomposition).",
    "reference_string": "{\"inputs\": {\"m1_m3_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-bromo-3-(m-nitrobenzoyl)propionic acid\"}], \"amount\": {\"mass\": {\"value\": 3.78, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-benzyl-3,4,5,6-tetrahydro-s-triazin-2(1H)thione\"}], \"amount\": {\"mass\": {\"value\": 2.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solvent\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The mixture was warmed until a clear solution\"}, {\"type\": \"CUSTOM\", \"details\": \"was obtained\"}, {\"type\": \"CUSTOM\", \"details\": \"Evaporation of the solvent\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"foam\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 5.3, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 83.0}}], \"texture\": {\"type\": \"FOAM\", \"details\": \"foam\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-6eb9be66809d4e40817bd9507f910e4f",
    "procedure_text": "To a suspension of N-{3-[5-(2-cyano-4-pyrimidinyl)-2-(4-morpholinyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,5-difluorobenzenesulfonamide (2.12 g, 3.80 mmol) in dichloromethane (DCM) (38.0 ml) at \u221278\u00b0 C. was added DIBAL-H (18.98 ml, 18.98 mmol). The yellow suspension was slowly warmed to RT and stirred 1 hr. The reaction was quenched with Rochelle's salts and stirred about 1 hr. 4N HCl was added to clear the emulsion. The HCl solution was extracted with DCM (3\u00d7). The aqueous was passed through celite and neutralize with 6N NaOH. Solid formed during neutralizing and was filtered to obtain N-{3-[5-[2-(aminomethyl)-4-pyrimidinyl]-2-(4-morpholinyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,5-difluorobenzenesulfonamide (1.57 g, 73%). MS (ESI): 563 [M+H]+.",
    "reference_string": "{\"inputs\": {\"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-{3-[5-(2-cyano-4-pyrimidinyl)-2-(4-morpholinyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,5-difluorobenzenesulfonamide\"}], \"amount\": {\"mass\": {\"value\": 2.12, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 38.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DIBAL-H\"}], \"amount\": {\"volume\": {\"value\": 18.98, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred 1 hr\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The reaction was quenched with Rochelle's salts\"}, {\"type\": \"STIRRING\", \"details\": \"stirred about 1 hr\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"ADDITION\", \"details\": \"4N HCl was added\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The HCl solution was extracted with DCM (3\\u00d7)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Solid formed during neutralizing and\"}, {\"type\": \"FILTRATION\", \"details\": \"was filtered\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-{3-[5-[2-(aminomethyl)-4-pyrimidinyl]-2-(4-morpholinyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,5-difluorobenzenesulfonamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.57, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 73.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 73.4}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-ecf9b2886778413b90451b130e4376e0",
    "procedure_text": "A solution of 4-hydroxy benzyl alcohol CAS No. [623-05-2] (10 g, 80.5 mmol) in ethanol (70 mL) was treated with 1, 3 bromochloro propane (16.0 g , 100 mmol) and potassium hydroxide (5.0 g, 89 mmol) was refluxed for 2 hours. The solution was cooled and filtered and then the filtrate concentrated. The concentrate was taken up in ether and washed with water, brine and dried over magnesium sulfate. The material was chromatographed on silica gel using ethyl acetate/hexanes (3:7) to yield 11.6 g of the product as a white solid: Mp=65\u00b0 C.; 1H NMR (DMSO) 7.21 (d, 2H, J=8.8 Hz), 6.88 (d, 2H, J=8.8 Hz), 5.03 (t, 1H, J=5.7 Hz), 4.40 (d, 2H, J=5.5 Hz), 4.05 (t, 2H, J=6.1 Hz), 3.77 (t, 2H, J=6.4 Hz); MS eI m/z 200.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-hydroxy benzyl alcohol\"}], \"reaction_role\": \"REACTANT\"}]}, \"m4_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"bromochloro propane\"}], \"amount\": {\"mass\": {\"value\": 16.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium hydroxide\"}], \"amount\": {\"mass\": {\"value\": 5.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 70.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"was refluxed for 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"The solution was cooled\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate concentrated\"}, {\"type\": \"WASH\", \"details\": \"washed with water, brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The material was chromatographed on silica gel\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 11.6, \"units\": \"GRAM\"}}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-46f931db46b84959a1daf371aa64bf13",
    "procedure_text": "This compound was obtained as a brown solid in 74% yield following the same procedure described in Scheme 21 for the synthesis of 2-[[2-[4-fluoro-3-(2,2,2-trifluoro-ethoxy)-phenyl]-ethyl]-(tetrahydrofuran-3-ylmethyl)amino]-N,N-dimethyl-acetamide, using 2-chloro-1-pyrrolidin-1-yl-ethanone as the reagent instead of 2-chloro-N,N-dimethyl-acetamide.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-[[2-[4-fluoro-3-(2,2,2-trifluoro-ethoxy)-phenyl]-ethyl]-(tetrahydrofuran-3-ylmethyl)amino]-N,N-dimethyl-acetamide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloro-1-pyrrolidin-1-yl-ethanone\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloro-N,N-dimethyl-acetamide\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"This compound was obtained as a brown solid in 74% yield\"}], \"outcomes\": [{\"products\": [{\"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 74.0}}]}]}]}"
  },
  {
    "reaction_id": "ord-8bd17b7af4194c948ef4c2a7edd88ef9",
    "procedure_text": "To a solution of 1,2-dibromo-1,2-di (4-bromobenzoyl) ethane (11.1 g, 0.02 mole) in 35 ml of THF was added a suspension of sodium 4-methyl phenoxide [prepared from 0.92 g (0.04 mole) Na and 4.32 g (0.04 mole) 4-methylphenol in 30 ml THF by refluxing for 4-5 hr]. The yellow mixture was refluxed for 2-3 hr (TLC followed) after which the THF was removed under reduced pressure. The residue was treated with water, and the solid was filtered, washed with water, dried (Na2SO4), and dissolved in chloroform. The chloroform solution was passed through a silica column (elution with 2-5% ether in hexane). The result was an of f white crystalline solid, 4.95 g (50%), mp 137\u00b0-8\u00b0 C. IR (KBr) 3087, 3035, 2868, 1687, 1646, 1587, 1572, 1557, 1502, 1399, 1364, 1194, 1068, 1009, 971, 876, 815, 772, 526. 1H NMR (CDCl3 /35\u00b0 C.) 7.92 (d, 2H, J=8.8), 7.65 (d, 2H, J=8.8), 7.55 (d, 2H, J=8.8), 7.48 (d, 2H, J=8.8), 7.27 (d, 2H, J=8.3), 7.11 (d, 2H, J=8.3), 6.32 (s, 1H), 2.4 (s, 3H). 13C NMR (CDCl3 /35\u00b0 C.) 189.4, 187.6, 168.4, 150.9, 136.6, 136.0, 133.4, 132.3, 131.8, 130.9, 130.3, 129.6, 129.2, 128.2, 120.6, 101.8, 20.95. MS m/e 500 (M+).",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,2-dibromo-1,2-di (4-bromobenzoyl) ethane\"}], \"amount\": {\"mass\": {\"value\": 11.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 35.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium 4-methyl phenoxide\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na\"}], \"amount\": {\"moles\": {\"value\": 0.04, \"units\": \"MOLE\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-methylphenol\"}], \"amount\": {\"moles\": {\"value\": 0.04, \"units\": \"MOLE\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"was removed under reduced pressure\"}, {\"type\": \"ADDITION\", \"details\": \"The residue was treated with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"the solid was filtered\"}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISSOLUTION\", \"details\": \"dissolved in chloroform\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The chloroform solution was passed through a silica column (elution with 2-5% ether in hexane)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-dcbc03a2e47e489185e4039b7223c38c",
    "procedure_text": "To 4-(hydroxymethyl)-5-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)pyridin-3-ol (26 mg, 0.076 mmol, 1 eq.) in CH3CN (10 mL) was added MnO2 (66 mg, 0.76 mmol, 10 eq.). The mixture was heated to 46\u00b0 C. with stirring O/N, cooled to rt, filtered, and concentrated to give 3-hydroxy-5-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde as a pale yellow oil. 1H NMR (400 MHz, CDCl3) \u03b4 11.06 (s, 1H), 10.35 (s, 1H), 8.70 (dd, J=4.7, 1.5 Hz, 1H), 8.11 (s, 1H), 7.89 (dd, J=7.9, 1.1 Hz, 1H), 7.80 (s, 1H), 7.53 (d, J=1.8 Hz, 1H), 7.36 (dd, J=7.9, 4.8 Hz, 1H), 6.27 (d, J=1.8 Hz, 1H), 5.14 (s, 2H), 4.61 (sep, J=6.6 Hz, 1H), 1.41 (d, 1=6.6 Hz, 6H). LRMS (M+H+) m/z 339.1",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(hydroxymethyl)-5-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)pyridin-3-ol\"}], \"amount\": {\"mass\": {\"value\": 26.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH3CN\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MnO2\"}], \"amount\": {\"mass\": {\"value\": 66.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 46.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooled to rt\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-hydroxy-5-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde\"}], \"isolated_color\": \"pale yellow\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-9017e212a87c4870ac6047b904c7db80",
    "procedure_text": "3 g of p-fluorobenzyl-triphenylphosphonium bromide (preparable from p-fluorobenzyl bromide and triphenylphosphine) are suspended in 50 ml of tert.butyl methyl ether. The suspension is treated at room temperature with 0.75 g of potassium tert.butylate and stirred for 1.5 hours. Subsequently, the mixture is treated dropwise at 0\u00b0 C. within 5 minutes with a solution of 1.40 g of trans-4-[trans-4-[2-(1,3-dioxolan-2-yl)ethyl]cyclohexyl]-cyclohexanecarboxaldehyde in 25 ml of tert.butyl methyl ether and stirred at room temperature for a further 24 hours. Thereafter, the reaction mixture is taken up diethyl ether, washed several times with water, dried over magnesium sulfate, filtered and concentrated. Chromatographic purification of the resulting crude product on silica gel with ethyl acetate/petroleum ether (vol. 3:97) gives \u03b2-[trans-4-[trans-4-(2-(1,3-dioxolan-2-yl)ethyl)-cyclohexyl]cyclohexyl]-4-fluorostyrene.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"p-fluorobenzyl-triphenylphosphonium bromide\"}], \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium tert.butylate\"}], \"amount\": {\"mass\": {\"value\": 0.75, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trans-4-[trans-4-[2-(1,3-dioxolan-2-yl)ethyl]cyclohexyl]-cyclohexanecarboxaldehyde\"}], \"amount\": {\"mass\": {\"value\": 1.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert.butyl methyl ether\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert.butyl methyl ether\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred for 1.5 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"stirred at room temperature for a further 24 hours\", \"duration\": {\"value\": 24.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"WASH\", \"details\": \"washed several times with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"Chromatographic purification of the resulting crude product on silica gel with ethyl acetate/petroleum ether (vol. 3:97)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate petroleum ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.5, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"\\u03b2-[trans-4-[trans-4-(2-(1,3-dioxolan-2-yl)ethyl)-cyclohexyl]cyclohexyl]-4-fluorostyrene\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-6b3706be756f46338cb8102b0037f72a",
    "procedure_text": "A solution of 4.48 g of 3-methyl-4-oxo-2-phenyl-4H-1-benzopyran-8-carbonyl chloride in 40 ml of chloroform was added dropwise over a period of 10 minutes at ambient temperature to a solution of 3.74 g of 3-[4-(2-methoxyphenyl)-1-piperazinyl]-propylamine, prepared as described in GB 2,161,807 and 1.97 g of triethylamine in 50 ml of chloroform. After stirring for 2 hours, the solution was washed first with 0.5N hydrochloric acid, secondly with a saturated aqueous sodium bicarbonate solution and finally with water. The chloroform solution was dried on anhydrous sodium sulfate and the solvent was evaporated off in vacuo. The residue (B) was worked up as described in Example 2 to give 6.67 g of the title compound, m.p. (177) 182\u00b0-186\u00b0 C. This represents an alternative route to the product of Example 2.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-methyl-4-oxo-2-phenyl-4H-1-benzopyran-8-carbonyl chloride\"}], \"amount\": {\"mass\": {\"value\": 4.48, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-[4-(2-methoxyphenyl)-1-piperazinyl]-propylamine\"}], \"amount\": {\"mass\": {\"value\": 3.74, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"mass\": {\"value\": 1.97, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring for 2 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"prepared\"}, {\"type\": \"WASH\", \"details\": \"the solution was washed first with 0.5N hydrochloric acid, secondly with a saturated aqueous sodium bicarbonate solution and finally with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The chloroform solution was dried on anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was evaporated off in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 6.67, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e8bf557bc4d74a2cbdf69c772b6a7bcb",
    "procedure_text": "The title compound was prepared in analogy to the synthesis of 6-[1-(3-ethoxy-4-hydroxy-benzyl)-piperidin-4-ylamino]-4-trifluoromethyl-nicotinic acid (example 201) from 6-(piperidin-4-ylamino)-4-trifluoromethyl-nicotinic acid methyl ester dihydrochloride (intermediate B7) and 4-methoxy-3-propoxy-benzaldehyde (intermediate E11) in a yield of 16.4 mg (23%). MS (ISP): 468.3 [M+H]+.",
    "reference_string": "{\"inputs\": {\"m0_m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-[1-(3-ethoxy-4-hydroxy-benzyl)-piperidin-4-ylamino]-4-trifluoromethyl-nicotinic acid\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-(piperidin-4-ylamino)-4-trifluoromethyl-nicotinic acid methyl ester dihydrochloride\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"intermediate B7\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-methoxy-3-propoxy-benzaldehyde\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-17c45796a931443daa6d53833095ef50",
    "procedure_text": "To 11.77 g of 1-(2-ethoxycarbonylmethyl)-2-(3-pyridyl)-3-methylindole in 400 ml of dry tetrahydrofuran at 0\u00b0 is added 60 ml of a 1 M solution of lithium aluminum hydride in tetrahydrofuran. This is allowed to stir at room temperature for 1 hour, then cooled by an ice bath and quenched successively with 2.26 ml of water, 2.26 ml of a 15% sodium hydroxide solution, and 6.78 ml of water. The mixture is filtered, concentrated in vacuo, and the residue dissolved in ether, washed with a saturated NaHCO3 solution, dried over MgSO4 and concentrated in vacuo. There is obtained the semi-solid 1-(2-hydroxyethyl)-2-(3-pyridyl)-3-methylindole which is used directly in the next step.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(2-ethoxycarbonylmethyl)-2-(3-pyridyl)-3-methylindole\"}], \"amount\": {\"mass\": {\"value\": 11.77, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium aluminum hydride\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 400.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"to stir at room temperature for 1 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooled by an ice bath\"}, {\"type\": \"CUSTOM\", \"details\": \"quenched successively with 2.26 ml of water, 2.26 ml of a 15% sodium hydroxide solution, and 6.78 ml of water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 2.26, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 6.78, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"The mixture is filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"DISSOLUTION\", \"details\": \"the residue dissolved in ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with a saturated NaHCO3 solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(2-hydroxyethyl)-2-(3-pyridyl)-3-methylindole\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2a662749f4664e22bc067d3020478785",
    "procedure_text": "The colourless solid (E)-3-(4-bromo-phenyl)-prop-2-en-1-ol was prepared by DIBAL-H reduction of (E)-ethyl 3-(4-bromo-phenyl)-acrylate (example 71a) as described for example 52b.",
    "reference_string": "{\"inputs\": {\"m0_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DIBAL-H\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(E)-ethyl 3-(4-bromo-phenyl)-acrylate\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(E)-3-(4-bromo-phenyl)-prop-2-en-1-ol\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-5f8a5fee1a294e6689badaa9c69fa8ab",
    "procedure_text": "3-(chloromethyl)-1-isopropylazetidine hydrochloride (2.8 g, 15.2 mmol), 4-(4-hydroxyphenyl)tetrahydropyran-4-carbonitrile (3.1 g, 15.2 mmol) and potassium carbonate (8.5 g, 61.6 mmol) were combined in DMF (40 ml) and stirred at 500 for 2 hours. Potassium iodide (0.5 g 3.0 mmol) was added and the mixture was stirred at 50\u00b0 for 18 hours then at 90-95\u00b0 for a further 5 hours. The reaction mixture was concentrated in vacuo then partitioned between ethyl acetate (80 ml) and water (50 ml). The ethyl acetate was washed with saturated NaCl (50 ml) then dried over Na2SO4 and concentrated in vacuo to give a brown semi-crystalline material which was triturated with diisopropyl ether (25 ml) to give the title compound as a beige powder (2.9 g, 60%). 1H NMR (400 MHz, CDCl3) \u03b47.38 (d, 2H), 6.91 (d, 2H), 4.08 (m, 4H), 3.89 (m, 2H), 3.41 (t, 2H), 3.02 (t, 2H), 2.87 (m, 1H), 2.31 (m, 1H), 2.15-2.00 (m, 4H), 0.94 (d, 6H).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Potassium iodide\"}], \"amount\": {\"mass\": {\"value\": 0.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(chloromethyl)-1-isopropylazetidine hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 2.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(4-hydroxyphenyl)tetrahydropyran-4-carbonitrile\"}], \"amount\": {\"mass\": {\"value\": 3.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 8.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred at 500 for 2 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"the mixture was stirred at 50\\u00b0 for 18 hours\", \"duration\": {\"value\": 18.0, \"units\": \"HOUR\"}}, {\"type\": \"WAIT\", \"details\": \"at 90-95\\u00b0 for a further 5 hours\", \"duration\": {\"value\": 5.0, \"units\": \"HOUR\"}}, {\"type\": \"CONCENTRATION\", \"details\": \"The reaction mixture was concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"then partitioned between ethyl acetate (80 ml) and water (50 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 80.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The ethyl acetate was washed with saturated NaCl (50 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaCl\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"then dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a brown semi-crystalline material which\"}, {\"type\": \"CUSTOM\", \"details\": \"was triturated with diisopropyl ether (25 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropyl ether\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.9, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 60.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 60.7}}], \"isolated_color\": \"beige\", \"texture\": {\"type\": \"POWDER\", \"details\": \"powder\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-189c5ebf90fb4674b2b639af22ac34f6",
    "procedure_text": "To a pyridine solution (1 mL) of 7-methyl-3-(3-trifluoromethylphenyl)-5,6,7,8-tetrahydrocinnolin-5-ol (61.6 mg, 0.2 mmol) obtained in Example 6 was added acetic anhydride (0.027 mL, 0.24 mmol) under ice cooling and subjected to reaction at room temperature for 2 hours. The reaction solution was concentrated as it is under reduced pressure, followed by purification of thus obtained residue using silica gel column chromatography (hexane/ethyl acetate=3/1) to obtain an objective compound (57.6 mg, 82.3%).",
    "reference_string": "{\"inputs\": {\"m3_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-methyl-3-(3-trifluoromethylphenyl)-5,6,7,8-tetrahydrocinnolin-5-ol\"}], \"amount\": {\"mass\": {\"value\": 61.6, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic anhydride\"}], \"amount\": {\"volume\": {\"value\": 0.027, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"subjected to reaction at room temperature for 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CONCENTRATION\", \"details\": \"The reaction solution was concentrated as it\"}, {\"type\": \"CUSTOM\", \"details\": \"followed by purification of thus obtained residue\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 57.6, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 82.3}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 82.2}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-daa76ef1a7d748b68ca7cd91b76f98f3",
    "procedure_text": "Prepared from 5-(5-methyl-[1,2,4]oxadiazol-3-yl)-4-phenyl-thiazol-2-ylamine and 3-methyl-butyryl chloride.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-(5-methyl-[1,2,4]oxadiazol-3-yl)-4-phenyl-thiazol-2-ylamine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-methyl-butyryl chloride\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-5393a9ad21014459a94220087709368c",
    "procedure_text": "130 g of diallyl-bicyclo[2.2.1]hept-5-ene-2-carbonyl chloride are added dropwide at 20\u00b0 C. within 30 minutes to a solution of 62.7 g of bisphenol A in 200 ml of pyridine. The mixture is then stirred for 1 hour at 80\u00b0 C. and then worked up as described in Example 2. This gives 162 g (95% of theory) of a brown, liquid resin with \u03b725 =3,165 mPas. By gel permeation chromatography (THF), the molecular weight is found to be 610 (Mn) or 691 (Mw).",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diallyl-bicyclo[2.2.1]hept-5-ene-2-carbonyl chloride\"}], \"amount\": {\"mass\": {\"value\": 130.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"bisphenol A\"}], \"amount\": {\"mass\": {\"value\": 62.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 80.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture is then stirred for 1 hour at 80\\u00b0 C.\"}, \"conditions_are_dynamic\": true}, \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-e3c161616f6341e48b91f93308480778",
    "procedure_text": "A 25 mL round-bottomed flask is charged with 4-(2,6-difluorophenoxy)-6-(4-methylthiazol-2-ylamino)nicotinaldehyde (534 mg, 1.54 mmol) and THF (10 mL). Methyl(triphenylphosphoranylidene)acetate (668 mg, 2.00 mmol) is added and the reaction mixture is stirred at room temperature. After 4 hours, additional methyl(triphenylphosphoranylidene)acetate (668 mg, 2.00 mmol) is added and the reaction mixture is and stirred overnight. The precipitate is filtered, concentrated, and purified by silica gel chromatography (1:1 EtOAc in hexanes) to afford (E)-methyl 3-(4-(2,6-difluorophenoxy)-6-(4-methylthiazol-2-ylamino)pyridin-3-yl)acrylate.",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(2,6-difluorophenoxy)-6-(4-methylthiazol-2-ylamino)nicotinaldehyde\"}], \"amount\": {\"mass\": {\"value\": 534.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Methyl(triphenylphosphoranylidene)acetate\"}], \"amount\": {\"mass\": {\"value\": 668.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl(triphenylphosphoranylidene)acetate\"}], \"amount\": {\"mass\": {\"value\": 668.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture is stirred at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"stirred overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"The precipitate is filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"purified by silica gel chromatography (1:1 EtOAc in hexanes)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(E)-methyl 3-(4-(2,6-difluorophenoxy)-6-(4-methylthiazol-2-ylamino)pyridin-3-yl)acrylate\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b8f2cda5d562436499d4eb7596a7cb78",
    "procedure_text": "1.6 g (0.0037 mol) of N-[2-(4-carbomethoxymethoxyphenyl)-1-methylethyl]-2-(2-acetamino-thiazol-4-yl)-morpholine in 100 ml of 18% strength hydrochloric acid are heated to reflux under nitrogen for 48 hours. 1.5 g of active charcoal are added to the reaction solution which is throughly stirred and filtered. The solution is then concentrated, and the product is dried in vacuo over potassium hydroxide.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-[2-(4-carbomethoxymethoxyphenyl)-1-methylethyl]-2-(2-acetamino-thiazol-4-yl)-morpholine\"}], \"amount\": {\"mass\": {\"value\": 1.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"charcoal\"}], \"amount\": {\"mass\": {\"value\": 1.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"is throughly stirred\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"to reflux under nitrogen for 48 hours\", \"duration\": {\"value\": 48.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"The solution is then concentrated\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"the product is dried in vacuo over potassium hydroxide\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium hydroxide\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-e6e1765775294f5eb390367d6d61ad34",
    "procedure_text": "A mixture containing 2.34 g (6.43 mmol) methyl ((3S,4S)-4-acetoxy-3-benzyloxycarbonylaminoazetidin-2-on-1-yl)-2-oxoacetate and 5 ml of water in 250 ml of methanol is left at room temperature for 2 days. The mixture is evaporated in vacuo and the residue dried in high vacuo and recrystallized from methylene chloride-n-hexane. In this way, 1.33 g (74%) of title compound of melting point 110\u00b0 to 113\u00b0 C. is obtained. Chromatography of the mother liquors on 70 g of silica gel using a 3:1 mixture of toluene and ethyl acetate (20 fractions, 70 ml each) affords 300 mg (17%) pure crystalline product, additionally. IR spectrum in methylene chloride: 3500, 1800, 1745, 1730, 1510 and 1210 cm-1.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl ((3S,4S)-4-acetoxy-3-benzyloxycarbonylaminoazetidin-2-on-1-yl)-2-oxoacetate\"}], \"amount\": {\"mass\": {\"value\": 2.34, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The mixture is evaporated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue dried in high vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"recrystallized from methylene chloride-n-hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride n-hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"DAY\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.33, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 74.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 74.3}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0494ca0ebf034c9986349693f81bd871",
    "procedure_text": "This compound was prepared according to General Method 16 (EXAMPLE 30) from (\u00b1)-2,3-dihydro-2-(hydroxymethyl)-7-isopropoxy-1-(2,2,2-trifluoroethyl)-9-(trifluoromethyl)-1H-[1,4]oxazino[3,2-g]quinoline (EXAMPLE 28) (10 mg, 0.024 mmol), NaH (4.7 mg, 0.12 mmol) and iodoethane (17 mg, 0.12 mmol) in 1.0 mL THF to afford 9.8 mg (89%) of (\u00b1)-2-(ethoxymethyl)-2,3-dihydro-7-isopropoxy-1-(2,2,2-trifluoroethyl)-9-(trifluoromethyl)-1H-[1,4]oxazino[3,2-g]quinoline, a yellow oil, after flash chromatography (5:1 hexanes:EtOAc). Data for (\u00b1)-2-(ethoxymethyl)-2,3-dihydro-7-isopropoxy-1-(2,2,2-trifluoroethyl)-9-(trifluoromethyl)-1H-[1,4]oxazino[3,2-g]quinoline: Rf 0.60 (5:1 hexanes: EtOAc); 1H NMR (400 MHz, CDCl3) \u03b4 7.29 (s, 1H), 7.14 (broad s, 1H), 7.00 (s, 1H), 5.48 (hept, 1H, J=6.2), 4.45 (dd, 1H, J=10.9, 1.5), 4.16 (dd, J=10.9, 2.5), 4.00-4.20 (m, 2H), 3.70 (broad t, 1H, J=6.8), 3.54-3.63 (m, 2H), 3.50 (q, 2H, J=6.9), 1.38 (d, 6H, J=6.2), 1.20 (t, 3H, J=7.0).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(\\u00b1)-2,3-dihydro-2-(hydroxymethyl)-7-isopropoxy-1-(2,2,2-trifluoroethyl)-9-(trifluoromethyl)-1H-[1,4]oxazino[3,2-g]quinoline\"}], \"amount\": {\"mass\": {\"value\": 10.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaH\"}], \"amount\": {\"mass\": {\"value\": 4.7, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"iodoethane\"}], \"amount\": {\"mass\": {\"value\": 17.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"This compound was prepared\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(\\u00b1)-2-(ethoxymethyl)-2,3-dihydro-7-isopropoxy-1-(2,2,2-trifluoroethyl)-9-(trifluoromethyl)-1H-[1,4]oxazino[3,2-g]quinoline\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 9.8, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 89.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-54e235bc1f3c4108a59f70dc40b40504",
    "procedure_text": "To an ethanol (7.6 mL) solution of the compound (50 mg) obtained in Example 8, an aqueous 2N-sodium hydroxide solution (1.0 mL) was added. The reaction solution was stirred at room temperature for 30 minutes. The reaction solution was neutralized with 2N-hydrochloric acid (1.0 mL) added thereto and the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane:methanol=7:3) to obtain the title compound having the following physical properties (38 mg).",
    "reference_string": "{\"inputs\": {\"m4_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound\"}], \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 7.6, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction solution was stirred at room temperature for 30 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"added\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the solvent was concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by silica gel column chromatography (dichloromethane:methanol=7:3)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-324ef88093034357ade38b42b7370446",
    "procedure_text": "Add pyridinium tribromide (7 g, 22 mmol) to a solution of 5-acetyl-2-bromo-pyridine (4 g, 20 mmol) in THF (100 mL) at room temperature. Stir the mixture for 16 h at ambient temperature under a nitrogen atmosphere. Quench the mixture with saturated aqueous NaHCO3 (50 mL, pH at 7.8). Extract the mixture with EtOAc (150 mL). Wash the organic layer with brine (50 mL) and concentrate in vacuo to obtain the desired intermediate as a dark brown oil (11.5 g) that was used without further purification. MS (ES+) m/z: 280.0 (M+H)+.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridinium tribromide\"}], \"amount\": {\"mass\": {\"value\": 7.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-acetyl-2-bromo-pyridine\"}], \"amount\": {\"mass\": {\"value\": 4.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"Stir the mixture for 16 h at ambient temperature under a nitrogen atmosphere\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Quench the mixture with saturated aqueous NaHCO3 (50 mL\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"Extract the mixture with EtOAc (150 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"Wash the organic layer with brine (50 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrate in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired intermediate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 11.5, \"units\": \"GRAM\"}}}], \"isolated_color\": \"dark brown\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-48bcadbbba7b4f4299bd816594d61a87",
    "procedure_text": "To an ice bath cooled stirred solution of 1,1,1,3,3,3-hexamethyldisilazane (2.5M, 4.1 mL, 19.5 mmol) in tetrahydrofuran (5 mL) under nitrogen, was added a hexane solution of butyl lithium (7.2 mL, 18 mmol) via syringe. The ice bath was removed and the solution was stirred for 30 minutes at room temperature. This solution then was added dropwise to an ice bath cooled solution of 3-cyclopentoxy-4-methoxybenzaldehyde (3.3 g, 15 mmol) in tetrahydrofuran (5 mL) and the mixture stirred for 20 minutes. An ethereal solution of ethylmagnesium bromide (3M, 10 mL, 30 mmol) then was added dropwise. The reaction solution was allowed to reach room temperature and then was stirred at room temperature. The reaction progress was monitored by HPLC (Waters Nova-Pak/EC 18 column, 3.9\u00d7150 mm, 4 micron, 1 mL/min, 240 nm, 35/65, CH3CN/0.1% H3PO4 (aq)) and after 3 hours no starting material remained. The reaction mixture was slowly poured into a saturated solution of ammonium chloride (100 mL). The resulting mixture was extracted with methylene chloride (3\u00d720 mL) and the combined extracts were dried over magnesium sulfate and concentrated in vacuo to yield 5.6 g of product which was further purified by flash column chromatography (silica gel, 250/10/1, methylene chloride/methanol/ammonium hydroxide) to afford 2.5 g (67%) of the product as an oil: 1H NMR (CDCl3) \u03b4 6.91-6.77 (m, 3H), 4.85-4.74 (m, 1H), 3.83 (s, 3H), 3.74 (t, J=6.8 Hz, 1H), 2.02-1.15 (m, 12H), 0.86 (t, J=7.4 Hz, 3H); 13C NMR (CDCl3) \u03b4 148.8, 147.5, 138.8, 118.4, 113.3, 111.8, 80.3, 57.4, 56.0, 32.7, 32.4, 10.9.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethylmagnesium bromide\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH3CN\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m9_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"butyl lithium\"}], \"amount\": {\"volume\": {\"value\": 7.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,1,1,3,3,3-hexamethyldisilazane\"}], \"amount\": {\"volume\": {\"value\": 4.1, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-cyclopentoxy-4-methoxybenzaldehyde\"}], \"amount\": {\"mass\": {\"value\": 3.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium chloride\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the solution was stirred for 30 minutes at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"To an ice bath cooled\"}, {\"type\": \"CUSTOM\", \"details\": \"The ice bath was removed\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"This solution then was added dropwise to an ice bath\"}, {\"type\": \"STIRRING\", \"details\": \"the mixture stirred for 20 minutes\", \"duration\": {\"value\": 20.0, \"units\": \"MINUTE\"}}, {\"type\": \"CUSTOM\", \"details\": \"to reach room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"STIRRING\", \"details\": \"was stirred at room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"The resulting mixture was extracted with methylene chloride (3\\u00d720 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"the combined extracts were dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 5.6, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-cef4b59b0bf043e89cdb88c77594afe5",
    "procedure_text": "5 g of 2-benzyl-4-chlorophenol, 2.6 ml of chloroacetone, 1.38 g of potassium carbonate and 0.34 g of potassium iodide are dissolved in 50 ml of acetone and boiled under reflux for 20 h. After cooling, the precipitate is filtered, concentrated by evaporation, the residue dissolved in ethyl acetate, the solution washed three times with a 1 n sodium hydroxide solution, then with saturated sodium chloride solution, dried with magnesium sulphate and concentrated by evaporation under vacuum. After recrystallisation from diethylether, 1-(2-benzyl-4-chlorophenoxy)-propan-2-one is obtained as a white powder with a melting point of 65-6\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-benzyl-4-chlorophenol\"}], \"amount\": {\"mass\": {\"value\": 5.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroacetone\"}], \"amount\": {\"volume\": {\"value\": 2.6, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 1.38, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium iodide\"}], \"amount\": {\"mass\": {\"value\": 0.34, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"under reflux for 20 h\", \"duration\": {\"value\": 20.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"After cooling\"}, {\"type\": \"FILTRATION\", \"details\": \"the precipitate is filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated by evaporation\"}, {\"type\": \"DISSOLUTION\", \"details\": \"the residue dissolved in ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"the solution washed three times with a 1 n sodium hydroxide solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"with saturated sodium chloride solution, dried with magnesium sulphate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium chloride\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulphate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated by evaporation under vacuum\"}, {\"type\": \"CUSTOM\", \"details\": \"After recrystallisation from diethylether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethylether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(2-benzyl-4-chlorophenoxy)-propan-2-one\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b917a88f2a4d41009e8d1afbd8676d81",
    "procedure_text": "A solution of 184 mg (0.504 mmol) of 6-(3,5-difluorophenyl)-2-(3-oxazol-2-ylbenzyl)-2H-pyridazin-3-one, 108 mg (0.605 mmol) of N-bromosuccinimide and 6.3 mg (0.026 mmol) of benzoyl peroxide in 1 ml of chlorobenzene is stirred at 80\u00b0 C. for 42 hours. The reaction mixture is evaporated and chromatographed on a silica-gel column with dichloromethane/methanol as eluent, giving 2-[3-(5-bromooxazol-2-yl)benzyl]-6-(3,5-difluorophenyl)-2H-pyridazin-3-one as yellowish crystals; ESI 444, 446.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-(3,5-difluorophenyl)-2-(3-oxazol-2-ylbenzyl)-2H-pyridazin-3-one\"}], \"amount\": {\"mass\": {\"value\": 184.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-bromosuccinimide\"}], \"amount\": {\"mass\": {\"value\": 108.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzoyl peroxide\"}], \"amount\": {\"mass\": {\"value\": 6.3, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chlorobenzene\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The reaction mixture is evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"chromatographed on a silica-gel column with dichloromethane/methanol as eluent\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-[3-(5-bromooxazol-2-yl)benzyl]-6-(3,5-difluorophenyl)-2H-pyridazin-3-one\"}], \"isolated_color\": \"yellowish\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-bcbcd2940b574b388f07e087930642da",
    "procedure_text": "To a mixture of 3.57 g of the 5-chloro-2-cyclopropyl-6-(4-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidine (60% pure) described in step 3 and 1.22 g (8.1 mmol) 4-formylphenylboronic acid in 25 mL 1,2-dimethoxyethane are added 273 mg (0.33 mmol) dichloro[1,1\u2032-bis(diphenylphosphino)ferrocene]palladium (II) and 14.5 mL of a sodium carbonate solution (10%). The resulting mixture was heated to 90\u00b0 C. under an inert gas atmosphere for 20 h. The reaction mixture is diluted with 100 mL water and 250 mL dichloromethane. After vigorous stirring for one hour, the organic phase is separated and the aqueous phase extracted twice with dichloromethane. The combined organic layers are washed with water and dried over sodium sulphate. The solvent is evaporated and the residue is purified by chromatography on silica gel (dichloromethane/methanol) to yield 1.68 g (31.6%) of the desired aldehyde contaminated with 2-cyclopropyl-6-(4-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidine. Despite the impurity the aldehyde is used in the next reaction.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,2-dimethoxyethane\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m7_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium carbonate\"}], \"amount\": {\"volume\": {\"value\": 14.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloro[1,1\\u2032-bis(diphenylphosphino)ferrocene]palladium\"}], \"amount\": {\"mass\": {\"value\": 273.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-chloro-2-cyclopropyl-6-(4-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidine\"}], \"amount\": {\"mass\": {\"value\": 3.57, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-formylphenylboronic acid\"}], \"amount\": {\"mass\": {\"value\": 1.22, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 90.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After vigorous stirring for one hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the organic phase is separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"the aqueous phase extracted twice with dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined organic layers are washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulphate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulphate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The solvent is evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue is purified by chromatography on silica gel (dichloromethane/methanol)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aldehyde\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.68, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 31.6}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-5c4f1371bcc047bfba1e64691b6249b6",
    "procedure_text": "51.0 g of ethyl (1-benzylpiperidin-4-ylidene)acetate was dissolved in 200 ml of dichloroethane. After adding 36.5 g of 1-chloroethyl chloroformate under ice-cooling, the resulting mixture was heated under reflux for 2 hours. After adding 100 ml of methanol, the resulting mixture was further heated under reflux for 40 minutes and then allowed to stand at room temperature overnight. Then 60 g of triethylamine was added to the reaction mixture under ice-cooling. Further, 300 ml of methanol was added thereto and the system was made homogeneous. Next, 47.2 g of tert-butyl dicarbonate was added and the resulting mixture was stirred at room temperature for 20 minutes. The reaction mixture was concentrated under reduced pressure, diluted with ethyl acetate, washed successively with 1 N hydrochloric acid, water, a saturated aqueous solution of sodium chloride and saturated sodium hydrogencarbonate and dried over anhydrous magnesium sulfate followed by filtration. After distilling off the solvent under reduced pressure, the crude crystals thus obtained were ground and washed with hexane to thereby give 15.2 g of the title compound. The filtrate was concentrated and the residue was purified by silica gel column chromatography (eluted with n-hexane/ethyl acetate) to thereby give 37.8 g of the additional title compound as colorless crystals.",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"mass\": {\"value\": 60.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl (1-benzylpiperidin-4-ylidene)acetate\"}], \"amount\": {\"mass\": {\"value\": 51.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloroethane\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-chloroethyl chloroformate\"}], \"amount\": {\"mass\": {\"value\": 36.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 300.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl dicarbonate\"}], \"amount\": {\"mass\": {\"value\": 47.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the resulting mixture was stirred at room temperature for 20 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooling\"}, {\"type\": \"TEMPERATURE\", \"details\": \"the resulting mixture was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"under reflux for 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"the resulting mixture was further heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"under reflux for 40 minutes\", \"duration\": {\"value\": 40.0, \"units\": \"MINUTE\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"cooling\"}, {\"type\": \"CONCENTRATION\", \"details\": \"The reaction mixture was concentrated under reduced pressure\"}, {\"type\": \"ADDITION\", \"details\": \"diluted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed successively with 1 N hydrochloric acid, water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"a saturated aqueous solution of sodium chloride and saturated sodium hydrogencarbonate and dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium chloride\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydrogencarbonate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"followed by filtration\"}, {\"type\": \"DISTILLATION\", \"details\": \"After distilling off the solvent under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"the crude crystals thus obtained\"}, {\"type\": \"WASH\", \"details\": \"washed with hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 15.2, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3823d9c81d4649ecb88938f545ecf520",
    "procedure_text": "This compound was prepared according to the procedure of Example 127, but the methyl 3-(R)-hydroxybutanoate was first alkylated with methyl iodide as described by Keck et al., (J. Org. Chem., 1985, 4317) to give methyl 3-(R)-hydroxy-2-(S)methylbutanoate. The latter was transformed into the thiol according to the procedure of Example 127.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 3-(R)-hydroxybutanoate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl iodide\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"This compound was prepared\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 3-(R)-hydroxy-2-(S)methylbutanoate\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-71253fccbf6f40d692e3e92d46550770",
    "procedure_text": "To a stirred, cooled solution of 0.11 mL (1.26 mmol) of chlorosulfonyl isocyanate in 5 mL of CH2Cl2 was added 0.13 mL of t-BuOH. The solution was stirred 10 min. and added to a stirred, cooled (0\u00b0 C.) solution of 231 mg (0.5 mmol) of 1-(2,4,6-trichlorophenyl)-3-isopropyl-6-(4-aminobenzyl)pyrazolo[3,4-d]pyrimidin-4-one and 0.2 mL (1.4 mmol) of Et3N in 5 mL of CH2Cl2. The solution was stirred 1 h warming to ambient temperature, and it was then poured into 1 N aq. HCl. The mixture was extracted with EtOAc, and the organic extract was washed (brine), dried (MgSO4), concentrated under reduced pressure, and chromatographed on silica gel (elution with 1:1 EtOAc-hexanes, then EtOAc) to afford 250 mg (78%) of 1-(2,4,6-trichlorophenyl)-3-isopropyl-6-(4-(t-butoxycarbonylaminosulfonamido)benzyl)pyrazolo[3,4-d]pyrimidin-4-one as a white solid. 1H NMR (300 MHz, DMSO) \u03b4 12.44(s, 1H); 11.12(br. s, 1H); 9.70(br. s, 1H); 7.97(s, 2H); 7.21(d, 2H, J=8.4 Hz); 7.02(d, 2H, J=8.4 Hz); 3.78(s, 2H); 3.19-3.30(m, 1H); 1.27(d, 6H, J=6.9 Hz); 1.21(s, 9H).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2_m3_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(2,4,6-trichlorophenyl)-3-isopropyl-6-(4-aminobenzyl)pyrazolo[3,4-d]pyrimidin-4-one\"}], \"amount\": {\"mass\": {\"value\": 231.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Et3N\"}], \"amount\": {\"volume\": {\"value\": 0.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chlorosulfonyl isocyanate\"}], \"amount\": {\"volume\": {\"value\": 0.11, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"t-BuOH\"}], \"amount\": {\"volume\": {\"value\": 0.13, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The solution was stirred 10 min.\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"added to a stirred\"}, {\"type\": \"STIRRING\", \"details\": \"The solution was stirred 1 h\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"EXTRACTION\", \"details\": \"The mixture was extracted with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"the organic extract\"}, {\"type\": \"WASH\", \"details\": \"was washed (brine)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"chromatographed on silica gel (\"}, {\"type\": \"WASH\", \"details\": \"elution with 1:1 EtOAc-hexanes\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc-hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 10.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(2,4,6-trichlorophenyl)-3-isopropyl-6-(4-(t-butoxycarbonylaminosulfonamido)benzyl)pyrazolo[3,4-d]pyrimidin-4-one\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 250.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 78.0}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-33d720bb089c4f3ab6bc572cd2e4be50",
    "procedure_text": "Into a 1-neck round-bottom flask were added [3-({5-chloro-4-[(3-methoxybenzyl)amino]pyrimidin-2-yl}amino)phenyl]methanol (0.66 g, 1.8 mmol) and 5 mL of methylene chloride. To the above mixture was slowly added a solution of boron tribromide in methylene chloride (2.7 mL, 2.7 mmol, 1.0 M) at 0\u00b0 C. The mixture was allowed to warm up to room temperature (\u201crt\u201d) and stirred overnight. The resultant mixture was cooled in a dry ice bath when water (10 mL) was added. The mixture was allowed to warm up to rt, followed by an addition of EtOAc. The aqueous layer was extracted with EtOAc twice. The organic layers were combined and solvent removed under vacuum. The crude was purified by prep-HPLC to give the desired product (730 mg, 99%). LCMS for C18H17BrClN4O (M+H)+: m/z=418.9, 420.9. 1H NMR (400 MHz, DMSO-d6): \u03b4 9.55 (s, 1H), 9.34 (br s, 1H), 8.18 (s, 1H), 8.04 (s, 1H), 7.68 (t, J=1.7 Hz, 1H), 7.41 (m, 1H), 7.16 (t, J=7.9 Hz, 1H), 7.09 (t, J=7.9 Hz, 1H), 6.98 (d, J=7.7 Hz, 1H), 6.70 (m, 1H), 6.59 (m, 1H), 4.58 (d, J=6.6 Hz, 2H), 4.49 (s, 2H).",
    "reference_string": "{\"inputs\": {\"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"resultant mixture\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"[3-({5-chloro-4-[(3-methoxybenzyl)amino]pyrimidin-2-yl}amino)phenyl]methanol\"}], \"amount\": {\"mass\": {\"value\": 0.66, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"boron tribromide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 2.7, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred overnight\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to warm up to rt\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"The aqueous layer was extracted with EtOAc twice\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"solvent removed under vacuum\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude was purified by prep-HPLC\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 730.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 99.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a96130ae8fd04eea9fe7fb53eeecbcf5",
    "procedure_text": "0.135 mole = 44 g of 7-benzyloxy-1-(1,3-dithia-2-cyclopentyl)-heptane-3-one were heated for 1 hour under nitrogen and under reflux in 1 liter of acetone with [0.275 mole] = 47 g of CuCl2. 2 H2O and [0.57 mole] = 44 g of CuO, the copper salts were filtered off and the filtrate was concentrated under reduced pressure. The residue was dissolved in ether, washed twice with 2N- HCl and thrice with water, dried and the solvent was removed by distillation under reduced pressure. The residue was distilled under reduced pressure. B.p.0.5 mm 185\u00b0-192\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-benzyloxy-1-(1,3-dithia-2-cyclopentyl)-heptane-3-one\"}], \"amount\": {\"mass\": {\"value\": 44.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CuCl2\"}], \"amount\": {\"mass\": {\"value\": 47.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"LITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"2 H2O and [0.57 mole] = 44 g of CuO, the copper salts were filtered off\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CuO\"}], \"amount\": {\"mass\": {\"value\": 44.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"copper\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate was concentrated under reduced pressure\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue was dissolved in ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed twice with 2N- HCl and thrice with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was removed by distillation under reduced pressure\"}, {\"type\": \"DISTILLATION\", \"details\": \"The residue was distilled under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"B.p.0.5 mm 185\\u00b0-192\\u00b0 C.\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-7ecdcca40b14496ca421c87850b1ae28",
    "procedure_text": "To a solution of tert-butyl N-[[4-[5-[6-(4-azidocyclohexen-1-yl)-3-(tert-butoxycarbonylamino)pyrazin-2-yl]-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-methyl-carbamate (103 mg, 0.17 mmol) in anhydrous THF (1.5 mL) was added triphenylphosphine (67 mg, 0.26 mmol) and the reaction mixture was stirred at room temperature for 1 h. Water (61 \u03bcL, 3.41 mmol) was added after 1 h, and the reaction mixture was heated at 65\u00b0 C. for 3 h. The reaction mixture was allowed to cool to room temperature and was partitioned between EtOAc/aqueous brine. The layers were separated and the aqueous layer was extracted once more with EtOAc. The combined organics were dried over Na2SO4, filtered and concentrated to dryness. The crude material was purified by silica gel column chromatography using 20% MeOH in EtOAc to yield tert-butyl N-[[4-[5-[6-(4-aminocyclohexen-1-yl)-3-(tert-butoxycarbonylamino)pyrazin-2-yl]-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-methyl-carbamate (21 mg, 21%). LC/MS m/z 578.3 [M+H]+.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl N-[[4-[5-[6-(4-azidocyclohexen-1-yl)-3-(tert-butoxycarbonylamino)pyrazin-2-yl]-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-methyl-carbamate\"}], \"amount\": {\"mass\": {\"value\": 103.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triphenylphosphine\"}], \"amount\": {\"mass\": {\"value\": 67.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 1.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Water\"}], \"amount\": {\"volume\": {\"value\": 61.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture was stirred at room temperature for 1 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"the reaction mixture was heated at 65\\u00b0 C. for 3 h\", \"duration\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 65.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"to cool to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"was partitioned between EtOAc/aqueous brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The layers were separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"the aqueous layer was extracted once more with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organics were dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated to dryness\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude material was purified by silica gel column chromatography\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude material\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl N-[[4-[5-[6-(4-aminocyclohexen-1-yl)-3-(tert-butoxycarbonylamino)pyrazin-2-yl]-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-methyl-carbamate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 21.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 21.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 21.4}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-13c0d936cba14b598e0e89a69bc3023e",
    "procedure_text": "1-[5-(5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenylcarbamoyl)-2-methyl-phenyl]-1H-imidazole-4-carboxylic acid ethyl ester (Example 3) (820 mg, 1.55 mmol) was dissolved in 5 mL of cold MeOH and a solution of 130 mg (3.10 mmol) of LiOH-H2O in 3 mL of water was added dropwise. The mixture was allowed to warm to room temperature and was then stirred for 4 h. A 1 N HOAc solution (3.2 mL) was then added and the mixture was diluted with 30 mL of water, and then was extracted with 75 mL of EtOAc. The extract was washed with water and brine, was dried with MgSO4, filtered, and concentrated to provide 631 mg (1.26 mmol, 81%) of 1-[5-(5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenylcarbamoyl)-2-methyl-phenyl]-1H-imidazole-4-carboxylic acid.",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-[5-(5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenylcarbamoyl)-2-methyl-phenyl]-1H-imidazole-4-carboxylic acid ethyl ester\"}], \"amount\": {\"mass\": {\"value\": 820.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"LiOH-H2O\"}], \"amount\": {\"mass\": {\"value\": 130.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HOAc\"}], \"amount\": {\"volume\": {\"value\": 3.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was then stirred for 4 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"was extracted with 75 mL of EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 75.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The extract was washed with water and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"was dried with MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-[5-(5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenylcarbamoyl)-2-methyl-phenyl]-1H-imidazole-4-carboxylic acid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 1.26, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 631.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 81.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 81.3}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-399448bb52c941dd811ebda77ed8a6e3",
    "procedure_text": "A mixture of 4-methylphenol (54 g) and 4-chlorobutyryl chloride (77.5 g) was dissolved in xylene (250 ml). The mixture was heated gently until, at about 130\u00b0 C., a vigorous reaction occurred. After the reaction had subsided, the mixture was heated at reflux for approximately 40 minutes, until the evolution of hydrogen chloride had ceased. The xylene was then removed in vacuo, and the residue was distilled to give 4-methylphenyl 4-chlorobutyrate (101 g), b.p. 116\u00b0-118\u00b0 C./0.2 mm Hg.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"xylene\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-methylphenol\"}], \"amount\": {\"mass\": {\"value\": 54.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-chlorobutyryl chloride\"}], \"amount\": {\"mass\": {\"value\": 77.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrogen chloride\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 130.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"a vigorous reaction\"}, {\"type\": \"TEMPERATURE\", \"details\": \"the mixture was heated\"}, {\"type\": \"CUSTOM\", \"details\": \"The xylene was then removed in vacuo\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"xylene\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"the residue was distilled\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-methylphenyl 4-chlorobutyrate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 101.0, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b86ddf1193ca4d96b7cdccd9a7ef9ed9",
    "procedure_text": "To a stirred suspension of 204 (349 mg, 1 mmol) in IPA (3 mL) at RT under nitrogen was added sequentially via syringe neat DIPEA (174 \u03bcL, 1 mmol) and neat tetrahydro-2H-pyran-4-amine (101 mg, 1 mmol). The mixture was heated to 90\u00b0 C. and became homogeneous. Heating was continued for 60 min them cooled to RT, diluted to 30 mL with EtOAc and was washed sequentially with 10% citric acid solution (2\u00d730 mL) and satd. aq. NaHCO3 (2\u00d730 mL). The organic phase was isolated, dried (MgSO4), filtered and concentrated to a clear oil. The oil was triturated with hexane/EtOAc (4/1) with sonication to produce a precipitate that was filtered and rinsed with hexane/EtOAc (4/1). The mother liquor was recovered and re-precipitated. Both precipitated batches were combined to afford 215 mg (58%) of tert-butyl 5,5-difluoro-2-(tetrahydro-2H-pyran-4-ylamino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate (206) as a white solid.",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"204\"}], \"amount\": {\"mass\": {\"value\": 349.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"IPA\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DIPEA\"}], \"amount\": {\"volume\": {\"value\": 174.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydro-2H-pyran-4-amine\"}], \"amount\": {\"mass\": {\"value\": 101.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 90.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"Heating\"}, {\"type\": \"TEMPERATURE\", \"details\": \"them cooled to RT\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"WASH\", \"details\": \"was washed sequentially with 10% citric acid solution (2\\u00d730 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"citric acid\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The organic phase was isolated\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated to a clear oil\"}, {\"type\": \"CUSTOM\", \"details\": \"The oil was triturated with hexane/EtOAc (4/1) with sonication\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"to produce a precipitate that\"}, {\"type\": \"FILTRATION\", \"details\": \"was filtered\"}, {\"type\": \"WASH\", \"details\": \"rinsed with hexane/EtOAc (4/1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The mother liquor was recovered\"}, {\"type\": \"CUSTOM\", \"details\": \"re-precipitated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 60.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl 5,5-difluoro-2-(tetrahydro-2H-pyran-4-ylamino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 215.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 58.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 58.0}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-bac188571f444d8580d69fd35daee3b3",
    "procedure_text": "A mixture of 0.72 g of 3-trifluoromethyl isonicotinic acid and 4 ml of thionyl chloride was heated to reflux for 1.5 hours. The reaction mixture was cooled to room temperature, and the reaction mixture was concentrated under reduced pressure to give 3-trifluoromethyl isonicotinic acid chloride. A mixture of the resultant 3-trifluoromethyl isonicotinic acid chloride and 4 ml of DMF was added dropwise to a mixture of 0.66 g of 2-amino-4-trifluoromethylphenol, 0.76 g of triethylamine, 4 ml of DMF while ice-cooling. The reaction mixture was stirred at room temperature for one hour and stirred while heating at 50\u00b0 C. for 2.5 hours. The reaction mixture was cooled to room temperature, and then water was added to the reaction mixture, followed by extraction with ethyl acetate twice. The combined organic layers were washed with water and a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was washed with diethyl ether to give 0.62 g of N-[2-hydroxy-5-(trifluoromethyl)phenyl]-3-(trifluoromethyl)isonicotinamide.",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-amino-4-trifluoromethylphenol\"}], \"amount\": {\"mass\": {\"value\": 0.66, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"mass\": {\"value\": 0.76, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-trifluoromethyl isonicotinic acid chloride\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred at room temperature for one hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooling\"}, {\"type\": \"STIRRING\", \"details\": \"stirred\"}, {\"type\": \"TEMPERATURE\", \"details\": \"while heating at 50\\u00b0 C. for 2.5 hours\", \"duration\": {\"value\": 2.5, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 50.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"The reaction mixture was cooled to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"followed by extraction with ethyl acetate twice\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined organic layers were washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"a saturated sodium chloride solution, dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium chloride\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"WASH\", \"details\": \"The residue was washed with diethyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-[2-hydroxy-5-(trifluoromethyl)phenyl]-3-(trifluoromethyl)isonicotinamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.62, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-126887e2e6394d5e837a097c177a4ffc",
    "procedure_text": "To a stirred solution of (S)-3-{4-[2-(4-hydroxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-6-ylmethoxy]-phenyl}-hex-4-ynoic acid ethyl ester (0.2 g, 0.43 mmol) in acetonitrile (20 mL) is added 4-bromo-2-methyl-butan-2-ol (0.14 g, 0.87 mmol) and cesium carbonate (0.41 g, 1.2 mmol) and the reaction mixture is stirred at room temperature for 2 hours. The reaction mixture is filtered and evaporated to dryness. The crude material is purified by silica gel chromatography (combiflash purifier 24 g redisep column) and is eluted with 15-20% EtOAc in hexane to give the title compound (0.23 g, 100%). LCMS m/z 542 (M+H)+.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(S)-3-{4-[2-(4-hydroxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-6-ylmethoxy]-phenyl}-hex-4-ynoic acid ethyl ester\"}], \"amount\": {\"mass\": {\"value\": 0.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-bromo-2-methyl-butan-2-ol\"}], \"amount\": {\"mass\": {\"value\": 0.14, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cesium carbonate\"}], \"amount\": {\"mass\": {\"value\": 0.41, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture is stirred at room temperature for 2 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The reaction mixture is filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated to dryness\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude material is purified by silica gel chromatography (combiflash purifier 24 g redisep column)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude material\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"is eluted with 15-20% EtOAc in hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.23, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 100.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-05c7a7d35dae46c982a00b13e58ad6f4",
    "procedure_text": "After 2.5 hours in reaction, 0.625 g of N-Boc-3-pyrrolidinone, 0.91 g of D-glucose, 1.8 g of L-alanine, and 3.3 mg of pyridoxal phosphate were added. Further, after five hours in reaction, 0.625 g of N-Boc-3-pyrrolidinone, 0.91 g of D-glucose, and 3.3 mg of pyridoxal phosphate were added. Furthermore, after nine hours in reaction, 0.25 g of N-Boc-3-pyrrolidinone, 0.36 g of D-glucose, 19 mg of NAD+, and 3.3 mg of pyridoxal phosphate were added. During the reaction, the reaction liquid was sampled. From the sample, N-Boc-3-aminopyrrolidine was extracted by the addition of ethyl acetate after basifying the sample with 6 N aqueous solution of sodium hydroxide. The amount of N-Boc-3-aminopyrrolidine produced was measured by analyzing N-Boc-3-aminopyrrolidine under the following GC conditions. Further, by the law of the art, N-Boc-3-aminopyrrolidine thus obtained was acted on by 3,5-dinitrobenzyl chloride to form a dinitrobenzyl derivative. After that, the dinitrobenzyl derivative was analyzed under the following HPLC conditions, whereby the optical purity thereof was measured. In the result, the amount of N-Boc-3-aminopyrrolidine produced after 23 hours in reaction was 2.14 g. The absolute configuration of N-Boc-3-aminopyrrolidine was (S), and the optical purity was 99.4% e.e.",
    "reference_string": "{\"inputs\": {\"m5_m6_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-Boc-3-pyrrolidinone\"}], \"amount\": {\"mass\": {\"value\": 0.625, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"D-glucose\"}], \"amount\": {\"mass\": {\"value\": 0.91, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridoxal phosphate\"}], \"amount\": {\"mass\": {\"value\": 3.3, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-Boc-3-pyrrolidinone\"}], \"amount\": {\"mass\": {\"value\": 0.625, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"D-glucose\"}], \"amount\": {\"mass\": {\"value\": 0.91, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"L-alanine\"}], \"amount\": {\"mass\": {\"value\": 1.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridoxal phosphate\"}], \"amount\": {\"mass\": {\"value\": 3.3, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m8_m9_m10_m11\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-Boc-3-pyrrolidinone\"}], \"amount\": {\"mass\": {\"value\": 0.25, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"D-glucose\"}], \"amount\": {\"mass\": {\"value\": 0.36, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NAD+\"}], \"amount\": {\"mass\": {\"value\": 19.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridoxal phosphate\"}], \"amount\": {\"mass\": {\"value\": 3.3, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"were added\"}, {\"type\": \"ADDITION\", \"details\": \"were added\"}, {\"type\": \"ADDITION\", \"details\": \"were added\"}, {\"type\": \"CUSTOM\", \"details\": \"During the reaction\"}, {\"type\": \"CUSTOM\", \"details\": \"the reaction liquid\"}, {\"type\": \"ALIQUOT\", \"details\": \"was sampled\"}, {\"type\": \"EXTRACTION\", \"details\": \"From the sample, N-Boc-3-aminopyrrolidine was extracted by the addition of ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-Boc-3-aminopyrrolidine\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-Boc-3-aminopyrrolidine\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4df7eec646da4e02b9c96763a3e8e825",
    "procedure_text": "2-[4-(2,4-Difluoro-phenyl)-4H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-benzo[e]azulene-9-carboxylic acid and N-methylpiperazine were reacted in the general amide coupling procedure to give 374. NMR: (CDCl3): 2.37 (3 H, s, Me), 2.37-2.51 (4 H, m), 3.13-3.17 (2 H, m), 3.51-3.78 (4 H, m), 4.32-4.35 (2 H, m), 6.98 (1 H, s, Ar), 7.05 (1 H, d, J 8.3, Ar), 7.12-7.17 (2 H, m, Ar), 7.24-7.27 (1 H, m, Ar), 7.42-7.48 (1 H, m, Ar), 7.61-7.62 (1 H, m, Ar) and 8.24 (1 H, s, Ar). MS: (ESI+) MH+=508.22",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-[4-(2,4-Difluoro-phenyl)-4H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-benzo[e]azulene-9-carboxylic acid\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-methylpiperazine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"amide\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"374\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-53addafcea4c43809d92e5bf04cc66c8",
    "procedure_text": "A mixture of 541 mg of tert.butyl 7-tritylamino-3-isopropyl-3-cepheme-4-carboxylate in 11 ml of nitromethane was cooled on an ice bath and a current of gaseous hydrochloric acid was passed therethrough for 15 minutes. The mixture was evaporated to dryness and the residue was taken up in ether. The ether solution was vacuum filtered and the residue was washed with ether and dried. The residue was taken up in 1 ml of water and the pH was adjusted to 4 by addition of pyridine. The mixture was vacuum filtered and the crystals were washed with water, with acetone and then with ether and dried to obtain 204 mg of dl cis 7-amino-3-isopropyl-3-cepheme-4-carboxylic acid in the form of colorless crystals melting towards 230\u00b0C with decomposition.",
    "reference_string": "{\"inputs\": {\"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert.butyl 7-tritylamino-3-isopropyl-3-cepheme-4-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 541.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"nitromethane\"}], \"amount\": {\"volume\": {\"value\": 11.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"was cooled on an ice bath\"}, {\"type\": \"CUSTOM\", \"details\": \"The mixture was evaporated to dryness\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"WASH\", \"details\": \"the residue was washed with ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"ADDITION\", \"details\": \"the pH was adjusted to 4 by addition of pyridine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"WASH\", \"details\": \"the crystals were washed with water, with acetone\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"with ether and dried\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cis 7-amino-3-isopropyl-3-cepheme-4-carboxylic acid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 204.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-90f5da147ffd4929a35ba84d64bb3447",
    "procedure_text": "In yet another example, when 2-(2-methylpropylamino)-4-(ethoxycarbonylamino)aniline (R is 2-methylpropyl, X is hydrogen) (13) was treated with trifluoroacetic acid in toluene as described above (Step D of Example 7), a 1:1 mixture of the intermediate 1-(2-methylpropyl)-2-trifluoromethyl-6-ethoxycarbonylaminobenzimidazole (6), and the uncyclized intermediate, N-trifluoromethylcarbonyl-2-[(trifluoromethylcarbonyl)(2-methylpropyl)amino]-4-(ethoxycarbonylamino)aniline (14) was obtained. Treatment of the mixture of the intermediate benzimidazole (6) and (14) with potassium carbonate and water in methanol resulted in the direct conversion of intermediate (14) to the intermediate benzimidazole (6).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(2-methylpropylamino)-4-(ethoxycarbonylamino)aniline\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trifluoroacetic acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(2-methylpropyl)-2-trifluoromethyl-6-ethoxycarbonylaminobenzimidazole\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-trifluoromethylcarbonyl-2-[(trifluoromethylcarbonyl)(2-methylpropyl)amino]-4-(ethoxycarbonylamino)aniline\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e3fcdb105a2744aa85dc7e9ee232aa01",
    "procedure_text": "A mixture of 1-{[4-(dibenzylamino)-6,7-dimethyl-2-propyl-1H-imidazo[4,5-c]pyridin-1-yl]methyl}cyclohexanol (1.50 g, 3.02 mmol), ammonium formate (2.84 g, 45.0 mmol), and 10% palladium on carbon (1.50 g) in methanol (60 mL) and ethanol (120 mL) was heated at 85\u00b0 C. for 2 h. More ammonium formate (1.00 g) was added and heating was continued of 3 h, then the reaction mixture was stirred overnight at rt. The mixture was filtered through CELITE filter agent and the filtrate was concentrated in vacuo. The crude product was purified using HPFC (gradient elution with 10-40% CMA/chloroform). The appropriate fractions were concentrated and the resulting solid was triturated with acetonitrile. A solid was isolated by filtration and dried at 100\u00b0 C. under vacuum to provide 1-[(4-amino-6,7-dimethyl-2-propyl-1H-imidazo[4,5-c]pyridin-1-yl)methyl]cyclohexanol as a white powder (0.61 g, 64%), mp 214.0-216.0\u00b0 C. Anal. Calcd for C18H29N4O C, 68.32; H, 8.92; N, 17.71. Found: C, 68.06; H, 8.65; N, 17.45",
    "reference_string": "{\"inputs\": {\"m1_m2_m4_m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-{[4-(dibenzylamino)-6,7-dimethyl-2-propyl-1H-imidazo[4,5-c]pyridin-1-yl]methyl}cyclohexanol\"}], \"amount\": {\"mass\": {\"value\": 1.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium formate\"}], \"amount\": {\"mass\": {\"value\": 2.84, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"palladium on carbon\"}], \"amount\": {\"mass\": {\"value\": 1.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 120.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium formate\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 85.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture was stirred overnight at rt\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"heating\"}, {\"type\": \"FILTRATION\", \"details\": \"The mixture was filtered through CELITE\"}, {\"type\": \"FILTRATION\", \"details\": \"filter agent\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate was concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude product was purified\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"HPFC (gradient elution with 10-40% CMA/chloroform)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"The appropriate fractions were concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"the resulting solid was triturated with acetonitrile\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"A solid was isolated by filtration\"}, {\"type\": \"CUSTOM\", \"details\": \"dried at 100\\u00b0 C. under vacuum\", \"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-[(4-amino-6,7-dimethyl-2-propyl-1H-imidazo[4,5-c]pyridin-1-yl)methyl]cyclohexanol\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.61, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 64.0}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"POWDER\", \"details\": \"powder\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-1a2e730f145440e69cc9ac4b321c54cc",
    "procedure_text": "A mixture of 6-amino-5-chloro-2-oxo-N-(4-piperidinylmethyl)-1,2-dihydro-3-pyridinecarboxamide dihydrochloride (step 2, 100 mg, 0.28 mmol), iodoethane (49 mg, 0.31 mmol) and potassium carbonate (172 mg, 1.25 mmol) in N,N-dimethylformamide (6 ml) was stirred at 60\u00b0 C. for 15 h. After cooling to room temperature, the solvent was removed in vacuo. The residue was suspended in tetrahydrofuran (50 ml), and the solution was filtered through a pad of Celite. The filtrate was concentrated in vacuo, and the obtained residue was chromatographed on a column of aminopropyl silica gel eluting with methanol/dichloromethane (1:2.5) to give 43 mg (49%) of the title compound as a white solid.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-amino-5-chloro-2-oxo-N-(4-piperidinylmethyl)-1,2-dihydro-3-pyridinecarboxamide dihydrochloride\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"iodoethane\"}], \"amount\": {\"mass\": {\"value\": 49.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 172.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 6.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at 60\\u00b0 C. for 15 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"After cooling to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was removed in vacuo\"}, {\"type\": \"FILTRATION\", \"details\": \"the solution was filtered through a pad of Celite\"}, {\"type\": \"CONCENTRATION\", \"details\": \"The filtrate was concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"the obtained residue was chromatographed on a column of aminopropyl silica gel eluting with methanol/dichloromethane (1:2.5)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aminopropyl silica gel\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 43.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 49.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 49.1}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-8e3071085f0044ba9029c4a0bb3ca6d4",
    "procedure_text": "(2R,5R)-2,5-Dibenzyl-N1-((S)-2-oxo-1-o-tolylazepan-3-yl)-N6-((4S,8R,10aS)-5-oxo-8-(trifluoromethyl)octahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-yl)hexanediamide was synthesized as described in General Procedure H using Intermediate 71 (12 mg, 0.022 mmol) and Intermediate 61 (5.0 mg, 0.019 mmol) to give a white solid (5.7 mg, 38% yield). Anal. Calcd. for C43H51F3N4O4S m/z 776.7. found: 777.6 (M+H)+; 1H NMR (400 MHz, CDCl3) \u03b4 ppm 7.34-7.03 (m, 11H), 7.04-6.89 (m, 3H), 5.12 (t, J=7.3 Hz, 1H), 4.85-4.67 (m, 2H), 4.35 (d, J=14.8 Hz, 1H), 3.98 and 3.80 (s, 3H), 3.97-3.82 (m, 1H), 3.49-3.08 (m, 8H), 2.93-2.52 (m, 6H), 2.51-2.26 (m, 2H), 2.26-2.13 (m, 1H), 2.05-1.53 (m, 9H), 1.54-1.16 (m, 3H).",
    "reference_string": "{\"inputs\": {\"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Intermediate 71\"}], \"amount\": {\"mass\": {\"value\": 12.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Intermediate 61\"}], \"amount\": {\"mass\": {\"value\": 5.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2R,5R)-2,5-Dibenzyl-N1-((S)-2-oxo-1-o-tolylazepan-3-yl)-N6-((4S,8R,10aS)-5-oxo-8-(trifluoromethyl)octahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-yl)hexanediamide\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 5.7, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 38.0}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-6bfb0027e3d947428603e31abe982407",
    "procedure_text": "Example 237 was synthesized in a similar manner to Example 236, except that 1-chloro-N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (Intermediate OOO) was used instead of 1-chloro-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)isoquinoline-6-sulfonamide (Intermediate X). Isolated 1-(2-cyano-4-(trifluoromethyl)phenyl)-N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide as an off-white solid. 1H NMR (400 MHz, DMSO-d6) \u03b4 ppm=12.87 (br. s., 1H), 8.51 (br. s., 1H), 8.29 (br. s., 1H), 7.84 (br. s., 1H), 7.78 (d, J=9.1 Hz, 1H), 7.36 (d, J=7.4 Hz, 3H), 7.32-7.22 (m, 2H), 7.18 (d, J=5.9 Hz, 1H), 6.87 (d, J=4.4 Hz, 1H), 5.59 (br. s., 1H), 4.36 (br. s., 1H), 3.92 (br. s., 1H), 2.02 (br. s., 2H), 1.90 (br. s., 2H). m/z (ESI) 437.2 (M+H)+.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-chloro-N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Intermediate X\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(2-cyano-4-(trifluoromethyl)phenyl)-N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-06240dd4bc814b9aa248286c697a9c90",
    "procedure_text": "The title compound was prepared in analogy to example 90, from [4-(4-fluoro-2-methoxy-phenyl)-pyridin-3-yl]-methyl-amine (example 129, intermediate) and 3-(2-oxa-6-azaspiro[3.3]heptan-6-ylsulfonyl)-5-(trifluoromethyl)benzoic acid after a reaction time of 90 hours at room temperature. The compound was purified by silica gel chromatography on a 20 g column using an MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100). Colorless solid (61%). MS (ESI): m/z=566.136 [M+H]+.",
    "reference_string": "{\"inputs\": {\"m0_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"[4-(4-fluoro-2-methoxy-phenyl)-pyridin-3-yl]-methyl-amine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(2-oxa-6-azaspiro[3.3]heptan-6-ylsulfonyl)-5-(trifluoromethyl)benzoic acid\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The compound was purified by silica gel chromatography on a 20 g column\"}, {\"type\": \"WASH\", \"details\": \"eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-heptane EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-dc185cd988f44ad59ad0acda7d79e51a",
    "procedure_text": "Prepared according to the procedure described in Example 134, Step 3, using 1-[4\u2032-(4-amino-3-methyl-isoxazol-5-yl)-biphenyl-4-yl]-cyclopropanecarboxylic acid ethyl ester and 2-bromo-6-cyclohexyloxy-pyridine.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-[4\\u2032-(4-amino-3-methyl-isoxazol-5-yl)-biphenyl-4-yl]-cyclopropanecarboxylic acid ethyl ester\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-bromo-6-cyclohexyloxy-pyridine\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Prepared\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-a25c7617a0a344f0b0da1211361af00b",
    "procedure_text": "1.02 g (4.61 mmol) of 2-(1-hydroxyethyl)-5-phenylpentanoic acid are reacted analogously to Example 39A with 620 mg (4.61 mmol) of 1-hydroxy-1H-benzotriazole, 930 mg (9.22 mmol) of 4-methylmorpholine, 880 mg (4.61 mmol) of N\u2032-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride and 1.00 g (3.84 mmol) of 6-(1-aminoethyl)-3-(4-methoxybenzyl)-1,2,4-triazin-5(4H)-one to give 2-(1-hydroxyethyl)-N-{1-[3-(4-methoxybenzyl)-5-oxo-4,5-dihydro-1,2,4-triazin-6-yl]ethyl}-5-phenylpentanamide.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(1-hydroxyethyl)-5-phenylpentanoic acid\"}], \"amount\": {\"mass\": {\"value\": 1.02, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-hydroxy-1H-benzotriazole\"}], \"amount\": {\"mass\": {\"value\": 620.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-methylmorpholine\"}], \"amount\": {\"mass\": {\"value\": 930.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N\\u2032-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 880.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-(1-aminoethyl)-3-(4-methoxybenzyl)-1,2,4-triazin-5(4H)-one\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(1-hydroxyethyl)-N-{1-[3-(4-methoxybenzyl)-5-oxo-4,5-dihydro-1,2,4-triazin-6-yl]ethyl}-5-phenylpentanamide\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a16c2a96f0ee47afa27828a370b6504b",
    "procedure_text": "(S)-3-Benzoyl-5-biphenyl-4-ylmethyl-1-((E)-styryl)-pyrrolidin-2-one (4a, R1=styryl, R4=phenyl) (1.0 g, 2.2 mmol) is dissolved in 5 mL of anhydrous tetrahydrofuran, add paraformaldehyde (80 mg, 2.6 mmol), DBU (434 mg, 2.8 mmol) and anhydrous Lithium chloride (186 mg, 4.4 mmol), reflux overnight under nitrogen atmosphere. The reaction mixture is cooled to room temperature, add 20 mL of toluene, wash with 5% HCl(aq), saturated Na2CO3 and brine, dry over anhydrous Na2SO4, evaporate the solvent under vacuum to give (R)-5-Biphenyl-4-ylmethyl-3-methylene-1-((E)-styryl)-pyrrolidin-2-one (1a, R1=styryl). Spectroscopic data as Example 23, Method 1.",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(S)-3-Benzoyl-5-biphenyl-4-ylmethyl-1-((E)-styryl)-pyrrolidin-2-one\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"paraformaldehyde\"}], \"amount\": {\"mass\": {\"value\": 80.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DBU\"}], \"amount\": {\"mass\": {\"value\": 434.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Lithium chloride\"}], \"amount\": {\"mass\": {\"value\": 186.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"reflux overnight under nitrogen atmosphere\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"WASH\", \"details\": \"wash with 5% HCl(aq), saturated Na2CO3 and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2CO3\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dry over anhydrous Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporate the solvent under vacuum\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-5-Biphenyl-4-ylmethyl-3-methylene-1-((E)-styryl)-pyrrolidin-2-one\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-74bf9c639bc940a8a6d2c04a8d369615",
    "procedure_text": "Magnesium turnings (190 mg, 7.4 mmol) was added to dry THF (15 mL) under argon. 1,4-dibromobenzene (2.43 g, 10.3 mmol) was added and the solution was heated to reflux for 30 min. 2-Methyl-2-morpholinopropanenitrile (1 g, 6.6 mmol) was dissolved into THF (30 mL) and added dropwise to the solution at reflux. The mixture was stirred for 2 h and cooled to rt. The reaction was quenched with sat. K2CO3 solution and extracted with CH2Cl2 (200 mL), dried over MgSO4 and concentrated to an orange oil. The crude mixture was purified on a Biotage silica column (2-15% MeOH in CH2Cl2) to give the title compound as a yellow oil (204 mg, 10%). MS ESI 284.0, 286.0 [M+H]+, calcd for [C13H18BrNO+H]+ 284.1, 286.1.",
    "reference_string": "{\"inputs\": {\"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,4-dibromobenzene\"}], \"amount\": {\"mass\": {\"value\": 2.43, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Magnesium\"}], \"amount\": {\"mass\": {\"value\": 190.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-Methyl-2-morpholinopropanenitrile\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred for 2 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"the solution was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to reflux for 30 min\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}}, {\"type\": \"ADDITION\", \"details\": \"added dropwise to the solution\"}, {\"type\": \"TEMPERATURE\", \"details\": \"at reflux\"}, {\"type\": \"CUSTOM\", \"details\": \"The reaction was quenched with sat. K2CO3 solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"K2CO3\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with CH2Cl2 (200 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated to an orange oil\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude mixture was purified on a Biotage silica column (2-15% MeOH in CH2Cl2)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude mixture\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 204.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 10.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 10.9}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d9fc8f5ec1ae43d9aacb8cefff6656c7",
    "procedure_text": "10 ml of a methylene cloride solution containing 554 mg (1.00 mmol) of 4-nitrobenzyl (1R,5S,6S)-2-(2-diethylcarbamoylphenylthio)-1-methyl-6-[1(R)-hydroxyethyl]-1-carbapen-2-em-3-carboxylate (prepared as described in Example 37) were cooled in an ice bath, and then 1.5 ml (1.5 mmol) of a 1M aqueous solution of sodium hydrogencarbonate and then 215 mg (1.00 mmol) of m-chloroperbenzoic acid (80% purity) were added, and the reaction solution was stirred for 90 minutes at the same temperature. At the end of this time, an aqueous solution of sodium sulfite was added to the reaction solution, and the mixture was stirred for 10 minutes to complete the reaction. The reaction solution was then diluted with methylene chloride, ice-cooled, washed with an aqueous solution of sodium hydrogencarbonate and condensed by evaporation under reduced pressure. The resulting residue was purified by column chromatography through 50 g of silica gel. Elution with ethyl acetate afforded 145 mg (yield 25%) of an isomer of the title compound of lower polarity (the isomer is a result of the configuration of the S-oxide), followed by 96 mg (yield 17%) of a higher polarity isomer of the title compound, both as foam-like solids.",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m7_m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-nitrobenzyl (1R,5S,6S)-2-(2-diethylcarbamoylphenylthio)-1-methyl-6-[1(R)-hydroxyethyl]-1-carbapen-2-em-3-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 554.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene cloride\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfite\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aqueous solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydrogencarbonate\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"m-chloroperbenzoic acid\"}], \"amount\": {\"mass\": {\"value\": 215.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction solution was stirred for 90 minutes at the same temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"were cooled in an ice bath\"}, {\"type\": \"STIRRING\", \"details\": \"the mixture was stirred for 10 minutes\", \"duration\": {\"value\": 10.0, \"units\": \"MINUTE\"}}, {\"type\": \"CUSTOM\", \"details\": \"the reaction\"}, {\"type\": \"TEMPERATURE\", \"details\": \"cooled\"}, {\"type\": \"WASH\", \"details\": \"washed with an aqueous solution of sodium hydrogencarbonate and condensed by evaporation under reduced pressure\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydrogencarbonate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The resulting residue was purified by column chromatography through 50 g of silica gel\"}, {\"type\": \"WASH\", \"details\": \"Elution with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 90.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 25.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2475cc011f924869915d7243da40fe20",
    "procedure_text": "0.11 g of 6-methyl-5-(3-methylisoxazol-5-yl)-1,2,3,4-tetrachlorobicyclo[2.2.1]hept-2en-7-one (a mixture of trans:cis=1:1) was dissolved in 1 ml of ethanol, and 0.06 g of sodium ethylate was added, while cooling with ice. The resulting solution was stirred for an hour at room temperature. The reaction solution was poured into 50 ml of ice-water, and extracted with 30 ml of ethyl acetate twice. The organic layer was washed with saturated salt water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. The obtained viscous liquid was purified on silica gel column chromatography (elution with n-hexane/ethyl acetate) to give 0.024 g of the title compound as white crystals. Melting point 86-88\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-methyl-5-(3-methylisoxazol-5-yl)-1,2,3,4-tetrachlorobicyclo[2.2.1]hept-2en-7-one\"}], \"amount\": {\"mass\": {\"value\": 0.11, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium ethylate\"}], \"amount\": {\"mass\": {\"value\": 0.06, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The resulting solution was stirred for an hour at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"while cooling with ice\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with 30 ml of ethyl acetate twice\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with saturated salt water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"The solvent was distilled off under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The obtained viscous liquid was purified on silica gel column chromatography (elution with n-hexane/ethyl acetate)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-hexane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.024, \"units\": \"GRAM\"}}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-6d5bb36fcd044070911f2bc5ccdb3479",
    "procedure_text": "1,8-Bis(dimethylaminonaphtalene (3.19 g, 14.9 mmol) was added to a solution of 4-(isopropoxy)phenyl acetic acid (2.89 g, 14.9 mmol) in dry tetrahydrofuran (18 mL) at rt under argon atmosphere. After 25 minutes stirring at rt diphenylphosphoryl azide (4.10 g, 14.9 mmol) was added dropwise and the mixture refluxed for 6 hours. It was allowed to cool to rt and then stored at \u221220\u00b0 C. overnight to precipitate out the ammonium phosphate salt. A mixture of diethyl ether and ethyl acetate (1:1 v/v, 25 mL) was added to the cold reaction mixture. The precipitate was filtered from the reaction mixture and washed with diethyl ether: ethyl acetate (1:1 v/v, 20 mL). The filtrate was evaporated to dryness giving 1-isocyanatomethyl-4-isopropoxybenzene as an oil (3.2 g), which was used in the next step without further purification.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylaminonaphtalene\"}], \"amount\": {\"mass\": {\"value\": 3.19, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(isopropoxy)phenyl acetic acid\"}], \"amount\": {\"mass\": {\"value\": 2.89, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 18.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diphenylphosphoryl azide\"}], \"amount\": {\"mass\": {\"value\": 4.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added dropwise\"}, {\"type\": \"TEMPERATURE\", \"details\": \"the mixture refluxed for 6 hours\", \"duration\": {\"value\": 6.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"to precipitate out the ammonium phosphate salt\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium phosphate salt\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"A mixture of diethyl ether and ethyl acetate (1:1 v/v, 25 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"was added to the cold reaction mixture\"}, {\"type\": \"FILTRATION\", \"details\": \"The precipitate was filtered from the reaction mixture\"}, {\"type\": \"WASH\", \"details\": \"washed with diethyl ether: ethyl acetate (1:1 v/v, 20 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The filtrate was evaporated to dryness\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-isocyanatomethyl-4-isopropoxybenzene\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 3.2, \"units\": \"GRAM\"}}}], \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-daf75b2467f8448793be2f98ccedae90",
    "procedure_text": "According to the general procedure (GP10), microwave-assisted Pictet-Spengler reaction (60 W; 140\u00b0 C.; 6.5 bars; 10 min.) between 2-(2-ethyl-4-iodo-imidazol-1-yl)-ethylamine (4.497 mmol) and 3-(3-chloro-4-trifluoromethyl-phenyl)-propionaldehyde (1.064 g; 4.497 mmol) afforded 8-[2-(3-chloro-4-trifluoromethyl-phenyl)-ethyl]-3-ethyl-1-iodo-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine. LC-MS: tR=0.81 min.; [M+H]+=483.73 g/mol.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(2-ethyl-4-iodo-imidazol-1-yl)-ethylamine\"}], \"amount\": {\"moles\": {\"value\": 4.497, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(3-chloro-4-trifluoromethyl-phenyl)-propionaldehyde\"}], \"amount\": {\"mass\": {\"value\": 1.064, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"8-[2-(3-chloro-4-trifluoromethyl-phenyl)-ethyl]-3-ethyl-1-iodo-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a12a8095cd2c4a3cb6f953e635ee092e",
    "procedure_text": "A solution of tert-butyl (3R)-6-cyclohexyl-3-(3-{[(2-methoxy-2-oxoethyl)amino]carbonyl}-1,2,4-oxadiazol-5-yl)hexanoate (Preparation 37) (440 mg, 1.00 mmol) in anhydrous dimethylsulphoxide (10 ml) was treated with iodomethane (310 \u03bcl, 5.00 mmol) and cesium carbonate (975 mg, 3.00 mmol) and the resulting mixture was heated at 40\u00b0 under a nitrogen atmosphere for 3 hours then stirred at room temperature for 17 hours. The mixture was diluted with water and extracted with diethyl ether (\u00d73). The combined organic extracts were washed with brine, dried over anhydrous sodium sulphate, filtered and the solvent removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with hexane:ethyl acetate (2:1) to afford the title compound as a colourless oil (315 mg)",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl (3R)-6-cyclohexyl-3-(3-{[(2-methoxy-2-oxoethyl)amino]carbonyl}-1,2,4-oxadiazol-5-yl)hexanoate\"}], \"amount\": {\"mass\": {\"value\": 440.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"iodomethane\"}], \"amount\": {\"volume\": {\"value\": 310.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cesium carbonate\"}], \"amount\": {\"mass\": {\"value\": 975.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylsulphoxide\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"then stirred at room temperature for 17 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"the resulting mixture was heated at 40\\u00b0 under a nitrogen atmosphere for 3 hours\", \"duration\": {\"value\": 3.0, \"units\": \"HOUR\"}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with diethyl ether (\\u00d73)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined organic extracts were washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous sodium sulphate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulphate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"the solvent removed under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by column chromatography on silica gel eluting with hexane:ethyl acetate (2:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 17.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 315.0, \"units\": \"MILLIGRAM\"}}}], \"isolated_color\": \"colourless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-958911e8b2634b08995553a22f322022",
    "procedure_text": "Using general procedure E, 1-azabicyclo[2.2.2]oct-3-yl[2-(5-bromo-2-fluorophenyl)propan-2-yl]carbamate (120 mg, 0.312 mmol), 2-methylpropylboronic acid (79.4 mg, 0.779 mmol) and palladium (II) acetate gave the title as a white solid compound (37 mg, 33%). 1H NMR (400 MHz, CDCl3) 7.08 (dd, J=2.0, 8.2 Hz, 1H), 6.95 (d, J=4.9 Hz, 1H), 6.93-6.85 (m, 1H), 5.23 (s, 1H), 4.72-4.52 (m, 1H), 3.20-2.47 (m, 6H), 2.41 (d, J=7.1 Hz, 2H), 1.89-1.76 (m, 1H), 2.02-1.26 (m, 5H), 1.70 (d, J=7.6 Hz, 6H), 0.88 (d, J=6.6 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) \u03b4 160.4, 158.0, 137.1, 137.1, 129.2, 129.1, 128.1, 116.2, 116.0, 71.2, 55.8, 54.2, 47.6, 46.7, 45.1, 30.5, 29.9, 28.6, 27.0, 25.6, 24.8, 22.5, 19.8, 19.5 ppm. Purity: 95.0% UPLCMS (210 nm); retention time 1.02 min; (M+1) 363.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-azabicyclo[2.2.2]oct-3-yl[2-(5-bromo-2-fluorophenyl)propan-2-yl]carbamate\"}], \"amount\": {\"mass\": {\"value\": 120.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-methylpropylboronic acid\"}], \"amount\": {\"mass\": {\"value\": 79.4, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"palladium (II) acetate\"}], \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 37.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 33.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d432ba8bbc154479bc98b34ef7661589",
    "procedure_text": "A mixture of 5.6 g of 1-(6-iodohexyl)-2,3-bis(phenylmethoxy) benzene, 2.1 g of 3-chloro-4-hydroxybenzoic acid methyl ester and 5.0 g of potassium carbonate in 50 mL of acetone was stirred at reflux for 20 hours. Workup as in Example 16, chromatography on 100 g of silica gel using 15% ethyl acetate-hexane and crystallization from ethyl acetate-hexane gave 3.7 g (59% yield), mp 68\u00b0-69\u00b0, 3-chloro-4-[6-[2,3-bis(phenylmethoxy)phenyl]hexyloxy]benzoic acid methyl ester.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(6-iodohexyl)-2,3-bis(phenylmethoxy) benzene\"}], \"amount\": {\"mass\": {\"value\": 5.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-chloro-4-hydroxybenzoic acid methyl ester\"}], \"amount\": {\"mass\": {\"value\": 2.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 5.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"at reflux for 20 hours\", \"duration\": {\"value\": 20.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"Workup as in Example 16, chromatography on 100 g of silica gel using 15% ethyl acetate-hexane and crystallization from ethyl acetate-hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-chloro-4-[6-[2,3-bis(phenylmethoxy)phenyl]hexyloxy]benzoic acid methyl ester\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 59.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-94b0d9ce196c40259209b5af224b92e4",
    "procedure_text": "Benzo[d][1,3]dioxole (3.05 g, 25 mmol) was dissolved in tetrahydrofuran (50 mL) and cooled to \u2212108\u00b0 C. utilizing a tetrahydrofuran/liquid nitrogen bath. sec-Butyllithium (1.4 M in cyclohexane; 19.64 mL, 27.5 mmol) was added dropwise, keeping the temperature below \u2212100\u00b0 C. The reaction mixture was then stirred at temperatures between \u2212100\u00b0 C. and \u2212108\u00b0 C. for 2 h to ensure complete deprotonation. 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (4.65 g, 25.00 mmol) was then added to the reaction mixture dropwise, keeping the temperature below \u2212100\u00b0 C. The reaction mixture was then allowed to warm to room temperature and partitioned between diethyl ether and water. The organic phase was extracted with water once again and the aqueous phases combined and acidified to pH 4 with HCl. The product was extracted with diethyl ether and the organic phase was dried and concentrated under vacuum. The product was purified by flash chromatography (silica gel) to provide the title compound as a white solid (2.14 g, 34.5%): 1H NMR (300 MHz, CDCl3) \u03b4 7.21 (dd, J=7.6, 1.4 Hz, 1H), 6.90 (dd, J=7.7, 1.5 Hz, 1H), 6.82 (t, J=7.6 Hz, 1H), 6.02 (s, 2H), 1.36 (s, 12H); EIMS m/z 248.",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Benzo[d][1,3]dioxole\"}], \"amount\": {\"mass\": {\"value\": 3.05, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sec-Butyllithium\"}], \"amount\": {\"volume\": {\"value\": 19.64, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane\"}], \"amount\": {\"mass\": {\"value\": 4.65, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -108.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was then stirred at temperatures between \\u2212100\\u00b0 C. and \\u2212108\\u00b0 C. for 2 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the temperature below \\u2212100\\u00b0 C\"}, {\"type\": \"CUSTOM\", \"details\": \"the temperature below \\u2212100\\u00b0 C\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to warm to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"partitioned between diethyl ether and water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The organic phase was extracted with water once again\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The product was extracted with diethyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the organic phase was dried\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under vacuum\"}, {\"type\": \"CUSTOM\", \"details\": \"The product was purified by flash chromatography (silica gel)\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.14, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 34.5}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 34.5}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-274d1c2fa5f141adb9ffc0b69b84484f",
    "procedure_text": "4.40 g of 4-(\u03b1-phenyl-2-tolyl)piperidine hydrochloride of Example 35 and 14 g K2CO3 in 50 ml of n-butanol are heated to reflux with stirring. To this is added 5.66 g 3-phenoxypropylbromide in 10 ml of n-butanol dropwise. The mixture is then refluxed for 24 hours. After cooling the suspension is suction filtered, washing the flask and filter cake with n-butanol. The combined filtrates are evaporated to an oil which is dissolved in 20 ml of isopropanol and made acid with HCl/ether. The hydrochloride is collected by suction filtration and washed with ether. The resultant product is recrystallized from isopropanol/ether to yield 1-(3-phenoxypropyl)-4-(\u03b1-phenyl-2-tolyl)piperidine, mp 139\u00b0-140\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-phenoxypropylbromide\"}], \"amount\": {\"mass\": {\"value\": 5.66, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-butanol\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(\\u03b1-phenyl-2-tolyl)piperidine hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 4.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"K2CO3\"}], \"amount\": {\"mass\": {\"value\": 14.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-butanol\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"with stirring\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"to reflux\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The mixture is then refluxed for 24 hours\", \"duration\": {\"value\": 24.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"After cooling the suspension\"}, {\"type\": \"FILTRATION\", \"details\": \"suction filtered\"}, {\"type\": \"WASH\", \"details\": \"washing the flask\"}, {\"type\": \"FILTRATION\", \"details\": \"filter cake with n-butanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-butanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The combined filtrates are evaporated to an oil which\"}, {\"type\": \"DISSOLUTION\", \"details\": \"is dissolved in 20 ml of isopropanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isopropanol\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"The hydrochloride is collected by suction filtration\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The resultant product is recrystallized from isopropanol/ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"resultant product\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isopropanol ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(3-phenoxypropyl)-4-(\\u03b1-phenyl-2-tolyl)piperidine\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3cf50841c95944369bb94afe2e1e83c7",
    "procedure_text": "Followed Scheme 4, route A. To a solution of 4-(4-chloro-6-hydroxyquinolin-2-yl)benzonitrile (65 mg, 0.23 mmol) in toluene (2 mL), was added TMSN3 (455 mg, 4.18 mmol) and Bu2SnO (15 mg, 0.069 mmol) at room temperature. The mixture was heated to reflux overnight. The volatiles were removed under reduced pressure. The residue was purified by prep-HPLC to afford Compound IV-11 (10 mg, 13.5%). 1H NMR (MeOD-d4, 500 MHz): \u03b4 8.34 (d, J=8.5 Hz, 2H), 8.21 (s, 1H), 8.19 (s, 2H), 8.07 (d, J=9.0 Hz, 1H), 7.51 (d, J=2.5 Hz, 1H), 7.47(dd, J=2.5 Hz, J=9.5 Hz, 1H). MS (ESI): m/z 324.0 [M+1]+.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(4-chloro-6-hydroxyquinolin-2-yl)benzonitrile\"}], \"amount\": {\"mass\": {\"value\": 65.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TMSN3\"}], \"amount\": {\"mass\": {\"value\": 455.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The mixture was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to reflux overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The volatiles were removed under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by prep-HPLC\"}, {\"type\": \"CUSTOM\", \"details\": \"to afford Compound IV-11 (10 mg, 13.5%)\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-98d59a58ccf449549ce5dfcde00cd7cb",
    "procedure_text": "Add potassium bis(trimethylsilyl)-amide (5.5 mL, 2.73 mmol, 0.5 M in toluene) to a solution of 3-{[3-(2-chloro-6-fluoro-phenyl)-5-methyl-isoxazole-4-carbonyl]-amino}-piperidine-1-carboxylic acid methyl ester (0.72 g, 1.82 mmol) in dimethylformamide (56 mL). After 5 minutes, quench the reaction with 1N HCl and concentrate. Partition the resulting material between 20% isopropanol/chloroform and 1N HCl. Wash the organic layer with saturated aqueous sodium bicarbonate solution and brine, dry over magnesium sulfate, and concentrate. Purify by flash chromatography on silica gel (eluting with 0\u20130.5% methanol/chloroform) to give 632 mg of the title compound as a white solid, 92% yield. 1H NMR: consistent with structure. MS (ion spray) 376 (M+).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium bis(trimethylsilyl)-amide\"}], \"amount\": {\"volume\": {\"value\": 5.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-{[3-(2-chloro-6-fluoro-phenyl)-5-methyl-isoxazole-4-carbonyl]-amino}-piperidine-1-carboxylic acid methyl ester\"}], \"amount\": {\"mass\": {\"value\": 0.72, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 56.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"quench\"}, {\"type\": \"CUSTOM\", \"details\": \"the reaction with 1N HCl\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrate\"}, {\"type\": \"CUSTOM\", \"details\": \"Partition the resulting material between 20% isopropanol/chloroform and 1N HCl\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isopropanol chloroform\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"Wash the organic layer with saturated aqueous sodium bicarbonate solution and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dry over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrate\"}, {\"type\": \"CUSTOM\", \"details\": \"Purify by flash chromatography on silica gel (eluting with 0\\u20130.5% methanol/chloroform)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 5.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 632.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 92.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 92.4}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a73b2e17151147c2a0de242bee8385f5",
    "procedure_text": "Add 4-[4-bromo-1-(2-dimethylamino-ethyl)-1H-imidazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester (1.0 g; 0.0024 mol; 1.0 equiv), 4-chloro phenyl boronic acid (0.58 g; 0.0037 mol; 1.5 equiv), 3M Na2CO3 solution (0.79 g; 0.0074 mol; 3.0 equiv) to ethanol (5 mL) and toluene (5 mL) and degas the reaction with argon. Add Pd(PPh3)4 (0.29 g; 0.00024 mol; 0.1 equiv) and microwave at 110\u00b0 C. for 20 min. Add EA and filter through a Celite\u00ae bed. Add saturated NaHCO3 aqueous and extract with EA. Evaporate the organic layer, and purify the residue over a silica gel column with methanol in DCM to give the title compound (0.8 g; crude).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-[4-bromo-1-(2-dimethylamino-ethyl)-1H-imidazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-chloro phenyl boronic acid\"}], \"amount\": {\"mass\": {\"value\": 0.58, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2CO3\"}], \"amount\": {\"mass\": {\"value\": 0.79, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd(PPh3)4\"}], \"amount\": {\"mass\": {\"value\": 0.29, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"degas\"}, {\"type\": \"CUSTOM\", \"details\": \"the reaction with argon\"}, {\"type\": \"FILTRATION\", \"details\": \"Add EA and filter through a Celite\\u00ae bed\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EA\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"Add saturated NaHCO3 aqueous and extract with EA\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EA\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Evaporate the organic layer\"}, {\"type\": \"CUSTOM\", \"details\": \"purify the residue over a silica gel column with methanol in DCM\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.8, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-02cd26076f4944fcb1da7dcd39b0dc3f",
    "procedure_text": "The 2-(4-nitro-3-methylphenylamino)propane-1,3-diol (11) obtained above was reduced with a boiling zinc/ammonium chloride/water/ethanol mixture. The corresponding amine was isolated in dihydrochloride form.",
    "reference_string": "{\"inputs\": {\"m0_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dihydrochloride\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(4-nitro-3-methylphenylamino)propane-1,3-diol\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"zinc ammonium chloride water ethanol\"}], \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"amine\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f837dbc9621a44f791271ff4e616f012",
    "procedure_text": "To a mixture of 4-[2-(3-benzyloxy-1-phenyl-1H-pyrazol-4-yl)ethyl]-1,3-thiazole (1.24 g) and acetonitrile (50 mL) was added iodotrimethylsilane (2.04 g) at room temperature. After stirring the reaction mixture at room temperature for 15 hrs., water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography, and eluted with ethyl acetate-hexane (1:2, v/v) to give 1-phenyl-4-[2-(1,3-thiazol-4-yl)ethyl]-1H-pyrazol-3-ol as colorless crystals (0.48 g, yield 52%). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 152-153\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-[2-(3-benzyloxy-1-phenyl-1H-pyrazol-4-yl)ethyl]-1,3-thiazole\"}], \"amount\": {\"mass\": {\"value\": 1.24, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"iodotrimethylsilane\"}], \"amount\": {\"mass\": {\"value\": 2.04, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring the reaction mixture at room temperature for 15 hrs\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"the mixture was extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with saturated brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"WASH\", \"details\": \"eluted with ethyl acetate-hexane (1:2\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-phenyl-4-[2-(1,3-thiazol-4-yl)ethyl]-1H-pyrazol-3-ol\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.48, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 52.0}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-11bbd67ff15f4ae5b7ff59308fcba4fe",
    "procedure_text": "Adapting literature known protocols (Tercel, et al., J. Med. Chem. 1995, 38, 1247-1252; U.S. Pat. No. 5,602,278; Kirkpatrick, et al., Anti-Cancer Drugs, 1994, 5, 467-472; and U.S. Pat. No. 7,399,785), tert-butyl 4-(tert-butoxycarbonylamino)-3-[4-(2-chloroethoxy(2-chloroethyl)amino)-2-methyl-phenyl]-3-methyl-butanoate (24a) is prepared by adding 3-chloroperoxybenzoic acid (1.42 g, 80 wt-%, 6.6 mmol) to a solution of tert-butyl 3-[4-[bis(2-chloroethyl)amino]-2-methyl-phenyl]-4-(tert-butoxycarbonylamino)-3-methyl-butanoate (7o) (2.52 g, 5.0 mmol) in dichloromethane (DCM) (30 mL) at about room temperature for about 2 h. The reaction is followed by TLC and/or LC/MS till completion. After quenching with a saturated aqueous solution of sodium hydrogencarbonate (NaHCO3), the reaction mixture is extracted with DCM (3\u00d7). Further aqueous work-up and purification by silica gel column chromatography yield the title compound (24a).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-chloroperoxybenzoic acid\"}], \"amount\": {\"mass\": {\"value\": 1.42, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl 3-[4-[bis(2-chloroethyl)amino]-2-methyl-phenyl]-4-(tert-butoxycarbonylamino)-3-methyl-butanoate\"}], \"amount\": {\"mass\": {\"value\": 2.52, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"7,399,785), tert-butyl 4-(tert-butoxycarbonylamino)-3-[4-(2-chloroethoxy(2-chloroethyl)amino)-2-methyl-phenyl]-3-methyl-butanoate (24a) is prepared\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl 4-(tert-butoxycarbonylamino)-3-[4-(2-chloroethoxy(2-chloroethyl)amino)-2-methyl-phenyl]-3-methyl-butanoate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"After quenching with a saturated aqueous solution of sodium hydrogencarbonate (NaHCO3)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydrogencarbonate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"the reaction mixture is extracted with DCM (3\\u00d7)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Further aqueous work-up and purification by silica gel column chromatography\"}], \"outcomes\": [{\"products\": [{\"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c7920d5acfde4de68091304b0425ca93",
    "procedure_text": "A solution of methyl 4-(3-chloro-4-ethyl-1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylate (135 mg, 0.47 mmol) in 6N sodium hydroxide (1.6 ml, 9.48 mmol) and tetrahydrofuran (5.4 ml) was stirred at 70\u00b0 C. in a sealed tube for 12 h. The resulting solution was cooled and then partitioned between H2O-DCM. The aqueous phase was adjusted to pH \u02dc4 and then washed several times with DCM. The combined organic fractions were dried over Na2SO4 and concentrated affording 4-(3-chloro-4-ethyl-1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylic acid (120 mg, 0.41 mmol, 87% yield) as a white foam: LCMS (ES) m/e 270, 272 (M, M+2)+.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 4-(3-chloro-4-ethyl-1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylate\"}], \"amount\": {\"mass\": {\"value\": 135.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"volume\": {\"value\": 1.6, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 5.4, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The resulting solution was cooled\"}, {\"type\": \"CUSTOM\", \"details\": \"partitioned between H2O-DCM\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O DCM\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed several times with DCM\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic fractions were dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(3-chloro-4-ethyl-1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylic acid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 0.41, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 120.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 87.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 87.2}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"FOAM\", \"details\": \"foam\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b604219712d94d01af249a4eb49c18c6",
    "procedure_text": "To a flask containing compound 7 (2.93 g, 11.9 mmol) in ethanol (500 mL) was added 10% Pd/C (300 mg). The mixture was degassed and stirred under a H2 atmosphere for 3 h 45. The catalyst was removed by filtration through Celite\u00ae 545, washed with ethanol (50 mL) and the filtrate was evaporated. The resulting crude product was purified by chromatography (Al2O3, CH2Cl2/EtOH, 99/1, v/v) to afford the title product 8 (1.69 g, 7.79 mmol) as a dark yellow solid. Yield 66%; Rf (Al2O3, CH2Cl2/EtOH, 99/1, v/v) 0.55; mp 181-183\u00b0 C.; IR (KBr)\u25a1 \u03bd 1299, 1487, 1613, 1701, 3202, 3431 \u25a1cm\u22121; 1H NMR (200 MHz, CDCl3) \u03b4 1.49 (t, 3H, J=7 Hz), 4.38 (m, 2H), 4.56 (q, 2H, J=7 Hz), 7.16 (d, 1H, J=2.5 Hz), 7.26 (dd, 1H, J=2.5, 9 Hz), 8.05 (d, 1H, J=9 Hz), 9.35 (s, 1H); MS m/z 217 (M+, 23), 145 (100), 117 (19), 90 (16), 63 (14).",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound 7\"}], \"amount\": {\"mass\": {\"value\": 2.93, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd/C\"}], \"amount\": {\"mass\": {\"value\": 300.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred under a H2 atmosphere for 3 h 45\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The mixture was degassed\"}, {\"type\": \"CUSTOM\", \"details\": \"The catalyst was removed by filtration through Celite\\u00ae 545\"}, {\"type\": \"WASH\", \"details\": \"washed with ethanol (50 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the filtrate was evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"The resulting crude product was purified by chromatography (Al2O3, CH2Cl2/EtOH, 99/1\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2 EtOH\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title product 8\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 7.79, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.69, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 66.0}}], \"isolated_color\": \"dark yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-08f5f815e8444c2fb9ec831e1523a006",
    "procedure_text": "A solution of sodium nitrite (0.96 g, 14 mmol) in H2O (5 mL) was added dropwise to a solution of 2,2-difluoro-1,3-benzodioxol-4-amine (2.0 g, 12 mmol) in 6 M HCl aqueous solution (12 mL, 72 mmol) at 0\u00b0 C. After stirring for 15 min at 0\u00b0 C., the mixture was added to a suspension of 2,4-pentanedione (1.2 mL, 12 mmol) and sodium acetate (5.9 g, 72 mmol) in MeOH (20 mL) pre-cooled at 0\u00b0 C. The formed precipitate was collected by filtration, washed with water and dissolved in AcOEt. The organic solution was washed with saturated NaHCO3 aqueous solution and brine, dried over MgSO4, filtered and concentrated under reduced pressure to give the title compound (3.0 g, 90% yield) as orange crystals: 1H NMR (300 MHz, CDCl3): \u03b4 ppm 2.49 (3H, s), 2.63 (3H, s), 6.88 (1H, dd, J=8.0, 1.1 Hz), 7.13 (1H, t, J=8.1 Hz), 7.30 (1H, dd, J=8.5, 1.1 Hz), 14.56 (1H, brs).",
    "reference_string": "{\"inputs\": {\"m1_m6_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium nitrite\"}], \"amount\": {\"mass\": {\"value\": 0.96, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,2-difluoro-1,3-benzodioxol-4-amine\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 12.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4_m5_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,4-pentanedione\"}], \"amount\": {\"volume\": {\"value\": 1.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium acetate\"}], \"amount\": {\"mass\": {\"value\": 5.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring for 15 min at 0\\u00b0 C.\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"pre-cooled at 0\\u00b0 C\", \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"FILTRATION\", \"details\": \"The formed precipitate was collected by filtration\"}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISSOLUTION\", \"details\": \"dissolved in AcOEt\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"AcOEt\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic solution was washed with saturated NaHCO3 aqueous solution and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 90.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 88.0}}], \"isolated_color\": \"orange\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2f6822f4b3d84e5c8faab5b8723b6257",
    "procedure_text": "A solution of 8.7 g (34.8 mmol) of 2-chloro-5-fluoro-6-methylsulfanylnicotinic acid ethyl ester (J. Med. Chem., 1993; 36:2676) and 5.7 g (100 mmol) of cyclopropylamine in 100 mL of acetonitrile is heated at reflux for 18 hours. After TLC showed the presence of unreacted starting material, 4.12 g (72 mmol) of cyclopropylamine is added and the reaction mixture is refluxed for 48 hours. The solvent is removed in vacuo and the residue is partitioned between dichloromethane (250 mL) and water (100 mL). The organic layer is washed with water, dried (MgSO4), filtered, and concentrated in vacuo. The residue is chromatographed over flash grade silica gel (230\u2013400 mesh) eluting with dichloromethane to give 6.5 g of the title compound, mp 67\u201369\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloro-5-fluoro-6-methylsulfanylnicotinic acid ethyl ester\"}], \"amount\": {\"mass\": {\"value\": 8.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cyclopropylamine\"}], \"amount\": {\"mass\": {\"value\": 5.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cyclopropylamine\"}], \"amount\": {\"mass\": {\"value\": 4.12, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"at reflux for 18 hours\", \"duration\": {\"value\": 18.0, \"units\": \"HOUR\"}}, {\"type\": \"ADDITION\", \"details\": \"is added\"}, {\"type\": \"TEMPERATURE\", \"details\": \"the reaction mixture is refluxed for 48 hours\", \"duration\": {\"value\": 48.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The solvent is removed in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue is partitioned between dichloromethane (250 mL) and water (100 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer is washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue is chromatographed over flash grade silica gel (230\\u2013400 mesh)\"}, {\"type\": \"WASH\", \"details\": \"eluting with dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 6.5, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 69.1}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d9e79f567a844d5592c9e0d45a468dea",
    "procedure_text": "Sodium hydride (209 mg) was suspended in DMF (10 mL), and to this suspension were added benzyl alcohol (564 mg) and a solution of 4,5-difluoro-N,N-dimethyl-2-nitrobenzamide (1.0 g) in DMF (3 mL). The mixture was stirred at 50\u00b0 C. for 2 hours, and then cooled with ice. After addition of 10% aqueous citric acid, the reaction mixture was extracted with ethyl acetate and the extract was washed with water and aqueous brine, dried over sodium sulfate, and concentrated. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=4:3) to give 5-benzyloxy-4-fluoro-N,N-dimethyl-2-nitrobenzamide (1.06 g).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"citric acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Sodium hydride\"}], \"amount\": {\"mass\": {\"value\": 209.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzyl alcohol\"}], \"amount\": {\"mass\": {\"value\": 564.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4,5-difluoro-N,N-dimethyl-2-nitrobenzamide\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 50.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at 50\\u00b0 C. for 2 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooled with ice\"}, {\"type\": \"EXTRACTION\", \"details\": \"the reaction mixture was extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"the extract was washed with water and aqueous brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=4:3)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-benzyloxy-4-fluoro-N,N-dimethyl-2-nitrobenzamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.06, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e7b1b1dcc77147ab928f62596f876276",
    "procedure_text": "Using the compound obtained in Example 367 and 4-bromo-1-butene, white powdery N-[2-(4-but-3-enyloxy-3-difluoromethoxy phenyl)oxazol-4-ylmethyl]-3-methylpicolinamide was obtained following the procedure of Example 98.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-bromo-1-butene\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-[2-(4-but-3-enyloxy-3-difluoromethoxy phenyl)oxazol-4-ylmethyl]-3-methylpicolinamide\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fa0d5d6a6a584e849e8e86840e0135c3",
    "procedure_text": "2-Fluoro-4-nitrotoluene (1.55 g, 10 mmol), N-bromosuccinimide (1.82 g, 10 mmol), and benzoyl peroxide (0.1 g, 0.4 mmol) were dissolved in CCl4 (50 mL). The mixture was heated at reflux, and irradiated with light (100 W bulb) for 4 hours. The reaction mixture was filtered and concentrated. The residue was dissolved in THF (50 mL) and morpholine (1.9 g, 22 mmol) was added to this solution. The mixture was stirred at ambient temperature for 1 hour, and then filtered. The filtrate was evaporated. The title compound was isolated by column chromatography in an amount of 710 mg (30% yield).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"morpholine\"}], \"amount\": {\"mass\": {\"value\": 1.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-Fluoro-4-nitrotoluene\"}], \"amount\": {\"mass\": {\"value\": 1.55, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-bromosuccinimide\"}], \"amount\": {\"mass\": {\"value\": 1.82, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzoyl peroxide\"}], \"amount\": {\"mass\": {\"value\": 0.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CCl4\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at ambient temperature for 1 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The mixture was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"at reflux\"}, {\"type\": \"CUSTOM\", \"details\": \"irradiated with light (100 W bulb) for 4 hours\", \"duration\": {\"value\": 4.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"The reaction mixture was filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue was dissolved in THF (50 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"The filtrate was evaporated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 30.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-21d3810c441940a5b666ea6f34bb2720",
    "procedure_text": "A flask containing 10.0 g 2-fluoro-4-(hexadecylamino)-benzoic acid, 3.3 g. lactic acid, 500 mg. toluenesulfonic acid and 500 ml. toluene is equipped with a Soxhlet extractor charged with activated 4 A Linde molecular sieves. The solution is refluxed for 24 hours, during which time the Soxhlet extractor is charged twice more with fresh sieves. The hot solution is filtered and left to cool, whereupon 1-carboxyethyl 2-fluoro-4-(hexadecylamino)benzoate separates as off-white crystals.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-fluoro-4-(hexadecylamino)-benzoic acid\"}], \"amount\": {\"mass\": {\"value\": 10.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lactic acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluenesulfonic acid\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"charged\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The solution is refluxed for 24 hours, during which time the Soxhlet extractor\", \"duration\": {\"value\": 24.0, \"units\": \"HOUR\"}}, {\"type\": \"ADDITION\", \"details\": \"is charged twice more with fresh sieves\"}, {\"type\": \"FILTRATION\", \"details\": \"The hot solution is filtered\"}, {\"type\": \"WAIT\", \"details\": \"left\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to cool, whereupon 1-carboxyethyl 2-fluoro-4-(hexadecylamino)benzoate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-carboxyethyl 2-fluoro-4-(hexadecylamino)benzoate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-Carboxyethyl 2-fluoro-4-(hexadecylamino)benzoate\"}]}]}]}"
  },
  {
    "reaction_id": "ord-35cf59e6d42748dba8317ecb596a1f3b",
    "procedure_text": "In a mixture of 2 ml of methanol and 2 ml of methylene chloride, 291 mg of 4-t-butylsulfinylaminopiperidine-1-carboxylic acid(4-t-butylphenyl)amide was dissolved. To the mixture, 570 mg of 80%-MMPP (magnesium monoperoxyphthalate hexahydrate) was added and the mixture was stirred at room temperature for 2 hours. The solution was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate anhydride. The solvent was removed under reduced pressure and the residue was purified by silica gel chromatography to give 130 mg of 4-t-butylsulfonylaminopiperidine-1-carboxylic acid(4-butylphenyl)amide (I-120).",
    "reference_string": "{\"inputs\": {\"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MMPP\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3_m4_m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-t-butylsulfinylaminopiperidine-1-carboxylic acid(4-t-butylphenyl)amide\"}], \"amount\": {\"mass\": {\"value\": 291.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at room temperature for 2 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"DISSOLUTION\", \"details\": \"was dissolved\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over magnesium sulfate anhydride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate anhydride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The solvent was removed under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was purified by silica gel chromatography\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-t-butylsulfonylaminopiperidine-1-carboxylic acid(4-butylphenyl)amide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 130.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-9157f3e5813746fcaade73b43ffdc756",
    "procedure_text": "To a solution of 8-chloro-6-(trifluoromethyl)imidazo[1,2-c]pyridine-2-carboxylic acid (63 mg, 0.24 mmol, prepared as described in Example 1 Step C) in a 1:1 mixture of t-butanol (5 mL) and dichloromethane (5 mL) was added 4-(dimethylamino)pyridine (88 mg, 0.71 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (117 mg, 0.60 mmol). The reaction mixture was stirred for 15 min, after which time 1-ethyl-3-methyl-1H-pyrazole-4-sulfonamide (41 mg, 0.22 mmol, the product of Step A) was added, and the reaction mixture was stirred at room temperature overnight. Dichloromethane (100 mL) was added and the mixture was washed with 1 N hydrochloric acid (3\u00d750 mL). The organic phase was separated, dried over magnesium sulfate, and concentrated under reduced pressure to afford a solid. The solid was suspended in a mixture of diethyl ether and hexane, filtered, and dried to afford 25 mg of the title compound, a compound of the present invention, as a solid, m.p. 189-190\u00b0 C. 1H NMR (CDCl3) \u03b4 9.85 (br s, 1H), 8.47 (s, 1H), 8.29 (s, 1H), 8.10 (s, 1H), 7.53 (s, 1H), 4.14 (q, 2H), 2.51 (s, 3H), 1.51 (t, 3H).",
    "reference_string": "{\"inputs\": {\"m6_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 117.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(dimethylamino)pyridine\"}], \"amount\": {\"mass\": {\"value\": 88.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m1_m2_m10\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"8-chloro-6-(trifluoromethyl)imidazo[1,2-c]pyridine-2-carboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 63.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"t-butanol\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m9\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-ethyl-3-methyl-1H-pyrazole-4-sulfonamide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"reaction_role\": \"REACTANT\"}]}, \"m7_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred for 15 min\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"the reaction mixture was stirred at room temperature overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"WASH\", \"details\": \"the mixture was washed with 1 N hydrochloric acid (3\\u00d750 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The organic phase was separated\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"to afford a solid\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 25.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-519f8bb17ca34ccd9864ba4ba603d41c",
    "procedure_text": "A solution of (1-benzhydryl-azetidin-3-yl)-acetaldehyde (0.30 g, 1.2 mmol), 5-fluoroindole (0.8 g, 6.0 mmol) and sodium hydroxide (0.6 g, 1.6 mmol) in methanol (20 mL) was refluxed for 6 hours. The reaction was quenched with water and extracted with methylene chloride (3\u00d7100 mL). The organic layer was washed with water (3\u00d780 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuum. The crude oil was column chromatographed on silica gel (30-40% ethyl acetate/hexane). The product-containing fractions were concentrated under vacuum to give 0.27 g (56%) of the title compound as a light yellow oil. 1H NMR (500 MHz, DMSO-D6): \u03b4 2.62 (t, J=6.4 Hz, 1H), 2.90-2.95 (m, 2H), 3.02 (t, J=6.1 Hz, 1H), 3.09 (s, 3H), 3.26-3.31 (m, 1H), 4.40 (br, 1H), 4.58 (d, J=8.8 Hz, 1H), 6.89 (m, 1H), 7.13-7.18 (m, 2H), 7.22-7.27 (m, 4H), 7.31-7.39 (m, 7H) 11.10 (br, 1H).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(1-benzhydryl-azetidin-3-yl)-acetaldehyde\"}], \"amount\": {\"mass\": {\"value\": 0.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-fluoroindole\"}], \"amount\": {\"mass\": {\"value\": 0.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"mass\": {\"value\": 0.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The reaction was quenched with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with methylene chloride (3\\u00d7100 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with water (3\\u00d780 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 80.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuum\"}, {\"type\": \"CUSTOM\", \"details\": \"chromatographed on silica gel (30-40% ethyl acetate/hexane)\"}, {\"type\": \"CONCENTRATION\", \"details\": \"The product-containing fractions were concentrated under vacuum\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.27, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 56.0}}], \"isolated_color\": \"light yellow\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-de4f5c31ca5d463384802e37a3b312e9",
    "procedure_text": "The compound was synthesized from of N-{2-amino-5-(4-t-butyloxycarbonyl-1,4-diazepan-1-yl)-phenyl}benzenesulfonamide and 1-naphthalenesulfonylchloride (61 mg, 0.27 mmol) to give 56 mg as purple solid. M+ 1 537.2 Calcd 537.15; 1HNMR \u03b4 8.67-8.64 (m, 1H), 8.10 (d, 1H), 8.02-7.98 (m, 1H), 7.89 (dd, 1H), 7.77-7.38 (m, 8H), 6.46 (d, 1H), 6.26 (d, 1H), 6.14 (dd, 1H), 3.54 (app t, 2H), 3.36-3.31 (m, 2H), 3.17 (app t, 2H), 2.05-1.96 (m, 2H).",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-{2-amino-5-(4-t-butyloxycarbonyl-1,4-diazepan-1-yl)-phenyl}benzenesulfonamide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-naphthalenesulfonylchloride\"}], \"amount\": {\"mass\": {\"value\": 61.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"to give 56 mg as purple solid\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-124e1a99573141e2990c3389df823c2d",
    "procedure_text": "A stirred solution of cyclohexylamine (266 ml, 2.32 mol), (E)-2-[2-(tert-butoxy)-2-oxoethyl]-5-phenyl-2-pentenoic acid (Preparation 165, 6889, 2.37 mol) and [(S)-2,2\u2032-bis(diphenylphosphino-1,1\u2032-binaphthyl]chloro(p-cymene)ruthenium chloride (4.4 g, 4.7 mmol) in methanol (6.9 litres) was heated to 60\u00b0 C., under hydrogen (60 p.s.i.), for 47 hours and then allowed to cool to room temperature (enantiomeric excess=88%). The mixture was filtered through celite and then the solvent was stripped and replaced with acetone by distillation at atmospheric pressure, at a constant volume of 4.2 litres. The resulting suspension was cooled to room temperature where it was stirred for 4 hours and then filtered. The residue was washed with acetone (2\u00d71 litre) and then dried in vacuo at 45\u00b0 C. for 16 hours to leave the title compound as a colourless solid (590 g, 64% yield, enantiomeric excess=98.9%, 97% pure by HPLC).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cyclohexylamine\"}], \"amount\": {\"volume\": {\"value\": 266.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(E)-2-[2-(tert-butoxy)-2-oxoethyl]-5-phenyl-2-pentenoic acid\"}], \"amount\": {\"moles\": {\"value\": 2.37, \"units\": \"MOLE\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(S)-2,2\\u2032-bis(diphenylphosphino-1,1\\u2032-binaphthyl]chloro(p-cymene)ruthenium chloride\"}], \"amount\": {\"mass\": {\"value\": 4.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 6.9, \"units\": \"LITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred for 4 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The mixture was filtered through celite\"}, {\"type\": \"DISTILLATION\", \"details\": \"replaced with acetone by distillation at atmospheric pressure, at a constant volume of 4.2 litres\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"The resulting suspension was cooled to room temperature where it\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"WASH\", \"details\": \"The residue was washed with acetone (2\\u00d71 litre)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried in vacuo at 45\\u00b0 C. for 16 hours\", \"duration\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 45.0, \"units\": \"CELSIUS\"}}}], \"outcomes\": [{\"reaction_time\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 590.0, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 64.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 65.0}}], \"isolated_color\": \"colourless\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c188826cea2546b18f2fd80aab10f97e",
    "procedure_text": "A 100 ml 4-neck round bottom flask, containing a magnetic stir bar and fitted with a thermometer, nitrogen inlet and distillation condenser, was charged with 75 ml of DMSO, 0.5 g of anhydrous K2CO3 and 22.8 g (0.15 mole) of CsF. The reaction mixture was heated to 115\u00b0 C. at 57 mm Hg so that about 20 ml of DMSO was distilled to dry the reaction mixture. The light yellow reaction mixture was cooled to 65\u00b0 C. and 20 g (0.1 mole) of 3-chloro-2-fluoro-5-(trifluoromethyl)pyridine was added through a pressure equalizing addition funnel which replaced the distillation condenser. After a dry ice condenser was attached to the flask the reaction temperature was maintained at 105\u00b0-115\u00b0 C. for 46.5 hours with constant agitation. The reaction mixture was black with dark solids on the sides of the flask. A short path distillation condenser was attached to the flask and 13 g of crude product was collected in a receiver, which was cooled in a dry ice/acetone bath (pressure=210 mm Hg; temperature (overhead)=85\u00b0-130\u00b0 C.; temperature (pot)=125\u00b0-160\u00b0 C). This crude product was extracted with water to remove any residual DMSO and dried over 4\u212b molecular sieves (11.5 g crude product; 11 g crude product after drying). The product was then transferred to a 25 ml round bottom flask and distilled at 102\u00b0 C. (uncorrected)/760 mm Hg through a Vigreaux\u00ae column resulting in 9.3 g of substantially pure 2,3-difluoro-5-(trifluoromethyl)pyridine. The isolated yield of desired product was calculated to be 48.4% of theoretical. The structure of the product was confirmed by its nuclear magnetic resonance (NMR) spectra. Elemental analysis results for the product were:",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMSO\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"K2CO3\"}], \"amount\": {\"mass\": {\"value\": 0.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CsF\"}], \"amount\": {\"mass\": {\"value\": 22.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMSO\"}], \"amount\": {\"volume\": {\"value\": 75.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-chloro-2-fluoro-5-(trifluoromethyl)pyridine\"}], \"amount\": {\"mass\": {\"value\": 20.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 65.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"A 100 ml 4-neck round bottom flask, containing a magnetic stir bar\"}, {\"type\": \"CUSTOM\", \"details\": \"fitted with a thermometer, nitrogen inlet and distillation condenser\"}, {\"type\": \"DISTILLATION\", \"details\": \"was distilled\"}, {\"type\": \"CUSTOM\", \"details\": \"to dry the reaction mixture\"}, {\"type\": \"ADDITION\", \"details\": \"addition funnel which\"}, {\"type\": \"CUSTOM\", \"details\": \"After a dry ice condenser was attached to the flask\"}, {\"type\": \"TEMPERATURE\", \"details\": \"the reaction temperature was maintained at 105\\u00b0-115\\u00b0 C. for 46.5 hours with constant agitation\", \"duration\": {\"value\": 46.5, \"units\": \"HOUR\"}}, {\"type\": \"DISTILLATION\", \"details\": \"A short path distillation condenser\"}, {\"type\": \"CUSTOM\", \"details\": \"was collected in a receiver, which\"}, {\"type\": \"TEMPERATURE\", \"details\": \"was cooled in a dry ice/acetone bath (pressure=210 mm Hg; temperature (overhead)=85\\u00b0-130\\u00b0 C.; temperature (pot)=125\\u00b0-160\\u00b0 C)\"}, {\"type\": \"EXTRACTION\", \"details\": \"This crude product was extracted with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"to remove any residual DMSO\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMSO\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over 4\\u212b molecular sieves (11.5 g crude product; 11 g crude product after drying)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"amount\": {\"mass\": {\"value\": 11.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"amount\": {\"mass\": {\"value\": 11.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The product was then transferred to a 25 ml round bottom flask\"}, {\"type\": \"DISTILLATION\", \"details\": \"distilled at 102\\u00b0 C. (uncorrected)/760 mm Hg through a Vigreaux\\u00ae column\", \"temperature\": {\"setpoint\": {\"value\": 102.0, \"units\": \"CELSIUS\"}}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,3-difluoro-5-(trifluoromethyl)pyridine\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-53a4bd77a9284749bfc840a3f5ec4a74",
    "procedure_text": "A mixture of dipropyl-(6,7,8,9-tetrahydro-3H-benzo[e]indol-7-yl)amine (55 mg, 0.20 mmol) and phosphorous oxychloride (130 \u03bcL, 213 mg, 1.39 mmol) in N,N-dimethylacetamide (200 \u03bcL) was heated at 80\u00b0 C. for 4 hours. After cooling 5M sodium hydroxide was added and the mixture was heated again for 0.5 hours. After cooling the mixture was extracted 3 times with ethyl acetate, dried (magnesium sulfate), filtered and evaporated to yield a residue to which 99% ethanol was added. This was then evaporated to dryness. A few repetitions of the last procedure yielded a residue of 56 mg (89%) of the product, which was further purified on silica using methanol as eluant to give the pure material as a solid.:",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dipropyl-(6,7,8,9-tetrahydro-3H-benzo[e]indol-7-yl)amine\"}], \"amount\": {\"mass\": {\"value\": 55.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"phosphorous oxychloride\"}], \"amount\": {\"volume\": {\"value\": 130.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylacetamide\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 80.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"TEMPERATURE\", \"details\": \"the mixture was heated again for 0.5 hours\", \"duration\": {\"value\": 0.5, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"After cooling the mixture\"}, {\"type\": \"EXTRACTION\", \"details\": \"was extracted 3 times with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (magnesium sulfate)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"to yield a residue to which 99% ethanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"CUSTOM\", \"details\": \"This was then evaporated to dryness\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 56.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 89.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a4da851c14a74098bb5e2caf7ba51835",
    "procedure_text": "To a solution of 3-benzyloxy-2-ethyl-1-(2-hydroxyethyl)pyridin-4-one hydrochloride (3.1 g, 0.01 mole; prepared as described in Example 2) in 100 ml of dry dimethylformamide was added dropwise triethylamine (7 ml, 0.05 mole) whilst stirring over 15 minutes under N2. Isobutyryl chloride (4.2 ml, 0.04 mole) was then added dropwise and the mixture was heated at 75\u00b0-78\u00b0 C. overnight under N2. The reaction was monitored by tlc (silica; 50% EtOH:50% EtOAc) and after filtration the dimethylformamide was removed under high vacuum by rotary evaporation. The solid residue was dissolved in 100 ml of dichloromethane and washed with 5% w/v aqueous NaHCO3 (3\u00d7100 ml) and water (2\u00d7100 ml). The organic layer was dried over Na2SO4, filtered and rotary evaporated to give a crude solid. Purification was achieved by recrystallization using activated charcoal in ethyl acetate. The filtrate was used for further crystallization of the solid from ethyl acetate to give the title compound in 40% yield, \u03b4(DMSO): 0.8-1.12 (15H, m), 2.3-2.8 (4H, m), 4.15 (4H, s), 5.9-6.1 (1H, d, 7 Hz), 7.5-7.7 (1H, d, 8 Hz).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Isobutyryl chloride\"}], \"amount\": {\"volume\": {\"value\": 4.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m2_m6_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-benzyloxy-2-ethyl-1-(2-hydroxyethyl)pyridin-4-one hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 3.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 7.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOH\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirring over 15 minutes under N2\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"the mixture was heated at 75\\u00b0-78\\u00b0 C. overnight under N2\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"after filtration the dimethylformamide\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"was removed under high vacuum by rotary evaporation\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The solid residue was dissolved in 100 ml of dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with 5% w/v aqueous NaHCO3 (3\\u00d7100 ml) and water (2\\u00d7100 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layer was dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"rotary evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a crude solid\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification\"}, {\"type\": \"CUSTOM\", \"details\": \"was achieved by recrystallization\"}, {\"type\": \"CUSTOM\", \"details\": \"The filtrate was used for further crystallization of the solid from ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 40.0}}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"\\u03b4(DMSO)\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-dfbd48d627d343898e9342f116779391",
    "procedure_text": "Employing ethyl 2-(2-methyl-3,4,5,6-tetrafluorobenzoyl)-3-ethoxyacrylate (10.0 g) and ethylamine gas, the procedure of Reference Example 21 is repeated to give ethyl 2-(2-methyl-3,4,5,6-tetrafluorobenzoyl)-3-ethylaminoacrylate (9.0 g, white crystals), which is then treated with 60% sodium hydride (1.30 g) as in Reference Example 22 to give ethyl 1-ethyl-5-methyl-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate (6.76 g), as pale yellow needles (recrystallized from dichloromethane - n-hexane), m.p. 197\u00b0-198\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 2-(2-methyl-3,4,5,6-tetrafluorobenzoyl)-3-ethoxyacrylate\"}], \"amount\": {\"mass\": {\"value\": 10.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethylamine\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 2-(2-methyl-3,4,5,6-tetrafluorobenzoyl)-3-ethylaminoacrylate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 9.0, \"units\": \"GRAM\"}}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e1c68e2827b44da0962e2bcf4acbee36",
    "procedure_text": "To a solution of the product of step B (3.8 g, 18.7 mmol) in acetic acid (20 mL) was added Pd/C 10% (380 mg) cautiously. The resulting mixture was hydrogenated at 50 psi H2 for 3 h. The reaction mixture was filtered through celite and washed with acetic acid (20 mL). The filtrate was concentrated in vacuo to yield 2-methylpiperidin-4-one acetate as a brown oil (2.98 g, >99%) which was sufficiently pure for the next step: 1H NMR (CD3OD, 400 MHz) \u03b4 3.24-3.19 (m, 1H), 2.86-2.81 (m, 1H), 2.74-2.67 (m, 1H), 2.51-2.49 (m, 2H), 2.37-2.28 (m, 2H), 2.22-2.18 (m, 1H), 2.12-2.02 (m, 2H), 1.08 (d, J=6.4 Hz, 3H).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"amount\": {\"mass\": {\"value\": 3.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd/C\"}], \"amount\": {\"mass\": {\"value\": 380.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The reaction mixture was filtered through celite\"}, {\"type\": \"WASH\", \"details\": \"washed with acetic acid (20 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"The filtrate was concentrated in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-methylpiperidin-4-one acetate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.98, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 99.0}}], \"isolated_color\": \"brown\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-98aacd7b53e845a197feb48e985e1a45",
    "procedure_text": "A solution of 1-F (0.76 g, 1.8 mmol), Boc2O (0.52 g, 2.4 mmol), pyridine (99 \u03bcL, 1.3 mmol), and NH4CO3H (0.22 g, 2.8 mmol) in dioxane (4 mL) and DMF (1 mL) was stirred at 25\u00b0 C. for 12 h. The reaction mixture was diluted with EtOAc (100 mL) and washed with 0.1 N HCl (2\u00d720 mL), saturated NaHCO3 (2\u00d720 mL), and brine (20 mL), dried with Na2SO4, filtered, and concentrated to give a crude residue which was purified using flash column chromatography (100% CH2Cl2\u219210% MeOH/CH2Cl2) to yield 1-G as a brown-red solid (0.76 g, 100%). 1H NMR (400 MHz, CDCl3): \u03b4 7.41 (d, J=8.2 Hz, 2H), 7.30 (d, J=8.2 Hz, 2H), 6.38 (s, 1H), 6.01 (br s, 1H), 5.45 (br s, 1H), 5.15\u20135.10 (m, 1H), 4.50\u20134.38 (m, 1H), 3.15 (dd, J=13.9, 6.8 Hz, 1H), 3.08 (dd, J=13.5, 6.5 Hz, 1H), 1.68 (s, 9H), 1.41 (s, 9H); LCMS found for C21H30N3O4S (M+H)+: m/z=420.",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3_m5_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-F\"}], \"amount\": {\"mass\": {\"value\": 0.76, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Boc2O\"}], \"amount\": {\"mass\": {\"value\": 0.52, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"amount\": {\"volume\": {\"value\": 99.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dioxane\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WASH\", \"details\": \"washed with 0.1 N HCl (2\\u00d720 mL), saturated NaHCO3 (2\\u00d720 mL), and brine (20 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried with Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a crude residue which\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude residue\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"was purified\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-G\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.76, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 100.0}}], \"isolated_color\": \"brown-red\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a56d107b87fd46fe9b034ad4b297ff74",
    "procedure_text": "4-(3,4-Dimethoxyphenyl)butyric acid (13 g, 58 mmol) was dissolved in dry THF (150 mL) then BH3.THF (110 mL, 1M solution, 110 mmol) was added drop wise with vigorous stirring under an argon atmosphere. The reaction mixture was then stirred overnight at room temperature. After this time, the reaction was quenched with water and 10% HCl solution at 0\u00b0 C. and extracted with ethyl acetate. The organic fraction was dried with sodium sulfate and passed through a pad of silica gel. The solvent was removed at reduced pressure to give 23 (12.0 g, 99%) as a clear oil. 1H NMR (300 MHz, CDCl3) \u03b4 1.62 (m, 4H), 2.0 (s, 1H), 2.62 (m, 2H), 3.65 (m, 2H), 3.82 (s, 3H), 3.84 (s, 3H) 6.67-6.82 (m, 3H).",
    "reference_string": "{\"inputs\": {\"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(3,4-Dimethoxyphenyl)butyric acid\"}], \"amount\": {\"mass\": {\"value\": 13.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"BH3.THF\"}], \"amount\": {\"volume\": {\"value\": 110.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"with vigorous stirring under an argon atmosphere\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"The reaction mixture was then stirred overnight at room temperature\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"After this time, the reaction was quenched with water and 10% HCl solution at 0\\u00b0 C.\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}]}, \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic fraction was dried with sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The solvent was removed at reduced pressure\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"23\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 12.0, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 99.0}}], \"isolated_color\": \"clear\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-67652aaee9214cc38b5eb659d2c83867",
    "procedure_text": "In a 1-liter three-necked flask equipped with a 200 ml dropping funnel were charged 87.61 g (0.66 mol) of anhydrous aluminum chloride and 150 ml of carbon disulfide, to which were added at room temperature through a dropping funnel p-cymene (47.0 ml, 0.301 mol) and methacryloyl chloride (33.0 ml, 0.338 mol) diluted with 30 ml of carbon disulfide. After stirring at room temperature for 5 hours, the reaction mixture was slowly poured on 1 kg of ice. After extraction of the reaction mixture with diethyl ether, the resulting organic layer was washed with an aqueous saturated solution of sodium hydrogen carbonate and with saline, and dried over sodium sulfate. Sodium sulfate was removed by filtration and the solvent was distilled off under reduced pressure.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"KILOGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"p-cymene\"}], \"amount\": {\"volume\": {\"value\": 47.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methacryloyl chloride\"}], \"amount\": {\"volume\": {\"value\": 33.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aluminum chloride\"}], \"amount\": {\"mass\": {\"value\": 87.61, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"carbon disulfide\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"carbon disulfide\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring at room temperature for 5 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"In a 1-liter three-necked flask equipped with a 200 ml\"}, {\"type\": \"EXTRACTION\", \"details\": \"After extraction of the reaction mixture with diethyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"the resulting organic layer was washed with an aqueous saturated solution of sodium hydrogen carbonate and with saline\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydrogen carbonate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Sodium sulfate was removed by filtration\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"the solvent was distilled off under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 5.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-6d8ecc4e3a064465908b9acb8cf1c3a3",
    "procedure_text": "A solution of triethylamine (1.4 ml) and 1.27 g. of 3-chloropropionylchloride in 5 ml. of DCNM was added to a solution of 1.73 g. of 5-hydroxy-1,4-naphthoquinone. The reaction mixture was stirred for 2 hours at room temperature. The solution was filtered and concentrated to a small volume and chromatographed on a silica gel column (ethylacetate-cyclohexane-DCM) to give 741 mg. of desired product.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-chloropropionylchloride\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-hydroxy-1,4-naphthoquinone\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 1.4, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred for 2 hours at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"of DCNM was added to a solution of 1.73 g\"}, {\"type\": \"FILTRATION\", \"details\": \"The solution was filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated to a small volume\"}, {\"type\": \"CUSTOM\", \"details\": \"chromatographed on a silica gel column (ethylacetate-cyclohexane-DCM)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethylacetate cyclohexane DCM\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"to give 741 mg\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-16ebb065b3f54bd6bf06620dc74a6728",
    "procedure_text": "To ethanolamine (9.0 ml, 149 mmol) in methylene chloride (100 ml) at 0\u00b0 C. was added benzyl chlorformate (10.0 ml, 70 mmol). The mixture was stirred at 0\u00b0 C. for 30 min, then at room temperature for 1 h, poured into ethyl acetate, washed with 2M HCl, saturated NaHCO3 solution, and brine, then dried over Na2SO4 and evaporated to provide 12.91 g (94%) of the desired compound as a white solid. 1H NMR (CDCl3, TMS) 7.47 (m,5H), 5.11 s,2H), 3.73 (m,2H), 3.38 (m,2H).",
    "reference_string": "{\"inputs\": {\"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanolamine\"}], \"amount\": {\"volume\": {\"value\": 9.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzyl chlorformate\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at 0\\u00b0 C. for 30 min\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WAIT\", \"details\": \"at room temperature for 1 h\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"WASH\", \"details\": \"washed with 2M HCl, saturated NaHCO3 solution, and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 12.91, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 94.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 94.5}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-bfcbb8402fa1477e8325d44e7341e5ba",
    "procedure_text": "Combine N,N\u2032-dibenzyl-2-((R)-2-bromo-3-phenylpropionylamino)malonamide (0.49 g, 0.97 mmol) and thioacetic acid (0.172 mL, 2.42 mmol) in dimethylformamide (15 mL). Degas by repeated cycles of vacuum and filing with nitrogen. Add cesium carbonate (0.473 g, 1.45 mmol). After 18 hours, dilute the reaction mixture with water and extract twice with ethyl acetate. Combine the organic layers, extract with brine, dry over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 3/2 ethyl acetate/hexane to give the title compound (46%).",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N\\u2032-dibenzyl-2-((R)-2-bromo-3-phenylpropionylamino)malonamide\"}], \"amount\": {\"mass\": {\"value\": 0.49, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"thioacetic acid\"}], \"amount\": {\"volume\": {\"value\": 0.172, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m4_m0\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate hexane\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cesium carbonate\"}], \"amount\": {\"mass\": {\"value\": 0.473, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Degas by repeated cycles of vacuum and filing with nitrogen\"}, {\"type\": \"EXTRACTION\", \"details\": \"extract twice with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extract with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dry over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filter\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporate in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a residue\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 18.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 46.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-032127406f844981bea35c7cb9bfb633",
    "procedure_text": "1-(3-Chloro-4-fluorophenyl)-6-fluoro-3-hydroxy-7-(3-aminopyrrolidin-1-yl)-1H-quinazoline-2,4-dione, trifluoroacetate;",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(3-Chloro-4-fluorophenyl)-6-fluoro-3-hydroxy-7-(3-aminopyrrolidin-1-yl)-1H-quinazoline-2,4-dione\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trifluoroacetate\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-51e28b072a844acda829b02566b5628f",
    "procedure_text": "2-Methyl-2-(4-nitro-imidazol-1-yl)-propionaldehyde was reacted with cis-2,6-dimethyl morpholine to provide the title compound: C13 NMR (100 MHz, CDCl3) 19.0, 25.7, 60.8, 61.5, 68.5, 72.0, 118.0, 134.5; MS m/z 283.2 (M+1).",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-Methyl-2-(4-nitro-imidazol-1-yl)-propionaldehyde\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cis-2,6-dimethyl morpholine\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b75bd1fea7944455acd779032b2d6ea8",
    "procedure_text": "Piperidine (0.20 mL) was added to a solution of (S)-1-(9H-fluoren-9-yl)-14,14-dimethyl-3,12-dioxo-10-(thiazol-2-ylmethyl)-2,13-dioxa-4,10-diazapentadecane-5-carboxylic acid (72.5 mg, 0.125 mmol) in DMF (1.0 mL). The mixture was stirred at room temperature for 2 hrs. Solvent was evaporated under reduce pressure to afford a residue, which was purified by flash chromatography over silica gel to afford (S)-2-amino-6-((2-tert-butoxy-2-oxoethyl)(thiazol-2-ylmethyl)amino)hexanoic acid (25 mg, 35%). 1H NMR (400 MHz, CD3OD) 7.70 (d, J=3.6 Hz, 1H), 7.53 (d, J=3.2 Hz, 1H), 4.15 (s, 2H), 3.52 (dd, J=7.2, 5.2 Hz, 1H), 3.38 (s, 2H), 2.73 (t, J=7.2 Hz, 2H), 1.91-1.76 (m, 2H), 1.60-1.44 (m, 13H); MS (ESI), 358 (M+H)+.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Piperidine\"}], \"amount\": {\"volume\": {\"value\": 0.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(S)-1-(9H-fluoren-9-yl)-14,14-dimethyl-3,12-dioxo-10-(thiazol-2-ylmethyl)-2,13-dioxa-4,10-diazapentadecane-5-carboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 72.5, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at room temperature for 2 hrs\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Solvent was evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"to afford a residue, which\"}, {\"type\": \"CUSTOM\", \"details\": \"was purified by flash chromatography over silica gel\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(S)-2-amino-6-((2-tert-butoxy-2-oxoethyl)(thiazol-2-ylmethyl)amino)hexanoic acid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 25.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 35.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b0e6f8f091394914b5c91aaf2ba37a13",
    "procedure_text": "A large (2-5 mL) microwave reactor flask was charged with 5,6-dichlorobenzimidazole (571 mg, 3.1 mmol), 1,2-epoxy-3,3-dimethylbutane (307 mg, 3.1 mmol), powdered anhydrous potassium carbonate (424 mg, 3.1 mmol) and DMF (1.5 mL). The reaction was then heated in a microwave reactor for 6 minutes at 160\u00b0 C. The reaction was then diluted with ethyl acetate and extracted with water three times. The organics were dried over MgSO4 and the solvent was removed. The residue was crystallized from CH2Cl2 to afford 653 mg (73%) of product as a white solid: 1H NMR (DMSO, 400 MHz) \u03b4 1.06 (s, 9H), 3.47 (dd, 1H, J=2.0, J2=10.4), 4.08 (dd, 1H, J1=10.5, J2=14.4), 4.47 (dd, 1H, J1=2.0, J2=14.4), 7.75 (s, 1H), 7.79 (s, 1H), 8.23 (s, 1H); HPLC-MS calcd. for C21H22Cl2N4O2 (M+H+) 287.1, found 287.3.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 1.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5,6-dichlorobenzimidazole\"}], \"amount\": {\"mass\": {\"value\": 571.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,2-epoxy-3,3-dimethylbutane\"}], \"amount\": {\"mass\": {\"value\": 307.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 424.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 160.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted with water three times\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organics were dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was removed\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was crystallized from CH2Cl2\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 653.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 73.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 73.3}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a4b6c11e1a6e4a48af9161ced78c9c90",
    "procedure_text": "To 10 ml of dimethyl sulfoxide was added 1.40 g (12.5 mmol) of potassium tert-butoxide, and to the solution was added 951 mg (10.0 mmol) of 5-aminopyrimidine while cooling with water. After stirring at room temperature for 1 hour, 0.54 ml (5.0 mmol) of 2-fluorobenzonitrile was added thereto while cooling with water, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was poured into ice-water, and the mixture was adjusted to pH 7.0 with 1 N hydrochloric acid, and filtered. The filter residue was dissolved in 200 ml of acetone, and the acetone solution was filtered. The filtrate was dried over magnesium sulfate, and the solvent was removed by distillation under reduced pressure to obtain 0.53 g (2.70 mmol) of 5-[N-(2cyanophenyl)amino]pyrimidine.",
    "reference_string": "{\"inputs\": {\"m8_m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium tert-butoxide\"}], \"amount\": {\"mass\": {\"value\": 1.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethyl sulfoxide\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-fluorobenzonitrile\"}], \"amount\": {\"volume\": {\"value\": 0.54, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-aminopyrimidine\"}], \"amount\": {\"mass\": {\"value\": 951.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring at room temperature for 1 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"the mixture was stirred at room temperature for 30 minutes\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The filter residue was dissolved in 200 ml of acetone\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"the acetone solution was filtered\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The filtrate was dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was removed by distillation under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-[N-(2cyanophenyl)amino]pyrimidine\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 2.7, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.53, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 54.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e10696dac19b4a7dbd79d20300f16d36",
    "procedure_text": "To a stirred solution of (1S)-1-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3,4-dihydro-1H-2-benzopyran-6-amine (0.15 g, 0.49 mmol) in ethyl acetate (18 mL), cooled to 0\u00b0 C., was added triethylamine (0.274 mL, 1.37 mmol) then 3-chloro-1-propanesulfonyl chloride (0.070 mL, 0.576 mmol), and the reaction mixture allowed to warm to room temperature. After stirring for 1 h, the reaction was basified with 1N sodium hydroxide (2.5 mL), and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO4), filtered and evaporated in vacuo to yield the title compound as an oil. This crude product was used in the next step without further purification.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"volume\": {\"value\": 2.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 0.274, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(1S)-1-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3,4-dihydro-1H-2-benzopyran-6-amine\"}], \"amount\": {\"mass\": {\"value\": 0.15, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 18.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-chloro-1-propanesulfonyl chloride\"}], \"amount\": {\"volume\": {\"value\": 0.07, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring for 1 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined organic extracts were washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0e5259f31ac845dbb4b124b976f9a35e",
    "procedure_text": "To a mixture of 7-bromo-4-(3,4-dichlorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinoline (500 mg, 1.35 mmol) which was prepared following similar method described in Steps A to C of Example 1 starting from 2-bromo-1-(3,4-dichlorophenyl)ethanone and 1-(3-bromophenyl)-N-methylmethanamine, pyridin-2-ol (154 mg, 1.62 mmol), N,N\u2032-dimethylethylene diamine (58 \u03bcl, 0.54 mmol), and potassium phosphate (572 mg, 2.69 mmol) in 1,4-dioxane (5 mL) was added copper(1) iodide (51 mg, 0.27 mmol). The mixture was degassed with argon and then heated to 110\u00b0 C. for 17 hours. The reaction mixture was diluted with water (20 mL) and extracted with methylene chloride (2\u00d725 mL). The combined organics were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was partially purified by column chromatography (methylene chloride to 90:9:1 methylene chloride/methanol/ammonium hydroxide) to give 1-(4-(3,4-dichlorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)pyridin-2(1H)-one (37 mg, 7%): ESI MS m/z 385 [M+H]+.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-bromo-4-(3,4-dichlorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinoline\"}], \"amount\": {\"mass\": {\"value\": 500.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N\\u2032-dimethylethylene diamine\"}], \"amount\": {\"volume\": {\"value\": 58.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(3-bromophenyl)-N-methylmethanamine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridin-2-ol\"}], \"amount\": {\"mass\": {\"value\": 154.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium phosphate\"}], \"amount\": {\"mass\": {\"value\": 572.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,4-dioxane\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"copper(1) iodide\"}], \"amount\": {\"mass\": {\"value\": 51.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-bromo-1-(3,4-dichlorophenyl)ethanone\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 110.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"was prepared\"}, {\"type\": \"CUSTOM\", \"details\": \"The mixture was degassed with argon\"}, {\"type\": \"ADDITION\", \"details\": \"The reaction mixture was diluted with water (20 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with methylene chloride (2\\u00d725 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organics were dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was partially purified by column chromatography (methylene chloride to 90:9:1 methylene chloride/methanol/ammonium hydroxide)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride methanol ammonium hydroxide\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(4-(3,4-dichlorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)pyridin-2(1H)-one\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 37.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 7.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 7.1}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2935942700bc4cbaa254aa1a19c6f93e",
    "procedure_text": "4-Acetyl-7-sulfamoyl-2,3,4,5-tetrahydrothieno[3,2-f]-1,4-thiazepin-1,1-dioxide (200 mg, 0.62 mmol) was dissolved in dry THF (10 mL), boron trifluoride etherate (0.15 mL) was added and the reaction mixture was refluxed for 0.5 hour. Borane dimethyl sulfide complex (0.7 mL) was added and the reaction mixture was refluxed for 1 hour. The reaction mixture was cooled and methanol and isopropanolic HCl were added. This solution was refluxed for 0.5 hours and the solvents removed. The residue was chromatographed on silica gel eluting with 10% methanol-methylene chloride. Appropriate fractions were combined, isopropanolic HCl added and the solvents evaporated to give 110 mg (27%) of the title compound as its hydrochloride salt. Recrystallization from isopropanol afforded analytically pure material as the hydrochloride salt solvated with one equivalent of isopropanol.",
    "reference_string": "{\"inputs\": {\"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"boron trifluoride etherate\"}], \"amount\": {\"volume\": {\"value\": 0.15, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-Acetyl-7-sulfamoyl-2,3,4,5-tetrahydrothieno[3,2-f]-1,4-thiazepin-1,1-dioxide\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"the reaction mixture was refluxed for 0.5 hour\", \"duration\": {\"value\": 0.5, \"units\": \"HOUR\"}}, {\"type\": \"ADDITION\", \"details\": \"Borane dimethyl sulfide complex (0.7 mL) was added\"}, {\"type\": \"TEMPERATURE\", \"details\": \"the reaction mixture was refluxed for 1 hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"The reaction mixture was cooled\"}, {\"type\": \"TEMPERATURE\", \"details\": \"This solution was refluxed for 0.5 hours\", \"duration\": {\"value\": 0.5, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"the solvents removed\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was chromatographed on silica gel eluting with 10% methanol-methylene chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"isopropanolic HCl added\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solvents evaporated\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 110.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 27.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-5786221343a147a7b635b71a989eac07",
    "procedure_text": "The title compound was prepared in accordance with the general method of Example 149(A), from 4-fluoro-2-nitro-benzaldehyde (180 mg, 1.06 mmol) and 4-trimethylsilanyl-but-3-ynylamine (200 mg, 1.40 mmol). The crude product was purified by by flash chromatography (cyclohexane/AcOEt 4:1) to yield 6-fluoro-2-(4-trimethylsilanyl-but-3-ynyl)-2H-indazole (310 mg, 1.06 mmol).",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-fluoro-2-nitro-benzaldehyde\"}], \"amount\": {\"mass\": {\"value\": 180.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-trimethylsilanyl-but-3-ynylamine\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The crude product was purified by by flash chromatography (cyclohexane/AcOEt 4:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cyclohexane AcOEt\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-fluoro-2-(4-trimethylsilanyl-but-3-ynyl)-2H-indazole\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 1.06, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 310.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-38782f1eb9814a8781eb985a0af58743",
    "procedure_text": "2-Chloro-9-cyclopentyl-7-ethylidene-5-methyl-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one (1.01 g, 3.30 mmol) in dry tetrahydrofuran (10 mL) was added to 1:1 molar 2 M lithium diisopropyl amide in tetrahydrofuran and hexamethyl phosphoramide (HMPA) (3.96 mmol each) in tetrahydrofuran (5 mL) at \u221278\u00b0 C. After 20 minutes, N-fluorobenzene sulfonimide (2.46 mmol) was added dropwise to it. Continued the reaction at \u221278\u00b0 C. for 30 minutes, and then elevated the temperature to 0\u00b0 C. for 30 minutes. After disappearing the starting material, cooled the reaction flask to \u221278\u00b0 C., then quenched with sat. ammonium chloride solution (6 mL). At room temperature, the resultant reaction mixture was taken into ethyl acetate (70 mL), washed with ammonium chloride solution and finally with water, dried over sodium sulphate and evaporated. Purified the product using column chromatography with hexane:ethyl acetate mixtures to give the product. 1H NMR (400 MHz, CHLOROFORM-d) \u03b4 ppm 1.53-2.10 (m, 8H) 3.38 (s, 3H) 3.63-3.88 (m, 1H) 4.12 (m, 1H) 4.96 (quin, J=8.59 Hz, 1H) 5.41 (d, J=11.12 Hz, 1H) 5.49 (dd, J=17.18, 2.02 Hz, 1H) 6.02 (ddd, J=17.37, 14.72, 10.86 Hz, 1H) 7.97 (s, 1H). [M+H] calculated for C15H18ClFN4O, 325. found 325.",
    "reference_string": "{\"inputs\": {\"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexamethyl phosphoramide\"}], \"amount\": {\"moles\": {\"value\": 3.96, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-fluorobenzene sulfonimide\"}], \"amount\": {\"moles\": {\"value\": 2.46, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 70.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium diisopropyl amide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-Chloro-9-cyclopentyl-7-ethylidene-5-methyl-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one\"}], \"amount\": {\"mass\": {\"value\": 1.01, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -78.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"at \\u221278\\u00b0 C\", \"temperature\": {\"setpoint\": {\"value\": -78.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"Continued the reaction at \\u221278\\u00b0 C. for 30 minutes\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"temperature\": {\"setpoint\": {\"value\": -78.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"to 0\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"for 30 minutes\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}}, {\"type\": \"CUSTOM\", \"details\": \"quenched with sat. ammonium chloride solution (6 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium chloride\"}], \"amount\": {\"volume\": {\"value\": 6.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"At room temperature, the resultant reaction mixture\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"WASH\", \"details\": \"washed with ammonium chloride solution and finally with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium chloride\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulphate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulphate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"Purified the product\"}, {\"type\": \"CUSTOM\", \"details\": \"ethyl acetate mixtures to give the product\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 20.0, \"units\": \"MINUTE\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-2c07656da277437f88a9d3ddd0e19e86",
    "procedure_text": "A solution of 2-Tetrazol-1-yl-benzoic acid (1.0 g, 5.2 mmol), ammonium chloride (0.56 g, 10.4 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2.0 g, 10.4 mmol), 1-hydroxy-7-azabenzotriazole (1.4 g, 10.4 mmol) and diisopropylethylamine (3.6 ml, 20.8 mmol) in N,N-dimethylformamide (15 ml) was stirred at room temperature overnight. Water was added and the reaction mixture was extracted with ethyl acetate. The combined organic layers were washed with brine. Drying and solvent evaporation gave 2-Tetrazol-1-yl-benzamide; 1H NMR (CD3OD, 400 MHz) \u03b49.44 (s, 1H), 7.72 (m, 4H).",
    "reference_string": "{\"inputs\": {\"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3_m4_m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-Tetrazol-1-yl-benzoic acid\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium chloride\"}], \"amount\": {\"mass\": {\"value\": 0.56, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-hydroxy-7-azabenzotriazole\"}], \"amount\": {\"mass\": {\"value\": 1.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropylethylamine\"}], \"amount\": {\"volume\": {\"value\": 3.6, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"the reaction mixture was extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined organic layers were washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Drying\"}, {\"type\": \"CUSTOM\", \"details\": \"solvent evaporation\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-Tetrazol-1-yl-benzamide\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e6294780804a4469b42ef8b5c88fab92",
    "procedure_text": "A solution of 28.5 g (0.084 mol) of N,N-bis(2-cyclohexanoyloxyethyl)methylamine (prepared as described in Example 22), 10.63 g (0.084 mol) of benzyl chloride and 200 ml of acetonitrile was heated at reflux for 2.5 hours and concentrated to an oil. Ether was added to the oil which induced crystallization. The white solid was collected, washed two times with ether and recrystallized from 2-butanone. The yield of product was 8.3 g; mp=143.5\u00b0-4.5\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-bis(2-cyclohexanoyloxyethyl)methylamine\"}], \"amount\": {\"mass\": {\"value\": 28.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzyl chloride\"}], \"amount\": {\"mass\": {\"value\": 10.63, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"at reflux for 2.5 hours\", \"duration\": {\"value\": 2.5, \"units\": \"HOUR\"}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated to an oil\"}, {\"type\": \"ADDITION\", \"details\": \"Ether was added to the oil which\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"crystallization\"}, {\"type\": \"CUSTOM\", \"details\": \"The white solid was collected\"}, {\"type\": \"WASH\", \"details\": \"washed two times with ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"recrystallized from 2-butanone\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-butanone\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-7bcebf46374b43cfbbc98a5f1ae7b846",
    "procedure_text": "0.9 g (2.3 mmol) of 9-(2-carboxyethyl)-3(R)-(4-pyridylsulphonamido)-1,2,3,4-tetrahydrocarbazole is dissolved in 50 ml of ethanol p.a., 3 ml of concentrated sulphuric acid are added and the mixture is boiled under reflux for 1.5 hours with stirring. After cooling to room temperature, 12.0 g of sodium hydrogen carbonate are added, water is added after the evolution of gas has ended and the mixture is extracted several times with ethyl acetate. The combined organic phases are dried with sodium sulphate and the solvent evaporated therefrom. The crude product is purified by chromatography on silica gel 60 (40-63 \u03bcm, Merck, eluant: CH2Cl2 :CH3OH=10:1). Rf =0.63 (CH2Cl2 :CH3OH=10:1)",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sulphuric acid\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"9-(2-carboxyethyl)-3(R)-(4-pyridylsulphonamido)-1,2,3,4-tetrahydrocarbazole\"}], \"amount\": {\"mass\": {\"value\": 0.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydrogen carbonate\"}], \"amount\": {\"mass\": {\"value\": 12.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"with stirring\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"under reflux for 1.5 hours\", \"duration\": {\"value\": 1.5, \"units\": \"HOUR\"}}, {\"type\": \"EXTRACTION\", \"details\": \"the mixture is extracted several times with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic phases are dried with sodium sulphate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulphate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude product is purified by chromatography on silica gel 60 (40-63 \\u03bcm, Merck, eluant: CH2Cl2 :CH3OH=10:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH3OH\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-4081eae955a246efaf3fb16cf3abaae7",
    "procedure_text": "Ethanol (100.5 ml) and water (3.975 ml) were added to 2-{4-amino-2-[(3-chloro-4-methoxy-5-methylpyridin-2-yl)methyl]-2,7-dihydro-6-thia-1,2,3,5-tetraazabenzo[cd]azulen-8-yl}-N-methylacetamide (3.00 g, 6.40 mmol), and the resulting mixture was then stirred at 25\u00b0 C. Thereafter, a water-ethanol solution (3.28 ml, 1.92 mmol) of 0.585 M hydrogen chloride that had been prepared by diluting concentrated hydrochloric acid (1.0 ml) with ethanol (19.0 ml) was added to the reaction mixture. A seed crystal (0.3 mg) was added to the mixture at the same temperature as described above, and a water-ethanol solution (6.56 ml, 3.84 mmol) of 0.585 M hydrogen chloride was added dropwise to the resulting mixture over 2 hours. The mixture was stirred for 30 minutes. Thereafter, concentrated hydrochloric acid (0.695 ml, 8.34 mmol) was added dropwise to the reaction mixture over 1 hour, and the resulting mixture was then stirred for 1 hour. The precipitated crystal was filtrated, was then washed with ethanol (15 ml), and was then dried under reduced pressure at 40\u00b0 C. for 14 hours, so as to obtain the above title compound (2.89 g, 5.96 mmol). Yield: 93%.",
    "reference_string": "{\"inputs\": {\"m11_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 3.975, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-{4-amino-2-[(3-chloro-4-methoxy-5-methylpyridin-2-yl)methyl]-2,7-dihydro-6-thia-1,2,3,5-tetraazabenzo[cd]azulen-8-yl}-N-methylacetamide\"}], \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ethanol\"}], \"amount\": {\"volume\": {\"value\": 100.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5_m10\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 19.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crystal\"}], \"amount\": {\"mass\": {\"value\": 0.3, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m9\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 0.695, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrogen chloride\"}], \"reaction_role\": \"REACTANT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water ethanol\"}], \"amount\": {\"volume\": {\"value\": 6.56, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water ethanol\"}], \"amount\": {\"volume\": {\"value\": 3.28, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrogen chloride\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 25.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the resulting mixture was then stirred at 25\\u00b0 C\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added to the reaction mixture\"}, {\"type\": \"ADDITION\", \"details\": \"was added dropwise to the resulting mixture over 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"STIRRING\", \"details\": \"The mixture was stirred for 30 minutes\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}}, {\"type\": \"STIRRING\", \"details\": \"the resulting mixture was then stirred for 1 hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"The precipitated crystal was filtrated\"}, {\"type\": \"WASH\", \"details\": \"was then washed with ethanol (15 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"was then dried under reduced pressure at 40\\u00b0 C. for 14 hours\", \"duration\": {\"value\": 14.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 40.0, \"units\": \"CELSIUS\"}}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 5.96, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.89, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 93.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d3de8ea16d2b4503bde245128650d790",
    "procedure_text": "(5-Methoxycarbonyl-2H-pyrazol-3-yl)-(2-phenyl-quinazolin-4-yl)-amine (III-73) (345 mg, 1 mmole in THF, 6 mL) was treated with NaOH (1M, 4.0 mL), stirred at 50\u00b0 C. for 5 hours, cooled to room temperature, and neutralised with 1M HCl. The mixture was concentrated in vacuo to remove THF then diluted with water and the resulting precipitate filtered. The residual solid was dried at 80\u00b0 C. under vacuum to afford III-72 as an off-white solid (312 mg, 94%): mp 289-291\u00b0 C. (dec.); 1H NMR (DMSO) \u03b4 7.45 (1H, br s), 7.50-7.60 (5H, m), 7.80-7.88 (2H, m), 7.40-7.50 (2H, m), 8.60-8.70 (1H, d), 10.70 (1H, s), 13.00-13.80 (2H, br s); IR (solid) 1699, 1624, 1607, 1570,1539, 1506, 1486, 1398, 1333, 1256, 1177, 1004, 827, 764, 705; MS 332.3(M+H)+.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(5-Methoxycarbonyl-2H-pyrazol-3-yl)-(2-phenyl-quinazolin-4-yl)-amine\"}], \"amount\": {\"volume\": {\"value\": 6.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 50.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred at 50\\u00b0 C. for 5 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooled to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CONCENTRATION\", \"details\": \"The mixture was concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"to remove THF\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"then diluted with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"the resulting precipitate filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"The residual solid was dried at 80\\u00b0 C. under vacuum\", \"temperature\": {\"setpoint\": {\"value\": 80.0, \"units\": \"CELSIUS\"}}}], \"outcomes\": [{\"reaction_time\": {\"value\": 5.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 312.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 94.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 94.2}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-21542976f9c44273810d60b4a75c6f3f",
    "procedure_text": "To a solution of methyl 1-(2-((trimethylsilyl)ethynyl)phenyl)cyclopropanecarboxylate (I5) (568 mg, 2.09 mmol) in DCM (20.0 mL) at 0\u00b0 C. was added TBAF (1.0 M in THF, 3.13 mL, 3.13 mmol). The resulting mixture was stirred at 0\u00b0 C. for 10 minutes then poured into water (50 mL). The aqueous layer was extracted with DCM (2\u00d750 mL), then the combined organic layers were washed with brine, dried over MgSO4 and the solvent was removed in vacuo. The residue was adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-25% EtOAc in petroleum benzine 40-60\u00b0 C.) to give the title compound K2 as an off-white solid (140 mg, 34%); 1H NMR (400 MHz, d6-DMSO) \u03b4 7.46 (dt, J=7.5, 0.8 Hz, 1H), 7.40-7.25 (m, 3H), 4.32 (s, 1H), 3.52 (s, 3H), 1.54 (q, J=4.1 Hz, 2H), 1.25-1.19 (m, 2H). LCMS-A: rt 5.921 min; m/z 201 [M+H]+.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2_m5_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 1-(2-((trimethylsilyl)ethynyl)phenyl)cyclopropanecarboxylate\"}], \"amount\": {\"mass\": {\"value\": 568.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TBAF\"}], \"amount\": {\"volume\": {\"value\": 3.13, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The resulting mixture was stirred at 0\\u00b0 C. for 10 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"The aqueous layer was extracted with DCM (2\\u00d750 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"the combined organic layers were washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was removed in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"purified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-25% EtOAc in petroleum benzine 40-60\\u00b0 C.)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"petroleum benzine\"}], \"reaction_role\": \"WORKUP\"}]}, \"temperature\": {\"setpoint\": {\"value\": 50.0, \"precision\": 10.0, \"units\": \"CELSIUS\"}}}], \"outcomes\": [{\"reaction_time\": {\"value\": 10.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 140.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 34.0}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-64394812060244268c4598283ba6a9dd",
    "procedure_text": "A mixture of JEFFAMINE\u00ae D-400 (160 g, 0.40m) and i-PrOH (120) was charged into a flask. Isophorone diisocyanate (44.4 g, 0.20) was added dropwise at 20\u00b0-25\u00b0 C. over a 1 hour period of time. The solvent in the product solution was removed by using a high vacuum. The resulting product was a colorless semisolid at room temperature. The analysis of amine indicated 1.59 meq/g.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"JEFFAMINE\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"0.40m\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"i-PrOH\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Isophorone diisocyanate\"}], \"amount\": {\"mass\": {\"value\": 44.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was charged into a flask\"}, {\"type\": \"CUSTOM\", \"details\": \"The solvent in the product solution was removed\"}, {\"type\": \"CUSTOM\", \"details\": \"at room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-d7a65ba9e5dc4672991d60756f442ae9",
    "procedure_text": "To a solution of 1-[4-(2-amino-propyl)-piperazin-1-yl]-ethanone (149 mg, 0.4 mmol) and triethylamine (TEA, 118 \u03bcl, 0.8 mmol) was added Lawesson's reagent (162 mg, 0.4 mmol) at RT. The reaction mixture was heated at reflux for 3 h to provide 1-[4-(2-aminopropyl)-piperazin-1-yl]-ethanethione (intermediate IVa). The solvent was evaporated and the residue was partitioned between ethyl ether and HCl (1 N), the organic layer was discarded and the aqueous layer was basified by addition of a saturated solution of K2CO3. The aqueous solution was extracted with ethyl acetate four times. The organic layers were combined, dried over sodium sulfate and evaporated. The crude mixture was used for the next coupling reaction. M+=202.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-[4-(2-amino-propyl)-piperazin-1-yl]-ethanone\"}], \"amount\": {\"mass\": {\"value\": 149.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 118.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Lawesson's reagent\"}], \"amount\": {\"mass\": {\"value\": 162.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The reaction mixture was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"at reflux for 3 h\", \"duration\": {\"value\": 3.0, \"units\": \"HOUR\"}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-[4-(2-aminopropyl)-piperazin-1-yl]-ethanethione\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-ed0abce153fe40dda6727a38841c1c00",
    "procedure_text": "To a stirred solution of 2-fluoro-4-bromoanisole (3.03 g, 14.8 mmol) in anhydrous THF (100 mL) was added n-butyllithium (1.6 M in hexanes, 10.2 mL, 16.3 mol) dropwise at \u221278\u00b0 C. The reaction mixture was stirred for 1 h and 80 (4.02 g, 16.3 mmol) dissolved in THF (20 mL) was added dropwise. The reaction mixture was warmed to \u221220\u00b0 C. over 1 h, water (100 mL) was added, and the volatiles were removed under reduced pressure. The mixture was extracted with ether (3\u00d7100 mL) and the combined extracts were washed with water (100 mL) and brine (100 mL). The mixture was dried over MgSO4 and concentrated. The residue was chromatographed on silica gel (20:1 to 5:1 hexanes:EtOAc) to afford 2.35 g (51%) of 81 as a white crystalline solid. 1H NMR (400 MHz, CDCl3): \u03b4 3.97 (s, 3H), 7.01 (t, J=8.4 Hz, 1H), 7.55-7.62 (m, 6H).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"80\"}], \"amount\": {\"mass\": {\"value\": 4.02, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m5_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-fluoro-4-bromoanisole\"}], \"amount\": {\"mass\": {\"value\": 3.03, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-butyllithium\"}], \"amount\": {\"volume\": {\"value\": 10.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -20.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred for 1 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added dropwise\"}, {\"type\": \"CUSTOM\", \"details\": \"the volatiles were removed under reduced pressure\"}, {\"type\": \"EXTRACTION\", \"details\": \"The mixture was extracted with ether (3\\u00d7100 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"the combined extracts were washed with water (100 mL) and brine (100 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The mixture was dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was chromatographed on silica gel (20:1 to 5:1 hexanes:EtOAc)\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"81\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.35, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 51.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 51.4}}], \"isolated_color\": \"white crystalline\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d25ab63211c94b05b43fe852f70b604f",
    "procedure_text": "{5-[(2-Trifluoromethyl-benzyl)-(4-fluoro-benzenesulfonyl)-amino]-2-propyl-benzoimidazol-1-yl}-acetic acid tert-butyl ester was treated with TFA (2 mL) for 2 hours, concentrated, and purified by preparative LCMS to give the title compound. 1H NMR (d6-DMSO) \u03b47.88 (d, 1H), 7.72 (m, 2H), 7.62 (m, 2H), 7.44 (m, 3H), 7.32 (d, 1H), 7.23 (d, 1H), 6.86 (dd, 1H), 5.03 (s, 2H), 4.95 (s, 2H), 2.67 (t, 2H), 1.72 (m, 2H), 0.96 (t, 3H). MS calculated for C26H23F4N3O4S\u2014H: 548, observed: 548.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"{5-[(2-Trifluoromethyl-benzyl)-(4-fluoro-benzenesulfonyl)-amino]-2-propyl-benzoimidazol-1-yl}-acetic acid tert-butyl ester\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TFA\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"purified by preparative LCMS\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-29c78f1395ef4a1992bd4f3af25b7f16",
    "procedure_text": "This compound was prepared from 1-phenyl-1H-pyrazole and acetaldehyde using the method described in example 100B and isolated as a yellow oil in 54% yield.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-phenyl-1H-pyrazole\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetaldehyde\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"isolated as a yellow oil in 54% yield\"}], \"outcomes\": [{\"products\": [{\"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 54.0}}]}]}]}"
  },
  {
    "reaction_id": "ord-98919ef0b08244c188a50d55e1b0a074",
    "procedure_text": "A mixture of 3.6 g of (2,4-dihydroxy-3-propylphenyl)(2-hydroxyphenyl)methanone, 1.4 ml of 5-bromopentane nitrile, 100 mg of sodium iodide, and 9.12 g of potassium carbonate in 50 ml of methyl ethyl ketone was heated to 70\u00b0 C. for approximately 18 hours. The mixture was cooled and partitioned between diethyl ether and water. The organic layer was separated, dried over magnesium sulfate, and evaporated to dryness. The resulting oil was purified by high pressure liquid chromatography over silica gel eluting with a 5-25% ethyl acetate in hexane gradient. Evaporation of the desired fractions and crystallization from diethyl ether/hexane provided 1.31 g of the title product, m.p. 81\u00b0-82\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2,4-dihydroxy-3-propylphenyl)(2-hydroxyphenyl)methanone\"}], \"amount\": {\"mass\": {\"value\": 3.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-bromopentane nitrile\"}], \"amount\": {\"volume\": {\"value\": 1.4, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium iodide\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 9.12, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl ethyl ketone\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 70.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The mixture was cooled\"}, {\"type\": \"CUSTOM\", \"details\": \"partitioned between diethyl ether and water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The organic layer was separated\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated to dryness\"}, {\"type\": \"CUSTOM\", \"details\": \"The resulting oil was purified by high pressure liquid chromatography over silica gel eluting with a 5-25% ethyl acetate in hexane gradient\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Evaporation of the desired\"}, {\"type\": \"CUSTOM\", \"details\": \"fractions and crystallization from diethyl ether/hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.31, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-1b11537cf8a8409bad8410731e20cb5e",
    "procedure_text": "A solution of compound 81 (0.5 g, 1.346 mmol) in dry methanol (20 mL) was treated with hydrazine hydrate (0.41 mL, 13.461 mmol) followed by Raney-Ni (0.1 g) and the resulting mixture was refluxed for 30 min. The reaction was brought to room temperature, filtered through celite bed, washed with CH2Cl2:methanol (1:1, 3 20 mL). The combined organic layer was evaporated and crude was purified by column chromatography (EtOAC: Hexanes, 1:1) to obtain compound 98 (0.43 g, 94%) as a foam. 1H NMR (DMSO-d6) \u03b4: 1.38-1.41 (m, 11H), 1.76-1.86 (m, 2H), 2.14-2.42 (m, 2H), 2.73 (s, 3H), 4.05-4.15 (m, 1H), 4.49 (s, 2H), 6.00 (brs, 1H), 6.48 (dd, 1H, J=1.8, 8.2 Hz), 6.99 (d, 1H, J=1.5 Hz), 7.05 (d, 1H, J=8.4 Hz), 7.16 (d, 1H, J=2.7 Hz), 10.60 (s, 1H); ESI-MS m/z (%): 364 (M+Na+, 7), 342 (MH+, 11), 286 (100).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ni\"}], \"amount\": {\"mass\": {\"value\": 0.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound 81\"}], \"amount\": {\"mass\": {\"value\": 0.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrazine hydrate\"}], \"amount\": {\"volume\": {\"value\": 0.41, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"the resulting mixture was refluxed for 30 min\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}}, {\"type\": \"CUSTOM\", \"details\": \"was brought to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"filtered through celite bed\"}, {\"type\": \"WASH\", \"details\": \"washed with CH2Cl2:methanol (1:1, 3 20 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2 methanol\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The combined organic layer was evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"crude was purified by column chromatography (EtOAC: Hexanes, 1:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound 98\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.43, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 94.0}}], \"texture\": {\"type\": \"FOAM\", \"details\": \"foam\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c84ac2dbbfd3438ea54fd87743b97984",
    "procedure_text": "A mixture of 4.9 g of decafluorobenzophenone and 2.7 g of trichloroacetic acid was added to 15 mL of hexamethylphosphoramide. The stirred reaction mixture was maintained at about 0\u00b0 C. for about 2 hours and then allowed to warm to room temperature and continue stirring at ambient temperature for the next 15 hours. The reaction mixture was characterized by GC and fluorine NMR to show a conversion of approximately 20% to the desired carbinol. This carbinol can be converted to the corresponding acrylate by methods previously described (cf. Example 24).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acrylate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"carbinol\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexamethylphosphoramide\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"decafluorobenzophenone\"}], \"amount\": {\"mass\": {\"value\": 4.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trichloroacetic acid\"}], \"amount\": {\"mass\": {\"value\": 2.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"carbinol\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"fluorine\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"continue stirring at ambient temperature for the next 15 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The stirred reaction mixture\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to warm to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-beb5a80539924462b21bb4ef310f3bf3",
    "procedure_text": "To a solution of thiazole-4-carboxylic acid 7.1 (1 g, 7.2 mmol) and carbonyldiimidazole (6.3 g, 38.7 mmol) in commercial dry DMF (50 mL) under N2 was stirred at 50\u00b0 C. for 20 min. Tert-butanol (8.6 g, 116.0 mmol) and DBU (5.8 mL, 38.7 mmol) were then successively added at once and the reaction was warmed at 60\u00b0 C. for 48 h. The RM was then allowed to cool down to RT and the pH was adjusted to 4 with a solution of HCl (2M, \u02dc80 mL). The mixture was diluted with water (250 mL) and extracted with Et2O (3\u00d7100 mL). The combined org. layers were washed with brine (250 mL), dried over MgSO4, concentrated and purified on silica gel using DCM to afford title product as yellowish oil (47%). Yield: 3.37 g (47%). LCMS: P=98%, rt=3.65 nm, m/z=186.",
    "reference_string": "{\"inputs\": {\"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"thiazole-4-carboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"carbonyldiimidazole\"}], \"amount\": {\"mass\": {\"value\": 6.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Tert-butanol\"}], \"amount\": {\"mass\": {\"value\": 8.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DBU\"}], \"amount\": {\"volume\": {\"value\": 5.8, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 80.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"to cool down to RT\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with Et2O (3\\u00d7100 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Et2O\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"layers were washed with brine (250 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"purified on silica gel\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title product\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 47.0}}], \"isolated_color\": \"yellowish\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d25a538c037e4e2195a93bde947a4d26",
    "procedure_text": "To a solution of 5-chloro-4-(1-methyl-1H-pyrazol-5-yl)-2-furancarboxylic acid (134 mg, 0.59 mmol), 2-{(2S)-2-amino-3-[2-(trifluoromethyl)phenyl]propyl}-1H-isoindole-1,3(2H)-dione (228 mg, 0.59 mmol)[prepared according to Preparation 6] and N,N-diisopropylethylamine (0.52 ml, 2.96 mmol) in Dichloromethane (4.6 ml) at 25\u00b0 C. was added bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (304 mg, 0.65 mmol) in one portion. The solution stirred at 25\u00b0 C. for 1 h and was then dry loaded onto silica and purified via column chromatography (silica, 30-70% EtOAc in hexanes) yielding 5-chloro-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-4-(1-methyl-1H-pyrazol-5-yl)-2-furancarboxamide (202 mg, 0.33 mmol, 55.8% yield) as a yellow oil: LCMS (ES) m/e 557, 559 (M, M+2)+.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m5_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-chloro-4-(1-methyl-1H-pyrazol-5-yl)-2-furancarboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 134.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-{(2S)-2-amino-3-[2-(trifluoromethyl)phenyl]propyl}-1H-isoindole-1,3(2H)-dione\"}], \"amount\": {\"mass\": {\"value\": 228.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-diisopropylethylamine\"}], \"amount\": {\"volume\": {\"value\": 0.52, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"bromo-tris-pyrrolidino-phosphonium hexafluorophosphate\"}], \"amount\": {\"mass\": {\"value\": 304.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 4.6, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 25.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The solution stirred at 25\\u00b0 C. for 1 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"was then dry\"}, {\"type\": \"CUSTOM\", \"details\": \"purified via column chromatography (silica, 30-70% EtOAc in hexanes)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-chloro-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-4-(1-methyl-1H-pyrazol-5-yl)-2-furancarboxamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 0.33, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 202.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 55.8}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 55.9}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-ebba085ddfba44fba0632948aa1012eb",
    "procedure_text": "Phosphorous oxychloride (4.60 g, 30 mmol) was added to dimethyl-formamide (32 ml) and stirred for 20 min at 0\u00b0 C. 2-Mercapto-3-methyl-6-(4-pyrimidyl)-3H-pyrimidine-4-one (4.40 g, 20 mmol) was added to the solution and stirred 5 min and then stirred at 70\u00b0 C. for 2 hours. The reaction mixture was poured into ice water, neutralized by solid potassium carbonate, and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and evaporated under reduced pressure. Purification of the residue by silica gel chromatography (ethyl acetate) gave the title compound (1.20 g, 27%).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-Mercapto-3-methyl-6-(4-pyrimidyl)-3H-pyrimidine-4-one\"}], \"amount\": {\"mass\": {\"value\": 4.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Phosphorous oxychloride\"}], \"amount\": {\"mass\": {\"value\": 4.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethyl-formamide\"}], \"amount\": {\"volume\": {\"value\": 32.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred for 20 min at 0\\u00b0 C\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"stirred 5 min\", \"duration\": {\"value\": 5.0, \"units\": \"MINUTE\"}}, {\"type\": \"STIRRING\", \"details\": \"stirred at 70\\u00b0 C. for 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 70.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification of the residue by silica gel chromatography (ethyl acetate)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 20.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.2, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 27.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 27.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-ba397eb2436f4cac995e066ee2e6835a",
    "procedure_text": "A solution of 4.9 g (0.0225 mole) of 2-chlorophenylsulfonyl isocyanate and 3.5 g (0.02 mole) of 2-amino-4-difluoromethoxy-6-methylpyrimidine in 70 ml of dioxan is stirred for 2 hours at 60\u00b0-70\u00b0 C. The reaction mixture is filtered and the filtrate is concentrated. The residue is triturated with ether to give 3.8 g (49.9% of theory) of N-(2-chlorophenylsulfonyl)-N'-(4-difluoromethoxy-6-methylpyridin-2-yl)urea with a melting point of 169\u00b0-170\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chlorophenylsulfonyl isocyanate\"}], \"amount\": {\"mass\": {\"value\": 4.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-amino-4-difluoromethoxy-6-methylpyrimidine\"}], \"amount\": {\"mass\": {\"value\": 3.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dioxan\"}], \"amount\": {\"volume\": {\"value\": 70.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The reaction mixture is filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate is concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue is triturated with ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(2-chlorophenylsulfonyl)-N'-(4-difluoromethoxy-6-methylpyridin-2-yl)urea\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 3.8, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 49.9}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-8fcd4bc7d8f940f39e07c07d32111dab",
    "procedure_text": "Cis-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2-(trifluoromethyl)benzyl)piperidine-1-carboxylate (1.30 g, 3.39 mmol) was subjected to chiral preparative HPLC (Column: Chiralcel OJ (250\u00d720), 5 \u03bcm particle size, mobile phase: Heptane/EtOH/FA 80/20/0.1, flow rate 18 mL/min) to yield (2R,4S)-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2-(trifluoromethyl)benzyl)piperidine-1-carboxylate (597 mg, 46%), Chiral purity 99.6% ee, Optical rotation [\u03b1]D20=\u22124.0 (acetonitrile, c=1) and (2S,4R)-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2-(trifluoromethyl)benzyl)piperidine-1-carboxylate (624 mg, 48%), Chiral purity 99.8% ee, Optical rotation [\u03b1]D20=+6.1 (acetonitrile, c=1).",
    "reference_string": "{\"inputs\": {\"m0_m5_m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Cis-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2-(trifluoromethyl)benzyl)piperidine-1-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 1.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Heptane EtOH\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2R,4S)-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2-(trifluoromethyl)benzyl)piperidine-1-carboxylate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 597.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 46.0}}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2S,4R)-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2-(trifluoromethyl)benzyl)piperidine-1-carboxylate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 624.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 48.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-5dcca113a1cb4086a266776922cbd8b1",
    "procedure_text": "In a similar manner as described for Intermediate 18, 6-(1-aminoethyl)-N-(3,4,5-trimethoxyphenyl)-1,2,4-triazin-3-amine (Intermediate 9) (200 mg, 0.65 mmol), 2-{[3-(trifluoromethyl)phenyl]amino}benzoic acid (240 mg, 0.85 mmol), diisopropylethylamine (0.34 mL, 1.95 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N\u2032,N\u2032-tetramethyluronium hexafluorophosphate (350 mg, 0.92 mmol) in dimethylformamide (5 mL) gave 2-{[3-(trifluoromethyl)phenyl]amino}-N-(1-{3-[(3,4,5-trimethoxyphenyl)amino]-1,2,4-triazin-6-yl}ethyl)benzamide (297 mg, 80%) as a yellow solid. MS m/z 568 (M+1).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Intermediate 18\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropylethylamine\"}], \"amount\": {\"volume\": {\"value\": 0.34, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Intermediate 9\"}], \"reaction_role\": \"REACTANT\"}]}, \"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-{[3-(trifluoromethyl)phenyl]amino}benzoic acid\"}], \"amount\": {\"mass\": {\"value\": 240.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"O-(7-azabenzotriazol-1-yl)-N,N,N\\u2032,N\\u2032-tetramethyluronium hexafluorophosphate\"}], \"amount\": {\"mass\": {\"value\": 350.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-(1-aminoethyl)-N-(3,4,5-trimethoxyphenyl)-1,2,4-triazin-3-amine\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-{[3-(trifluoromethyl)phenyl]amino}-N-(1-{3-[(3,4,5-trimethoxyphenyl)amino]-1,2,4-triazin-6-yl}ethyl)benzamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 297.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 80.0}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-270f98d710454cc3a53add8be2d85a33",
    "procedure_text": "This was prepared using the same procedure as for 2-(4-(2-amino-5-bromo-3-nitropyridin-4-yl)piperazin-1-yl)-N-(thiazol-2-yl)acetamide, but here using 4,5-dichloro-3-nitropyridin-2-amine (22 mg, 0.106 mmol), iPrOH (1 mL), DIPEA (0.2 mL) and 1-(1-(pyridin-4-yl)ethyl)piperazine.3\u00d7HCl (1.1 eq, 0.116 mmol, 35 mg). Filtration and washing as previously described gave the product (28 mg, 73%) as a yellow solid; \u03b4H (500 MHz, DMSO-d6) 1.30 (d, J=6.7 Hz, 3H, CHCH3), 2.42 (s, br, 2H, piperazine NCH2), 2.53 (s, br, 2H, piperazine NCH2), 3.05 (s, br, 4H, piperazine N(CH2)2), 3.54 (q, J=6.8 Hz, 1H, CHCH3), 6.94 (s, br, 2H, NH2), 7.34 (d, J=6.0 Hz, 2H, pyridine H-2 & H-6), 8.04 (s, 1H, chloropyridine H-6), 8.51 (d, J=6.0 Hz, 2H, pyridine H-3 & H-5);",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(1-(pyridin-4-yl)ethyl)piperazine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"iPrOH\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(4-(2-amino-5-bromo-3-nitropyridin-4-yl)piperazin-1-yl)-N-(thiazol-2-yl)acetamide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4,5-dichloro-3-nitropyridin-2-amine\"}], \"amount\": {\"mass\": {\"value\": 22.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"mass\": {\"value\": 35.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DIPEA\"}], \"amount\": {\"volume\": {\"value\": 0.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"This was prepared\"}, {\"type\": \"FILTRATION\", \"details\": \"Filtration\"}, {\"type\": \"WASH\", \"details\": \"washing\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 28.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 73.0}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-36c542539aeb44e18a9a04e6b65ad261",
    "procedure_text": "A solution of 2,2,2-trimethylacetamide (0.046 g, 0.454 mmol) in DCE (2 mL) was treated with oxalyl chloride (0.040 mL, 0.454 mmol), stirred at RT for 0.5 h, then heated at 75\u00b0 C. for 1 h. The mixture was cooled to RT, added to a solution of N-(4-((6-amino-2-methylpyridin-3-yl)oxy)pyridin-2-yl)isobutyramide (0.10 g, 0.349 mmol) and TEA (0.1 mL, 0.70 mmol) in THF (2 mL) and stirred at RT for 1 h. The mixture was concentrated to dryness, the residue treated with EtOAc, washed with brine, dried over Na2SO4 and concentrated to dryness. The material was treated with EtOAc, allowed to stand at RT overnight and the resulting solid collected via filtration and dried to afford N-((5-((2-isobutyramidopyridin-4-yl)oxy)-6-methylpyridin-2-yl)carbamoyl)pivalamide (63 mg, 42%) as a white solid. 1H NMR (400 MHz, DMSO-d6): \u03b4 11.17 (s, 1H), 10.50 (s, 1H), 10.42 (br s, 1H), 8.18 (d, J=5.7 Hz, 1H), 7.92 (m, 1H), 7.63 (d, J=8.8 Hz, 1H), 7.60 (d, J=2.4 Hz, 1H), 6.66 (dd, J=5.7, 2.4 Hz, 1H), 2.69 (m, 1H), 2.24 (s, 3H), 1.22 (s, 9H), 1.02 (d, J=6.8 Hz, 6H); MS (ESI) m/z: 414.2 (M+H+).",
    "reference_string": "{\"inputs\": {\"m3_m4_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(4-((6-amino-2-methylpyridin-3-yl)oxy)pyridin-2-yl)isobutyramide\"}], \"amount\": {\"mass\": {\"value\": 0.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TEA\"}], \"amount\": {\"volume\": {\"value\": 0.1, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m5_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,2,2-trimethylacetamide\"}], \"amount\": {\"mass\": {\"value\": 0.046, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"oxalyl chloride\"}], \"amount\": {\"volume\": {\"value\": 0.04, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCE\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred at RT for 0.5 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"heated at 75\\u00b0 C. for 1 h\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 75.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"The mixture was cooled to RT\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"STIRRING\", \"details\": \"stirred at RT for 1 h\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CONCENTRATION\", \"details\": \"The mixture was concentrated to dryness\"}, {\"type\": \"ADDITION\", \"details\": \"the residue treated with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated to dryness\"}, {\"type\": \"ADDITION\", \"details\": \"The material was treated with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WAIT\", \"details\": \"to stand at RT overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"the resulting solid collected via filtration\"}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 0.5, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-((5-((2-isobutyramidopyridin-4-yl)oxy)-6-methylpyridin-2-yl)carbamoyl)pivalamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 63.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 42.0}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-9c743158058e40108ac20cc83d2f5d6d",
    "procedure_text": "A solution of 90 g. (0.345 mol) of \u03b2-chloroethyl-{\u03b1[tricyclo-(2.2.1.02.6)hept-3-ylidene]-benzyl}-ether and 69 g. (1.53 mol) of ethylamine in 250 ml. of anhydrous benzene was heated for 5 hours to 140\u00b0 C. in a 1 litre capacity autoclave. After cooling, the ethylamine hydrochloride was filtered off under suction, the mother liquor concentrated in vacuo and the residue subjected to acid-alkaline working up. The basic fraction was fractionated in vacuo.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"\\u03b2-chloroethyl-{\\u03b1[tricyclo-(2.2.1.02.6)hept-3-ylidene]-benzyl}-ether\"}], \"amount\": {\"moles\": {\"value\": 0.345, \"units\": \"MOLE\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethylamine\"}], \"amount\": {\"moles\": {\"value\": 1.53, \"units\": \"MOLE\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzene\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"After cooling\"}, {\"type\": \"FILTRATION\", \"details\": \"the ethylamine hydrochloride was filtered off under suction\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethylamine hydrochloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"the mother liquor concentrated in vacuo\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-7a011c6c5dae4ed2badb4c755c69e913",
    "procedure_text": "In a sealed tube were introduced 7-bromo-2-methyl-quinoline (500 mg, 2.25 mmol, 1.0 eq), PdCl2(PPh3)3 (79 mg, 0.11 mmol, 5% mol), copper iodide (21 mg, 0.11 mmol, 5% mol), and triphenylphosphine (106 mg, 0.39 mmol, 20% mol). Then, DMF (5 mL) was added followed by diethylamine (3.5 mL, 34 mmol, 15 eq) and trimethylsilylacetylene (350 \u03bcL, 2.5 mmol, 1.1 eq). The mixture was heated at 110\u00b0 C. overnight. After cooling down the solvent was evaporated and the crude product was purified by column chromatography (Florisil, Cyclohexane-EtOAc 95:5) to afford 2-methyl-7-trimethylsilanylethynyl-quinoline as a white solid (435 mg, 81%).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethylamine\"}], \"amount\": {\"volume\": {\"value\": 3.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trimethylsilylacetylene\"}], \"amount\": {\"volume\": {\"value\": 350.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m6_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-bromo-2-methyl-quinoline\"}], \"amount\": {\"mass\": {\"value\": 500.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"PdCl2(PPh3)3\"}], \"amount\": {\"mass\": {\"value\": 79.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triphenylphosphine\"}], \"amount\": {\"mass\": {\"value\": 106.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"copper iodide\"}], \"amount\": {\"mass\": {\"value\": 21.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 110.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"After cooling down the solvent\"}, {\"type\": \"CUSTOM\", \"details\": \"was evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"the crude product was purified by column chromatography (Florisil, Cyclohexane-EtOAc 95:5)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Florisil\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Cyclohexane EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-methyl-7-trimethylsilanylethynyl-quinoline\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 435.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 81.0}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-68a8e6639b0640aab9a1d516a044c1b7",
    "procedure_text": "248 mg of NaH (about 50% in oil) were placed in 12 ml of abs. DMF under argon. 2.45 g of diethyl (4-carbethoxybenzyl)phosphonate were added thereto at 0\u00b0 and the mixture was subsequently stirred at room temperature for about 2 hours until the H2 evolution had finished. The mixture was cooled to \u221210\u00b0 C. and 2.20 g of (5RS,9SR,10RS)-10-t-butyldimethylsilyloxy-2-formyl-3-heptyloxy-5,9-dimethyl-6,7,8,9-tetrahydro-5,9-methano-5H-benzocycloheptene dissolved in 10 ml of abs. DMF were slowly added dropwise thereto. Then, the cooling bath was removed and the mixture was left to react at room temperature for 2 hours. It was then poured into ice/NH4Cl solution, extracted with diethyl ether, washed with NaCl solution, dried over Na2SO4 and concentrated. Flash chromatography on SiO2 (hexane/ethyl acetate 98/2) gave 2.32 g of ethyl (E)-4-[2-[(5RS,9SR,10RS)-10-t-butyldimethylsilyloxy-3-heptyloxy-5,9-dimethyl-6,7,8,9-tetrahydro-5,9-methano-5H-benzocyclohepten-2-yl]vinyl]benzoate as a yellowish oil.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(5RS,9SR,10RS)-10-t-butyldimethylsilyloxy-2-formyl-3-heptyloxy-5,9-dimethyl-6,7,8,9-tetrahydro-5,9-methano-5H-benzocycloheptene\"}], \"amount\": {\"mass\": {\"value\": 2.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaH\"}], \"amount\": {\"mass\": {\"value\": 248.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice NH4Cl\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl (4-carbethoxybenzyl)phosphonate\"}], \"amount\": {\"mass\": {\"value\": 2.45, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"at 0\\u00b0 and the mixture was subsequently stirred at room temperature for about 2 hours until the H2 evolution\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The mixture was cooled to \\u221210\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": -10.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"Then, the cooling bath was removed\"}, {\"type\": \"WAIT\", \"details\": \"the mixture was left\"}, {\"type\": \"CUSTOM\", \"details\": \"to react at room temperature for 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with diethyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with NaCl solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaCl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"SiO2\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl (E)-4-[2-[(5RS,9SR,10RS)-10-t-butyldimethylsilyloxy-3-heptyloxy-5,9-dimethyl-6,7,8,9-tetrahydro-5,9-methano-5H-benzocyclohepten-2-yl]vinyl]benzoate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.32, \"units\": \"GRAM\"}}}], \"isolated_color\": \"yellowish\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-5e2c5c28ae374204b230dc38cfaa2f99",
    "procedure_text": "0.5 g (0.69 mmol) (R)-1-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-2-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate are dissolved in 10 ml of methanol at ambient temperature. After the addition of 100 \u03bcl sulphuric acid (48% in water) the mixture is stirred for 3 hours at ambient temperature. After about 5 ml of methanol has been evaporated off, 1 ml of tert-butylmethylether is added, whereupon an oil is precipitated. After removal of the supernatant solvent the residue is combined with 5 ml acetone, during which time crystallisation sets in. The precipitate formed is filtered and dried for 12 hours at 30\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-1-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-2-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 0.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sulphuric acid\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"is stirred for 3 hours at ambient temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"After about 5 ml of methanol has been evaporated off\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"1 ml of tert-butylmethylether is added, whereupon an oil\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butylmethylether\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"is precipitated\"}, {\"type\": \"CUSTOM\", \"details\": \"After removal of the supernatant solvent the residue\"}, {\"type\": \"CUSTOM\", \"details\": \"is combined with 5 ml acetone, during which time crystallisation sets in\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The precipitate formed\"}, {\"type\": \"FILTRATION\", \"details\": \"is filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"dried for 12 hours at 30\\u00b0 C.\", \"duration\": {\"value\": 12.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 30.0, \"units\": \"CELSIUS\"}}}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-c395f635f38f47a995f26ed631b2d125",
    "procedure_text": "To a solution of the product of Example 1B (0.220 g, 1.0 mmol) and the product of EXAMPLE 1C (0.268 g, 1.0 mmol) in anhydrous THF (10 mL) under nitrogen at 0\u00b0 C. was added sodium hydride (95%, 0.10 g, 4.0 mmol). The reaction was heated to reflux for 3 hours, cooled to 0\u00b0 C., and to it was added dropwise glacial acetic acid (2 mL). The resulting mixture was heated to reflux for 2 hours, cooled to ambient temperature, and diluted with aqueous hydrochloric acid (0.1 M, 10 mL). The resulting precipitate was collected by filtration, washed with water and diethyl ether and dried to give the title compound (0.130 g, 33%). MS (ESI\u2212) m/z 397 (M\u2212H)\u2212.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m5_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"amount\": {\"mass\": {\"value\": 0.22, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"amount\": {\"mass\": {\"value\": 0.268, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydride\"}], \"amount\": {\"mass\": {\"value\": 0.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The reaction was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to reflux for 3 hours\", \"duration\": {\"value\": 3.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"The resulting mixture was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to reflux for 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"cooled to ambient temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"The resulting precipitate was collected by filtration\"}, {\"type\": \"WASH\", \"details\": \"washed with water and diethyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.13, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 33.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4bd65df298b643d681ea08624d373df6",
    "procedure_text": "To a solution of tert-butyl (2S)-2-(3-ethoxy-3-oxopropanoyl)-1-pyrrolidinecarboxylate (5.0 g, 17.5 mmol) in benzene (50 ml) and piperidine (0.3 ml, 3 mmol) was added 4-carboxybenzaldehyde (2.63 g, 17.5 mmol), and the mixture was refluxed for 3 h. The cooled solution was washed with 0.1 N HCl twice. The aqueous layer was extracted three times with ether. The combined organic phases were dried (Na2SO4) and concentrated to give C as a tan solid (5.54 g, 76% yield). LCMS m/z 416 (M\u2212H), 833 (2M\u2212H).",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl (2S)-2-(3-ethoxy-3-oxopropanoyl)-1-pyrrolidinecarboxylate\"}], \"amount\": {\"mass\": {\"value\": 5.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"piperidine\"}], \"amount\": {\"volume\": {\"value\": 0.3, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-carboxybenzaldehyde\"}], \"amount\": {\"mass\": {\"value\": 2.63, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzene\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"the mixture was refluxed for 3 h\", \"duration\": {\"value\": 3.0, \"units\": \"HOUR\"}}, {\"type\": \"WASH\", \"details\": \"The cooled solution was washed with 0.1 N HCl twice\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The aqueous layer was extracted three times with ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic phases were dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 5.54, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 76.0}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e1b2070f8933452b8157f7206bab5ae3",
    "procedure_text": "Charge a 12 L, 3-neck flask, equipped with a stirrer, condenser, heating mantle and thermometer with N-Acetyl-6-Iodo-Anthranilic acid (400 grams) and 2.5 L concentrated HCl. Adjust the temperature to 50-55\u00b0 C. and maintain for 24 hours. Higher temperatures may decompose the product. Chill the reaction to less than 5\u00b0 C. in an ice bath, filter the product, wash the filter \u201ccake\u201d with acetone, then diethylether. Air dry the product. Yield was 340 grams. (Theoretical yield=374.4 grams). Melting point (m.p.) at 176-180\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-Acetyl-6-Iodo-Anthranilic acid\"}], \"amount\": {\"mass\": {\"value\": 400.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 2.5, \"units\": \"LITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"Charge a 12 L, 3-neck flask\"}, {\"type\": \"CUSTOM\", \"details\": \"equipped with a stirrer, condenser\"}, {\"type\": \"CUSTOM\", \"details\": \"to 50-55\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 52.5, \"precision\": 2.5, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"maintain for 24 hours\", \"duration\": {\"value\": 24.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"Chill\"}, {\"type\": \"CUSTOM\", \"details\": \"the reaction to less than 5\\u00b0 C. in an ice bath\"}, {\"type\": \"FILTRATION\", \"details\": \"filter the product\"}, {\"type\": \"WASH\", \"details\": \"wash the\"}, {\"type\": \"FILTRATION\", \"details\": \"filter \\u201ccake\\u201d with acetone\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Air dry the product\"}, {\"type\": \"CUSTOM\", \"details\": \"at 176-180\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 178.0, \"precision\": 2.0, \"units\": \"CELSIUS\"}}}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-d1ee6329cc40473cbf08bb546affae6c",
    "procedure_text": "Typically, about 118 kg of a mixture of C10:0 and C8:0 fatty acids (55:45 weight ratio) is preheated to the esterification temperature and adjusted to the requisite pressure. This fatty acid mixture is used to esterify about 16.8 kg of monobehenin at an 18:1 acid to monobehenin mole ratio at esterification temperature 245\u00b0 C. (The monobehenin is commercially produced by molecular distillation of behenic acid/glycerol reaction products and comprises 98.1% monoglyceride, 0.5% diglyceride, 0.1% free glycerol, and 0.3% diglycerol.) The monobehenin is added incrementally as a liquid over a 60 minute period to the melted fatty acids. The esterification pressure ranges from 700 mmHg to 1520 mmHg. A pressure of 700 mmHg is initially used, but is increased as necessary to prevent the mixture containing the fatty acids from boiling over.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"mixture\"}], \"amount\": {\"mass\": {\"value\": 118.0, \"units\": \"KILOGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"monobehenin\"}], \"amount\": {\"mass\": {\"value\": 16.8, \"units\": \"KILOGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"C8:0\"}], \"reaction_role\": \"REACTANT\"}]}, \"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"fatty acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"monobehenin\"}], \"reaction_role\": \"REACTANT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"monobehenin\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"C10:0\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"at esterification temperature 245\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 245.0, \"units\": \"CELSIUS\"}}}], \"outcomes\": [{\"products\": [{\"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-39e0ede68a744241b7f1cacc2864a4db",
    "procedure_text": "1-Hexyl-3,4-dimethyl-4-(3-vinylphenyl)piperidine (Example 26, 200 mg, 0.67 mmol) was dissolved in a mixture of water (2 mL) and acetone (18 mL). 4-methylmorpholine N-oxide (172 mg, 1.47 mmol) was added with stirring followed by osmium tetroxide (200 \u03bcL, 2.5% w/w in tert-butanol). The reaction mixture was stirred at room temperature for 4 hours before the solvent was removed by evaporation in vacuo. The residue was partitioned between dichloromethane (25 mL) and water (25 mL). The organic phase was separated and dried (Na2SO4). Concentration in vacuo gave a residue which was purified by column chromatography on silica gel (10 g) eluted with a gradient of ethyl acetate:hexane:ammonium hydroxide solution (50:49:1 to 60:33:1), followed by ethyl acetate:methanol:ammonium hydroxide solution (94:5:1). Combination of the appropriate fractions and evaporation to dryness in vacuo gave the product as a yellow oil (145 mg).",
    "reference_string": "{\"inputs\": {\"m1_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-Hexyl-3,4-dimethyl-4-(3-vinylphenyl)piperidine\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"amount\": {\"volume\": {\"value\": 18.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-methylmorpholine N-oxide\"}], \"amount\": {\"mass\": {\"value\": 172.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"osmium tetroxide\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"with stirring\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"The reaction mixture was stirred at room temperature for 4 hours before the solvent\", \"duration\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"was removed by evaporation in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was partitioned between dichloromethane (25 mL) and water (25 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The organic phase was separated\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"Concentration in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"gave a residue which\"}, {\"type\": \"CUSTOM\", \"details\": \"was purified by column chromatography on silica gel (10 g)\"}, {\"type\": \"WASH\", \"details\": \"eluted with a gradient of ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Combination of the appropriate fractions and evaporation to dryness in vacuo\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 145.0, \"units\": \"MILLIGRAM\"}}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-9f0e2c20d87c47a3b39e3df0be15bee1",
    "procedure_text": "(R)-tert-Butyl 4-amino-2-benzyl-9-methyl-3-oxo-2,3,4,5-tetrahydro-1H-benzo[c]azepin-8-ylcarbamate was reacted in a manner analogous to the preparation of (R)-tert-butyl 2-benzyl-7-methyl-3-oxo-4-(4-(2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxamido)-2,3,4,5-tetrahydro-1H-benzo[c]azepin-8-ylcarbamate. Title compound was obtained as off-white solid in 94% yield.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-tert-Butyl 4-amino-2-benzyl-9-methyl-3-oxo-2,3,4,5-tetrahydro-1H-benzo[c]azepin-8-ylcarbamate\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-tert-butyl 2-benzyl-7-methyl-3-oxo-4-(4-(2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxamido)-2,3,4,5-tetrahydro-1H-benzo[c]azepin-8-ylcarbamate\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Title compound\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 94.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-6d347d740c6e4775b8e0120476bb6945",
    "procedure_text": "To a stirred mixture of 1-azabicyclo[2.2.1]heptan-3-one hydrochloride (1.06 g) and benzophenone (1.82 g) in dry THF (5 ml) at -78\u00b0 C. under argon was added a solution of lithium bis(trimethylsilyl)amide (18 ml, 1.0M in THF). The solution was stirred at -78\u00b0 C. for 1 h, allowed to warm to room temperature and stirred for 48 h. The mixture was poured onto water and extracted with dichloromethane (\u00d74). The combined extracts were dried (Na2SO4), evaporated in vacuo, and the residue was purified by chromatography on silica using a gradient elution of 10-30% ethyl acetate in dichloromethane to afford the title compound as a white solid:",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-azabicyclo[2.2.1]heptan-3-one hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 1.06, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzophenone\"}], \"amount\": {\"mass\": {\"value\": 1.82, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium bis(trimethylsilyl)amide\"}], \"amount\": {\"volume\": {\"value\": 18.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -78.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The solution was stirred at -78\\u00b0 C. for 1 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"to warm to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"STIRRING\", \"details\": \"stirred for 48 h\", \"duration\": {\"value\": 48.0, \"units\": \"HOUR\"}}, {\"type\": \"ADDITION\", \"details\": \"The mixture was poured onto water\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with dichloromethane (\\u00d74)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined extracts were dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was purified by chromatography on silica using\"}, {\"type\": \"WASH\", \"details\": \"a gradient elution of 10-30% ethyl acetate in dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-1d49a952f8dd438abde976df9ff9f3ea",
    "procedure_text": "Under ice-cooling, to a solution of N-(4,5-dihydronaphtho[1,2-d][1,3]thiazol-2-yl)propanamide (1.70 g, 6.6 mmol) in tetrahydrofuran (30 mL) was added lithium aluminum hydride (749 mg, 20 mmol), and the mixture was stirred at room temperature for 3 hrs. Sodium sulfate 10 hydrate (9.6 g, 30 mmol) was added, and the mixture was stirred at room temperature for 1 hr. Insoluble material was filtered off, and the filtrate was concentrated. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=4:1) to give the title compound (1.32 g, yield 82%) as a yellow powder.",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(4,5-dihydronaphtho[1,2-d][1,3]thiazol-2-yl)propanamide\"}], \"amount\": {\"mass\": {\"value\": 1.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium aluminum hydride\"}], \"amount\": {\"mass\": {\"value\": 749.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Sodium sulfate 10 hydrate\"}], \"amount\": {\"mass\": {\"value\": 9.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at room temperature for 3 hrs\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"the mixture was stirred at room temperature for 1 hr\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"Insoluble material was filtered off\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate was concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by silica gel column chromatography (hexane/ethyl acetate=4:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.32, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 82.0}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"POWDER\", \"details\": \"powder\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-9969f836007041ab8b54b2b4cccd7083",
    "procedure_text": "To 2-fluoro-4-iodonicotinaldehyde (11.33 g, 45.1 mmol) in THF (200 mL) was added hydrazine (5.67 ml, 181 mmol) dropwise. The resulting mixture was stirred at RT under a nitrogen atmosphere for 5 h. The reaction was concentrated, diluted with 10:1 acetone/MeOH and filtered through a pad of silica gel. Removed most of the solvent in vacuo, then diluted with some hexanes and filtered resulting solid. Dried to yield 4-iodo-1H-pyrazolo[3,4-b]pyridine as an off-white solid. MS m/z=246 [M+1]+. Calc'd for C6H4IN3: 245.02.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-fluoro-4-iodonicotinaldehyde\"}], \"amount\": {\"mass\": {\"value\": 11.33, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrazine\"}], \"amount\": {\"volume\": {\"value\": 5.67, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The resulting mixture was stirred at RT under a nitrogen atmosphere for 5 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"The reaction was concentrated\"}, {\"type\": \"ADDITION\", \"details\": \"diluted with 10:1 acetone/MeOH\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone MeOH\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered through a pad of silica gel\"}, {\"type\": \"CUSTOM\", \"details\": \"Removed most of the solvent in vacuo\"}, {\"type\": \"ADDITION\", \"details\": \"diluted with some hexanes\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"resulting solid\"}, {\"type\": \"CUSTOM\", \"details\": \"Dried\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 5.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-iodo-1H-pyrazolo[3,4-b]pyridine\"}], \"isolated_color\": \"off-white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-775edce57c634e2f8b5e1c09ef232f25",
    "procedure_text": "A solution of tert-butyl 4-[(6-methoxy-3-oxo-2,3-dihydrobenzofuran-7-yl)-ethynyl]piperidine-1-carboxylate (0.157 g, 0.423 mmol) synthesized in Example B55, Step 1 in ethyl acetate/ethanol (1:1, 3 mL) was added with 5% palladium/carbon (wetted with 50% water, 0.0500 g), and the mixture was stirred overnight at room temperature under a hydrogen atmosphere. The reaction mixture was filtered through Celite, the filtrate was concentrated, and the resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain tert-butyl (Z)-4-[2-(6-methoxy-3-oxo-2,3-dihydrobenzofuran-7-yl)vinyl]piperidine-1-carboxylate (0.0610 g, 39%).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl 4-[(6-methoxy-3-oxo-2,3-dihydrobenzofuran-7-yl)-ethynyl]piperidine-1-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 0.157, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate ethanol\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"palladium/carbon\"}], \"amount\": {\"mass\": {\"value\": 0.05, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred overnight at room temperature under a hydrogen atmosphere\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The reaction mixture was filtered through Celite\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate was concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"the resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl (Z)-4-[2-(6-methoxy-3-oxo-2,3-dihydrobenzofuran-7-yl)vinyl]piperidine-1-carboxylate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.061, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 39.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-214dcb20e6ca45cb9425c23334069072",
    "procedure_text": "A solution of propargyl amine (4.41 g, 5.13 mL, 80 mmol) in MeCN (30 mL) was added to a stirred solution of 3-(trifluoromethyl)phenyl isocyanate (15.0 g, 12.12 mL, 80 mmol) in MeCN (60 mL) under a nitrogen atmosphere. The reaction mixture was cooled with a RT cooling bath and the rate of addition was such that the internal temperature did not exceed 35\u00b0 C. After 1.5 h the mixture was concentrated in vacuo. EtOAc (10 ml) was added to the residue and the mixture was sonicated for 2 minutes. The resultant slurry was diluted with cyclohexane (40 ml). The mixture was stirred for 10 minutes and the solid was then recovered by filtration. The mother liquors were concentrated in vacuo and the residue dissolved in EtOAc (10 mL). Dilution with cyclohexane (90 ml) precipitated a second batch of product which was recovered by filtration. The two batches were combined as an ethyl acetate solution and concentrated in vacuo to afford the title compound as a fawn solid (16.65 g).",
    "reference_string": "{\"inputs\": {\"m1_m3_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"propargyl amine\"}], \"amount\": {\"volume\": {\"value\": 5.13, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(trifluoromethyl)phenyl isocyanate\"}], \"amount\": {\"volume\": {\"value\": 12.12, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeCN\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeCN\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred for 10 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooling bath\"}, {\"type\": \"ADDITION\", \"details\": \"the rate of addition\"}, {\"type\": \"CUSTOM\", \"details\": \"did not exceed 35\\u00b0 C\", \"temperature\": {\"setpoint\": {\"value\": 35.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CONCENTRATION\", \"details\": \"After 1.5 h the mixture was concentrated in vacuo\", \"duration\": {\"value\": 1.5, \"units\": \"HOUR\"}}, {\"type\": \"ADDITION\", \"details\": \"EtOAc (10 ml) was added to the residue\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the mixture was sonicated for 2 minutes\", \"duration\": {\"value\": 2.0, \"units\": \"MINUTE\"}}, {\"type\": \"ADDITION\", \"details\": \"The resultant slurry was diluted with cyclohexane (40 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cyclohexane\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"the solid was then recovered by filtration\"}, {\"type\": \"CONCENTRATION\", \"details\": \"The mother liquors were concentrated in vacuo\"}, {\"type\": \"DISSOLUTION\", \"details\": \"the residue dissolved in EtOAc (10 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Dilution with cyclohexane (90 ml) precipitated a second batch of product which\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cyclohexane\"}], \"amount\": {\"volume\": {\"value\": 90.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"was recovered by filtration\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 10.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 16.65, \"units\": \"GRAM\"}}}], \"isolated_color\": \"fawn\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-92b76a4414124e0bac97819365c60e29",
    "procedure_text": "1-(azetidin-1-yl)-2-[4-(benzyloxy)-2-methylphenyl]ethanone (440 mg, 1.490 mmol) was dissolved in ethanol (3 ml) and palladium hydroxide on carbon (20%) (105 mg, 0.149 mmol) added. The mixture was stirred under an atmosphere of hydrogen gas at RT overnight. The mixture was filtered and the filtrate concentrated under reduced pressure to afford the title compound. LC/MS (m/z): 206 (M+H)+.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(azetidin-1-yl)-2-[4-(benzyloxy)-2-methylphenyl]ethanone\"}], \"amount\": {\"mass\": {\"value\": 440.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"palladium hydroxide on carbon\"}], \"amount\": {\"mass\": {\"value\": 105.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred under an atmosphere of hydrogen gas at RT overnight\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The mixture was filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate concentrated under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-04eaf81929c3482c84d6cf29c0238eb3",
    "procedure_text": "20 g. of 6-ethoxycarbonylmethyl-1,3,5(10),6-estratetraene-3,17\u03b2-diol is hydrogenated in 280 ml. of tetrahydrofuran and 280 ml. of methanol in the presence of 2 g. of Pd/CaCO3 (10%) until 1 millimole of hydrogen has been absorbed per millimole of substance. The thus-obtained product is 6\u03b2-ethoxycarbonylmethyl-1,3,5(10)-estratriene-3,17\u03b2-diol as a foamy mass. The same compound is also produced by the analogous hydrogenation of 6-ethoxycarbonylmethylene-1,3,5(10)-estratriene-3,17\u03b2-diol. The preparation of 6\u03b2-ethoxycarbonylmethyl-1,3,5(10)-estratriene-3,17\u03b2-diol can be simplified by hydrolyzing the crude product of the Reformatskii reaction, freeing the thus-obtained hydrolyzate from by-products by fractional filtration over silica gel, and hydrogenating the evolved mixture of 6-ethoxycarbonylmethyl-1,3,-5(10),6-estratetraene-3,17\u03b2-diol and 6-ethoxycarbonylmethylene-1,3,5(10)-estratriene-3,17\u03b2-diol as indicated above.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6\\u03b2-ethoxycarbonylmethyl-1,3,5(10)-estratriene-3,17\\u03b2-diol\"}], \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m5_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrogen\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd CaCO3\"}], \"reaction_role\": \"CATALYST\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-ethoxycarbonylmethyl-1,3,5(10),6-estratetraene-3,17\\u03b2-diol\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-ethoxycarbonylmethylene-1,3,5(10)-estratriene-3,17\\u03b2-diol\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e9e09ea8bd984af38c69108a27d73b95",
    "procedure_text": "To a solution of (3,5-Dimethyl-pyridin-2-ylmethyl)-piperidin-4-yl-(1-pyridin-2-yl-ethyl)-amine (194 mg, 0.60 mmol) in 2-propanol (3 mL) was added trimethylsilyl-isocyanate (85 \u03bcL, 0.63 mmol). The resultant solution was stirred at room temperature overnight then concentrated. Purification of the crude material by column chromatography on silica gel (10:1:1 CH2Cl2-MeOH\u2014NH4OH) gave COMPOUND 262 (200 mg, 88%) as a white solid. 1H NMR (CDCl3) \u03b4 0.96-1.02 (m, 1H), 1.45-1.49 (m, 4H), 1.52-1.86 (m, 2H), 2.26 (s, 3H), 2.27 (s, 3H), 2.53-2.62 (m, 1H), 2.71-2.80 (m, 1H), 2.89-2.96 (m, 1H), 3.77-3.97 (m, 5H), 4.37 (s, 2H), 7.10-7.25 (m, 2H), 7.39 (d, 1H, J=7.8 Hz), 7.57-7.62 (m, 1H), 8.19 (br s, 1H), 8.51 (d, 1H, J=3.9 Hz); 13C NMR (CDCl3) \u03b4 13.61, 15.79, 16.16, 27.90, 28.13, 42.22, 42.27, 49.35, 52.87, 55.61, 119.60, 121.54, 129.51, 130.57, 133.80, 136.93, 144.14, 146.25, 152.72, 156.04, 160.52; ES-MS m/z 368 (M+H). Anal. Calcd. For C21H29N5O.0.8H2O: C, 66.05; H, 8.08; N, 18.34. Found: C, 65.9281; H, 7.73; N, 18.18.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(3,5-Dimethyl-pyridin-2-ylmethyl)-piperidin-4-yl-(1-pyridin-2-yl-ethyl)-amine\"}], \"amount\": {\"mass\": {\"value\": 194.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trimethylsilyl-isocyanate\"}], \"amount\": {\"volume\": {\"value\": 85.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-propanol\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"resultant solution\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"then concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification of the crude material by column chromatography on silica gel (10:1:1 CH2Cl2-MeOH\\u2014NH4OH)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude material\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2 MeOH NH4OH\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"COMPOUND 262\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 88.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 90.7}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0d41e20a8a9e4fe6a37bc62dd32dfdb5",
    "procedure_text": "A commercial nonene yielded 59% dialkylate when reacted for 10 hours with diphenylamine under the conditions of Example 1. The nonene, after passing in the vapor phase over a 75 cc catalyst bed of F-24 at 650\u00b0 F. for 5 seconds, was converted to a high reactivity alkene which yielded 71% dinonyl diphenylamine under the reaction conditions of Example 1 after 10 hours reaction time.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diphenylamine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"nonene\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"catalyst\"}], \"amount\": {\"volume\": {\"value\": 75.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"alkene\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dinonyl diphenylamine\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 71.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-691523f304ef4fe3ab455fb125707058",
    "procedure_text": "To a solution of 5-methoxy-3-formyl-2H-chromene-2-carboxylic acid ethyl ester (Example 7, step 1) (1.0 g, 3.81 mmol) in methanol (20 mL) containing molecular sieves (0.7 g) was added commercially available (S)-2-amino-4-methyl-pentanoic acid methyl ester (0.77 g, 6.86 mmol) and N,N\u2032-diisopropylethylamine (0.99 mL, 7.63 mmol). The mixture was stirred at 25\u00b0 C. for 10 hours. At this time, sodium cyanoborohydride (0.48 g, 7.63 mmol) and acetic acid (0.8 mL, 13.72 mmol) were added simultaneously to the reaction mixture, and the reaction mixture was stirred for additional 16 hours at 25\u00b0 C. The reaction mixture was then filtered through celite and washed with methanol. The filtrate was concentrated in vacuo. Flash column chromatography (eluant-ethyl acetate:petroleum ether 1:9, Rf=0.45) over neutral alumina afforded 5-methoxy-3-[((S)-1-methoxycarbonyl-3-methyl-butylamino)-methyl]-2H-chromene-2-carboxylic acid ethyl ester (0.45 g, 43.3%) as an oil.",
    "reference_string": "{\"inputs\": {\"m2_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-methoxy-3-formyl-2H-chromene-2-carboxylic acid ethyl ester\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium cyanoborohydride\"}], \"amount\": {\"mass\": {\"value\": 0.48, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 0.8, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(S)-2-amino-4-methyl-pentanoic acid methyl ester\"}], \"amount\": {\"mass\": {\"value\": 0.77, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N\\u2032-diisopropylethylamine\"}], \"amount\": {\"volume\": {\"value\": 0.99, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 25.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at 25\\u00b0 C. for 10 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"the reaction mixture was stirred for additional 16 hours at 25\\u00b0 C\", \"duration\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 25.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"FILTRATION\", \"details\": \"The reaction mixture was then filtered through celite\"}, {\"type\": \"WASH\", \"details\": \"washed with methanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"The filtrate was concentrated in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 10.0, \"units\": \"HOUR\"}, \"products\": [{\"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-methoxy-3-[((S)-1-methoxycarbonyl-3-methyl-butylamino)-methyl]-2H-chromene-2-carboxylic acid ethyl ester\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.45, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 43.3}}], \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-11cccc0c9ee1433eb2881163e7379c3a",
    "procedure_text": "13.7 mg (325 \u03bcmol) of lithium hydroxide monohydrate are added to a solution of 19 mg (32.5 \u03bcmol) of methyl 4-[(4E)-3-[4-(methoxycarbonyl)benzyl]-5-{2-[4-(2-oxopyrrolidin-1-yl)butoxy]-phenyl}pent-4-en-1-yl]benzoate (Example 36A) in 0.5 ml of dioxane and 0.5 ml of 2 M aqueous sodium hydroxide solution, and the mixture is stirred at room temperature for 16 h. The mixture is then adjusted to pH 2 using 1 M hydrochloric acid and extracted twice with ethyl acetate. The combined organic phases are dried over sodium sulfate, filtered and concentrated. The residue obtained is purified by preparative HPLC. This gives 1.8 mg (3.2 \u03bcmol, 10.0% of theory) of the title compound.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium hydroxide monohydrate\"}], \"amount\": {\"mass\": {\"value\": 13.7, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 4-[(4E)-3-[4-(methoxycarbonyl)benzyl]-5-{2-[4-(2-oxopyrrolidin-1-yl)butoxy]-phenyl}pent-4-en-1-yl]benzoate\"}], \"amount\": {\"mass\": {\"value\": 19.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dioxane\"}], \"amount\": {\"volume\": {\"value\": 0.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"volume\": {\"value\": 0.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture is stirred at room temperature for 16 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted twice with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic phases are dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue obtained\"}, {\"type\": \"CUSTOM\", \"details\": \"is purified by preparative HPLC\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-79445c799dbd4d70b5768edf22c70bde",
    "procedure_text": "To a solution of 8-((6-iodobenzo[d][1,3]dioxol-5-yl)thio-9H-purin-6-amine (39 mg, 0.09 mmol) in DMF (2 mL) was added 3-chloro-N-isopropylpropane-1-sulfonamide (100 mg, 0.45 mmol) and Cs2CO3 (62 mg, 0.19 mmol). The resulting mixture was stirred at room temperature overnight. The reaction mixture was condensed under vacuum and the residue was purified by Prep TLC (CH2Cl2:NH3-MeOH (7N), 20:1) to yield WS54 as a white solid (14 mg, 26%). 1H NMR (500 MHz, CDCl3/MeOH-d4): \u03b4 8.00 (s, 1H), 7.19 (s, 1H), 6.86 (s, 1H), 5.86 (s, 2H), 4.17 (t, J=7.3 Hz, 2H), 3.34 (septet, J=6.6 Hz, 1H), 2.89 (t, J=7.6 Hz, 2H), 2.05-2.13 (m, 2H), 0.99 (d, J=6.6 Hz, 6H); HRMS (ESI) m/z [M+H]+ calcd. for C15H22IN6O4S2, 577.0189. found 577.0194.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(6-iodobenzo[d][1,3]dioxol-5-yl)thio-9H-purin-6-amine\"}], \"amount\": {\"mass\": {\"value\": 39.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-chloro-N-isopropylpropane-1-sulfonamide\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Cs2CO3\"}], \"amount\": {\"mass\": {\"value\": 62.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The resulting mixture was stirred at room temperature overnight\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"condensed under vacuum\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was purified by Prep TLC (CH2Cl2:NH3-MeOH (7N), 20:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH3 MeOH\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 14.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 26.0}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c231143eab2a4a9290729ced9a8af7a9",
    "procedure_text": "82.5 g of ethyl p-aminobenzoate was dissolved in 500 ml of toluene, to the solution was added 83.4 g of N,N-diethylthiocarbamoyl chloride and the mixture was refluxed by heating for 8 hours. After cooling with ice, 100 ml of concentrated hydrochloric acid was added to the reaction mixture and then the toluene layer was separated and washed with water. The toluene was distilled off under reduced pressure and the residual oily product was crystallized from methanol to obtain 77.1 g of ethyl p-isothiocyanatobenzoate. Yield: 74.5%. Melting Point: 52\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl p-aminobenzoate\"}], \"amount\": {\"mass\": {\"value\": 82.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-diethylthiocarbamoyl chloride\"}], \"amount\": {\"mass\": {\"value\": 83.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"the mixture was refluxed\"}, {\"type\": \"TEMPERATURE\", \"details\": \"by heating for 8 hours\", \"duration\": {\"value\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"ADDITION\", \"details\": \"was added to the reaction mixture\"}, {\"type\": \"CUSTOM\", \"details\": \"the toluene layer was separated\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"The toluene was distilled off under reduced pressure\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the residual oily product was crystallized from methanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl p-isothiocyanatobenzoate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 77.1, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 74.5}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 74.5}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-7411d0b69c7c4090ac2d36e7ea434626",
    "procedure_text": "A mixture of 1,1-dimethylethyl 4-(3-bromo-4-{[(3-chlorophenyl)sulfonyl]amino}-6-methylthieno[2,3-b]pyridin-2-yl)-1H-pyrazole-1-carboxylate (Description 75) (100 mg, 0.171 mmol), 3-(morpholino)phenylboronic acid, pinacol ester (74.3 mg, 0.257 mmol), potassium carbonate (95 mg, 0.685 mmol) and tetrakis(triphenylphosphine)palladium(0) (3.96 mg, 3.43 \u03bcmol) were weighed into a microwave vial. 1,4-Dioxane (1.5 mL), DMF (0.75 mL) and water (0.38 mL) were added and the mixture heated in a microwave at 110\u00b0 C. for 30 min. At this point, both reaction mixtures were combined and concentrated. Purification by chromatography on silica, eluting with a gradient of 0-100% ethyl acetate in DCM, followed by MDAP (acidic conditions), afforded the title compound (44 mg). LCMS (A) m/z: 566 [M+1]+, Rt 1.24 min (acidic).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,1-dimethylethyl 4-(3-bromo-4-{[(3-chlorophenyl)sulfonyl]amino}-6-methylthieno[2,3-b]pyridin-2-yl)-1H-pyrazole-1-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(morpholino)phenylboronic acid\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pinacol ester\"}], \"amount\": {\"mass\": {\"value\": 74.3, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 95.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrakis(triphenylphosphine)palladium(0)\"}], \"amount\": {\"mass\": {\"value\": 3.96, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m5_m8_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,4-Dioxane\"}], \"amount\": {\"volume\": {\"value\": 1.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 0.38, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 0.75, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 110.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"At this point, both reaction mixtures\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification by chromatography on silica\"}, {\"type\": \"WASH\", \"details\": \"eluting with a gradient of 0-100% ethyl acetate in DCM\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 44.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-6a263f5187f048248cdb624506acfa04",
    "procedure_text": "To a solution of [2-(2,5-dichloro-phenoxy)-pyridin-3-yl]-(3,4-dihydro-2H-quinoxalin-1-yl)-methanone (60 mg, 0.15 mmol, 1.0 equiv; Example 122) in anhydrous DMF (0.5 mL) was added N-ethyldiisopropylamine (96 mg, 129 \u03bcL, 0.75 mmol, 5.0 equiv; [CAS RN 7087-68-5]) and ethyl bromoacetate (55.1 mg, 37 \u03bcL, 0.33 mmol, 2.2 equiv; [CAS RN 105-36-2]) and the reaction mixture heated by microwave irradiation to 100\u00b0 C. for 2 h. Removal of the solvent under reduced pressure and purification by preparative HPLC on reversed phase (Xterra\u00ae PrepMSC 18, 5 \u03bcM, 19\u00d750 mm column equipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax\u00ae SD-300 pumps, a Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water provided 42.7 mg (62%) of the title compound as a light yellow powder. MS (ISP): 486.1 [M+H]+.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"[2-(2,5-dichloro-phenoxy)-pyridin-3-yl]-(3,4-dihydro-2H-quinoxalin-1-yl)-methanone\"}], \"amount\": {\"mass\": {\"value\": 60.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-ethyldiisopropylamine\"}], \"amount\": {\"volume\": {\"value\": 129.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl bromoacetate\"}], \"amount\": {\"volume\": {\"value\": 37.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 0.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Removal of the solvent\"}, {\"type\": \"CUSTOM\", \"details\": \"under reduced pressure and purification by preparative HPLC on reversed phase (Xterra\\u00ae PrepMSC 18, 5 \\u03bcM, 19\\u00d750 mm column\"}, {\"type\": \"CUSTOM\", \"details\": \"equipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax\\u00ae SD-300 pumps\"}, {\"type\": \"WASH\", \"details\": \"a Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"340S\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile water\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 42.7, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 62.0}}], \"isolated_color\": \"light yellow\", \"texture\": {\"type\": \"POWDER\", \"details\": \"powder\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-6690e4e233b04273a1556d42de26523c",
    "procedure_text": "To 20 ml of a solution containing 2.70 g of 3-(4-tert-butylphenyl)-7-isopropyl-2-methyl-1-oxo-1,2,3,4-tetrahydroisoquinoline- 4-carboxylic acid (mixture of diastereomers) in dimethylsulfoxide, 1.10 g of sodium carbonate was added and the resulting mixture was heated at 150\u00b0 C. for 12 hours. After the reaction, the solvent was evaporated under reduced pressure and 200 ml of water was added thereto. The resultant was extracted with ethyl acetate (50 ml\u00d73) The organiclayers were combined and washed with saturated aqueous sodium chloride solution and the resultant was dried over anhydrous magnesium sulfate. After evaporating the solvent under reduced pressure, the residue was purified by column chromatography on silica gel (hexane/ethyl acetate=5/1 v/v) to obtain 2.10 g of 3-(4-tertbutylphenyl)-7-isopropyl-2-methyl-l,2,3,4-tetrahydroisoquinoline-1-one.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(4-tert-butylphenyl)-7-isopropyl-2-methyl-1-oxo-1,2,3,4-tetrahydroisoquinoline- 4-carboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 2.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium carbonate\"}], \"amount\": {\"mass\": {\"value\": 1.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylsulfoxide\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 150.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"CUSTOM\", \"details\": \"After the reaction\"}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was evaporated under reduced pressure and 200 ml of water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"EXTRACTION\", \"details\": \"The resultant was extracted with ethyl acetate (50 ml\\u00d73) The\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with saturated aqueous sodium chloride solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"the resultant was dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"After evaporating the solvent under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was purified by column chromatography on silica gel (hexane/ethyl acetate=5/1 v/v)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(4-tertbutylphenyl)-7-isopropyl-2-methyl-l,2,3,4-tetrahydroisoquinoline-1-one\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.1, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-97a23a7e4e0a4305a30d1357c4059166",
    "procedure_text": "To a stirred solution of 7-bromo-pyrrolo[2,1-f][1,2,4]triazin-4-ylamine (5.27 g, 24.7 mmol) in anhydrous THF (40 mL) was added chlorotrimethylsilane (5.9 g, 54.4 mmol) at rt. The reaction mixture was stirred at rt for 2 hours and cooled in an ice water bath. 2-propylmagnesium chloride in THF (52 mL, 104 mmol, 2.0 M) was added dropwise, and the reaction mixture was allowed stirred at rt for 2 hours. The reaction was cooled to 0\u00b0 C. with an ice bath, and 2-formyl-cyclopropanecarboxylic acid ethyl ester (4.6 g, 32 mmol) was added. The reaction mixture was stirred at rt for 1 hour. The mixture was quenched with saturated, aqueous ammonium chloride (20 mL) In ice water bath. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (100 mL). The combined organic layer was washed with water, brine, dried by Na2SO4, filtered and concentrated. The crude product was separated by column (30% EtOAc/70% Hexane) to give 2.0 g (30%) of product. 1H NMR (300 MHz, DMSO-d6) \u03b4 8.80 (s, 1 H), 8.75 (bs, 2 H), 6.80 (s, 1 H), 6.60 (m, 1 H), 5.40 (s, 1 H), 5.0-4.8 (m, 1 H), 4.0 (m, 2 H), 1.9-1.8 (m, 2 H), 1.2 (t, 3 H), 1.0 (m, 2 H); ES-MS m/z 277.34 [M+H]+, HPLC RT (min) 1.51.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-formyl-cyclopropanecarboxylic acid ethyl ester\"}], \"amount\": {\"mass\": {\"value\": 4.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-propylmagnesium chloride\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 52.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m5_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-bromo-pyrrolo[2,1-f][1,2,4]triazin-4-ylamine\"}], \"amount\": {\"mass\": {\"value\": 5.27, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chlorotrimethylsilane\"}], \"amount\": {\"mass\": {\"value\": 5.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred at rt for 2 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooled in an ice water bath\"}, {\"type\": \"STIRRING\", \"details\": \"the reaction mixture was allowed stirred at rt for 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"The reaction was cooled to 0\\u00b0 C. with an ice bath\", \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"STIRRING\", \"details\": \"The reaction mixture was stirred at rt for 1 hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The mixture was quenched with saturated, aqueous ammonium chloride (20 mL) In ice water bath\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium chloride\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The organic layer was separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"the aqueous layer was extracted with ethyl acetate (100 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined organic layer was washed with water, brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried by Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude product was separated by column (30% EtOAc/70% Hexane)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 30.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-bbb69e4e0b0342f487838cacdcf13c8c",
    "procedure_text": "5.84 Grams of 4-hydroxy-6-(3-trifluoromethylphenylthio)-2-hexanone were dissolved in 58 ml of toluene, and 0.62 g of oxalic acid was added thereto. The resulting mixture was refluxed for 4 hours with stirring, allowed to cool and then treated in the same manner as in Production example 34. Thus, 5.26 g of 6-(3-trifluoromethylphenylthio)-3-hexen-2-one (trans : cis =2.9 : 1) were obtained (purity: 98.5%). Further, the product was column chromatographed to obtain a purified product having a refractive index (n25.5) of 1.5222. The yield was 94.5%.",
    "reference_string": "{\"inputs\": {\"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-hydroxy-6-(3-trifluoromethylphenylthio)-2-hexanone\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 58.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"oxalic acid\"}], \"amount\": {\"mass\": {\"value\": 0.62, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"with stirring\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The resulting mixture was refluxed for 4 hours\", \"duration\": {\"value\": 4.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"to cool\"}, {\"type\": \"ADDITION\", \"details\": \"treated in the same manner as in Production example 34\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-(3-trifluoromethylphenylthio)-3-hexen-2-one\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 5.26, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 94.5}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-98d2148843df4d7aad845423c9262846",
    "procedure_text": "Trifluoroacetic acid (0.061 ml, 0.091 g, 0.794 mmol, 0.5 eq) was added dropwise to a stirred solution of dimethyl 5-(3-hydroxypyrrolidin-1-yl)isophthalate (0.4434 g, 1.59 mmol, 1 eq), anhydrous pyridine (0.135 ml, 0.13 g, 1.67 mmol, 1.05 eq), anhydrous DMSO (0.124 ml, 0.13 g, 1.67 mmol, 1.05 eq), and 1,3-dicyclohexylcarbodiimide (0.655 g, 3.18 mmol, 2 eq) in 5 ml anhydrous benzene at \u00b0 C. under Ar. After stirring at 0\u00b0 C. to room temperature overnight the reaction was diluted with Et2O/H2O and stirred for 20 h. The mixture was filtered through cotton and the layers were separated. The organic layer was washed with water (\u00d73), brine (\u00d71), and dried over Na2SO4. The inorganics were filtered off and the solvent was removed in vacuo. Purification via flash chromatography yielded only crude product. Purification via a second column yielded 0.201 g (0.73 mmol, 46% yield) of dimethyl 5-(3-oxopyrrolidin-1-yl)isophthalate.",
    "reference_string": "{\"inputs\": {\"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Et2O H2O\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3_m4_m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Trifluoroacetic acid\"}], \"amount\": {\"volume\": {\"value\": 0.061, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethyl 5-(3-hydroxypyrrolidin-1-yl)isophthalate\"}], \"amount\": {\"mass\": {\"value\": 0.4434, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"amount\": {\"volume\": {\"value\": 0.135, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMSO\"}], \"amount\": {\"volume\": {\"value\": 0.124, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,3-dicyclohexylcarbodiimide\"}], \"amount\": {\"mass\": {\"value\": 0.655, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzene\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring at 0\\u00b0 C. to room temperature overnight the reaction\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"stirred for 20 h\", \"duration\": {\"value\": 20.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"The mixture was filtered through cotton\"}, {\"type\": \"CUSTOM\", \"details\": \"the layers were separated\"}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with water (\\u00d73), brine (\\u00d71)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"The inorganics were filtered off\"}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was removed in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification via flash chromatography\"}, {\"type\": \"CUSTOM\", \"details\": \"yielded only crude product\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification via a second column\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethyl 5-(3-oxopyrrolidin-1-yl)isophthalate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 0.73, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.201, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 46.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0f2d229416c74ebea1c1d88f665fceac",
    "procedure_text": "A solution of 2 g (0.005 mole) of 6-(2-chlorophenyl)-1,8-dichloro-4H-imidazo[1,5-a] [1,4]benzodiazepine-3-carboxylic acid, methyl ester 0.7 g (0.012 mole) of potassium hydroxide, 60 ml of methanol and 2 ml of water was refluxed under argon for 2.5 hrs. The solution was evaporated in vacuo at 50\u00b0-60\u00b0. An aqueous solution of the residue was acidified with acetic acid to give a gelatinous, white precipitate. The precipitate was collected by filtration, washed with water and air dried on the funnel overnight to give off-white solid. Recrystallization from a solution of ethanol and methylene chloride gave white plates with mp 250\u00b0-253\u00b0 (dec).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-(2-chlorophenyl)-1,8-dichloro-4H-imidazo[1,5-a] [1,4]benzodiazepine-3-carboxylic acid, methyl ester\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium hydroxide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The solution was evaporated in vacuo at 50\\u00b0-60\\u00b0\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a gelatinous, white precipitate\"}, {\"type\": \"FILTRATION\", \"details\": \"The precipitate was collected by filtration\"}, {\"type\": \"WASH\", \"details\": \"washed with water and air\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried on the funnel overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"to give off-white solid\"}, {\"type\": \"CUSTOM\", \"details\": \"Recrystallization from a solution of ethanol and methylene chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"gave white plates with mp 250\\u00b0-253\\u00b0 (dec)\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-(2-Chlorophenyl)-1,8-dichloro-4H-imidazo[1,5-a] [1,4]benzodiazepine-3-carboxylic acid\"}]}]}]}"
  },
  {
    "reaction_id": "ord-379a16ecfc1b441cabee3edfc7c8a0f4",
    "procedure_text": "Following the general method as outlined in Example 20, starting from 6-chloro-pyrimidine-4-carboxylic acid (1H-indazol-5-yl)-amide (Intermediate 16) and cyclohexyl-(2-methoxy-ethyl)-amine (Intermediate 26), the title compound was obtained as a yellow solid.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Intermediate 26\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-chloro-pyrimidine-4-carboxylic acid (1H-indazol-5-yl)-amide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Intermediate 16\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cyclohexyl-(2-methoxy-ethyl)-amine\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-9e84607c5afe4ca7a014fa60dc391a19",
    "procedure_text": "To a solution of 116 mg (0.25 mmol) acetic acid (S)-{(3,4-dimethyl-phenyl)-[2-(5-trifluoromethyl-pyridin-2-yl)-ethyl]-carbamoyl}-phenyl-methyl ester in 1.2 mL tetrahydrofuran were added 0.6 mL water and 11.4 mg (0.27 mmol) lithium hydroxide monohydrate. The mixture was stirred at room temperature overnight. The mixture was diluted with water and extracted 3 times with ethyl acetate. The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The crude oil was purified with flash column chromatography on silica eluting with a gradient formed from heptane and ethylacetate to provide 0.098 g (93%) of the title compound as a colorless oil. MS(m/e): 429.2 [M+H]+.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m3_m5_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid (S)-{(3,4-dimethyl-phenyl)-[2-(5-trifluoromethyl-pyridin-2-yl)-ethyl]-carbamoyl}-phenyl-methyl ester\"}], \"amount\": {\"mass\": {\"value\": 116.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium hydroxide monohydrate\"}], \"amount\": {\"mass\": {\"value\": 11.4, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 1.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 0.6, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at room temperature overnight\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted 3 times with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic layers were dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude oil was purified with flash column chromatography on silica eluting with a gradient\"}, {\"type\": \"CUSTOM\", \"details\": \"formed from heptane and ethylacetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"heptane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethylacetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.098, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 93.0}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fc7668ceaf434ba88052462476315243",
    "procedure_text": "To a solution of phenylmethyl({4-[(2S,4R)-1-acetyl-4-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]phenyl}methyl)methylcarbamate (for a preparation see intermediate 81) (1 g, 1.793 mmol) in methanol (50 mL) was added acetyl chloride (2 mL, 28.1 mmol). The resulting mixture was stirred at room temperature for 3 h then concentrated in vacuovacuo. The residue was loaded on a 50 g SCX column, then eluted with MeOH (3 column volume (CV)) followed by 2N NH3 in methanol (4 CV). The ammonia fractions were combined and evaporated in vacuovacuo. Purification of the residue obtained by flash chromatography on silica gel (40 g column, gradient:0 to 5% (2N NH3 in MeOH) in DCM) gave phenylmethyl ({4-[(2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]phenyl}methyl)methylcarbamate (581 mg, 1.27 mmol, 71%) as a colourless oil which solidified on standing.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"phenylmethyl({4-[(2S,4R)-1-acetyl-4-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]phenyl}methyl)methylcarbamate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"intermediate 81\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetyl chloride\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The resulting mixture was stirred at room temperature for 3 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"then concentrated in vacuovacuo\"}, {\"type\": \"WASH\", \"details\": \"eluted with MeOH (3 column volume (CV))\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated in vacuovacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification of the residue\"}, {\"type\": \"CUSTOM\", \"details\": \"obtained by flash chromatography on silica gel (40 g column, gradient:0 to 5% (2N NH3 in MeOH) in DCM)\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"phenylmethyl ({4-[(2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]phenyl}methyl)methylcarbamate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 1.27, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 581.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 71.0}}], \"isolated_color\": \"colourless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a57125519aa74f23ae7467e386e1062f",
    "procedure_text": "A mixture of 2-guanidino-4-(4-aminobutyl)thiazole (0.43 g.) and 1,1-di(methylthio)-2-nitroethylene (0.33 g.) in acetonitrile (15 ml.) was heated under reflux for 1 hour. The mixture evaporated to dryness and 33% w/v ethanolic methylamine (200 ml.) added. The mixture was stirred for 5 days at room temperature, then filtered and the filtrate evaporated to dryness. The residue was crystallized from ethanol to give 1-[4-(2-guanidinothiazol-4-yl)butylamino]-1-methylamino-2-nitroethylene, m.p. 225\u00b0 C. (decomposed).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-guanidino-4-(4-aminobutyl)thiazole\"}], \"amount\": {\"mass\": {\"value\": 0.43, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,1-di(methylthio)-2-nitroethylene\"}], \"amount\": {\"mass\": {\"value\": 0.33, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred for 5 days at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"under reflux for 1 hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The mixture evaporated to dryness and 33%\"}, {\"type\": \"ADDITION\", \"details\": \"added\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"the filtrate evaporated to dryness\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was crystallized from ethanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 5.0, \"units\": \"DAY\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-[4-(2-guanidinothiazol-4-yl)butylamino]-1-methylamino-2-nitroethylene\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-90ec1c63679341569c7e0360a3c59bf1",
    "procedure_text": "To a solution of ethyl 2-(4-bromophenyl)-3-[2-(chloromethyl)-1,3-dioxolan-2-yl]propanoate (1-3) (27 g, 71.5 mmol) cooled to \u221278\u00b0 C. in DMF (200 mL) was added NaH (8.58 g, 214 mmol) and the reaction was allowed to slowly warm from \u221278\u00b0 C. to rt. Once at rt, 1N NaOH (100 mL) was added and the reaction mixture was stirred over night. The crude reaction mixture was poured into saturated sodium bicarbonate and washed with chloroform. The aqueous layer was acidified with HCl, extracted with chloroform, dried over sodium sulfate filtered and concentrated. The crude residue was purified by column chromatography eluting with 1-50% EtOAc/Hexane. The appropriate fractions were concentrated and recrystallized from EtOAc/hexane to give 2-(4-bromophenyl)-5,8-dioxaspiro[3.4]octane-2-carboxylic acid (1-4) as a white solid. MS (M+H)+: 314.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaH\"}], \"amount\": {\"mass\": {\"value\": 8.58, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 2-(4-bromophenyl)-3-[2-(chloromethyl)-1,3-dioxolan-2-yl]propanoate\"}], \"amount\": {\"mass\": {\"value\": 27.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture was stirred over night\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"to slowly warm from \\u221278\\u00b0 C. to rt\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude reaction mixture\"}, {\"type\": \"WASH\", \"details\": \"washed with chloroform\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with chloroform\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude residue was purified by column chromatography\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude residue\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"eluting with 1-50% EtOAc/Hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc Hexane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"The appropriate fractions were concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"recrystallized from EtOAc/hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(4-bromophenyl)-5,8-dioxaspiro[3.4]octane-2-carboxylic acid\"}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2fce41c9f5754deb9bfd45af4072096c",
    "procedure_text": "N-(3-(6-Chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)acrylamide (50 mg, 0.130 mmol), 3-fluoro-4-morpholinoaniline (23.00 mg, 0.117 mmol) and Cs2CO3 (50.9 mg, 0.156 mmol) were dissolved in toluene (5 mL) in a sealable microwave compatible reaction tube, then Pd2(dba)3 (2.386 mg, 2.61 \u03bcmol) and Xantphos (3.01 mg, 5.21 \u03bcmol) were added. The reaction tube was sealed and the reaction was heated under microwave irradiation (60 min, 200\u00b0 C., 3 atm). Reaction progress was monitored by TLC. After completion of the reaction, the solvent was removed by vacuum and compound was purified by column chromatography. 1H NMR (400 MHz, CD3OD): \u03b4 8.64 (s, 1H), 8.26 (s, 1H), 7.92 (d, 1H, J=7.6 Hz), 7.82 (dd, 1H, J=2.4 and 15.2 Hz), 7.68 (m, 1H), 7.48 (t, 1H, J=7.6 Hz), 7.35 (dd, 1H, J=1.6 and 8.8 Hz), 6.95 (t, 1H, J=8.8 Hz), 6.43 (m, 2H), 5.87 (dd, 1H, J=2.4 and 10.4 Hz), 5.80 (dd, 1H, J=2.8 and 8.8 Hz), 4.11 (m, 1H), 3.82 (m, 4H), 3.75 (m, 1H), 3.00 (m, 4H), 2.60 (m, 1H), 2.13 (m, 1H), 1.97 (m, 1H), 1.83-1.73 (m, 3H); ESI-MS: [M+H]+.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(3-(6-Chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)acrylamide\"}], \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-fluoro-4-morpholinoaniline\"}], \"amount\": {\"mass\": {\"value\": 23.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Cs2CO3\"}], \"amount\": {\"mass\": {\"value\": 50.9, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m6_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Xantphos\"}], \"amount\": {\"mass\": {\"value\": 3.01, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd2(dba)3\"}], \"amount\": {\"mass\": {\"value\": 2.386, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 200.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The reaction tube was sealed\"}, {\"type\": \"CUSTOM\", \"details\": \"Reaction progress\"}, {\"type\": \"CUSTOM\", \"details\": \"After completion of the reaction\"}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was removed by vacuum and compound\"}, {\"type\": \"CUSTOM\", \"details\": \"was purified by column chromatography\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-be11d30e2c0f4f0ebe0021a9729b7ff5",
    "procedure_text": "To a solution of (2E)-3-(4-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}phenyl)acrylic acid (936 mg, crude) in DMF (10 mL) was added was added O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (442 mg), HOBt (588 mg), and EDCI (676 mg) and the resulting mixture was stirred at ambient temperature for 3 hours. The reaction mixture was diluted with water and extracted with AcOEt. The organic phase was washed with sat NH4Cl at solution, sat NaHCO3 aq solution, and brine, and dried over Na2SO4. The solvent was removed in vacuo and the residue was purified by preparative thin layer chromatography (chloroform:methanol=10:1) to give (2E)-3-(4-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}phenyl)-N-(tetrahydro-2H-pyran-2-yloxy)acrylamide (945 mg) as pale yellow form.",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2E)-3-(4-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}phenyl)acrylic acid\"}], \"amount\": {\"mass\": {\"value\": 936.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"O-(tetrahydro-2H-pyran-2-yl)hydroxylamine\"}], \"amount\": {\"mass\": {\"value\": 442.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HOBt\"}], \"amount\": {\"mass\": {\"value\": 588.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EDCI\"}], \"amount\": {\"mass\": {\"value\": 676.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the resulting mixture was stirred at ambient temperature for 3 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted with AcOEt\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"AcOEt\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic phase was washed with sat NH4Cl at solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH4Cl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The solvent was removed in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was purified by preparative thin layer chromatography (chloroform:methanol=10:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2E)-3-(4-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}phenyl)-N-(tetrahydro-2H-pyran-2-yloxy)acrylamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 945.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f82d02ae12bd4e0cbd96e9329d9ca9e1",
    "procedure_text": "A stirred refluxing solution of 4-(4-chlorobenzoyl)-3-chlorotoluene (2.65 g, 9.99 mmol) and dibenzoylperoxide (100 mg, 0.413 mmol) in benzene (100 ml) was treated in portions with an intimate mixture of N-bromosuccinimide (2.2 g, 12. mmol) and dibenzoylperoxide (100 mg, 0.413 mmol). The mixture was refluxed 1.5 hours, cooled, and filtered. The filtrate was evaporated under vacuum, triturated with diethyl ether (100 ml), and filtered. The filtrate was evaporated under vacuum and the residue was chromatographed on silica gel (500 g) eluted with 97:3 (v/v) n-hexane-ethyl acetate using a preparative highperformance liquid chromatograph to provide 1.69 g (49%) of 4-(4-chlorobenzoyl)-3-chlorobenzyl bromide, m.p. 88\u00b0-90\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m4_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(4-chlorobenzoyl)-3-chlorotoluene\"}], \"amount\": {\"mass\": {\"value\": 2.65, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzene\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dibenzoylperoxide\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-bromosuccinimide\"}], \"amount\": {\"mass\": {\"value\": 2.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dibenzoylperoxide\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The mixture was refluxed 1.5 hours\", \"duration\": {\"value\": 1.5, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"cooled\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"The filtrate was evaporated under vacuum\"}, {\"type\": \"CUSTOM\", \"details\": \"triturated with diethyl ether (100 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"The filtrate was evaporated under vacuum\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was chromatographed on silica gel (500 g)\"}, {\"type\": \"WASH\", \"details\": \"eluted with 97:3 (v/v) n-hexane-ethyl acetate using a preparative highperformance liquid chromatograph\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-hexane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(4-chlorobenzoyl)-3-chlorobenzyl bromide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.69, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 49.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 49.2}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f3f38a5f9f944ce6bdeecddba2bdbe6e",
    "procedure_text": "2,6-Dichloropurine (2.5 g, 13.23 mmol) and cyclohexylamine (1.51 mL, 13.2 mmol) were dissolved in acetonitrile (25 mL) and heated to 50\u00b0 C. for 5 days. The white precipitate was collected by filtration and used without further purification.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,6-Dichloropurine\"}], \"amount\": {\"mass\": {\"value\": 2.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cyclohexylamine\"}], \"amount\": {\"volume\": {\"value\": 1.51, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 50.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The white precipitate was collected by filtration\"}, {\"type\": \"CUSTOM\", \"details\": \"used without further purification\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-ef3fc7d994174f9abf2ab24fdc672067",
    "procedure_text": "The title compound was prepared in a similar manner to that described in Reference Example 12 using 4-[(4-benzyloxy-2-methylphenyl)methyl]-1,2-dihydro-5-isopropyl-3H-pyrazol-3-one and 2,3,4,6-tetra-O-pivaloyl-\u03b1-D-glucopyranosyl bromide (Kunz, H.; Harreus, A. Liebigs Ann. Chem. 1982, 41-48 Velarde, S.; Urbina, J.; Pena, M. R. J. Org. Chem. 1996, 61, 9541-9545) instead of 4-{[4-(2-benzyloxycarbonyl-2-methylpropoxy)phenyl]-methyl}-1,2-dihydro-5-isopropyl-3H-pyrazol-3-one and acetobromo-\u03b1-D-glucose, respectively.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetobromo-\\u03b1-D-glucose\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-[(4-benzyloxy-2-methylphenyl)methyl]-1,2-dihydro-5-isopropyl-3H-pyrazol-3-one\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,3,4,6-tetra-O-pivaloyl-\\u03b1-D-glucopyranosyl bromide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-{[4-(2-benzyloxycarbonyl-2-methylpropoxy)phenyl]-methyl}-1,2-dihydro-5-isopropyl-3H-pyrazol-3-one\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-663fbccc59ea4e929fead880ce853af2",
    "procedure_text": "Following the general procedure A, 4,4\u2032-(6-chloro-1,3,5-triazine-2,4-diyl)dimorpholine was coupled with 3-cyanophenylboronic acid pinacol ester with reaction time of 15 h. Column chromatography (hexane/ethyl acetate 1:1) gave 57% of the title compound as an colorless solid.",
    "reference_string": "{\"inputs\": {\"m3_m0\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane ethyl acetate\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4,4\\u2032-(6-chloro-1,3,5-triazine-2,4-diyl)dimorpholine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-cyanophenylboronic acid pinacol ester\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 57.0}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-1f15add2935f490b9c439aef4909601b",
    "procedure_text": "An amount of 1-(4-chlorobutyl)-9-(3-chloro-4-fluoroanilino)-2,3-dihydro-1H-[1,4]oxazino[3,2-g]quinoline-8-carbonitrile (150 mg, 0.34 mmol) was stirred in N,N-dimethylformamide (1.5 ml), and to this were added sodium iodide (76 mg, 0.51 mmol), tetrabutyl ammonium iodide (25.9 mg, 0.07 mmol), and dimethylamine in tetrahydrofuran (2M) (5.4 mL, 10.8 mmol). The mixture was heated at 45\u00b0 C. for 4 hours, cooled to room temperature, and stirred with ethyl acetate and saturated sodium bicarbonate solution. After separation of the layers, the organic layer was dried over sodium sulfate and evaporated to an oil. Purification was performed by preparative thin layer chromatography (60% acetone in methanol) to give a yellow solid (89 mg, 58% yield), m.p. 105\u00b0 C.; 1H NMR (DMSO-d6) \u03b4 9.50-9.00 (bs, 1H), 8.20 (s, 1H), 7.33 (t, 1H), 7.26 (dd, 1H), 7.23 (s, 1H), 7.07 (m, 2H), 4.30 t, 2H), 3.37 (m, 4H), 2.18 (t, 2H), 2.06 (s, 6H), 1.55 (m, 2H), 1.40 (m, 2H); HRMS (EI) m/z 453.1736 (M+1).",
    "reference_string": "{\"inputs\": {\"m8_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(4-chlorobutyl)-9-(3-chloro-4-fluoroanilino)-2,3-dihydro-1H-[1,4]oxazino[3,2-g]quinoline-8-carbonitrile\"}], \"amount\": {\"mass\": {\"value\": 150.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 1.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m7_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium iodide\"}], \"amount\": {\"mass\": {\"value\": 76.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylamine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 5.4, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrabutyl ammonium iodide\"}], \"amount\": {\"mass\": {\"value\": 25.9, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 45.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooled to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"After separation of the layers\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"the organic layer was dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated to an oil\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 89.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 58.0}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-311afd4a87b14749aa867a06227778b2",
    "procedure_text": "To a mixture of ethyl-3-(5-nitro-1H-benzimidazol-1-yl)-3-phenyl-2-propenoate and ethyl-3-(6-nitro-1H-benzimidazol-1-yl)-3-phenyl-2-propenoate (5.34 g, 15.8 mmol) in a mixture of ethanol and water (10:1, 66 mL) was added palladium on carbon (801 mg, 10% w/w Pd) and ammonium formate (6.0 g, 95 mmol). The suspension was heated to reflux, and was stirred at this temperature for 1.5 hours. The reaction mixture was allowed to cool to room temperature, then filtered through Celite\u00ae, and the filter pad washed several times with ethanol. The combined filtrates were evaporated in vacuo, and the residue was purified by flash column chromatography on silica gel, eluting with a mixture of dichloromethane and methanol (99:1) to give, in order of elution, ethyl 3-(6-amino-1H-benzimidazol-1-yl)-3-phenylpropanoate, [LCMS (Method A, Mobile Phase I) RT=3.33 min, MH+ 310] and ethyl 3-(5-amino-1H-benzimidazol-1-yl)-3-phenylpropanoate (1.96 g), [LCMS (Method A, Mobile Phase I) RT=3.35 min, MH+ 310].",
    "reference_string": "{\"inputs\": {\"m6_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 66.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m8_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium formate\"}], \"amount\": {\"mass\": {\"value\": 6.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"palladium on carbon\"}], \"amount\": {\"mass\": {\"value\": 801.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl-3-(5-nitro-1H-benzimidazol-1-yl)-3-phenyl-2-propenoate\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl-3-(6-nitro-1H-benzimidazol-1-yl)-3-phenyl-2-propenoate\"}], \"amount\": {\"mass\": {\"value\": 5.34, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at this temperature for 1.5 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The suspension was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to reflux\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered through Celite\\u00ae\"}, {\"type\": \"WASH\", \"details\": \"the filter pad washed several times with ethanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The combined filtrates were evaporated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was purified by flash column chromatography on silica gel\"}, {\"type\": \"WASH\", \"details\": \"eluting with a mixture of dichloromethane and methanol (99:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.5, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 3-(6-amino-1H-benzimidazol-1-yl)-3-phenylpropanoate\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Phase I\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 3-(5-amino-1H-benzimidazol-1-yl)-3-phenylpropanoate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.96, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-55ad54801b3c49feaf5c458d752f702d",
    "procedure_text": "A solution of (E)-3-(4-chlorophenyl)-2-(4-(2-(dimethylamino)vinyl)-3-nitrophenyl)quinazolin-4(3H)-one (0.340 g, 0.76 mmol) in a 3:1 mixture of EtOH/DMF (50 mL) was flushed with N2. Pd/C (0.034 g, 10 wt %) was added the reaction was flushed with H2 for 1.5 hours. After filtering through diatomaceous earth, the filtrate was concentrated. Purification by flash chromatography on silica gel, eluting with 5% to 70% EtOAc in heptane, afforded the title compound as a white solid (0.105 g, 37%). 1H-NMR (300 MHz, DMSO-d6, mixture of rotamers): \u03b411.34 (s, 0.5H), 11.25 (s, 0.5H), 8.16-8.29 (m, 1H), 7.86-8.00 (m, 1H), 7.71-7.82 (m, 1H), 7.49-7.67 (m, 3H), 7.29-7.48 (m, 5H), 6.87-7.05 (m, 1H), 6.37-6.42 (m, 0.5H), 6.25-6.26 (m, 0.5H). MS (APCI) m/z: 372 (M+H)+.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(E)-3-(4-chlorophenyl)-2-(4-(2-(dimethylamino)vinyl)-3-nitrophenyl)quinazolin-4(3H)-one\"}], \"amount\": {\"mass\": {\"value\": 0.34, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOH DMF\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"was flushed with N2\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N2\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"Pd/C (0.034 g, 10 wt %) was added the reaction\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd/C\"}], \"amount\": {\"mass\": {\"value\": 0.034, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"was flushed with H2 for 1.5 hours\", \"duration\": {\"value\": 1.5, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"After filtering through diatomaceous earth\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate was concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification by flash chromatography on silica gel\"}, {\"type\": \"WASH\", \"details\": \"eluting with 5% to 70% EtOAc in heptane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"heptane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.105, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 37.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 37.2}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a2dc18fb47ed4f82b80012fd61c62f3d",
    "procedure_text": "Prepared according to Method M (Example 206) using (4-aminopyridin-2-yl)[1-(2-{[tert-butyl(dimethyl)silyl]oxy}-1,1-dimethylethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl]methanone (Preparation 27) and 3-trifluoromethylphenylacetic acid at 70\u00b0 C. The residue was purified over neutral alumina eluting with 50%-60% EtOAc in hexane followed by acid deprotection using 10% HCl in dioxane at room temperature for 18 hours. The reaction was concentrated in vacuo and purified using preparative HPLC to afford the title compound.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(4-aminopyridin-2-yl)[1-(2-{[tert-butyl(dimethyl)silyl]oxy}-1,1-dimethylethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl]methanone\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-trifluoromethylphenylacetic acid\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Prepared\"}, {\"type\": \"CUSTOM\", \"details\": \"at 70\\u00b0 C\", \"temperature\": {\"setpoint\": {\"value\": 70.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified over neutral alumina eluting with 50%-60% EtOAc in hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"at room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"for 18 hours\", \"duration\": {\"value\": 18.0, \"units\": \"HOUR\"}}, {\"type\": \"CONCENTRATION\", \"details\": \"The reaction was concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"purified\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-086a62092f284368b6d3d708a4702ef5",
    "procedure_text": "5,7-Dichloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (208 mg, 0.439 mmol), LiCl (56 mg, 1.32 mmol), and CsOH (221 mg, 1.32 mmol) were combined, then a solution of N-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)acetamide (115 mg, 0.439 mmol) in 1,4-dioxane (3 mL) was added followed by water (300 uL). The mixture was purged with nitrogen, then tetrakis(triphenylphosphinepalladium(0) (51 mg, 0.044 mmol) was added and the flask was lowered into a 100\u00b0 C. oil bath and heated at 100\u00b0 C. for 3 h. The mixture was allowed to cool, then diluted with ethyl acetate and rinsed with water 2\u00d7 then brine and dried (MgSO4). Chromatography eluting with 40-50% ethyl acetate in hexanes to give a colorless oil (210 mg, 83% yield). MS (ES+) m/z 573.1 (M+1).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5,7-Dichloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one\"}], \"amount\": {\"mass\": {\"value\": 208.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"LiCl\"}], \"amount\": {\"mass\": {\"value\": 56.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m4_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)acetamide\"}], \"amount\": {\"mass\": {\"value\": 115.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,4-dioxane\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 300.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CsOH\"}], \"amount\": {\"mass\": {\"value\": 221.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The mixture was purged with nitrogen\"}, {\"type\": \"ADDITION\", \"details\": \"tetrakis(triphenylphosphinepalladium(0) (51 mg, 0.044 mmol) was added\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrakis\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"was lowered into a 100\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"to cool\"}, {\"type\": \"ADDITION\", \"details\": \"diluted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"rinsed with water 2\\u00d7\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"brine and dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"Chromatography eluting with 40-50% ethyl acetate in hexanes\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"oil\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 210.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 83.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 83.4}}], \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-42c11ae563e647699bb0ee65cb204937",
    "procedure_text": "0.06 g of 5,10-bis(2-ethylhexyloxy)-1,6-dithia-dicyclopenta[b,g]naphthalene-2,7-dicarboxylic acid diethyl ester (0.009 mmol) was dissolved in 0.5 mL of THF:Methanol (1:1), and 0.2 mL of water and 0.01 g of lithium hydroxide (0.04 mmol) were added thereto and stirred at room temperature for 8 hours. Again, the mixture was further stirred at 50\u00b0 C. for 8 hours, the solvent was removed, and a temperature was lowered to 0\u00b0 C., and the resultant was acidified by 2N HCl solution, thereby obtaining 0.04 g of the title compound (74.0%).",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5,10-bis(2-ethylhexyloxy)-1,6-dithia-dicyclopenta[b,g]naphthalene-2,7-dicarboxylic acid diethyl ester\"}], \"amount\": {\"mass\": {\"value\": 0.06, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF Methanol\"}], \"amount\": {\"volume\": {\"value\": 0.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 0.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium hydroxide\"}], \"amount\": {\"mass\": {\"value\": 0.01, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred at room temperature for 8 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"Again, the mixture was further stirred at 50\\u00b0 C. for 8 hours\", \"duration\": {\"value\": 8.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 50.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was removed\"}, {\"type\": \"CUSTOM\", \"details\": \"was lowered to 0\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.04, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 74.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4a035f416b864d13bd1b41db6400c8a0",
    "procedure_text": "By operating as in Example 1, starting from 6.75 g of potassium meta-cresolate and from 5.5 g of acetophenone, 0.55 g of benzoylacetic acid were obtained.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium meta-cresolate\"}], \"amount\": {\"mass\": {\"value\": 6.75, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetophenone\"}], \"amount\": {\"mass\": {\"value\": 5.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzoylacetic acid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.55, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-dc19acee24d3492390588de04e1f0683",
    "procedure_text": "To a solution of (S)-(+)-2-amino-1-propanol (200 g, 2.66 mol) in purified water (400 mL) was added sodium bicarbonate (246 g, 2.93 mol). To this mixture was added benzyl chloroformate (500 g, 2.93 mol) in tetrahydrofuran (800 mL) at an internal temperature of 20\u00b0 C. or below. Subsequently, the resulting reaction mixture was stirred at room temperature for 16 hours. After confirming the disappearance of the starting materials by TLC, the reaction mixture was then extracted with ethyl acetate. The organic layer was washed with 0.5 N hydrochloric acid, saturated aqueous sodium bicarbonate, and saturated brine, and then dried over anhydrous sodium sulfate. The resulting solution was filtered and concentrated under reduced pressure. The residue was crystallized from petroleum ether to give the target product as a white solid (403 g, yield 72.3%).",
    "reference_string": "{\"inputs\": {\"m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzyl chloroformate\"}], \"amount\": {\"mass\": {\"value\": 500.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 800.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(S)-(+)-2-amino-1-propanol\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"amount\": {\"mass\": {\"value\": 246.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 400.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at room temperature for 16 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Subsequently, the resulting reaction mixture\"}, {\"type\": \"EXTRACTION\", \"details\": \"the reaction mixture was then extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with 0.5 N hydrochloric acid, saturated aqueous sodium bicarbonate, and saturated brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"The resulting solution was filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was crystallized from petroleum ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"petroleum ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 403.0, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 72.3}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 72.4}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-6f0b50cbd7bd494d8dbc29f241df89df",
    "procedure_text": "To a stirred solution of 7.45 parts of N-[chloro(2,6-dichlorophenyl)methylene]-2-methylbenzenamine in 150 parts of trichloromethane is added a solution of 4.88 parts of potassium cyanide and 8.5 parts of N,N,N-triethylbenzenemethanaminium chloride in 8 parts of water while stirring vigorously. Stirring is continued for 30 minutes at room temperature. The organic phase is separated, washed twice with water, dried, filtered and evaporated. The residue is dissolved in petroleumether and the solution is decanted from some insoluble tar. The petroleumether is evaporated in vacuo. The residue is purified by column-chromatography over silica gel using trichloromethane as eluent. The pure fractions are collected and the eluent is evaporated. The residue is crystallized from 17.5 parts of petroleumether, yielding 2.8 parts of 2,6-dichloro-\u03b1-[(2-methylphenyl)imino]benzeneacetonitrile; mp. 55\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-[chloro(2,6-dichlorophenyl)methylene]-2-methylbenzenamine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trichloromethane\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium cyanide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N,N-triethylbenzenemethanaminium chloride\"}], \"reaction_role\": \"CATALYST\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"while stirring vigorously\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"Stirring\"}, {\"type\": \"CUSTOM\", \"details\": \"The organic phase is separated\"}, {\"type\": \"WASH\", \"details\": \"washed twice with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue is dissolved in petroleumether\"}, {\"type\": \"CUSTOM\", \"details\": \"the solution is decanted from some insoluble tar\"}, {\"type\": \"CUSTOM\", \"details\": \"The petroleumether is evaporated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue is purified by column-chromatography over silica gel\"}, {\"type\": \"CUSTOM\", \"details\": \"The pure fractions are collected\"}, {\"type\": \"CUSTOM\", \"details\": \"the eluent is evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue is crystallized from 17.5 parts of petroleumether\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,6-dichloro-\\u03b1-[(2-methylphenyl)imino]benzeneacetonitrile\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f1011d0dbbc044e58501829eee3cb3e4",
    "procedure_text": "A mixture of 230 mg (1.29 mmol) of 4-chloro-3,5-difluoro-1,2-phenylenediamine and 125 mg (1.38 mmol) of oxalic acid in 4 mL of 2N HCl was refluxed for 3 h and cooled to room temperature. The mixture was filtered and washed by water, dried to leave a brown solid (245 mg, 82%), mp>250\u00b0 C. 1H NMR (DMSO-d6), 6.921 (d, 1, J=9.61), 12.143 (s, 1), 12.168 (s, 1). MS, 232 (M+, 100), 204 (80), 176 (40), 149 (70), 171 (80). HRMS calcd for C8H335ClF2N2O2, 231.9848, found 231.9851.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-chloro-3,5-difluoro-1,2-phenylenediamine\"}], \"amount\": {\"mass\": {\"value\": 230.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"oxalic acid\"}], \"amount\": {\"mass\": {\"value\": 125.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"was refluxed for 3 h\", \"duration\": {\"value\": 3.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"The mixture was filtered\"}, {\"type\": \"WASH\", \"details\": \"washed by water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 245.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 82.0}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0d5b25fb4db34038bc92ae52f32a856e",
    "procedure_text": "To a stirring solution of 4.48 g (20 mmol) of 2-chloro-5-trifluoromethyl-benzoic acid suspended in 40 mL of conc. H2SO4 at \u221220\u00b0 C. was added dropwise a cold solution of 1.05 eq of potassium nitrate dissolved in 12 mL of sulfuric acid. The reaction mixture was stirred \u221220\u00b0 C. for 15 min then warmed up to r.t. overnight. The mixture was poured into a beaker containing ice. The resulting solid was collected, washed with cold water and dried to give 4.8 g (90%) of 2-chloro-3-nitro-5-trifluoromethyl-benzoic acid as a solid. LCMS: 270 (M+1)+.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sulfuric acid\"}], \"amount\": {\"volume\": {\"value\": 12.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloro-5-trifluoromethyl-benzoic acid\"}], \"amount\": {\"mass\": {\"value\": 4.48, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium nitrate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2SO4\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -20.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred \\u221220\\u00b0 C. for 15 min\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"then warmed up to r.t. overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"ADDITION\", \"details\": \"The mixture was poured into a beaker\"}, {\"type\": \"ADDITION\", \"details\": \"containing ice\"}, {\"type\": \"CUSTOM\", \"details\": \"The resulting solid was collected\"}, {\"type\": \"WASH\", \"details\": \"washed with cold water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloro-3-nitro-5-trifluoromethyl-benzoic acid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 4.8, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 90.0}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fbe480f34c1044e5911b20596c2e8090",
    "procedure_text": "4-{4-[4-(3-[1,4]Oxazepan-4-yl-propoxy)-phenyl]-tetrahydro-pyran-4-carbonyl}-piperazine-1-carboxylic acid tert-butyl ester (260 mg, 0.48 mmol) was dissolved in a solution of hydrogen chloride in dioxane (4M, 5 ml) and was stirred at room temperature for 2 hours. The solvent was removed in vacuo and the residue dissolved in DCM (10 ml) and washed with saturated sodium bicarbonate solution (15 ml). The organic layer was dried over Na2SO4 and concentrated in vacuo before purifying the residue using column chromatography, eluting with a gradient of DCM:MeOH:NH3 (from 99:1:0.1 to 92:8:0.8) to afford the title compound as a white solid (80 mg, 37%). 1H NMR (400 MHz, d6-DMSO) \u03b4 1.70-1.88 (m, 6H), 2.08 (m, 2H), 2.52-2.63 (m, 6H), 3.04-3.35 (m, 8H), 3.58 (m, 4H), 3.64 (m, 2H), 3.72 (m, 2H), 3.98 (t, 2H), 6.92 (d, 2H), 7.12 (d, 2H). LRMS ESI+ m/z 432 [MH]+.",
    "reference_string": "{\"inputs\": {\"m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-{4-[4-(3-[1,4]Oxazepan-4-yl-propoxy)-phenyl]-tetrahydro-pyran-4-carbonyl}-piperazine-1-carboxylic acid tert-butyl ester\"}], \"amount\": {\"mass\": {\"value\": 260.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrogen chloride\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dioxane\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at room temperature for 2 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The solvent was removed in vacuo\"}, {\"type\": \"DISSOLUTION\", \"details\": \"the residue dissolved in DCM (10 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with saturated sodium bicarbonate solution (15 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layer was dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"before purifying the residue\"}, {\"type\": \"WASH\", \"details\": \"eluting with a gradient of DCM\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH3\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 80.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 37.0}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a2dfe94ceb2340df987fa4681c2cd094",
    "procedure_text": "3.9 g (30 mmol) 4-dibenzylaminocyclohexanone are dissolved in 100 ml dichloromethane and stirred with 3.9 g (45 mmol) morpholine and 9.5 g (45 mmol) sodium triacetoxyborohydride for 12 h at RT. Then the mixture is combined with water and potassium carbonate, the organic phase is separated off, dried and the solvent is eliminated in vacuo. The residue is purified through a silica gel column (approx 20 ml silica gel; approx 500 ml of ethyl acetate 90/methanol 10+1% conc. ammonia). The required fractions are evaporated down in vacuo.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"morpholine\"}], \"amount\": {\"mass\": {\"value\": 3.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium triacetoxyborohydride\"}], \"amount\": {\"mass\": {\"value\": 9.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-dibenzylaminocyclohexanone\"}], \"amount\": {\"mass\": {\"value\": 3.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the organic phase is separated off\"}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue is purified through a silica gel column (approx 20 ml silica gel; approx 500 ml of ethyl acetate 90/methanol 10+1% conc. ammonia)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonia\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The required fractions are evaporated down in vacuo\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-f5f01aef1e9844a2b52d9d14c93fb823",
    "procedure_text": "A solution of 173 mg (0.35 mmol) of tert-butyl (3RS,4RS)-4-(3-bromophenyl)-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate in 6 ml of methanol was treated with 6 ml of a 2N solution of hydrogen chloride in MeOH and stirred at 50\u00b0 C. for 4 hours. Subsequently, the mixture was partitioned between ethyl acetate and a 5% sodium hydrogen carbonate solution, the organic phase was dried over magnesium sulphate and finally the solvent was removed under reduced pressure. The crude product was purified by chromatography on silica gel with a 10:1:0.1 mixture of methylene chloride, MeOH and 25% ammonia and the eluent. There were obtained 126 mg (91% of theory) of (3RS,4RS)-4-(3-bromophenyl)-3-(naphthalen-2-ylmethoxy)-piperidine as a light yellow oil. MS: 396, 398 (M+H)+.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl (3RS,4RS)-4-(3-bromophenyl)-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 173.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrogen chloride\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 6.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 50.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred at 50\\u00b0 C. for 4 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Subsequently, the mixture was partitioned between ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"a 5% sodium hydrogen carbonate solution, the organic phase was dried over magnesium sulphate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydrogen carbonate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulphate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"finally the solvent was removed under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude product was purified by chromatography on silica gel with a 10:1:0.1 mixture of methylene chloride, MeOH and 25% ammonia\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonia\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(3RS,4RS)-4-(3-bromophenyl)-3-(naphthalen-2-ylmethoxy)-piperidine\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 126.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 91.0}}], \"isolated_color\": \"light yellow\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-796dadd078c9483c93624e5110cf532c",
    "procedure_text": "A solution of sodium hydroxide 10N (0.300 mL; 3.0 mmol) was added to a mixture of methyl 2-(4-(4-chloro-2-methoxyphenyl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoate (0.095 g; 0.254 mmol) in methanol (3 mL). The mixture was heated at 60\u00b0 C. in a sealed tube for 18 h and then concentrated under reduced pressure. The residue was dissolved in water and the pH of the solution was adjusted between 2 and 3 by addition of a solution of hydrochloric acid 6N until a precipitate formed. The precipitate was collected by filtration and dried under reduced pressure over phosphorus pentoxide to afford 0.078 g (84%) of the title compound as a yellow solid.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"volume\": {\"value\": 0.3, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 2-(4-(4-chloro-2-methoxyphenyl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoate\"}], \"amount\": {\"mass\": {\"value\": 0.095, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue was dissolved in water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"the pH of the solution was adjusted between 2 and 3 by addition of a solution of hydrochloric acid 6N until a precipitate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"formed\"}, {\"type\": \"FILTRATION\", \"details\": \"The precipitate was collected by filtration\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried under reduced pressure over phosphorus pentoxide\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"phosphorus pentoxide\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.078, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 84.0}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-8792fb059d49427884229ef2ba721fcb",
    "procedure_text": "The compound of Example 1C (15 g, 24.2 mmol) and the compound of Example 1H (11 g, 26.5 mmol), were combined with NaI (2.7 g), and diisopropylethylamine (3.12 g) in 400 mL of acetonitrile in a 1 liter pressure bottle. The solution was heated at 100\u00b0 C. TLC (EtOAc:hexane, 60:40) or HPLC was checked for the completion of the reaction; no starting material was observed after 16 hours. The reaction mixture was cooled to ambient temperature and filtered through Celite; the solvents were removed in vacuo. The crude material was diluted with EtOAc (500 mL) and washed with saturated ammonium chloride solution (2\u00d7100 ml). The solvent was removed in vacuo, and the crude material was loaded on silica gel column to elute with hexane/EtOAc (3:2-1:1-2:3). Pure fractions were collected and concentrated to provide 14.5 g (63.3%) of the titled compound.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropylethylamine\"}], \"amount\": {\"mass\": {\"value\": 3.12, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaI\"}], \"amount\": {\"mass\": {\"value\": 2.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound\"}], \"amount\": {\"mass\": {\"value\": 15.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound\"}], \"amount\": {\"mass\": {\"value\": 11.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 400.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m7_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The reaction mixture was cooled to ambient temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"filtered through Celite\"}, {\"type\": \"CUSTOM\", \"details\": \"the solvents were removed in vacuo\"}, {\"type\": \"ADDITION\", \"details\": \"The crude material was diluted with EtOAc (500 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude material\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with saturated ammonium chloride solution (2\\u00d7100 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium chloride\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The solvent was removed in vacuo\"}, {\"type\": \"WASH\", \"details\": \"to elute with hexane/EtOAc (3:2-1:1-2:3)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Pure fractions were collected\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"titled compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 14.5, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 63.3}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f93c0b8c71f24745bb72eba7f3fd6efa",
    "procedure_text": "Manganese dioxide (67 g) was added to a solution of (5-cyclopropyl-6-methoxypyridin-2-yl)methanol (14.1 g) in chloroform (200 mL), and the mixture was stirred at 65\u00b0 C. for one hour. The reaction solution was filtered through celite and the filtrate was concentrated to give 5-cyclopropyl-6-methoxypyridine-2-carbaldehyde (11 g, 85%).",
    "reference_string": "{\"inputs\": {\"m3_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(5-cyclopropyl-6-methoxypyridin-2-yl)methanol\"}], \"amount\": {\"mass\": {\"value\": 14.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Manganese dioxide\"}], \"amount\": {\"mass\": {\"value\": 67.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 65.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at 65\\u00b0 C. for one hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The reaction solution was filtered through celite\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate was concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-cyclopropyl-6-methoxypyridine-2-carbaldehyde\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 11.0, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 85.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b0862ea211a3449fa60f07216b404483",
    "procedure_text": "To a solution of 7-amino-4-(1,4-dioxaspiro[4.5]dec-8-yl)-2-methyl-2,3-dihydro-1H-isoindol-1-one (1.64 g, 5.42 mmol) in THF (60 mL) was added aqueous 3.0 M HCl (1.81 mL), the resulting mixture was stirred at rt overnight. The mixture to 0\u00b0 C., diluted with water and basified to pH \u02dc10 with 1M NaOH. The aqueous mixture was extracted with EtOAc (3\u00d7) and the combined organic fractions were washed with brine, dried over sodium sulfate, filtered, and concentrated to afford the title compound. 1H NMR (400 MHz, DMSO-d6) \u03b4 7.11 (d, J=8.34 Hz, 1H), 6.53 (d, J=8.34 Hz, 1H), 5.88 (s, 2H), 4.41 (s, 2H), 3.00 (s, 3H), 2.56 (dt, J=6.06, 14.15 Hz, 2H), 2.21-2.30 (m, 2H), 1.96-2.04 (m, 2H), 1.78-1.91 (m, 2H); MS (ES+): m/z: 260.1517 [MH+]. HPLC: tR=1.06 min (UPLC TOF MS: polar\u20143 min).",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-amino-4-(1,4-dioxaspiro[4.5]dec-8-yl)-2-methyl-2,3-dihydro-1H-isoindol-1-one\"}], \"amount\": {\"mass\": {\"value\": 1.64, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 1.81, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the resulting mixture was stirred at rt overnight\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"The aqueous mixture was extracted with EtOAc (3\\u00d7)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"the combined organic fractions were washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-523715f226624d8faab37a9541c985ab",
    "procedure_text": "The process of Example 1 is repeated, replacing 64.3 parts of 5-nitro-1,4,4a,9a-tetrahydroanthraquinone by 71.3 parts of 5-nitro-2,3-dimethyl-1,4,4a,9a-tetrahydroanthraquinone (obtained from 1-nitronaphthoquinone and 2,3-dimethyl-1,4-butadiene by Diels-Alder reaction), to give 61.9 parts of 1-amino-6,7-dimethylanthraquinone in 99% purity, corresponding to a yield of 99% of theory.",
    "reference_string": "{\"inputs\": {\"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-nitro-1,4,4a,9a-tetrahydroanthraquinone\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-nitro-2,3-dimethyl-1,4,4a,9a-tetrahydroanthraquinone\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"61.9\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-amino-6,7-dimethylanthraquinone\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 99.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d19a5bc7388f44cdb6b51ab334a88387",
    "procedure_text": "0.50 g of ethyl 2-[6-[3-[4-(diphenylmethoxy)piperidino]propylamino]-3-oxo[1,2,4]triazolo[4,3-b]pyridazin-2(3H)-yl]-2-methylpropionate was dissolved in 3 ml of ethanol; 2.2 ml of a 1 N aqueous solution of sodium hydroxide was added, followed by stirring at room temperature for 24 hours. After the ethanol was distilled off under reduced pressure, the residue was diluted with water and washed with ethyl acetate. To the water layer, 2.2 ml of 1 N hydrochloric acid was added; the mixture was saturated with sodium chloride and extracted with ethyl acetate-tetrahydrofuran (2:1); the extract was washed with saturated saline and dried over magnesium sulfate. After concentration under reduced pressure, the residue was powdered by the addition of ethyl acetate, collected by filtration, washed with ethyl acetate, and dried, to yield 0.203 g of the title compound.",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 2-[6-[3-[4-(diphenylmethoxy)piperidino]propylamino]-3-oxo[1,2,4]triazolo[4,3-b]pyridazin-2(3H)-yl]-2-methylpropionate\"}], \"amount\": {\"mass\": {\"value\": 0.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aqueous solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"by stirring at room temperature for 24 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"DISTILLATION\", \"details\": \"After the ethanol was distilled off under reduced pressure\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"the residue was diluted with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"To the water layer, 2.2 ml of 1 N hydrochloric acid was added\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 2.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate-tetrahydrofuran (2:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate tetrahydrofuran\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"the extract was washed with saturated saline\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"After concentration under reduced pressure\"}, {\"type\": \"ADDITION\", \"details\": \"the residue was powdered by the addition of ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"collected by filtration\"}, {\"type\": \"WASH\", \"details\": \"washed with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 24.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.203, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4ba45557a8a04282a9d02185ce8889f7",
    "procedure_text": "4-(5-Methyl-2-nitro-phenyl)-piperazine-1-carboxylic acid benzyl ester (5.60 g; 15.7 mmol) and SnCl2.H2O (17.5 g; 77.6 mmol) were refluxed in 100 mL ethanol for 2\u00bd hours. Ethanol was removed in vacuo. The residue was poured into 300 mL saturated NaHCO3. The mixture was extracted with ethyl acetate (2\u00d7250 mL). The organic phase was washed with brine (2\u00d7100 mL), dried with MgSO4, filtered through a pad of silica and concentrated in vacuo to give 4.71 g (14.5 mmol; 91.6%) 4-(2-amino-5-methyl-phenyl)-piperazine-1-carboxylic acid benzyl ester.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(5-Methyl-2-nitro-phenyl)-piperazine-1-carboxylic acid benzyl ester\"}], \"amount\": {\"mass\": {\"value\": 5.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"SnCl2.H2O\"}], \"amount\": {\"mass\": {\"value\": 17.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Ethanol was removed in vacuo\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ethanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"The residue was poured into 300 mL saturated NaHCO3\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"amount\": {\"volume\": {\"value\": 300.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The mixture was extracted with ethyl acetate (2\\u00d7250 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic phase was washed with brine (2\\u00d7100 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried with MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered through a pad of silica\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(2-amino-5-methyl-phenyl)-piperazine-1-carboxylic acid benzyl ester\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 14.5, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 4.71, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 91.6}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-ac547328ce2642608bde253a3d202bd5",
    "procedure_text": "A homogeneous mixture of 2-fluoronicotinic acid (Aldrich, 0.45 g, 3.2 mmol), in anhydrous THF (12 mL), was treated with oxalyl chloride (0.56 mL, 6.4 mmol) followed by anhydrous DMF (2 drops). After heating at reflux for 1.5 hours, the reaction mixture was concentrated in vacuo to afford 2-fluoronicotinoyl chloride as a residue which was used without further purification. The residue was dissolved in anhydrous THF (8 mL), anhydrous DCM (2 mL), pyridine (1 mL) and DMF (to a total volume of 16 mL). This homogeneous 2-fluoronicotinoyl chloride mixture (2 mL) was then added to a rapidly stirred mixture of o-toluidine (Aldrich, 0.17 mL, 1.6 mmol) in anhydrous THF (2 mL). After 15 hours, the reaction was quenched with water, and then extracted with 10% isopropanol in chloroform. The organic layer was washed once with sat. aq. NaHCO3, once with sat. aq. NaCl, then dried over anhydrous Na2SO4 and concentrated in vacuo to afford the desired product (0.084 g, 91%) as a pale orange solid which was used without further purification. MS(ESI+) m/z 231 (M+H)+.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-fluoronicotinoyl chloride\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"o-toluidine\"}], \"amount\": {\"volume\": {\"value\": 0.17, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"was used without further purification\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue was dissolved in anhydrous THF (8 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 8.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the reaction was quenched with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with 10% isopropanol in chloroform\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isopropanol\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed once with sat. aq. NaHCO3, once with sat. aq. NaCl\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaCl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.084, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 91.0}}], \"isolated_color\": \"pale orange\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-6919478c4a2e42578130c083ff8bd794",
    "procedure_text": "2.2 Grams of 3-methoxy-4-cyano-5-methylsulfonylisothiazole was dissolved in 20 ml of DMF, and 1.5 g of 3-butyn-1-ol and 4.3 g of 30% KOH were added at room temperature with stirring, after which the reaction solution was stirred for 2 hours. The reaction solution was ice-cooled to 5\u00b0 to 10\u00b0 C., 5.1 g of iodine and 3.2 g of potassium iodide were added thereto with stirring, and then 6.6 g of 10% KOH was added dropwise. The temperature of the reaction solution was returned to room temperature, and after stirring for 1 hour, water was added to the reaction solution, which was then extracted with ethyl acetate. The extract was washed with water, dried and concentrated under reduced pressure to obtain crude crystals. The crystals were recrystallized from ether to obtain 2.1 g of crystals having a melting point of 71\u00b0 to 73\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"KOH\"}], \"amount\": {\"mass\": {\"value\": 6.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-butyn-1-ol\"}], \"amount\": {\"mass\": {\"value\": 1.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"KOH\"}], \"amount\": {\"mass\": {\"value\": 4.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"iodine\"}], \"amount\": {\"mass\": {\"value\": 5.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium iodide\"}], \"amount\": {\"mass\": {\"value\": 3.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-methoxy-4-cyano-5-methylsulfonylisothiazole\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"with stirring\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"after which the reaction solution was stirred for 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"cooled to 5\\u00b0 to 10\\u00b0 C.\"}, {\"type\": \"STIRRING\", \"details\": \"with stirring\"}, {\"type\": \"CUSTOM\", \"details\": \"was returned to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"STIRRING\", \"details\": \"after stirring for 1 hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"EXTRACTION\", \"details\": \"was then extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The extract was washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"to obtain crude crystals\"}, {\"type\": \"CUSTOM\", \"details\": \"The crystals were recrystallized from ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crystals\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.1, \"units\": \"GRAM\"}}}], \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-448a072a0ba047ce91ad947116f26636",
    "procedure_text": "2-Amino-3-nitro-benzoic acid (1.8 g, 9.9 mmol) and methylamine hydrochloride (1.33 g, 19.8 mmol), were stirred in dry CH2Cl2 (30 ml)/DMF (5 mL) at 0\u00b0 C. EDC, (2.83 g, 14.8 mmol) and DIEA (4.92 mL, 27.7 mmol) were added, and the solution stirred 3 h while warming to r.t. The reaction was concentrated in vacuo and purified by silica gel chromatography (8% MeOH/CHCl3) to give 1.42 g (74%) of 2-amino-N-methyl-3-nitro-benzamide as a yellow solid. 1H NMR (300 MHz, DMSO-d6) \u03b4 8.58 (br s, 1H), 8.23 (br s, 2H), 8.15 (dd, 1H, J=8.1, 1.8 Hz), 7.82 (dd, 1H, J=8.1, 1.8 Hz), 6.68 (t, 1H, J=8.1 Hz), 2.76 (d, 3H, J=4.5 Hz).",
    "reference_string": "{\"inputs\": {\"m1_m2_m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-Amino-3-nitro-benzoic acid\"}], \"amount\": {\"mass\": {\"value\": 1.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylamine hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 1.33, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EDC\"}], \"amount\": {\"mass\": {\"value\": 2.83, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DIEA\"}], \"amount\": {\"volume\": {\"value\": 4.92, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the solution stirred 3 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"The reaction was concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"purified by silica gel chromatography (8% MeOH/CHCl3)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH CHCl3\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-amino-N-methyl-3-nitro-benzamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.42, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 74.0}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2fda4775f84c4779be76f778d2ed894c",
    "procedure_text": "A 1M solution of LiAlH4 in THF (15.9 ml) was mixed with THF (15.9 ml) and cooled, under nitrogen in an ice bath. To this solution was added, dropwise, with stirring, a solution of the product from Step I (3.0 g, 0.0076 mol) in THF (30.7 ml). The mixture was kept in the ice bath for 1 hour and then treated cautiously with a saturated potassium sodium tartrate solution (16.1 ml). This mixture was stirred at ambient temperature for 45 minutes and extracted with EtOAc. The extract was washed with water, dried (MgSO4) and concentrated. The residue was chromatographed on silica gel with 10-20% MeOH--CHCl3. A solution of the product in Et2O was washed with NaHCO3 and concentrated to give 1.86 g of the titled compound which is a compound of Formula I'. The mass spectrum had m/z 382 (M+). Theory for C20H34N2O3S: 382.2290; measured: 382.2291.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice\"}], \"reaction_role\": \"REACTANT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 30.7, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m6_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"LiAlH4\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 15.9, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 15.9, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium sodium tartrate\"}], \"amount\": {\"volume\": {\"value\": 16.1, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"dropwise, with stirring\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooled, under nitrogen in an ice bath\"}, {\"type\": \"ADDITION\", \"details\": \"To this solution was added\"}, {\"type\": \"STIRRING\", \"details\": \"This mixture was stirred at ambient temperature for 45 minutes\", \"duration\": {\"value\": 45.0, \"units\": \"MINUTE\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The extract was washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was chromatographed on silica gel with 10-20% MeOH\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"A solution of the product in Et2O was washed with NaHCO3\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Et2O\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"titled compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.86, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-612407150c004baaa946f753ae10cd97",
    "procedure_text": "7-Benzyloxy-2-methyl-1-naphthalen-2-ylmethyl-1H-benzoimidazole (211 mg) in methanol (12 mL) and acetic acid (1.0 mL) was hydrogenated in presence of 10% Pd\u2014C at 45 psi for 20 h. Reaction mixture was filtered through a pad of celite. The filtrate was concentrated to afford 2-methyl-3-naphthalen-2-ylmethyl-1H-benzoimidazol-4-ol, I-111 (211 mg).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-Benzyloxy-2-methyl-1-naphthalen-2-ylmethyl-1H-benzoimidazole\"}], \"amount\": {\"mass\": {\"value\": 211.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 12.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd\\u2014C\"}], \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Reaction mixture\"}, {\"type\": \"FILTRATION\", \"details\": \"was filtered through a pad of celite\"}, {\"type\": \"CONCENTRATION\", \"details\": \"The filtrate was concentrated\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-methyl-3-naphthalen-2-ylmethyl-1H-benzoimidazol-4-ol\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-82ad386a6f0943d0973879553f08fe19",
    "procedure_text": "To a solution of 4-iodo-1-trityl-1H-imidazole (1 eq) in THF at room temperature was added ethylmagnesium bromide (1.2 eq) under dry conditions. After stirring for 90 minutes, zinc chloride (1.2 eq) was added to the reaction mixture. After stirring for another 90 minutes, tetrakis(triphenylphosphine)palladium (10%) and 5-bromo-2-methylpyridine (1.2 eq) were added to the reaction mixture. Following that, the reaction mixture was heated in a 70\u00b0 C. oil bath overnight. Upon cooling, the reaction was diluted with dichloromethane and washed with a EDTA buffer (at approximately pH 9), NaCl, dried over sodium sulfate, filtered and concentrated. The crude product was disolved in ethanol and concentrated HCl was added to the solution at room temperature. The reaction mixture was heated in a 50\u00b0 C. oil bath for 2 hours. Upon cooling, the reaction was filtered and washed with ethyl ether to yield 5-(1H-imidazol-4-yl)-2-methyl-pyridine (63%). MH+(160)",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"zinc chloride\"}], \"reaction_role\": \"CATALYST\"}]}, \"m7_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-bromo-2-methylpyridine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrakis(triphenylphosphine)palladium\"}], \"reaction_role\": \"CATALYST\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-iodo-1-trityl-1H-imidazole\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethylmagnesium bromide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 70.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring for 90 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"After stirring for another 90 minutes\", \"duration\": {\"value\": 90.0, \"units\": \"MINUTE\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"Upon cooling\"}, {\"type\": \"WASH\", \"details\": \"washed with a EDTA buffer (at approximately pH 9), NaCl\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EDTA\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaCl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"ADDITION\", \"details\": \"concentrated HCl was added to the solution at room temperature\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}]}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"The reaction mixture was heated in a 50\\u00b0 C. oil bath for 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 50.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"Upon cooling\"}, {\"type\": \"FILTRATION\", \"details\": \"the reaction was filtered\"}, {\"type\": \"WASH\", \"details\": \"washed with ethyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 90.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-(1H-imidazol-4-yl)-2-methyl-pyridine\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 63.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a0dc4f8caf9b40a8a52f18219a1981c1",
    "procedure_text": "The example No. I (2) was repeated (using cyclodecadiene (CDD) as cycloolefin). In this case as well, a 1:1 reaction between olefin and ozone was found.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"( 2 )\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cyclodecadiene\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"olefin\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ozone\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-8c27c92fe9d643638860ded7ac9c7e20",
    "procedure_text": "A mixture of 8-(pyridin-2-yl)pyrido[2,3-d]pyridazin-5(6H)-one 8 (50 mg, 0.22 mmol), ethyl bromide (20 \u03bcL, 0.27 mmol), potassium carbonate (303 mg, 2.2 mmol), and dimethylformamide (1.5 mL) was heated in a sealed tube at 60\u00b0 C. for 30 minutes. After cooling to ambient temperature, the reaction mixture was poured into 15 mL of saturated brine and extracted with 3\u00d720 mL of ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal phase flash chromatography eluting with 0-10% methanol in dichloromethane over 16 minutes Like fractions containing product were pooled, concentrated under reduced pressure, and dried at 60\u00b0 C. overnight to give 6-ethyl-8-(pyridin-2-yl)pyrido[2,3-d]pyridazin-5(6H)-one (46 mg, 0.19 mmol), RL-6. 1H NMR (400 MHz, Chloroform-d) \u03b4 9.15 (s, 1H), 9.02 (s, 1H), 8.80 (d, J=8.3 Hz, 1H), 8.23 (s, 1H), 8.04 (s, 1H), 7.71 (dd, J=8.1, 4.6 Hz, 1H), 7.56 (s, 1H), 4.48 (q, J=7.1 Hz, 2H), 1.52 (t, J=7.2 Hz, 3H). LCMS: (M+H)+, 253.",
    "reference_string": "{\"inputs\": {\"m0_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"RL-6\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"8-(pyridin-2-yl)pyrido[2,3-d]pyridazin-5(6H)-one\"}], \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl bromide\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 303.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 1.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"After cooling to ambient temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with 3\\u00d720 mL of ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic extracts were dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by normal phase flash chromatography\"}, {\"type\": \"WASH\", \"details\": \"eluting with 0-10% methanol in dichloromethane over 16 minutes Like fractions\", \"duration\": {\"value\": 16.0, \"units\": \"MINUTE\"}, \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"containing product\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"dried at 60\\u00b0 C. overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-ethyl-8-(pyridin-2-yl)pyrido[2,3-d]pyridazin-5(6H)-one\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 0.19, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 46.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-94da1f01bfb24c70883426de48529bc8",
    "procedure_text": "A solution of 4-(chloro(isocyanato)methyl)-3-fluorobenzonitrile (Step 1, 3.05 g, 14.5 mmol) in dichloromethane (10 mL) is added to a solution of 3-(3-(trifluoromethyl)-phenylamino)cyclopent-2-enone (3.50 g, 14.5 mmol) in dichloromethane (10 mL), and the mixture is heated at reflux over night. All volatiles are removed under reduced pressure, and the residue is purified by reversed phase HPLC (Agilent ZORBAX\u2122 SB-C18, gradient of acetonitrile in water, 0.1% formic acid). Yield: 474 mg; ESI mass spectrum [M+H]+=416; Retention time HPLC: 0.94 min (Z017_504). LB5FAI00917",
    "reference_string": "{\"inputs\": {\"m1_m3_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(chloro(isocyanato)methyl)-3-fluorobenzonitrile\"}], \"amount\": {\"mass\": {\"value\": 3.05, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(3-(trifluoromethyl)-phenylamino)cyclopent-2-enone\"}], \"amount\": {\"mass\": {\"value\": 3.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"the mixture is heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"at reflux over night\"}, {\"type\": \"CUSTOM\", \"details\": \"All volatiles are removed under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue is purified by reversed phase HPLC (Agilent ZORBAX\\u2122 SB-C18, gradient of acetonitrile in water, 0.1% formic acid)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"formic acid\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"0.94 min (Z017_504)\", \"duration\": {\"value\": 0.94, \"units\": \"MINUTE\"}, \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"( Z017_504 )\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-98518565e6424e62aadd258f4d6a9b12",
    "procedure_text": "Carbazole was mixed in an amount of 16.47 g (98.52 mmol) with 31.0 g (197.04 mmol) of bromobenzene, 10.44 g (98.52 mmol) of sodium carbonate, 0.4 g (8.0 mmol) of copper-(I) chloride, and 3.0 g (8.0 mmol) of tetraphenylphosphonium chloride. This mixture was reacted at 115-125\u00b0 C. for 2 hours in a nitrogen stream. After the reaction, 50 mL of toluene and 100 mL of water were added and the resultant mixture was subjected to liquid separation. Thereafter, the organic layer was washed with water and dried with anhydrous sodium sulfate. After the drying agent was removed by filtration, 15.6 g of activated clay was added. The resultant mixture was stirred at 50-55\u00b0 C. for 1 hour and the clay was removed by filtration. The toluene was concentrated under reduced pressure and 352 mL of methanol was added to the residue. The resultant solution was subjected to crystallization. Thus, the target compound (I-27) was obtained as white crude crystals in an amount of 22.7 g (yield, 94.8%). The target compound obtained had a melting point of 96-97\u00b0 C. and a content as determined by HPLC of 99.8% (HPLC conditions: column, ODS-80TM; eluent, acetonitrile/water (V/V=65/35); buffer, triethylamine and acetic acid each in an amount of 0.1%; detection UV, 254 nm; flow rate, 1.0 mL/min)",
    "reference_string": "{\"inputs\": {\"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m9\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m4_m10\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3_m6_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Carbazole\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"bromobenzene\"}], \"amount\": {\"mass\": {\"value\": 31.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium carbonate\"}], \"amount\": {\"mass\": {\"value\": 10.44, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetraphenylphosphonium chloride\"}], \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"copper-(I) chloride\"}], \"amount\": {\"mass\": {\"value\": 0.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 52.5, \"precision\": 2.5, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The resultant mixture was stirred at 50-55\\u00b0 C. for 1 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"This mixture was reacted at 115-125\\u00b0 C. for 2 hours in a nitrogen stream\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 120.0, \"precision\": 5.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"ADDITION\", \"details\": \"were added\"}, {\"type\": \"CUSTOM\", \"details\": \"the resultant mixture was subjected to liquid separation\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"resultant mixture\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"Thereafter, the organic layer was washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried with anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"After the drying agent was removed by filtration, 15.6 g of activated clay\"}, {\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"CUSTOM\", \"details\": \"the clay was removed by filtration\"}, {\"type\": \"CONCENTRATION\", \"details\": \"The toluene was concentrated under reduced pressure and 352 mL of methanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 352.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"was added to the residue\"}, {\"type\": \"CUSTOM\", \"details\": \"The resultant solution was subjected to crystallization\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"resultant solution\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Thus, the target compound (I-27) was obtained as white crude crystals\"}, {\"type\": \"CUSTOM\", \"details\": \"in an amount of 22.7 g (yield, 94.8%)\"}, {\"type\": \"CUSTOM\", \"details\": \"The target compound obtained\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-48430a3a63cb4897823958ef18efe905",
    "procedure_text": "A solution of 4-chloro-3-nitro-phenol (2.0 g, 11.5 mmol), 1-bromomethyl-benzene (2.01 g, 11.5 mmol), potassium carbonate (1.65 g, 12.0 mmol) and tetrabutylammonium iodide (0.005 g, 0.0135 mmol) in N,N-dimethylformamide (5 ml) was stirred at room temperature for 16 hours. Afterwards, ice water (10 mL) was added to the solution and the resultant solid was collected by filtration and dried in a vacuum oven to provide the title compound (3.0 g, 99%).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-chloro-3-nitro-phenol\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-bromomethyl-benzene\"}], \"amount\": {\"mass\": {\"value\": 2.01, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 1.65, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrabutylammonium iodide\"}], \"amount\": {\"mass\": {\"value\": 0.005, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"the resultant solid was collected by filtration\"}, {\"type\": \"CUSTOM\", \"details\": \"dried in a vacuum oven\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 99.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-9b622d1bdefb48fc927e90a6d1222aa4",
    "procedure_text": "The ligand N,N-bis[(2-quinolyl)methyl]-(S)-methly-L-cysteine was prepared from the dropwise addition of (S)-methyl-L-cysteine methylester hydrochloride (2.0 g, 10.8 mmol) in 10 mL DMF to a stirring solution of 2-bromomethylquinoline (4.8 g, 21.6 mmol) and sodium bicarbonate (4.1 g, 49 mmol) in 40 mL. The mixture was allowed to react for 4 h at 80\u00b0 C. Evaporation of the solvent followed by column chromatography with 3:1 hexancs:ethyl acetate (Rf 0.3) afforded the ester of the ligand (1.7 g, 82%). Saponification was achieved by stirring the ester (1.9 g, 4.4 mmol) in 8 mL THF with LiOH(4.6 mL, 1M) for 2.5 h. The solution was then extracted with methylene chloride, and the aqueous layer acidified with 0.5M HClO4 to pH 6. Several extractions with methylene chloride followed by drying and evaporation of the solvent afforded the crude acid. Purification by column chromatography with ethyl acetate afforded the pure ligand (0.57 g, 31%).",
    "reference_string": "{\"inputs\": {\"m0_m2_m5_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(S)-methyl-L-cysteine methylester hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-bromomethylquinoline\"}], \"amount\": {\"mass\": {\"value\": 4.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"amount\": {\"mass\": {\"value\": 4.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"to react for 4 h at 80\\u00b0 C\", \"duration\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 80.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"Evaporation of the solvent\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-bis[(2-quinolyl)methyl]-(S)-methly-L-cysteine\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ligand\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.7, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 82.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-29564bd823e6442aa6cea2482aa468ea",
    "procedure_text": "A solution of 4-chloro-6-fluoro-1-(4-methoxy-benzyl)-2-oxo-1,2-dihydro-[1,8]-naphthyridine-3-carboxylic acid ethyl ester (76) (6.0 g, 15.35 mmol) in neat TFA was refluxed for 3 h. The solution was cooled and the excess TFA was distilled under vacuum. The residue was suspended in saturated NaHCO3 solution, sonicated briefly and filtered. The solids were washed by water, and dried at room temperature to yield 4.1 g (98%) of 4-chloro-6-fluoro-2-oxo-1,2-dihydro-[1,8]-naphthyridine-3-carboxylic acid ethyl ester (78) as white solids. MP: 217\u00b0 C.; 1H-NM (DMSO-d6): 1.28 (t, J=7.2 Hz, 3H), 4.35 (q, J=7.2 Hz, 2H), 8.24 (dd, J=2.8, 8.0 Hz, 1H), 8.75 (d, J=2.8 Hz, 1H), 13.00 (s, 1H); EIMS: 271 (M+1).",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-chloro-6-fluoro-1-(4-methoxy-benzyl)-2-oxo-1,2-dihydro-[1,8]-naphthyridine-3-carboxylic acid ethyl ester\"}], \"amount\": {\"mass\": {\"value\": 6.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TFA\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The solution was cooled\"}, {\"type\": \"DISTILLATION\", \"details\": \"the excess TFA was distilled under vacuum\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TFA\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"sonicated briefly\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"WASH\", \"details\": \"The solids were washed by water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried at room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-chloro-6-fluoro-2-oxo-1,2-dihydro-[1,8]-naphthyridine-3-carboxylic acid ethyl ester\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 4.1, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 98.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 98.7}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solids\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-9847d721c17545bf873d71a3fb0553e2",
    "procedure_text": "Stir a solution of 5-(methyl-propylcarbamoyl)-isophthalic acid diethyl ester (2.02 g, 6.3 mmol), NaOH (0.25 g, 6.3 mmol) and ethanol (32 mL) at room temperature overnight. Add 0.2 N HCl (60 mL) and extract with ethyl acetate (2\u00d750 mL). Dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with 50:50 ethyl acetate:hexanes with 1% acetic acid then 100% ethyl acetate with 1% acetic acid) to give the title compound as an oil (1.4 g, 75%).",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-(methyl-propylcarbamoyl)-isophthalic acid diethyl ester\"}], \"amount\": {\"mass\": {\"value\": 2.02, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"amount\": {\"mass\": {\"value\": 0.25, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 32.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extract with ethyl acetate (2\\u00d750 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"Dry (magnesium sulfate)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrate\"}, {\"type\": \"CUSTOM\", \"details\": \"purify (silica gel chromatography\"}, {\"type\": \"WASH\", \"details\": \"eluting with 50:50 ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.4, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 75.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 75.8}}], \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-62aa6c7355a64ab5a7a6887dc3106789",
    "procedure_text": "In a 2-liter three-necked flask equipped with a stirrer, a thermometer, a reflux condenser, and a nitrogen gas inlet tube, 360.0 g of methyl ethyl ketone was inserted and the temperature was raised to 75\u00b0 C. While the temperature inside the flask was maintained at 75\u00b0 C., a mixed solution containing 180.0 g of phenoxyethyl acrylate, 162.0 g of methyl methacrylate, 18.0 g of acrylic acid, 72 g of methyl ethyl ketone, and 1.44 g of \u201cV-601\u201d (manufactured by Wako Pure Chemical Industries, Ltd.) was added dropwise at a constant rate so that the dropwise addition was completed in 2 hours. After completion of the dropwise addition, a solution containing 0.72 g of \u201cV-601\u201d and 36.0 g of methyl ethyl ketone was added to this, and after the mixture was stirred for 2 hours at 75\u00b0 C., a solution containing 0.72 g of \u201cV-601\u201d and 36.0 g of isopropanol was added thereto and stirred for 2 hours at 75\u00b0 C. After this, the temperature was raised to 85\u00b0 C. and stirring was continued for another 2 hours and a resin solution of a phenoxyethyl acrylate/methyl methacrylate/acrylic acid (=50/45/5 [mass ratio]) copolymer was obtained.",
    "reference_string": "{\"inputs\": {\"m6_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"V-601\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isopropanol\"}], \"amount\": {\"mass\": {\"value\": 36.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"V-601\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl ethyl ketone\"}], \"amount\": {\"mass\": {\"value\": 36.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m10\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl ethyl ketone\"}], \"amount\": {\"mass\": {\"value\": 360.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3_m9_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"phenoxyethyl acrylate\"}], \"amount\": {\"mass\": {\"value\": 180.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl methacrylate\"}], \"amount\": {\"mass\": {\"value\": 162.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acrylic acid\"}], \"amount\": {\"mass\": {\"value\": 18.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"V-601\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl ethyl ketone\"}], \"amount\": {\"mass\": {\"value\": 72.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 75.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred for 2 hours at 75\\u00b0 C.\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"In a 2-liter three-necked flask equipped with a stirrer\"}, {\"type\": \"TEMPERATURE\", \"details\": \"While the temperature inside the flask was maintained at 75\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 75.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"ADDITION\", \"details\": \"was added dropwise at a constant rate so that the dropwise addition\"}, {\"type\": \"ADDITION\", \"details\": \"After completion of the dropwise addition\"}, {\"type\": \"ADDITION\", \"details\": \"was added to this, and after the mixture\"}, {\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"STIRRING\", \"details\": \"stirred for 2 hours at 75\\u00b0 C\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 75.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"After this, the temperature was raised to 85\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 85.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"STIRRING\", \"details\": \"stirring\"}, {\"type\": \"WAIT\", \"details\": \"was continued for another 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-40391afbc5f9440a8af3585611fab939",
    "procedure_text": "To a solution of N'-(2,4-difluorophenyl)-N-[5-(4,5-diphenyl-1H-imidazol-2-ylthio)pentyl]-N-heptylurea (0.59 g, 0.001 mol) in methylene chloride (50 mL) cooled to -78\u00b0 was added, dropwise, a solution of metachloroperbenzoic acid (0.286 g, 0.0017 mol) in methylene chloride (10 mL). The reaction mixture was stirred at -78\u00b0 for 1 hour and then allowed to warm to ambient temperature. The reaction mixture was then cooled to 0\u00b0 and then added, dropwise, was a solution of saturated sodium bisulfite. The layers were separated and the organic layer was washed with saturated sodium bisulfite. The layers were separated and the sodium chloride solution dried over magnesium sulfate and concentrated under vacuum. The residue (0.76 g) was chromatographed with 1:1 hexane-ethyl acetate to give the title compound (0.43 g, 0.00071 mol) as a yellow solid, mp 77\u00b0-79\u00b0. 1H NMR (CDCl3) \u03b48.1-7.9(m,1H), 7.6-7.2 (m,10H), 6.9-6.7(m,2H), 6.4(d,1H,J=3.3Hz), 3.4-3.1(m,6H), 2.0-1.1(m,18H), 0.9(t,3H,J=6.4Hz).",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N'-(2,4-difluorophenyl)-N-[5-(4,5-diphenyl-1H-imidazol-2-ylthio)pentyl]-N-heptylurea\"}], \"amount\": {\"mass\": {\"value\": 0.59, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"metachloroperbenzoic acid\"}], \"amount\": {\"mass\": {\"value\": 0.286, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bisulfite\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred at -78\\u00b0 for 1 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The reaction mixture was then cooled to 0\\u00b0\"}, {\"type\": \"ADDITION\", \"details\": \"added\"}, {\"type\": \"CUSTOM\", \"details\": \"The layers were separated\"}, {\"type\": \"WASH\", \"details\": \"the organic layer was washed with saturated sodium bisulfite\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bisulfite\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The layers were separated\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"the sodium chloride solution dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium chloride\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under vacuum\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue (0.76 g) was chromatographed with 1:1 hexane-ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"residue\"}], \"amount\": {\"mass\": {\"value\": 0.76, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 0.00071, \"units\": \"MOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.43, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 71.0}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-aefacd492a7b4d518bdec825f3cdd990",
    "procedure_text": "Boc-3-hydroxypiperidine (Alfa Aesar, Ward Hill, Mass., USA; 80 mg, 0.4 mmol) and triphenylphosphine (136 mg, 0.52 mmol) were added to a solution of 4-(4-methanesulfonyl-phenoxy)-1H-pyrazolo[3,4-d]pyrimidine (Intermediate 31; 100 mg, 0.34 mmol) in tetrahydrofuran (1 mL). The mixture was cooled to 0\u00b0 C., and then diisopropylazodicarboxylate (102 \u03bcL, 0.52 mmol) was added. The mixture was stirred overnight, then silica gel (\u02dc500 mg) was added, the solvents were evaporated and the product was eluted from a silica gel column with 50% ethyl acetate/hexanes to give 3-[4-(4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (10.5 mg, 6.5%) as a solid.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Boc-3-hydroxypiperidine\"}], \"amount\": {\"mass\": {\"value\": 80.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triphenylphosphine\"}], \"amount\": {\"mass\": {\"value\": 136.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(4-methanesulfonyl-phenoxy)-1H-pyrazolo[3,4-d]pyrimidine\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Intermediate 31\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropylazodicarboxylate\"}], \"amount\": {\"volume\": {\"value\": 102.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred overnight\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"silica gel (\\u02dc500 mg) was added\"}, {\"type\": \"CUSTOM\", \"details\": \"the solvents were evaporated\"}, {\"type\": \"WASH\", \"details\": \"the product was eluted from a silica gel column with 50% ethyl acetate/hexanes\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-[4-(4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 10.5, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 6.5}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 6.5}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-54b6a1ae658847098b6712a12ab02c19",
    "procedure_text": "6-Chloro-N-(3-methoxyphenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine 6 was reacted with quinoline-3-boronic acid using General Procedure A. Purification on silica yielded 117. NMR: (CDCl3): 3.90 (s, 3H, CH3), 4.17 (s, 3H, CH3), 6.90 (dd, H, ArH, J=2.4, 8.32), 7.20 (d, H, ArH, J=7.92), 7.35 (d, H, ArH, J=11.36), 7.41 (t, H, ArH, J=8.11), 7.51 (s, H, NH), 7.62 (t, H, ArH, J=7.51), 7.79 (t, H, ArH, J=6.970, 8.00 (d, H, ArH, J=8.12), 8.20 (d, H, ArH, J=8.43), 9.30 (d, H, ArH, J=1.8), 10.07 (d, H, ArH, J=2.09). MS: (ESI+) MH+=383.23",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-Chloro-N-(3-methoxyphenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"quinoline-3-boronic acid\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Purification on silica\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"117\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2cf8359757694e178b0fe0770e9370cb",
    "procedure_text": "A mixture of 3-nitrophenol (4 g, 28.8 mmol), 2-chloro-N-cyclopropylacetamide (4.61 g, 34.5 mmol), K2CO3 (7.95 g, 57.5 mmol) and 18-CROWN-6 (0.228 g, 0.863 mmol) in N,N-Dimethylformamide (30.0 ml) was stirred under N2 atmosphere for 18 hrs at 50\u00b0 C. After cooling to RT, the reaction mixture was partitioned between EtOAc (250 ml) and water (250 ml). Aq. phase was re-extracted with EtOAc (200 ml). Combined organic layer was washed with brine (100 ml), dried over sodium sulphate and the solvent was evaporated under vacuum. Crude residue was purified by flash chromatography to obtain N-cyclopropyl-2-(3-nitrophenoxy)acetamide (4.21 gm).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m5_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-nitrophenol\"}], \"amount\": {\"mass\": {\"value\": 4.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloro-N-cyclopropylacetamide\"}], \"amount\": {\"mass\": {\"value\": 4.61, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"K2CO3\"}], \"amount\": {\"mass\": {\"value\": 7.95, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-Dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"18-CROWN-6\"}], \"amount\": {\"mass\": {\"value\": 0.228, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 50.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred under N2 atmosphere for 18 hrs at 50\\u00b0 C\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"After cooling to RT\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture was partitioned between EtOAc (250 ml) and water (250 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"Aq. phase was re-extracted with EtOAc (200 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"Combined organic layer was washed with brine (100 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulphate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulphate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was evaporated under vacuum\"}, {\"type\": \"CUSTOM\", \"details\": \"Crude residue was purified by flash chromatography\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 18.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-cyclopropyl-2-(3-nitrophenoxy)acetamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 4.21, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 61.9}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3fabf70d78fc4e7895990ba0cd36b0ea",
    "procedure_text": "To a 2 L round bottom flask purged with argon was added successively: germanium tetrachloride (200 g [0.9346 mol]), tetramethyl disiloxane (125 g[0.93 mol]), and acrylic acid (70.0 g[0.97 mol]). The reaction flask was purged with argon then sealed by placement of a ground glass stopper with a teflon sleeve and secured via teflon tape. The slightly cloudy mixture changed to a clear, colorless homogeneous solution within about 2 hours, and this was stirred for seven days at ambient temperature. The volatile components were removed via vacuum (0.5 to 5 mmHg) while the product mixture was heated to an internal temperature of 70\u00b0 C.-80\u00b0 C., where it was a homogeneous, clear and colorless viscous solution (melt). Evacuation was continued until no more distillate was observed (ca. 2 hours). This was cooled to an ambient temperature to yield a white amorphous solid. To this was added 950 mL of concentrated HCl. The resulting heterogeneous mixture was warmed to an internal temperature of 60\u00b0 C.-70\u00b0 C., and stirred for four hours. The cooled mixture was extracted 3 times with 500 mL of dichloromethane. The combined extracts were evaporated under reduced pressure via rotary evaporator to give a while amorphous solid. This was dissolved in ca. 1 L boiling hexane (until a clear colorless homogeneous hot solution was obtained), and let cool gently to ambient temperature. The product, trichlorogermane propionic acid, was isolated via suction filtration, washed once with hexane to give fine prisms, mp 75\u00b0 C.-79\u00b0 C. This was immediately taken up (vigorous reaction), with careful addition of 850 mL of ammonium hydroxide (29% ammonia). The resulting turbid mixture was stirred for 4 days at ambient temperature (the mixture changes to a clear, colorless homogeneous solution within 3 hours). To this homogeneous solution was added dropwise over two hours through a reflux condenser 400 mL of concentrated sulfuric acid. NOTE: This is a very vigorous reaction and should be handled with extreme care. A white precipitate formed after addition of ca. 375 mL of acid. The pot was stirred for 48 hours, and then the white solid was isolated via suction filtration, washed successively with 2\u00d7150 mL water, 1\u00d7150 mL acetone, and 1\u00d7200 mL of diethyl ether, then this brilliant white solid was air dried overnight, and then taken up with 150 mL hot water, then cooled and filtered to yield 78.84 g (50%) of analytically pure carboxyethyl germanium sesquioxide.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 950.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"germanium tetrachloride\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetramethyl disiloxane\"}], \"amount\": {\"mass\": {\"value\": 125.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acrylic acid\"}], \"amount\": {\"mass\": {\"value\": 70.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"this was stirred for seven days at ambient temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"To a 2 L round bottom flask purged with argon\"}, {\"type\": \"ADDITION\", \"details\": \"was added successively\"}, {\"type\": \"CUSTOM\", \"details\": \"The reaction flask was purged with argon\"}, {\"type\": \"CUSTOM\", \"details\": \"then sealed by placement of a ground glass stopper with a teflon sleeve\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"teflon\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"within about 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The volatile components were removed via vacuum (0.5 to 5 mmHg) while the product mixture\"}, {\"type\": \"TEMPERATURE\", \"details\": \"was heated to an internal temperature of 70\\u00b0 C.-80\\u00b0 C., where it\"}, {\"type\": \"CUSTOM\", \"details\": \"(ca. 2 hours)\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"This was cooled to an ambient temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"to yield a white amorphous solid\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The resulting heterogeneous mixture was warmed to an internal temperature of 60\\u00b0 C.-70\\u00b0 C.\"}, {\"type\": \"STIRRING\", \"details\": \"stirred for four hours\", \"duration\": {\"value\": 4.0, \"units\": \"HOUR\"}}, {\"type\": \"EXTRACTION\", \"details\": \"The cooled mixture was extracted 3 times with 500 mL of dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The combined extracts were evaporated under reduced pressure via rotary evaporator\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a while amorphous solid\"}, {\"type\": \"DISSOLUTION\", \"details\": \"This was dissolved in ca. 1 L\"}, {\"type\": \"CUSTOM\", \"details\": \"was obtained), and\"}, {\"type\": \"TEMPERATURE\", \"details\": \"let cool gently to ambient temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}], \"outcomes\": [{\"reaction_time\": {\"value\": 7.0, \"units\": \"DAY\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trichlorogermane propionic acid\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4f369910b121440998f40a296777283f",
    "procedure_text": "Commercially available 1-(4-methylphenyl)-1-cyclopropane carboxylic acid is treated with nitronium tetrafluoroborate in sulfolane to afford 1-(4-methyl-3-nitrophenyl)-1-cyclopropane carboxylic acid. This is converted to 1-(4-methyl-3-nitrophenyl)-1-bromocyclopropane by treatment with mercuric oxide and bromine in methylene chloride. Reduction with zinc dust in the presence of calcium chloride in aqueous ethanol affords 5-cyciopropyl-2-methylaniline. Conversion to 4-cyclopropyl-5-(2-imidazolinylamino)-7-methylbenzimidazole is completed in the same manner as 4-ethyl-5-(2-imidazolinylamino)-7-methylbenzimidazole (see Example 2).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(4-methylphenyl)-1-cyclopropane carboxylic acid\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"nitronium tetrafluoroborate\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sulfolane\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(4-methyl-3-nitrophenyl)-1-cyclopropane carboxylic acid\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-79db79f0e7314e74bf8b77db0dda2ecc",
    "procedure_text": "Oxo(phenyl)acetaldehyde methylhydrazone (5.46 mmol, 886 mg) synthesized in Reference Synthetic Example 36 and (4-t-butylphenyl)(oxo)acetaldehyde (5 mmol, 951 mg) were dissolved in acetic acid (26 mL) and stirred at 100\u00b0 C. for about 2 hours. Then, the solvent was evaporated, and the residue was recrystallized from chloroform/n-hexane to give the desired product as a yellow solid (993 mg, yield 59%).",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Oxo(phenyl)acetaldehyde methylhydrazone\"}], \"amount\": {\"mass\": {\"value\": 886.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(4-t-butylphenyl)(oxo)acetaldehyde\"}], \"amount\": {\"mass\": {\"value\": 951.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 26.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred at 100\\u00b0 C. for about 2 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Then, the solvent was evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was recrystallized from chloroform/n-hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform n-hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 993.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 59.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 59.4}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f347339a177f4ab8a08748288e49560e",
    "procedure_text": "2.0 g of N'-[(3,4-dimethoxy-5-nitrobenzoyl)oxy] acetamidine are held at reflux temperature for 1 hour in 20 ml of glacial acetic acid. After distillation of the acetic acid, the crystalline residue is recrystallized from ether/hexane. There is obtained 5-(3,4-dimethoxy-5-nitrophenyl)-3-methyl-1,2,4-oxadiazole in the form of colorless crystals of m.p. 111\u00b0.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N'-[(3,4-dimethoxy-5-nitrobenzoyl)oxy] acetamidine\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"DISTILLATION\", \"details\": \"After distillation of the acetic acid\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the crystalline residue is recrystallized from ether/hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-(3,4-dimethoxy-5-nitrophenyl)-3-methyl-1,2,4-oxadiazole\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-ddacdf4d8f37420db869bf211d415f1c",
    "procedure_text": "5.5 g of 2-(4,6-dimethoxy-2-pyrimidinyloxy)benzaldoxime and 7.1 g of propargyl bromide were dissolved in 100 ml of N,N-dimethylformamide containing 1.4 g of potassisum carbonate, and the solution was stirred at 100\u00b0 C. for 4 hours. After the reaction mixture was allowed to cool down, it was poured into water, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel chromatography (developer: n-hexane:ethyl acetate=10:1) to obtain 4.8 g of 0-(2-propynyl)-2-(4,6-dimethoxy-2-pyrimidinyloxy)benzaldoxime as an oily substance.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(4,6-dimethoxy-2-pyrimidinyloxy)benzaldoxime\"}], \"amount\": {\"mass\": {\"value\": 5.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"propargyl bromide\"}], \"amount\": {\"mass\": {\"value\": 7.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"carbonate\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the solution was stirred at 100\\u00b0 C. for 4 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"to cool down\"}, {\"type\": \"EXTRACTION\", \"details\": \"followed by extraction with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layer was dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by silica gel chromatography (developer: n-hexane:ethyl acetate=10:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-hexane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"0-(2-propynyl)-2-(4,6-dimethoxy-2-pyrimidinyloxy)benzaldoxime\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 4.8, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-367e9adaa1a147929b9813828fdfaf83",
    "procedure_text": "The chlorination of the 2,4,5-trifluorobenzoic acid is carried out in the melt, under pressure and/or in a solvent, for example chlorosulphonic acid or oleum, in the presence of halogen transfer agents, for example iodine. 2,4,5-Trifluoro-3-chlorobenzoic acid is obtained in this reaction. However, since the reaction mixture still contains unchanged starting material and some 2,4,5,-trifluoro-3,6-dichlorobenzoic acid, the crude mixture is treated, without intermediate isolation, with thionyl chloride. The desired 2,4,5-trifluoro-3-chlorobenzoyl chloride is then obtained by fractional distillation. However, it is more favorable to carry out the separation by distillation of the acid fluorides.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,4,5,-trifluoro-3,6-dichlorobenzoic acid\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude mixture\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"thionyl chloride\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,4,5-trifluoro-3-chlorobenzoyl chloride\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-1686af1b3e7e4569801f25dcbd230f9b",
    "procedure_text": "5-(5-Ethynyl-2-isobutoxy-3-pyridinyl)-2-methyl-3-propyl-2,6-dihydro-7H-pyrazolo[4,3-a]pyrimidin-7-one (Example 27) (200 mg, 0.54 mmol) and trimethylsilylazide (630 mg, 5.4 mmol) were stirred at 170\u00b0 C. in a sealed pressure vessel for 14 h. The reaction mixture was cooled and partitioned between ethyl acetate and saturated sodium bicarbonate solution. The brown precipitate was filtered off and the 2 phases separated. The organic phase was washed with more sodium bicarbonate solution and brine, dried with (MgSO4) and concentrated. This residue was combined with the original precipitate and purified by flash column chromatography (gradient elution from dichloromethane to 5% methanol:dichloromethane) to give 109 mg of a white solid (49%).",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-(5-Ethynyl-2-isobutoxy-3-pyridinyl)-2-methyl-3-propyl-2,6-dihydro-7H-pyrazolo[4,3-a]pyrimidin-7-one\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trimethylsilylazide\"}], \"amount\": {\"mass\": {\"value\": 630.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The reaction mixture was cooled\"}, {\"type\": \"CUSTOM\", \"details\": \"partitioned between ethyl acetate and saturated sodium bicarbonate solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"The brown precipitate was filtered off\"}, {\"type\": \"CUSTOM\", \"details\": \"the 2 phases separated\"}, {\"type\": \"WASH\", \"details\": \"The organic phase was washed with more sodium bicarbonate solution and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried with (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"purified by flash column chromatography (gradient elution from dichloromethane to 5% methanol:dichloromethane)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"white solid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 109.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 49.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 49.4}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-5ca3b1e5bc004b10baa0f9877e80e145",
    "procedure_text": "The title compound was prepared according to general method A as described above in Example 1 by reacting 2-[(R)-2-amino-1-propylthio]benzothiazole hydrochloride (prepared as described in Example 5) (0.89 g, 3.0 mmol) with 9-(2,3,5-tri-O-acetyl-\u03b2-D-ribofuranosyl)-6-chloro-2-methyl-9H-purine (1.07 g, 2.5 mmol) [prepared from 2-methylinosine (Journal of Organic Chemistry, 1967, 32, 3258-3260) by standard acylation and chlorination steps]. Deacylation of the purified 2',3',5'-tri-O-acetyl-N-[(R)-1-(2-benzothiazolyl)thio-2-propyl]-2-methyladenosine using sodium methoxide in methanol to provide the desired N-[(R)-1-(2-benzothiazolyl)thio-2-propyl]-2-methyladenosine (0.28 g, 11%) (following column chromatography), 1H NMR (DMSO-d6) \u03b41.40 (3H, d, --CHCH3), 2.30 (3H, s, --CH3), 3.50-3.77 (4H, m, H-5'a and H-5'b and --CH2 --), 3.98 (1H, d, H-4'), 4.13 (1H, d, H-3'), 4.63 (1H, q, H-2'), 4.86 (1H, br, --CHCH3), 5.19, 5.42 (2H, 2d, 2'- and 3'-OH), 5.70 (1H, t, 5'-OH), 5.85 (1H, d, H-1'), 7.36, 7.47 (2H, 2t, Ar--H), 7.80-7.96 (2H, m, Ar--H), 8.0 (1H, s, N--H), 8.26 (1H, s, H-8), 8.52 (1H, s, N--H). HPLC retention time 22.4 min [gradient elution, 20-80% acetonitrile/water (containing 0.1% TFA)].",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium methoxide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-[(R)-2-amino-1-propylthio]benzothiazole hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 0.89, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"9-(2,3,5-tri-O-acetyl-\\u03b2-D-ribofuranosyl)-6-chloro-2-methyl-9H-purine\"}], \"amount\": {\"mass\": {\"value\": 1.07, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2',3',5'-tri-O-acetyl-N-[(R)-1-(2-benzothiazolyl)thio-2-propyl]-2-methyladenosine\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The title compound was prepared\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-[(R)-1-(2-benzothiazolyl)thio-2-propyl]-2-methyladenosine\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.28, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 11.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-10e2a34e58614bb0b44c8f3b5b5b59d3",
    "procedure_text": "Under the conditions of Example 2(a), 3.633 g (10 mmol) of 4-[N-(4-fluoro-2-trifluoromethylphenyl)sulfamoyl]benzoic acid, 1.536 g (10 mmol) of L-alanine ethyl ester hydrochloride, 1.531 g (10 mmol) of hydroxybenzotriazole, hydrate, as well as 1.012 g (10 mmol) of triethylamine and 2.063 g (10 mmol) of dicyclohexylcarbodiimide are reacted and worked up analogously. The crude product is chromatographed on silica gel. The title compound is eluted with ethyl acetate.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-[N-(4-fluoro-2-trifluoromethylphenyl)sulfamoyl]benzoic acid\"}], \"amount\": {\"mass\": {\"value\": 3.633, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"L-alanine ethyl ester hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 1.536, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydroxybenzotriazole, hydrate\"}], \"amount\": {\"mass\": {\"value\": 1.531, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"mass\": {\"value\": 1.012, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dicyclohexylcarbodiimide\"}], \"amount\": {\"mass\": {\"value\": 2.063, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The crude product is chromatographed on silica gel\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The title compound is eluted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-deefc191e6d5456da08f9a77fd254cde",
    "procedure_text": "A 10-mL single-neck round-bottomed flask equipped with a magnetic stirrer was purged with nitrogen, charged with 104a (196 mg, 0.89 mmol), 37% solution of formaldehyde in water (35 mg, 1.16 mmol) and anhydrous methanol (3 mL). A solution of sodium cyanoborohydride (169 mg, 2.68 mmol) and anhydrous zinc chloride (183 mg, 1.34 mmol) in anhydrous methanol (3 mL) was added, and the reaction was stirred at room temperature for 1 h. After this time, 1N aqueous sodium hydroxide (2 mL) was added, and the methanol was evaporated under reduced pressure. The remaining aqueous solution was extracted with ethyl acetate (3\u00d725 mL). The organic layers were combined, washed with water (20 mL) and brine (20 mL) and dried over magnesium sulfate. The drying agent was removed by filtration and the filtrate concentrated under reduced pressure to afford 104b in 100% yield (210 mg) as a yellow solid: mp 185-186\u00b0 C.; 1H NMR (300 MHz, DMSO-d6) \u03b4 8.18 (d, 2H, J=8.1 Hz), 8.05 (d, 1H, J=3.6 Hz), 7.63 (d, 2H, J=7.8 Hz), 3.82 (s, 1H), 3.45 (m, 1H), 3.17 (m, 1H), 2.95 (m, 1H), 2.56 (m, 1H), 2.06 (s, 3H); MS (ESI+) m/z 236 (M+H).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"104a\"}], \"amount\": {\"mass\": {\"value\": 196.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"formaldehyde\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"mass\": {\"value\": 35.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5_m9_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium cyanoborohydride\"}], \"amount\": {\"mass\": {\"value\": 169.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"zinc chloride\"}], \"amount\": {\"mass\": {\"value\": 183.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction was stirred at room temperature for 1 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"A 10-mL single-neck round-bottomed flask equipped with a magnetic stirrer\"}, {\"type\": \"CUSTOM\", \"details\": \"was purged with nitrogen\"}, {\"type\": \"CUSTOM\", \"details\": \"the methanol was evaporated under reduced pressure\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The remaining aqueous solution was extracted with ethyl acetate (3\\u00d725 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with water (20 mL) and brine (20 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The drying agent was removed by filtration\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate concentrated under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"104b\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 100.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c922cc9b35e54dfa8bc53a909857f975",
    "procedure_text": "A mixture of 24.9 g (0.2 mol) of O-ethylisourea hydrochloride and 21.5 g (0.14 mol) of methyl 4-chloroacetoacetate in 100 ml of methanol is treated at 0\u00b0-5\u00b0 C. during 10 minutes with a solution of 7.55 g (0.33 mol) of sodium in 100 ml of methanol. The mixture is stirred at 0\u00b0 C. for 2 hours and at room temperature for 18 hours and the solvent is then removed by evaporation under reduced pressure. The residue is dissolved in 300 ml of water and the solution is adjusted to a pH-value of 6. The resulting crystallline product is filtered off, washed with diethyl ether and dried at 40\u00b0 C. In this manner there is obtained 2-ethoxy-4-chloromethyl-6-hydroxy-pyrimidine, m.p. 157\u00b0-159\u00b0 C. By back-extracting the aqueous filtrate three times with 150 ml of chloroform each time there is obtained an additional amount of this product, m.p. 159\u00b0-161\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium\"}], \"amount\": {\"mass\": {\"value\": 7.55, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"O-ethylisourea hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 24.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 4-chloroacetoacetate\"}], \"amount\": {\"mass\": {\"value\": 21.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}, \"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture is stirred at 0\\u00b0 C. for 2 hours and at room temperature for 18 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the solvent is then removed by evaporation under reduced pressure\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue is dissolved in 300 ml of water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 300.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"The resulting crystallline product is filtered off\"}, {\"type\": \"WASH\", \"details\": \"washed with diethyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried at 40\\u00b0 C\", \"temperature\": {\"setpoint\": {\"value\": 40.0, \"units\": \"CELSIUS\"}}}], \"outcomes\": [{\"reaction_time\": {\"value\": 18.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-ethoxy-4-chloromethyl-6-hydroxy-pyrimidine\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a8fef984ec894256b679a8892df9dcb9",
    "procedure_text": "To a stirred solution of (1-phenyl-cyclohexyl)-methanol (251) (43.0 g, 225.97 mmol) in dichloromethane (250.0 mL) was added Et3N (63.0 mL, 451.9 mmol), followed by drop-wise addition of mesyl chloride (21.0 mL, 271.16 mmol) at 0\u00b0 C. and the reaction mixture was stirred at room temperature for 1 h. After completion of the reaction, the reaction mixture was quenched by the addition of water and extracted with dichloromethane. The organic layer was then washed with water and brine and dried over sodium sulfate and concentrated under reduced pressure to get a crude product. It was purified by normal silica gel column chromatography (using 5% ethyl acetate in hexane) to get methanesulfonic acid 1-phenyl-cyclohexylmethyl ester (252) (49.3 g, 81.0%) as a white solid.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(1-phenyl-cyclohexyl)-methanol\"}], \"amount\": {\"mass\": {\"value\": 43.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Et3N\"}], \"amount\": {\"volume\": {\"value\": 63.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"mesyl chloride\"}], \"amount\": {\"volume\": {\"value\": 21.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture was stirred at room temperature for 1 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"After completion of the reaction\"}, {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture was quenched by the addition of water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was then washed with water and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"to get a crude product\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"It was purified by normal silica gel column chromatography (using 5% ethyl acetate in hexane)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanesulfonic acid 1-phenyl-cyclohexylmethyl ester\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 49.3, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 81.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 81.3}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-83b20329bb164226903c16e7271c606a",
    "procedure_text": "The 7-methoxy-5H-pyrimido[5,4-b]indole-2-carboxylic acid ethyl ester is produced analogously, but starting with 2-amino-4-methoxybenzonitrile.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-methoxy-5H-pyrimido[5,4-b]indole-2-carboxylic acid ethyl ester\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-amino-4-methoxybenzonitrile\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-718fe1ce1a1746b78c6ebc4d36a73bed",
    "procedure_text": "In 250 ml of dichloromethane was suspended 22.4 g of anhydrous aluminium chloride. While stirring, 22.4 ml of butylmercaptan was added. After the mixture was stirred at room temperature for 1 hour, 17.7 g of 3-(4-methoxyphenyl)-1(4-methylphenyl)-1H-pyrazolo[3,4-b]pyridine was added thereto under ice-cooling. After the mixture was stirred at room temperature for 4 hours, the reaction mixture was poured into about 1 l of ice-water. The resulting crystals were collected by filtration, washed with water and recrystallized from methanol to give 13.8 g of 3-(4-hydroxyphenyl)-1-(4-methyl- phenyl)-1H-pyrazolo[3,4-b]pyridine, m.p. 201\u00b0-203\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"LITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aluminium chloride\"}], \"amount\": {\"mass\": {\"value\": 22.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"butylmercaptan\"}], \"amount\": {\"volume\": {\"value\": 22.4, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(4-methoxyphenyl)-1(4-methylphenyl)-1H-pyrazolo[3,4-b]pyridine\"}], \"amount\": {\"mass\": {\"value\": 17.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"While stirring\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"After the mixture was stirred at room temperature for 1 hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"under ice-cooling\"}, {\"type\": \"STIRRING\", \"details\": \"After the mixture was stirred at room temperature for 4 hours\", \"duration\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"The resulting crystals were collected by filtration\"}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"recrystallized from methanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(4-hydroxyphenyl)-1-(4-methyl- phenyl)-1H-pyrazolo[3,4-b]pyridine\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 13.8, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-5296d70fa7d9404ab1af5b9f0eb44566",
    "procedure_text": "A suspension of 1-methyl-5-phenyl-3-(pyrrolidin-1-yl)-1H-pyrazolo[3,4-c]pyridazin-4-ol (117 mg) in POCl3 (1.9 mL) was heated to 60\u00b0 C. for 2.5 h. The mixture was concentrated in vacuo and the residue was partitioned between CH2Cl2 and sat. aq. NaHCO3 solution. The layers were separated and the aqueous was extracted with CH2Cl2, the combined organics were dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel to give the title compound (81 mg).",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-methyl-5-phenyl-3-(pyrrolidin-1-yl)-1H-pyrazolo[3,4-c]pyridazin-4-ol\"}], \"amount\": {\"mass\": {\"value\": 117.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"POCl3\"}], \"amount\": {\"volume\": {\"value\": 1.9, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"The mixture was concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was partitioned between CH2Cl2 and sat. aq. NaHCO3 solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The layers were separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"the aqueous was extracted with CH2Cl2\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"the combined organics were dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by chromatography on silica gel\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 81.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b9974c5c7fe5468f817288c09d92cfd8",
    "procedure_text": "Under argon a solution of (1R,2S,3R)-3-tert-butoxycarbonylamino-1-chloro-1,2,3,4-tetrahydro-2-naphthalenol (BOC-amino-cis-chlorohydrin) (500 mg) in anhydrous tetrahydrofuran was refluxed with isoamylamine (1.0 ml) and triethylamine (250 \u03bcl ) for 5 hours at 90\u00b0 C. The mixture was poured in aqueous 5% sodium bicarbonate and extracted with methylene chloride. The organic solution was dried over magnesium sulfate and evaporated under vacuum to yield an oil. Crystallization of this oil in hexane yielded the title compound as a white solid (270 mg).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m5_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(1R,2S,3R)-3-tert-butoxycarbonylamino-1-chloro-1,2,3,4-tetrahydro-2-naphthalenol\"}], \"amount\": {\"mass\": {\"value\": 500.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isoamylamine\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted with methylene chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic solution was dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated under vacuum\"}, {\"type\": \"CUSTOM\", \"details\": \"to yield an oil\"}, {\"type\": \"CUSTOM\", \"details\": \"Crystallization of this oil in hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 270.0, \"units\": \"MILLIGRAM\"}}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d1911f2aadaf40039489131386042ec3",
    "procedure_text": "To an aqueous solution of 55 m moles(7.6 g) of 4-hydroxybenzoic acid and 65 m moles(2.6 g) of sodium hydroxide in 200 ml of water, 65 m moles(10.6 g) of carbobenzoxychloride was added dropwise at 0\u00b0 C. After 24 hours, the precipitate was washed with water, filtered, and dried, then purified by column chromatography to obtain 15.0 g of 4-carbobenzoxyoxybenzoic acid [m.p. 181.9\u00b0-183.1\u00b0 C\u27e7 (yield: 99%)",
    "reference_string": "{\"inputs\": {\"m1_m2_m4_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-hydroxybenzoic acid\"}], \"amount\": {\"mass\": {\"value\": 7.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"mass\": {\"value\": 2.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"carbobenzoxychloride\"}], \"amount\": {\"mass\": {\"value\": 10.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WASH\", \"details\": \"the precipitate was washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"CUSTOM\", \"details\": \"purified by column chromatography\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 24.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-carbobenzoxyoxybenzoic acid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 15.0, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 99.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-41b06f54a12b4729bb17d214cfb73421",
    "procedure_text": "66.3 g (0.03 mol) of the foregoing 3-carboethoxy-2-cyano-2-hydroxy-3,5-dimethylcyclopentanone and 30.2 g (0.4 mol) of anhydrous sodium acetate are treated with 350 ml of water. The mixture is refluxed for 6 hours. For the working-up, the mixture is adjusted to pH 7 with saturated sodium hydrogen carbonate solution and then extracted four times with methylene chloride. The organic phases are dried over sodium sulphate, concentrated and dried in a high vacuum for 1 hour. (The product can, however, also be directly crystallised from the reaction mixture). There are obtained 42.6 g (73%) of crystalline 2-carboethoxy-2,4-dimethylcyclopent-4-en-5-olone of melting point 92\u00b0-93\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-carboethoxy-2-cyano-2-hydroxy-3,5-dimethylcyclopentanone\"}], \"amount\": {\"mass\": {\"value\": 66.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium acetate\"}], \"amount\": {\"mass\": {\"value\": 30.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 350.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydrogen carbonate\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The mixture is refluxed for 6 hours\", \"duration\": {\"value\": 6.0, \"units\": \"HOUR\"}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted four times with methylene chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic phases are dried over sodium sulphate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulphate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"dried in a high vacuum for 1 hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"(The product can, however, also be directly crystallised from the reaction mixture)\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-carboethoxy-2,4-dimethylcyclopent-4-en-5-olone\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 42.6, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 73.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-58f559364c1d420cb123878f1c915fee",
    "procedure_text": "To a solution of 5-methyl-4-pyridin-3-yl-1H-pyrimidin-2-one (100 mg, 0.53 mmol) in DMSO (2 ml), 60% NaH (23 mg, 0.59 mmol) was added portionwise. After heating the mixture at 60\u00b0 C. for 1 hour, 1-bromo-4-chloro-butane (100 mg, 0.59 mmol) dissolved in DMSO (0.8 ml) was added at 60\u00b0 C. and the heating was maintained for further 2 hours. After cooling to room temperature, water was added and the mixture extracted with diethyl ether to remove the dialkylated product and finally with ethyl acetate. Ethyl acetate was washed with brine, dried (Na2SO4) and evaporated to afford 100 mg of the title compound as yellow oil (68% yield).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-bromo-4-chloro-butane\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMSO\"}], \"amount\": {\"volume\": {\"value\": 0.8, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m5_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-methyl-4-pyridin-3-yl-1H-pyrimidin-2-one\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaH\"}], \"amount\": {\"mass\": {\"value\": 23.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMSO\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added at 60\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"the heating was maintained for further 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"After cooling to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"the mixture extracted with diethyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"to remove the dialkylated product\"}, {\"type\": \"WASH\", \"details\": \"Ethyl acetate was washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 68.0}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a7d9a462b0cf4b75b180d0c552ebfe50",
    "procedure_text": "The procedure of Synthesis Example 1 was repeated except that 2-(1H-imidazol-1-yl)ethanol was used instead of the triethanolamine, and 2-naphthoyl chloride was used instead of the benzoyl chloride, to give 2-(1H-imidazol-1-yl)ethyl 2-naphthalenecarboxylate in a yield of 81%.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(1H-imidazol-1-yl)ethanol\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-naphthoyl chloride\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The procedure of Synthesis Example 1\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(1H-imidazol-1-yl)ethyl 2-naphthalenecarboxylate\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 81.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0a2cf5f9c1ef416083e1abf734d75bb4",
    "procedure_text": "To a suspended solution of 4-(3-indolyl)piperidine (2.0 g, 10 mmol) and 1-(3-chloropropyl)-4-phenylpiperidine hydrochloride (3.1 g, 11.2 mmol) in DMF (60 mL) was added potassium carbonate (5.5 g, 40 mmol), and the mixture was stirred at 100\u00b0 C. for 4 hours. After the precipitated salt was filtered off, the filtrate was concentrated, water (50 mL) was added to the filtrate, and the mixture was extracted with chloroform. After drying over anhydrous sodium sulfate, the chloroform layer was concentrated to afford a crude product. The crude product was purified by column chromatography on a silica gel (silica gel NH-DM 1020 produced by Fuji Silysia Chemical Ltd., eluent; chloroform) and was then recrystallized from ethyl acetate to afford a free form (1.6 g, yield: 40%) of the title compound as white crystals. After adding hydrochloric acid/methanol to a solution of the free form (1.6 g) in methanol, the mixture was concentrated and was then recrystallized from methanol/ether to afford the title compound (1.8 g) as white crystals.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(3-indolyl)piperidine\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(3-chloropropyl)-4-phenylpiperidine hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 3.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 5.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at 100\\u00b0 C. for 4 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"After the precipitated salt was filtered off\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate was concentrated\"}, {\"type\": \"ADDITION\", \"details\": \"water (50 mL) was added to the filtrate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"the mixture was extracted with chloroform\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"After drying over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"the chloroform layer was concentrated\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"to afford a crude product\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The crude product was purified by column chromatography on a silica gel (silica gel NH-DM 1020 produced by Fuji Silysia Chemical Ltd., eluent; chloroform)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"was then recrystallized from ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.6, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 40.0}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b684eed9054641449ac96551555fa824",
    "procedure_text": "3-Chloroperoxybenzoic acid (0.66 g) was added to a solution of benzocyclobutene aldehyde (0.2 g) in methylene chloride (10 mL) at 0\u00b0 C. The mixture was stirred for 30 minutes at 0\u00b0 C. and then warmed to room temperature. Stirring was continued for 12 hours at room temperature. Potassium floride (0.3 g) was added and stirring continued for an additional two hours. The reaction mixture was filtered, washed with sodium bisulfite solution and the solvent was removed by flash column chromatography. Liquid chromatographic analysis found a yield to hydroxy benzocyclobutene of approximately 55 percent and no benzocyclobutene carboxylic acid, with the balance comprising unidentified materials characterized as undesired product.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-Chloroperoxybenzoic acid\"}], \"amount\": {\"mass\": {\"value\": 0.66, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzocyclobutene aldehyde\"}], \"amount\": {\"mass\": {\"value\": 0.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Potassium floride\"}], \"amount\": {\"mass\": {\"value\": 0.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred for 30 minutes at 0\\u00b0 C.\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"warmed to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"STIRRING\", \"details\": \"Stirring\"}, {\"type\": \"WAIT\", \"details\": \"was continued for 12 hours at room temperature\", \"duration\": {\"value\": 12.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"STIRRING\", \"details\": \"stirring\"}, {\"type\": \"WAIT\", \"details\": \"continued for an additional two hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"The reaction mixture was filtered\"}, {\"type\": \"WASH\", \"details\": \"washed with sodium bisulfite solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bisulfite\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was removed by flash column chromatography\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydroxy benzocyclobutene\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-7aa1a81e3bd3494a8e9c0b86bbb93c8e",
    "procedure_text": "To a mixture of methyl 4-amino-3-chlorophenylacetate (1.00 g, 5.01 mmol) and 2-methylphenyl isocyanate (0.60 ml, 5.01 mmol) in THF (20 ml) was added Et3 N (0.14 ml, 1.00 mmol) at room temperature. After 1 day stirring, 2-methylphenyl isocyanate (0.60 ml, 5.01 mmol) was added to the reaction mixture and stirred 17 h. The reaction mixture was concentrated in vacuo. The residue was triturated by the addition of n-hexane to give methyl 3-chloro-4-[N\u2032-(2-methylphenyl) ureido]phenylacetate (1.23 g, 74%) as a colorless powder. 1H-NMR (CDCl3) \u03b4 2.34 (s, 3H), 3.54 (s, 2H), 3.68 (s, 3H), 6.24 (br, 1H1), 6.99 (br, 1H), 7.15 (dd, J=8.3, 2.0 Hz, 1H), 7.21\u20137.31 (m, 5H), 7.44 (d, J=7.6 Hz, 1H), 8.20 (d, J=8.5 Hz, 1H); MS (ESI) m/z 333 (M++1), 335 (M++3).",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 4-amino-3-chlorophenylacetate\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-methylphenyl isocyanate\"}], \"amount\": {\"volume\": {\"value\": 0.6, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-methylphenyl isocyanate\"}], \"amount\": {\"volume\": {\"value\": 0.6, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After 1 day stirring\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added Et3 N (0.14 ml, 1.00 mmol) at room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"STIRRING\", \"details\": \"stirred 17 h\", \"duration\": {\"value\": 17.0, \"units\": \"HOUR\"}}, {\"type\": \"CONCENTRATION\", \"details\": \"The reaction mixture was concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was triturated by the addition of n-hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"DAY\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 3-chloro-4-[N\\u2032-(2-methylphenyl) ureido]phenylacetate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.23, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 74.0}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"POWDER\", \"details\": \"powder\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-86fa245e671c47dfa2404ec56cd61447",
    "procedure_text": "To a stirred mixture of ethyl 5-[(2-pyrrolidinyl)methylamino]pyridine-2 carboxylate (230 mg, 0.923 mmol), 3-methoxy-4-[N\u2032-(2-methylphenyl)ureido]phenylacetic acid (290 mg, 0.923 mmol), 4-DMAP (145 mg, 1.15 mmol) in DMF (7 ml) was added EDC.HCl (225 mg, 1.15 mmol) at room temperature. The resulting mixture was stirred at room temperature for 20 hr. The mixture was pored into ice-water. The solid was collected, washed with water and air-dried. The crude solid was purified by silica gel (30 ml) column chromatography with CHCl3-EtOH (98:2, v/v) as eluent to give ethyl 5-[[1-[3-methoxy4-[N\u2032-(2-methylphenyl)ureido]phenylacetyl]-2-pyrrolidinyl]methylamino]pyridine-2-carboxylate (400 mg, 80%) as fine needles. IR (KBr) n 3325, 1709, 1618, 1585, 1531 cm\u2212; 1H-NMR (CDCl3) \u03b4 1.39 (t, J=7 Hz, 3 H), 1.73\u20132.07 (series of m, 4 H), 2.28 (s, 3 H), 3.12 and 3.49 (each m, each 1 H), 3.60 (s, 2 H), 4.39 (br q, J=7 Hz, 2 H), 4.53 (m, 1 H), 6.07 (br s, 1 H), 6.23 (br s, 1 H), 6.75\u20136.77 (series of s and m, 2 H), 6.82 (dd, J=3.0 and 8.5 Hz, 1 H), 7.09\u20137.22 (series of m, 3 H), 7.49 (d, J=8.0 Hz, 1 H), 7.90 (d, J=8.5 Hz, 1H), 7.98 (d, J=2.6 Hz, 1H), 8.06 (d, J=8.8 Hz, 1H); MS (FAB) m/z 546 (M++1); Anal. Calcd for C30H35N5O5.1.5\u00d7H2O: C, 52.92; H, 6.69; N, 12.23. Found: C, 63.11; H, 6.48; N, 11.96.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 5-[(2-pyrrolidinyl)methylamino]pyridine-2 carboxylate\"}], \"amount\": {\"mass\": {\"value\": 230.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-methoxy-4-[N\\u2032-(2-methylphenyl)ureido]phenylacetic acid\"}], \"amount\": {\"mass\": {\"value\": 290.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-DMAP\"}], \"amount\": {\"mass\": {\"value\": 145.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 7.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EDC.HCl\"}], \"amount\": {\"mass\": {\"value\": 225.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The resulting mixture was stirred at room temperature for 20 hr\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The solid was collected\"}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"air-dried\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude solid was purified by silica gel (30 ml) column chromatography with CHCl3-EtOH (98:2\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CHCl3 EtOH\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 20.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 5-[[1-[3-methoxy4-[N\\u2032-(2-methylphenyl)ureido]phenylacetyl]-2-pyrrolidinyl]methylamino]pyridine-2-carboxylate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 400.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 80.0}}], \"isolated_color\": \"fine\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"needles\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-8d288e7b2d2e4b09bf859050e488502a",
    "procedure_text": "A solution of N-{4-[2-oxo-3-(4-phenoxyphenyl)-2,3-dihydroimidazol-1-yl]phenyl}acetamide (4.0 g) in ethanol (100 ml) was heated to reflux with hydrochloric acid (20% strength, 30 ml) for 16 hours. After cooling, ammonia solution (10% strength) was added until the reaction was basic. The precipitated solid was filtered off and dried in a vacuum oven at 40\u00b0 C. The product with the molecular weight of 343.39 (C21H17N3O2); MS (ESI): 344 ([M+H]+) was obtained in this way.",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-{4-[2-oxo-3-(4-phenoxyphenyl)-2,3-dihydroimidazol-1-yl]phenyl}acetamide\"}], \"amount\": {\"mass\": {\"value\": 4.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonia\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"After cooling\"}, {\"type\": \"FILTRATION\", \"details\": \"The precipitated solid was filtered off\"}, {\"type\": \"CUSTOM\", \"details\": \"dried in a vacuum oven at 40\\u00b0 C\", \"temperature\": {\"setpoint\": {\"value\": 40.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"MS (ESI): 344 ([M+H]+) was obtained in this way\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-efea9be364c343f2848730dcecb35827",
    "procedure_text": "A solution of (5-Acetyl-4-fluoro-2-methyl-phenyl)-carbamic acid tert-butyl ester (425 mg) and (1,1-dimethoxy-ethyl)-dimethyl-amine (653 mg) in DMF (2 ml) was heated at 90\u00b0 C. for 3 hours, then cooled to room temperature. Solvent was removed under reduced pressure, and the residue was dissolved in a mixture of EtOH (25 ml) and THF (5 ml). The mixture was cooled to 0\u00b0 C., and hydrazine hydrate (5 ml) at 0\u00b0 C. was added. The mixture was stirred for 16 hours at room temperature, then concentrated under reduced pressure. The residue was purified by \u201cflash chromatography\u201d (0 to 30% EtOAc in hexanes) to give 370 mg of [4-fluoro-2-methyl-5-(5-methyl-1H-pyrazol-3-yl)-phenyl]-carbamic acid tert-butyl ester.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(5-Acetyl-4-fluoro-2-methyl-phenyl)-carbamic acid tert-butyl ester\"}], \"amount\": {\"mass\": {\"value\": 425.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(1,1-dimethoxy-ethyl)-dimethyl-amine\"}], \"amount\": {\"mass\": {\"value\": 653.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred for 16 hours at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Solvent was removed under reduced pressure\"}, {\"type\": \"DISSOLUTION\", \"details\": \"the residue was dissolved in a mixture of EtOH (25 ml) and THF (5 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOH\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"The mixture was cooled to 0\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"ADDITION\", \"details\": \"hydrazine hydrate (5 ml) at 0\\u00b0 C. was added\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrazine hydrate\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}, \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by \\u201cflash chromatography\\u201d (0 to 30% EtOAc in hexanes)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"[4-fluoro-2-methyl-5-(5-methyl-1H-pyrazol-3-yl)-phenyl]-carbamic acid tert-butyl ester\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 370.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-6baff0ddd6914e7dae5ca9487f2da7b7",
    "procedure_text": "The title compound was prepared by treating the ketal of step B with HCl in water following the procedure described in step B of Example 2. MS (M+H)+ 269.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ketal\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d3cd2d1fa35640c18b799d7adfdf72a4",
    "procedure_text": "To a mixture of methyl 2-(4-(4\u2032-amino-[1,1\u2032-biphenyl]-4-yl)-2-oxabicyclo[2.2.2]octan-1-yl)acetate (0.323 g, 0.918 mmol) in toluene (35 ml) was added benzyl alcohol (2.377 ml, 22.95 mmol), titanium(IV) isopropoxide (0.807 ml, 2.75 mmol) and 4 A molecular sieves (5 g, 0.918 mmol). The reaction mixture was heated at 120\u00b0 C. for 48 hours. The resulting mixture was taken up in EtOAc and filtered. The filtrate was subsequently washed with water, then brine. The organic portion dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography (10 to 50% EtOAc/Heptane) to give the title compound after drying (270 mg, yield 68.8% yield). LC/MS, ESI-MS(+) m/z 428.1, RT 1.59 (Condition R).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 2-(4-(4\\u2032-amino-[1,1\\u2032-biphenyl]-4-yl)-2-oxabicyclo[2.2.2]octan-1-yl)acetate\"}], \"amount\": {\"mass\": {\"value\": 0.323, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 35.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzyl alcohol\"}], \"amount\": {\"volume\": {\"value\": 2.377, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"titanium(IV) isopropoxide\"}], \"amount\": {\"volume\": {\"value\": 0.807, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 120.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"WASH\", \"details\": \"The filtrate was subsequently washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic portion dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by flash chromatography (10 to 50% EtOAc/Heptane)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc Heptane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 68.8}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-1ca1acbde0954d429e959c13c68ac337",
    "procedure_text": "Slightly excess gadolinium oxide was dissolved in concentrated nitric acid under heating to effect the reaction. After 1 hour, the reaction liquid was filtered and the filtrate was cooled to precipitate crystalline gadolinium nitrate. Yield: 62%.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"gadolinium oxide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"nitric acid\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"under heating\"}, {\"type\": \"CUSTOM\", \"details\": \"the reaction\"}, {\"type\": \"CUSTOM\", \"details\": \"the reaction liquid\"}, {\"type\": \"FILTRATION\", \"details\": \"was filtered\"}, {\"type\": \"TEMPERATURE\", \"details\": \"the filtrate was cooled\"}, {\"type\": \"CUSTOM\", \"details\": \"to precipitate crystalline gadolinium nitrate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"gadolinium nitrate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"gadolinium nitrate\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 62.0}}]}]}]}"
  },
  {
    "reaction_id": "ord-c8953e5a7bae47da85658f7ddd4aae78",
    "procedure_text": "Under inert-gas atmosphere, 3.1 g (7.9 mmol) of triphenylmethyl phosphonium iodide and 0.24 g (8 mmol) of sodium hydride (80% in paraffin oil) in 20 ml of DMSO in an ultrasound bath are brought to reaction at about 55\u00b0 C. After 10 minutes, 80 mg (0.16 mmol, about 60%) of 3,16\u03b1-dihydroxyestra-1,3,5(10)-triene-9 carbaldehyde is added to the solution, and the mixture is allowed to react for 60 more minutes at about 55\u00b0 C. in an ultrasound bath. After water is added, it is extracted with ethyl acetate. The collected organic phases are washed with water, and the organic phase is concentrated by evaporation in a vacuum.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triphenylmethyl phosphonium iodide\"}], \"amount\": {\"mass\": {\"value\": 3.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydride\"}], \"amount\": {\"mass\": {\"value\": 0.24, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMSO\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,16\\u03b1-dihydroxyestra-1,3,5(10)-triene-9 carbaldehyde\"}], \"amount\": {\"mass\": {\"value\": 80.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"to react for 60 more minutes at about 55\\u00b0 C. in an ultrasound bath\", \"temperature\": {\"setpoint\": {\"value\": 55.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"it is extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The collected organic phases are washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"the organic phase is concentrated by evaporation in a vacuum\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 10.0, \"units\": \"MINUTE\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-76966bda2d314fe886bdf11aa8da9d11",
    "procedure_text": "To a mixture of 6-chloro-2-propoxy-nicotinonitrile (0.54 g, 3.0 mmol) and 3H-benzo[c][1,2]oxaborole-1,5-diol (0.40 g, 2.0 mmol) in DMF (10 mL) was added potassium carbonate (0.83 g, 6.0 mmol). The resulting suspension was heated at 95\u00b0 C. for 48 h. DMF was removed under reduced pressure, the residue was diluted with EtOAc (50 mL), washed with water (10 mL) and brine (2\u00d710 mL), dried over Na2SO4, filtered, and concentrated to give brown oil. Purification was accomplished by reverse phase preparative HPLC using MeOH/H2O (0.1% AcOH) as the eluent to yield the title compound (0.25 g, 26%) as a white solid. 1H NMR (400 MHz, DMSO-d6) \u03b4 ppm 9.25 (s, 1H), 8.24 (d, J=8.2 Hz, 1H), 7.79 (d, J=7.8 Hz, 1H), 7.29 (s, 1H), 7.17-7.22 (m, 1H), 6.69 (d, J=8.6 Hz, 1H), 4.99 (s, 2H), 4.07 (t, J=6.8 Hz, 2H), 1.65-1.55 (m, 2H), 0.81 (t, J=7.4 Hz, 3H); MS (ES) m/z: 311 (M+1)+; HPLC purity 98.36% (Maxplot), 97.66% (220 nm).",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-chloro-2-propoxy-nicotinonitrile\"}], \"amount\": {\"mass\": {\"value\": 0.54, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3H-benzo[c][1,2]oxaborole-1,5-diol\"}], \"amount\": {\"mass\": {\"value\": 0.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 0.83, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 95.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"DMF was removed under reduced pressure\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"the residue was diluted with EtOAc (50 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with water (10 mL) and brine (2\\u00d710 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"to give brown oil\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.25, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 26.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 40.3}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fe7252b065f6485fb1ff1e7a9e938a78",
    "procedure_text": "1,1,1-Triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one (221 mg, 0.520 mmol) was added to a solution of 1-[2-(1-adamantyl)ethyl]-3-[3-hydroxy-3-(4-pyridyl)propyl]-1-pentylurea (100 mg, 0.234 mmol) in anhydrous dichloromethane (2 ml) under ice-cooling, the temperature was raised to room temperature, and the mixture was stirred for one hour. The reaction mixture was cooled with ice again, ethyl acetate (10 ml), a saturated aqueous sodium sulfite solution (5 ml) and a saturated aqueous sodium hydrogencarbonate solution (5 ml) were added to the reaction mixture, and the whole was stirred for 15 minutes. The reaction mixture was distributed with ethyl acetate (50 ml) and water (10 ml), and the organic layer was washed with a saturated aqueous sodium sulfite solution (5 ml), a saturated aqueous sodium hydrogencarbonate solution (5 ml) and a saturated aqueous sodium chloride solution (25 ml) successively. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to give 87.3 mg (87.8%) of the titled compound as colorless crystals.",
    "reference_string": "{\"inputs\": {\"m1_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,1,1-Triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one\"}], \"amount\": {\"mass\": {\"value\": 221.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-[2-(1-adamantyl)ethyl]-3-[3-hydroxy-3-(4-pyridyl)propyl]-1-pentylurea\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m8_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfite\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydrogencarbonate\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred for one hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooling\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The reaction mixture was cooled with ice again\"}, {\"type\": \"STIRRING\", \"details\": \"the whole was stirred for 15 minutes\", \"duration\": {\"value\": 15.0, \"units\": \"MINUTE\"}}, {\"type\": \"WASH\", \"details\": \"the organic layer was washed with a saturated aqueous sodium sulfite solution (5 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfite\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layer was dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was evaporated under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"titled compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 87.3, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 87.8}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 87.7}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c2ae446310ef408ba53016b0c5f36377",
    "procedure_text": "To a stirred solution of 2-(3-fluoro-4-(methylsulfonylmethyl)phenyl)propanoic acid (68 mg, 0.231 mmol) and (1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine (60 mg, 0.231 mmol) in THF (1.8 mL) were added O-(1H-Benzotriazol-1-yl)-N,N,N\u2032,N\u2032-tetramethyluronium tetrafluorborat (73 mg, 0.231 mmol), 1-hydroxybenzotriazole (30 mg, 0.231 mmol) and N-ethyldiisopropylamine (0.078 mL, 0.462 mmol). The reaction mixture was stirred for 48 h at room temperature, concentrated in vacuo and the residue was purified by CC (eluent: ethyl acetate/cyclohexane (3:2)) to give N-[[2-(3-Chlorophenyl)-5-(trifluoromethyl)-2H-pyrazol-3-yl]-methyl]-2-[3-fluoro-4-(methylsulfonyl-methyl)-phenyl]-propionamide (83 mg, 69%).",
    "reference_string": "{\"inputs\": {\"m1_m2_m6_m3_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(3-fluoro-4-(methylsulfonylmethyl)phenyl)propanoic acid\"}], \"amount\": {\"mass\": {\"value\": 68.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine\"}], \"amount\": {\"mass\": {\"value\": 60.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"O-(1H-Benzotriazol-1-yl)-N,N,N\\u2032,N\\u2032-tetramethyluronium tetrafluorborat\"}], \"amount\": {\"mass\": {\"value\": 73.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-hydroxybenzotriazole\"}], \"amount\": {\"mass\": {\"value\": 30.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-ethyldiisopropylamine\"}], \"amount\": {\"volume\": {\"value\": 0.078, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 1.8, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred for 48 h at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was purified by CC (eluent: ethyl acetate/cyclohexane (3:2))\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate cyclohexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 48.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-[[2-(3-Chlorophenyl)-5-(trifluoromethyl)-2H-pyrazol-3-yl]-methyl]-2-[3-fluoro-4-(methylsulfonyl-methyl)-phenyl]-propionamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 83.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 69.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 69.4}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-1a1dd00f509044da995cd59ed83b6dc2",
    "procedure_text": "Similar procedure as described in example 131 was used, starting from (1-chloro-5-methoxy-isoquinolin-3-yl)-(5-methyl-1H-pyrazol-3-yl)-amine and thiophene-3-boronic acid to give (5-methyl-1H-pyrazol-3-yl)-(1-thiophen-3-yl-5-methoxy-isoquinolin-3-yl)-amine. LC-MS m/e 337(MH+).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(1-chloro-5-methoxy-isoquinolin-3-yl)-(5-methyl-1H-pyrazol-3-yl)-amine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"thiophene-3-boronic acid\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(5-methyl-1H-pyrazol-3-yl)-(1-thiophen-3-yl-5-methoxy-isoquinolin-3-yl)-amine\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-7f45d1040ba5436893ba3729611625b6",
    "procedure_text": "To a solution of 2-chloro-5-(2-chloroethylamino)-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide (WO 99/29661) (0.2 g) and N,N-diisopropylethylamine (0.27 ml) in ethanol (5 ml) was added sodium iodide (0.08 g) and 2-methoxyethylamine (0.11 g). The reaction vessel was sealed and the reaction mixture heated at 90\u00b0 C. for 15 h before concentration under reduced pressure. The residue was partitioned between ethyl acetate and sodium hydrogencarbonate solution, and the aqueous phase extracted with additional ethyl acetate. The combined organic phases were dried (MgSO4) and concentrated under reduced pressure. The residue was purified by NPHPLC (eluting with 0-25% ethanol in dichloromethane) to afford 5-(N-(2-methoxyethyl)-2-aminoethyl)amino-2-chloro-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide as a semi-solid. This was converted to the hydrochloride salt by stirring with 4M HCl in dioxane and concentrated under reduced pressure to leave the title compound as a white solid (0.085 g).",
    "reference_string": "{\"inputs\": {\"m1_m2_m5_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloro-5-(2-chloroethylamino)-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide\"}], \"amount\": {\"mass\": {\"value\": 0.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-diisopropylethylamine\"}], \"amount\": {\"volume\": {\"value\": 0.27, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium iodide\"}], \"amount\": {\"mass\": {\"value\": 0.08, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-methoxyethylamine\"}], \"amount\": {\"mass\": {\"value\": 0.11, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 90.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The reaction vessel was sealed\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was partitioned between ethyl acetate and sodium hydrogencarbonate solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydrogencarbonate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"the aqueous phase extracted with additional ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic phases were dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by NPHPLC (eluting with 0-25% ethanol in dichloromethane)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-(N-(2-methoxyethyl)-2-aminoethyl)amino-2-chloro-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide\"}], \"texture\": {\"type\": \"SEMI_SOLID\", \"details\": \"semi-solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-32b09cbbb31745a0b6f7d73ea045b67e",
    "procedure_text": "To a solution of N-[3-(3-amidinophenyl)-2-(E)-propenyl]-N-[3-carbamoyl-4-[1-(4,5-dihydro-3H-pyrrol-2-yl)piperidin-4-yloxy]phenyl]methanesulfonamide dihydrochloride (0.29 g) obtained in example 99(b) in a mixture of dichloromethane (3 ml) and acetonitrile (3 ml) were added successively 4-nitrophenyl acetate (0.09 g) and triethylamine (0.26 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature for 4 hours. After stirring, to the reaction mixture was added dichloromethane, and the organic layer was washed successively with a 0.5N aqueous sodium hydroxide solution and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of dichloromethane and methanol (50:0\u02dc47:3). The solid obtained was dissolved in water and then lyophilized to afford the title compound (0.16 g, yield: 58%) as a pale yellow amorphous solid.",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-nitrophenyl acetate\"}], \"amount\": {\"mass\": {\"value\": 0.09, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 0.26, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-[3-(3-amidinophenyl)-2-(E)-propenyl]-N-[3-carbamoyl-4-[1-(4,5-dihydro-3H-pyrrol-2-yl)piperidin-4-yloxy]phenyl]methanesulfonamide dihydrochloride\"}], \"amount\": {\"mass\": {\"value\": 0.29, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"with stirring under ice-\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooling\"}, {\"type\": \"STIRRING\", \"details\": \"the resulting mixture was stirred at room temperature for 4 hours\", \"duration\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"STIRRING\", \"details\": \"After stirring, to the reaction mixture\"}, {\"type\": \"WASH\", \"details\": \"the organic layer was washed successively with a 0.5N aqueous sodium hydroxide solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium chloride\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue obtained\"}, {\"type\": \"CUSTOM\", \"details\": \"was purified by chromatography on a silica gel column\"}, {\"type\": \"CUSTOM\", \"details\": \"The solid obtained\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.16, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 58.0}}], \"isolated_color\": \"pale yellow amorphous\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d65053ea7503467ab1c0b6176704454c",
    "procedure_text": "A small screw cap test tube was charged with 2-tert-Butyl-5-methyl-2H-pyrazole-3-carboxylic acid [4-(3-hydroxymethylene-2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-amide (as prepared in Example 65, 100 mg, 0.225 mmol) and THF (2 mL). To the resulting solution was added 4-(4-methyl-piperazin-1-yl)-phenylamine (47 mg, 0.25 mmol), and the mixture was stirred for 24 h at 65\u00b0 C. Subsequently, the reaction mixture was cooled to room temperature. Hexanes were added to the reaction mixture. The solid precipitate that formed was washed with \u02dc1 mL of i-prOH yielding 42% (59 mg, 0.0955 mmol) of the title compound.",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-tert-Butyl-5-methyl-2H-pyrazole-3-carboxylic acid [4-(3-hydroxymethylene-2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-amide\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(4-methyl-piperazin-1-yl)-phenylamine\"}], \"amount\": {\"mass\": {\"value\": 47.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Hexanes\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 65.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred for 24 h at 65\\u00b0 C\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"A small screw cap test tube\"}, {\"type\": \"TEMPERATURE\", \"details\": \"Subsequently, the reaction mixture was cooled to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The solid precipitate that formed\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 24.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 0.0955, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 59.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 42.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 42.4}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e1ceeb8e0c9940f089fb81cd067fbcc5",
    "procedure_text": "Using an analogous procedure to that described in Example 25, 3-(1-tert-butoxycarbonylpiperidin-4-yloxy)-4-methoxybenzoic acid was reacted with N-(3-amino-4-methylphenyl)-3-morpholinobenzamide to give N-[2-methyl-5-(3-morpholinobenzamido)phenyl]-3-(1-tert-butoxycarbonylpiperidin-4-yloxy)-4-methoxybenzamide in 48% yield and that product was treated with trifluoroacetic acid. The reaction mixture was evaporated, water (40 ml) was added to the residue and the mixture was basified by the addition of 1N aqueous sodium hydroxide solution. The water was decanted and the residue was titurated under diethyl ether. The resultant solid was isolated, dissolved in water (30 ml) and basified by the addition of potassium carbonate. The precipitate was isolated and dried. There was thus obtained the title compound in 26% yield; NMR Spectrum: (DMSOd6) 1.48 (m, 2H), 1.9 (m, 2H), 2.18 (s, 3H), 3.19 (m, 4H), 3.75 (m, 4H), 3.83 (s, 3H), 4.39 (m, 1H), 7.1 (m, 2H), 7.21 (d, 1H), 7.4 (m, 3H), 7.6 (m, 3H), 7.79 (s, 1H), 9.72 (s, 1H), 10.1 (s, 1H); Mass Spectrum: M+H+ 545.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(1-tert-butoxycarbonylpiperidin-4-yloxy)-4-methoxybenzoic acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(3-amino-4-methylphenyl)-3-morpholinobenzamide\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-[2-methyl-5-(3-morpholinobenzamido)phenyl]-3-(1-tert-butoxycarbonylpiperidin-4-yloxy)-4-methoxybenzamide\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 48.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-59da4fe92784490793d710adc4254d62",
    "procedure_text": "With additional reference to FIG. 2, the aluminum-containing residue or char from the kiln is introduced into a batch or continuous reactor 26 as by conveyor 29 and mixed therein with a sulfuric acid solution, as from vessel 27, heated water, as from vessel 28, direct steam, as from source 30 and preferably using thermal energy recovered from the hot gases in steam boiler 22 by various heat exchangers associated with vessels 27 and 28 and steam source 30 in a manner well-known to those of ordinary skill in the art. Mixing of the components in the reactor 26 is preferably accomplished by mechanical agitation, as by stirrer 32. The temperature of the aqueous streams entering the reactor 26 is preferably in the range of from about 80\u00b0 C. to about 100\u00b0 C. Reaction of the components in the reactor is believed to produce an aqueous solution of aluminum sulfate by the reaction:",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aluminum\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sulfuric acid\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"is introduced into a batch or continuous reactor 26 as by conveyor 29\"}, {\"type\": \"ADDITION\", \"details\": \"mixed\"}, {\"type\": \"CUSTOM\", \"details\": \"as from vessel 28, direct steam, as from source 30 and preferably using thermal\"}, {\"type\": \"CUSTOM\", \"details\": \"energy recovered from the hot gases in steam boiler 22\"}, {\"type\": \"TEMPERATURE\", \"details\": \"by various heat exchangers\"}, {\"type\": \"ADDITION\", \"details\": \"Mixing of the components in the reactor 26\"}, {\"type\": \"CUSTOM\", \"details\": \"is preferably accomplished by mechanical agitation, as by stirrer\"}, {\"type\": \"CUSTOM\", \"details\": \"is preferably in the range of from about 80\\u00b0 C. to about 100\\u00b0 C\"}, {\"type\": \"CUSTOM\", \"details\": \"Reaction of the components in the reactor\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aluminum sulfate\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-961d5d32bcab4ca9ab16422c7d2bda17",
    "procedure_text": "To a stirring solution of 1-Boc-isonipecotic acid (15.26 g, 66.55 mmol) in methanol (135 mL) was added sodium methoxide (3.8 g, 66.8 mmol). After stirring for 1 h, the solvent was removed in vacuo. A portion of the residue (8.92 g, 35.5 mmol) was suspended in dichloromethane (95 mL) and oxalyl chloride (4 mL, 45 mmol) was added, followed by a couple of drops of N,N-dimethylformamide. After stirring for 1 h, the solvent was removed in vacuo. The residue was suspended in dichloromethane (45 mL) and added to a solution of 2-amino-N-(5-chloropyridin-2-yl)-5-iodobenzamide (8.86 g, 23.7 mmol), N,N-diisopropylethylamine (5 mL, 28 mmol), and 4-(N,N-dimethylamino)pyridine (0.33 g, 2.7 mmol) in dichloromethane (50 mL). After stirring 19 h, the reaction mixture was partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The organic phase was dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was slurried in diethyl ether and filtered to give 8.6 g (62%) of a pink solid.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"oxalyl chloride\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 95.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m9\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"reaction_role\": \"CATALYST\"}]}, \"m1_m7_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-Boc-isonipecotic acid\"}], \"amount\": {\"mass\": {\"value\": 15.26, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium methoxide\"}], \"amount\": {\"mass\": {\"value\": 3.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 135.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5_m6_m10_m11\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-amino-N-(5-chloropyridin-2-yl)-5-iodobenzamide\"}], \"amount\": {\"mass\": {\"value\": 8.86, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-diisopropylethylamine\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(N,N-dimethylamino)pyridine\"}], \"amount\": {\"mass\": {\"value\": 0.33, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"residue\"}], \"amount\": {\"mass\": {\"value\": 8.92, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring for 1 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the solvent was removed in vacuo\"}, {\"type\": \"STIRRING\", \"details\": \"After stirring for 1 h\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was removed in vacuo\"}, {\"type\": \"STIRRING\", \"details\": \"After stirring 19 h\", \"duration\": {\"value\": 19.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture was partitioned between dichloromethane and saturated aqueous sodium bicarbonate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic phase was dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pink solid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 8.6, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 62.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 62.0}}], \"isolated_color\": \"pink\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a4fc48a1bda84bb7b99a4df6caaf3503",
    "procedure_text": "A flame-dried 2 L Parr hydrogenation bottle was charged with (Z)-methyl 3-(4-amino-3,5-dimethylphenyl)-2-(benzyloxycarbonyl)acrylate (84.5 g, 239 mmoles), dichloromethane (300 mL), and methanol (300 mL). The bottle was swirled so that a light brown suspension was formed. The mixture was degassed using a flow of nitrogen for 30 min. To this was quickly added (\u2212)-1,2-bis((2R,5R)-2,5-diethylphospholano)-benzene(cyclooctadiene) rhodium (I) tetrafluoroborate ([(2R,5R)-Et-DuPhosRh]BF4) (2.11 g, 3.20 mmoles). The bottle was immediately attached to a Parr Hydrogenator. After 5 cycles of hydrogen (60 psi) and vacuum, the bottle was pressurized to 65 psi and the suspension was agitated at room temperature for 16 h. The reaction had become homogeneous. The reaction mixture was concentrated, and the resulting residue purified by flash chromatography (silica gel, 1:9 ethyl acetate/dichloromethane) to give 82.9 g (98%). 1H-NMR (DMSO-d6) \u03b4 2.04 (s, 6H), 2.65 (dd, J=13.4, 9.8 Hz, 1H), 2.82 (dd, J=13.7, 5.2Hz, 1H), 3.62 (s, 3H), 4.15-4.10 (m, 1H), 4.41 (s, 2H), 5.00 (s, 2H), 6.68 (s, 2H), 7.37-7.28 (m, 5H), 7.70 (d, J=7.9 Hz, 1H); 13C-NMR (DMSO-d6) \u03b4 17.7, 35.9, 51.7, 56.1, 65.3, 120.4, 124.0, 127.5, 127.7, 128.2, 128.3, 136.9, 142.6, 155.9, 172.5.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrogen\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(Z)-methyl 3-(4-amino-3,5-dimethylphenyl)-2-(benzyloxycarbonyl)acrylate\"}], \"amount\": {\"mass\": {\"value\": 84.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 300.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 300.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(\\u2212)-1,2-bis((2R,5R)-2,5-diethylphospholano)-benzene(cyclooctadiene) rhodium (I) tetrafluoroborate\"}], \"amount\": {\"mass\": {\"value\": 2.11, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the suspension was agitated at room temperature for 16 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"was formed\"}, {\"type\": \"CUSTOM\", \"details\": \"The mixture was degassed\"}, {\"type\": \"CUSTOM\", \"details\": \"for 30 min\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}}, {\"type\": \"CONCENTRATION\", \"details\": \"The reaction mixture was concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"the resulting residue purified by flash chromatography (silica gel, 1:9 ethyl acetate/dichloromethane)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"to give 82.9 g (98%)\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-e8662bcafb114d57af3f8470c654d7d1",
    "procedure_text": "2-(4-Nitrophenyl)-5-(4-trifluoromethylphenyl)-N-(2-thiazolyl)-imidazole-4-carboxamide (0.42 g) obtained in Example 49 was hydrogenated in methanol using palladium. The catalyst was filtered off and the residue was concentrated to give 2-(4-aminophenyl)-5-(4-trifluoromethylphenyl)-N-(2-thiazolyl)imidazole-4-carboxamide (0.25 g), melting point 175-177\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(4-Nitrophenyl)-5-(4-trifluoromethylphenyl)-N-(2-thiazolyl)-imidazole-4-carboxamide\"}], \"amount\": {\"mass\": {\"value\": 0.42, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"palladium\"}], \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The catalyst was filtered off\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the residue was concentrated\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(4-aminophenyl)-5-(4-trifluoromethylphenyl)-N-(2-thiazolyl)imidazole-4-carboxamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.25, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-766ce82f828640b7993ab55ffc140d5d",
    "procedure_text": "4.8 g (0.03 mole) of 3-diazooxindole and 2.4 g (0.035 mole) of the propiolamide are taken up in benzene (250 ml) and refluxed overnight under a stream of nitrogen. The light tan precipitates that form are filtered off and dried in a vacuum oven for 4 hours. Yield: 4.4 g. Additional refluxing of the filtrate gives 900 mg of product. Total yield: 5.3 g (77.4%).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-diazooxindole\"}], \"amount\": {\"mass\": {\"value\": 4.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"propiolamide\"}], \"amount\": {\"mass\": {\"value\": 2.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzene\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"refluxed overnight under a stream of nitrogen\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The light tan precipitates that form\"}, {\"type\": \"FILTRATION\", \"details\": \"are filtered off\"}, {\"type\": \"CUSTOM\", \"details\": \"dried in a vacuum oven for 4 hours\", \"duration\": {\"value\": 4.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"Additional refluxing of the filtrate\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 900.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-41e2392d557742a881815db385dda39f",
    "procedure_text": "6.15 g (18.1 mmoles) of (2-Chloro-5-methyl-pyridin-3-yl)-[2-(4-fluoro-phenyl)-1-pyridin-4-yl-ethylidene]-amine are dissolved in 100 mL of dimethylformamide under nitrogen. 6.4 g of DABCO (56 mmoles) and 610 mg of bis(triphenylphosphine)palladium dichloride are subsequently added to the reaction mixture which is stirred for 5 hours at 120\u00b0 C. The cooled reaction mixture is then poured into water and extracted with ethyl acetate. The organic phase is washed with water and dried over magnesium sulfate. The solid residue after concentration is recrystallized into ethyl acetate to afford 5.3 g of 3-(4-Fluoro-phenyl)-6-methyl-2-pyridin-4-yl-1H-pyrrolo[3,2-b]pyridine as a yellowish solid.",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2-Chloro-5-methyl-pyridin-3-yl)-[2-(4-fluoro-phenyl)-1-pyridin-4-yl-ethylidene]-amine\"}], \"amount\": {\"mass\": {\"value\": 6.15, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DABCO\"}], \"amount\": {\"mass\": {\"value\": 6.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"bis(triphenylphosphine)palladium dichloride\"}], \"amount\": {\"mass\": {\"value\": 610.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 120.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"is stirred for 5 hours at 120\\u00b0 C\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The cooled reaction mixture\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic phase is washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"The solid residue after concentration\"}, {\"type\": \"CUSTOM\", \"details\": \"is recrystallized into ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 5.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(4-Fluoro-phenyl)-6-methyl-2-pyridin-4-yl-1H-pyrrolo[3,2-b]pyridine\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 5.3, \"units\": \"GRAM\"}}}], \"isolated_color\": \"yellowish\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-87296c1b6aa84989981ba95ca63b397d",
    "procedure_text": "To a solution of 3-(2\u2032-fluoro-4-hydroxy-5\u2032-methoxybiphenyl-2-yl)-2,2-dimethylpropanenitrile (136 mg), ethyl 3-cyclopropyl-3-(3-(hydroxymethyl)phenyl)propanoate (136 mg) and tributylphosphine (0.22 mL) in toluene (5.0 mL) was added 1,1\u2032-(azodicarbonyl)dipiperidine (225 mg), and the mixture was stirred at room temperature for 1 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (203 mg) as a colorless oil.",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3_m5_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(2\\u2032-fluoro-4-hydroxy-5\\u2032-methoxybiphenyl-2-yl)-2,2-dimethylpropanenitrile\"}], \"amount\": {\"mass\": {\"value\": 136.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 3-cyclopropyl-3-(3-(hydroxymethyl)phenyl)propanoate\"}], \"amount\": {\"mass\": {\"value\": 136.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tributylphosphine\"}], \"amount\": {\"volume\": {\"value\": 0.22, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,1\\u2032-(azodicarbonyl)dipiperidine\"}], \"amount\": {\"mass\": {\"value\": 225.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at room temperature for 1 hr\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"the mixture was extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The extract was washed with saturated brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The solvent was evaporated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was purified by silica gel column chromatography (ethyl acetate/hexane)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 203.0, \"units\": \"MILLIGRAM\"}}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-490d59e178904e6ab2a12fd830b922e7",
    "procedure_text": "A stirred solution of N-(1-buten-1-yl)piperidine [Mannich, D.; Ber. 1936, 69, 2106] (4.2 g, 29.9 mmol) and acrylonitrile (2.1 g, 38.8 mmol) in acetonitrile (25 mL) was heated at reflux for 18 hours. Acetic acid and water (10 mL, 1:1) was added and the reaction was heated an additional 4 hours. The acetonitrile was removed in vacuo and the residue was taken up in ether (60 mL). The ether was washed with water (2\u00d740 mL), saturated sodium bicarbonate/water (40 mL), dried (magnesium sulfate), concentrated in vacuo and then distilled to afford the title compound (1.6 g, 42%) as a colorless liquid. bp 132\u00b0 C. (18 mm);",
    "reference_string": "{\"inputs\": {\"m1_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(1-buten-1-yl)piperidine\"}], \"amount\": {\"mass\": {\"value\": 4.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acrylonitrile\"}], \"amount\": {\"mass\": {\"value\": 2.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Acetic acid\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"at reflux for 18 hours\", \"duration\": {\"value\": 18.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"the reaction was heated an additional 4 hours\", \"duration\": {\"value\": 4.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The acetonitrile was removed in vacuo\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The ether was washed with water (2\\u00d740 mL), saturated sodium bicarbonate/water (40 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate water\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (magnesium sulfate)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"DISTILLATION\", \"details\": \"distilled\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.6, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 42.0}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"liquid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-8f2a4e9863b0401ab2a22d6a422b98fb",
    "procedure_text": "A mixture of 100 g. (0.615 mole) of 4-chloro-1,2-diethylpyrazolidine and 200 ml. of concentrated ammonium hydroxide in a closed steel chamber was heated at 150\u00b0 C. for approximately 36 hours. The cooled reaction mixture was extracted with isopropyl ether, the aqueous layer saturated with potassium carbonate and continuously extracted with chloroform for six hours. The dried chloroform extract (sodium sulfate) was concentrated at reduced pressure and the residue distilled at 113\u00b0-115\u00b0 C./40 mm. to give 40.5 g. (45.5%) of product.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-chloro-1,2-diethylpyrazolidine\"}], \"amount\": {\"moles\": {\"value\": 0.615, \"units\": \"MOLE\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium hydroxide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"steel\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"A mixture of 100 g\"}, {\"type\": \"CUSTOM\", \"details\": \"The cooled reaction mixture\"}, {\"type\": \"EXTRACTION\", \"details\": \"was extracted with isopropyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isopropyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"the aqueous layer saturated with potassium carbonate and continuously extracted with chloroform for six hours\", \"duration\": {\"value\": 6.0, \"units\": \"HOUR\"}, \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The dried chloroform extract (sodium sulfate)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"was concentrated at reduced pressure\"}, {\"type\": \"DISTILLATION\", \"details\": \"the residue distilled at 113\\u00b0-115\\u00b0 C./40 mm\"}, {\"type\": \"CUSTOM\", \"details\": \"to give 40.5 g\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-a90a9029da164bd38de7d8f4864cfc8f",
    "procedure_text": "A round bottom flask (fitted with glass inlet and outlet) was charged with 60 ml DCM followed by Et2Zn (60 mmol, 60 ml, 1 M in hexane) and cooled to 0\u00b0 C. TFA (60 mmol, 4.62 ml dissolved in 30 ml DCM) was slowly added to the stirring solution. The reaction was stirred for 20 minutes, followed by addition of CH2I2 (60 mmol, 4.83 ml dissolved in 20 ml DCM) and 20 minutes further stirring. At this point, (1-Difluoromethyl-vinyloxy)-triisopropyl-silane DCM (11.98 mmol, 3 g dissolved in 30 mL) was added and the mixture warmed to rt and stirred for 1 hour. The reaction was then quenched with 1 N HCl and water and extracted two times with hexane. The combined organics were washed with saturated NaHCO3 and dried over sodium sulfate and concentrated, providing (1-difluoromethyl-cyclopropoxy)-triisopropyl-silane which was used crude in the next reaction.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(1-Difluoromethyl-vinyloxy)-triisopropyl-silane DCM\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Et2Zn\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TFA\"}], \"amount\": {\"volume\": {\"value\": 4.62, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2I2\"}], \"amount\": {\"volume\": {\"value\": 4.83, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction was stirred for 20 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"A round bottom flask (fitted with glass inlet and outlet)\"}, {\"type\": \"STIRRING\", \"details\": \"further stirring\"}, {\"type\": \"TEMPERATURE\", \"details\": \"the mixture warmed to rt\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"STIRRING\", \"details\": \"stirred for 1 hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The reaction was then quenched with 1 N HCl and water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted two times with hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined organics were washed with saturated NaHCO3\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 20.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(1-difluoromethyl-cyclopropoxy)-triisopropyl-silane\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fcf99e8a98824f6ab2a801c98bca4c2f",
    "procedure_text": "To a solution of (R,E)-N-(4-bromo-2,5-difluorobenzylidene)-2-methylpropane-2-sulfinamide (7.2 g, 22.2 mmol in CH2Cl2 (200 mL) cooled to 0\u00b0 C. (water/ice bath) under nitrogen, was added 3M methyl magnesium bromide (29.6 mL, 89 mmol) in Et2O. Reaction mixture allowed to stir for 5 hours at 0\u00b0 C. then quenched with the slow addition of a saturated solution of NH4Cl. Aqueous mixture adjusted to pH 8 with HCl (1 N) and extracted with DCM. Organic phases combined, washed with water, brine, dried (Na2SO4), filtered and concentrated onto silica gel. Silica gel column chromatography (EtOAc/Heptane 30 to 100%) provided (R)\u2014N\u2014((S)-1-(4-bromo-2,5-difluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (6.86 g, 20.2 mmol, 91% yield) LCMS m/z 342.1 (M+H)+, Rt 0.96 min.",
    "reference_string": "{\"inputs\": {\"m4_m0\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc Heptane\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl magnesium bromide\"}], \"amount\": {\"volume\": {\"value\": 29.6, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Et2O\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m5_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R,E)-N-(4-bromo-2,5-difluorobenzylidene)-2-methylpropane-2-sulfinamide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water ice\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"to stir for 5 hours at 0\\u00b0 C.\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Reaction mixture\"}, {\"type\": \"CUSTOM\", \"details\": \"then quenched with the slow addition of a saturated solution of NH4Cl\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH4Cl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with DCM\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with water, brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated onto silica gel\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 5.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)\\u2014N\\u2014((S)-1-(4-bromo-2,5-difluorophenyl)ethyl)-2-methylpropane-2-sulfinamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 20.2, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 6.86, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 91.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-02812345a39e44c38a6902f52ba32a6d",
    "procedure_text": "To a solution of N-(3-fluoro-4-(7-hydroxyquinolin-4-yloxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (200 mg, 0.413 mmol) in DMA (3 mL) was added 3-(7-hydroxy-5-azaspiro[2.4]heptane-5-yl)propyl methanesulfonate (154 mg, 0.619 mmol) and Cs2CO3 (268 mg, 0.826 mmol). The reaction was then stirred at rt for 40 hrs. The solvent was removed and the residue was partioned between saturated NaHCO3 aqueous solution (10 mL) and CHCl3 (25 mL). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by a silica gel column chromatography (100:15:1(v/v/v) EtOAc/CH3OH/Et3N) to afford a pale yellow solid (192 mg, 73%).",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(3-fluoro-4-(7-hydroxyquinolin-4-yloxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(7-hydroxy-5-azaspiro[2.4]heptane-5-yl)propyl methanesulfonate\"}], \"amount\": {\"mass\": {\"value\": 154.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Cs2CO3\"}], \"amount\": {\"mass\": {\"value\": 268.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMA\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction was then stirred at rt for 40 hrs\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The solvent was removed\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layer was dried over anhydrous Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by a silica gel column chromatography (100:15:1(v/v/v) EtOAc/CH3OH/Et3N)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc CH3OH Et3N\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 40.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 192.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 73.0}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0d1d7bbf4d9a4d268251ff6820b0155c",
    "procedure_text": "Bromine (35 mL, 660 mmol) was added dropwise to a suspension of isatoic anhydride (100 g, 610 mmol) in 1.6 L water at 50\u00b0 C. This temperature was maintained for an additional 2 hours. After cooling the solution to room temperature, the solid was filtered and washed twice with water and twice with acetone, yielding 125.6 g (85%) 6-bromo-1H-benzo[d][1,3]oxazine-2,4-dione as a pink solid.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Bromine\"}], \"amount\": {\"volume\": {\"value\": 35.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isatoic anhydride\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 1.6, \"units\": \"LITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"This temperature was maintained for an additional 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"the solid was filtered\"}, {\"type\": \"WASH\", \"details\": \"washed twice with water and twice with acetone\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-bromo-1H-benzo[d][1,3]oxazine-2,4-dione\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 125.6, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 85.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 85.1}}], \"isolated_color\": \"pink\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-14ae98291cd8462d965cf4ead4204460",
    "procedure_text": "Following the procedure of Example 97, the reaction of imidazole with 2-chloro-6-ethyl-4-(3-nitrobenzylamino)-thieno-[2,3-d]-pyrimidine gives 2-(imidazol-1-yl)-6-ethyl-4-(3-nitrobenzylamino)-thieno-[2,3-d]-pyrimidine.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"imidazole\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloro-6-ethyl-4-(3-nitrobenzylamino)-thieno-[2,3-d]-pyrimidine\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(imidazol-1-yl)-6-ethyl-4-(3-nitrobenzylamino)-thieno-[2,3-d]-pyrimidine\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-833350f76b0d45298dfe49e0745dfc35",
    "procedure_text": "3.9 g (35 mmol) of potassium tert-butoxide were added a little at a time to 5 g (33 mmol) of methyl hydroxybenzoate in 200 ml of dimethylformamide. After about 15 min, a further 7.3 g (33 mmol) of 2-(bromomethyl)naphthalene were added and the reaction mixture was heated to 100\u00b0 C. for about 3 h. The reaction mixture was then poured into ice-water and the product was extracted with ethyl acetate. The organic phase was dried and concentrated under reduced pressure. 8.4 g (88%) of the product were obtained.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium tert-butoxide\"}], \"amount\": {\"mass\": {\"value\": 3.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl hydroxybenzoate\"}], \"amount\": {\"mass\": {\"value\": 5.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(bromomethyl)naphthalene\"}], \"amount\": {\"mass\": {\"value\": 7.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"the product was extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The organic phase was dried\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 8.4, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 88.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d53036dfe1bf44709a5d0b4d0c5b6496",
    "procedure_text": "This compound was prepared from cyanamide, ethyl-[2-(4-isothiocyanato-phenoxy)-ethyl]-carbamic acid tert-butyl ester of Example 129 and 2-bromo-1-(2,3-dihydro-benzofuran-5-yl)ethanone (from Example 141) following a procedure similar to Example 132. Mass spectrum (ES) MH+=425.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cyanamide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl-[2-(4-isothiocyanato-phenoxy)-ethyl]-carbamic acid tert-butyl ester\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-bromo-1-(2,3-dihydro-benzofuran-5-yl)ethanone\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-9362d9d8bb4f40b3b1cd41825c183e44",
    "procedure_text": "A 500 mL, 3-necked, round-bottomed flask is charged with 150 mL of water, 21.4 g (0.1 mole) of 5-methoxy-2,4-dinitrophenol and 1.0 g of 10% palladium on carbon catalyst. The reaction is stirred under a nitrogen atmosphere for 3 to 4 minutes. The stirred reaction mixture is heated to 55\u00b0 C. and hydrogen gas is sparged below the surface of the reaction mixture. After 10 minutes, 19.8 g (0.2 mole) of concentrated HCl is added through the condenser while hydrogenation is continued for 4 hours. The catalyst is removed by filtration and the filtrate is passed into a solution consisting of 0.5 g of stannous chloride dihydrate and 25 mL of concentrated HCl. This solution is then saturated with dry HCl gas and charged to a 600 mL 5 Hastalloy B autoclave. The reactor is heated to 150\u00b0 C. for 18 hours and cooled to 25\u00b0 C. The resulting product is isolated by filtration and dried under nitrogen to yield 19.7 g (90% yield) of crude 4,6-diaminoresorcinol dihydrochloride.",
    "reference_string": "{\"inputs\": {\"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"mass\": {\"value\": 19.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m4_m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-methoxy-2,4-dinitrophenol\"}], \"amount\": {\"mass\": {\"value\": 21.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"palladium on carbon\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 55.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction is stirred under a nitrogen atmosphere for 3 to 4 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The stirred reaction mixture\"}, {\"type\": \"CUSTOM\", \"details\": \"hydrogen gas is sparged below the surface of the reaction mixture\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrogen\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WAIT\", \"details\": \"After 10 minutes\", \"duration\": {\"value\": 10.0, \"units\": \"MINUTE\"}}, {\"type\": \"WAIT\", \"details\": \"is continued for 4 hours\", \"duration\": {\"value\": 4.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The catalyst is removed by filtration\"}, {\"type\": \"ADDITION\", \"details\": \"saturated with dry HCl gas and charged to a 600 mL 5 Hastalloy B autoclave\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5\"}], \"amount\": {\"volume\": {\"value\": 600.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"The reactor is heated to 150\\u00b0 C. for 18 hours\", \"duration\": {\"value\": 18.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 150.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"cooled to 25\\u00b0 C\", \"temperature\": {\"setpoint\": {\"value\": 25.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The resulting product is isolated by filtration\"}, {\"type\": \"CUSTOM\", \"details\": \"dried under nitrogen\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.5, \"precision\": 0.5, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4,6-diaminoresorcinol dihydrochloride\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 19.7, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 90.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-559e759ffd6d4bc2a937377745952339",
    "procedure_text": "In the same apparatus and procedures as EXAMPLE 1, 37.5 g (0.153 mole) of 3-(ethylphenyl)-1,1-dichloro-1-silabutane and 100 \u03bcl of 1% chloroplatinic acid solution in isopropanol were placed and then 5 g (0.061 mole) of 1,5-hexadiene was added dropwise for 5 min. The solution was reacted for 14 hours at reflux under the dry nitrogen atmosphere. Vacuum distillation gave 24.6 g (190\u00b0-192\u00b0 C./0.03 mmHg) of bis[{2-(ethylphenyl)propyl}dichlorosilyl]hexane in 69.8% yield.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroplatinic acid\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(ethylphenyl)-1,1-dichloro-1-silabutane\"}], \"amount\": {\"mass\": {\"value\": 37.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,5-hexadiene\"}], \"amount\": {\"mass\": {\"value\": 5.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isopropanol\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The solution was reacted for 14 hours\", \"duration\": {\"value\": 14.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"at reflux under the dry nitrogen atmosphere\"}, {\"type\": \"DISTILLATION\", \"details\": \"Vacuum distillation\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"bis[{2-(ethylphenyl)propyl}dichlorosilyl]hexane\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 24.6, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 69.8}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 69.9}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e470237bd19f428ea490dd1eebd4b825",
    "procedure_text": "(4R,5S)-1-(3,4-diaminophenyl)-3-(4-methoxybenzyl)-5-(4-methoxyphenyl)-4-methylimidazolidin-2-one (0.105 g, 0.24 mmol) obtained from step F was dissolved in 3 mL triethyl orthoformate. The reaction was stirred for 30 minutes at reflux. After cooling the solvent was removed and the remains were dissolved in 8 mL trifluoroacetic acid. The reaction was stirred for 14 hours at ambient temperature. The TFA was removed under reduced pressure and the residue was re-dissolved in 20 mL of buffer (pH7) and three times extracted by means of 25 mL dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtrated and the solvent was removed under reduced pressure. The final product was purified by FPLC using a chloroform-methanol gradient (0\u219210%). The product elutes at about 5% methanol.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(4R,5S)-1-(3,4-diaminophenyl)-3-(4-methoxybenzyl)-5-(4-methoxyphenyl)-4-methylimidazolidin-2-one\"}], \"amount\": {\"mass\": {\"value\": 0.105, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethyl orthoformate\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction was stirred for 30 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"at reflux\"}, {\"type\": \"TEMPERATURE\", \"details\": \"After cooling the solvent\"}, {\"type\": \"CUSTOM\", \"details\": \"was removed\"}, {\"type\": \"DISSOLUTION\", \"details\": \"the remains were dissolved in 8 mL trifluoroacetic acid\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trifluoroacetic acid\"}], \"amount\": {\"volume\": {\"value\": 8.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"STIRRING\", \"details\": \"The reaction was stirred for 14 hours at ambient temperature\", \"duration\": {\"value\": 14.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The TFA was removed under reduced pressure\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TFA\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISSOLUTION\", \"details\": \"the residue was re-dissolved in 20 mL of buffer (pH7) and three times\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted by means of 25 mL dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined organic layers were washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtrated\"}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was removed under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The final product was purified by FPLC\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"final product\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-80a5cf3f10e94968af72a483feed1a6a",
    "procedure_text": "To a solution of N-(azepan-3-yl)-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (0.6 g, 1.6 mmol), in DMF (10 mL) was added EDCI (335 mg, 1.9 mmol), HOBt (250 mg, 1.9 mmol), 2-(3,5-dichlorophenylamino)acetic acid (342 mg, 1.6 mmol) and DIEA (301 mg, 2.3 mmol) at 0\u00b0 C. The reaction mixture was stirred at rt overnight, diluted with EtOAc (100 mL) and washed with water (50 mL). The organic layer was dried over Na2SO4 and evaporated in vacuo to give the crude compound that purified by column chromatography (silica gel, gradient MeOH in CH2Cl2) to afford the titled compound (800 mg, 87%). LC-MS: m/z [M+1]=587.",
    "reference_string": "{\"inputs\": {\"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m6_m2_m3_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(azepan-3-yl)-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine\"}], \"amount\": {\"mass\": {\"value\": 0.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EDCI\"}], \"amount\": {\"mass\": {\"value\": 335.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HOBt\"}], \"amount\": {\"mass\": {\"value\": 250.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(3,5-dichlorophenylamino)acetic acid\"}], \"amount\": {\"mass\": {\"value\": 342.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DIEA\"}], \"amount\": {\"mass\": {\"value\": 301.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred at rt overnight\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WASH\", \"details\": \"washed with water (50 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layer was dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"to give the crude compound\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude compound\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"that purified by column chromatography (silica gel, gradient MeOH in CH2Cl2)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"titled compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 800.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 87.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-bd61aafcf9a147cc823c14e5e2decd5b",
    "procedure_text": "A mixture of (S)-tert-butyl (1-(N-(3-(5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl)propylsulfonamido)-3-methyl-1-oxobutan-2-yl)carbamate (50 mg, 0.07 mmol) and a saturated solution of HCl in EtOAc (2 mL) was stirred at rt for 2 h. The mixture was concentrated in vacuo to afford the title compound as a white solid (49 mg, 99%). The title compound was characterized by LC-MS as shown below:",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(S)-tert-butyl (1-(N-(3-(5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl)propylsulfonamido)-3-methyl-1-oxobutan-2-yl)carbamate\"}], \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"The mixture was concentrated in vacuo\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 49.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 99.0}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3dc684b374ab44179724569d62cddcdc",
    "procedure_text": "A solution of n-tridecanoic acid (Sigma Chemical Co, 12.5 g), 2,4,5-trichlorophenol (11.5 g), and N,N'-dicyclohexylcarbodiimide (12.0 g) in methylene chloride (650 ml) is stirred at room temperature for 16 hours. The reaction mixture is then filtered and dried in vacuo to give 2,4,5-trichlorophenyl tridecanoate (22 g). The material is purified by column chromatography over silica gel (Woelm) using toluene as the eluent. Fractions are monitored by TLC using a shortwave UV light for detection. Fractions containing the purified product are pooled and concentrated in vacuo to dryness.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-tridecanoic acid\"}], \"amount\": {\"mass\": {\"value\": 12.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,4,5-trichlorophenol\"}], \"amount\": {\"mass\": {\"value\": 11.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N'-dicyclohexylcarbodiimide\"}], \"amount\": {\"mass\": {\"value\": 12.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 650.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The reaction mixture is then filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"dried in vacuo\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,4,5-trichlorophenyl tridecanoate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 22.0, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4c84ba239e85480abbb28e64f1d775f6",
    "procedure_text": "Pyridinium p-toluenesulfonate (1.8 mg, 7 \u03bcmol) was added to a solution of (8E,12E,14E)-7-acetoxy-3-(t-butyldimethylsiloxy)-6,21-dihydroxy-6,10,12,16,20-pentamethyl-18,19-epoxytricosa-8,12,14-trien-11-olide (44 mg, 67 \u03bcmol) obtained in Example B10 and ethyl vinyl ether (98 mg, 1.35 mmol) in methylene chloride (3 mL), and the mixture was stirred at room temperature for 18 hours. The reaction solution was diluted with ethyl acetate, washed with distilled water and brine, dried over anhydrous magnesium sulfate and evaporated. The resulting residue was purified by silica gel column chromatography (Kanto silica gel 60N, 40 to 50 \u03bcm, ethyl acetate:hexane=1:4 to 1:2) to obtain the title compound (35 mg, 66%) as a colorless oil.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pyridinium p-toluenesulfonate\"}], \"amount\": {\"mass\": {\"value\": 1.8, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(8E,12E,14E)-7-acetoxy-3-(t-butyldimethylsiloxy)-6,21-dihydroxy-6,10,12,16,20-pentamethyl-18,19-epoxytricosa-8,12,14-trien-11-olide\"}], \"amount\": {\"mass\": {\"value\": 44.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl vinyl ether\"}], \"amount\": {\"mass\": {\"value\": 98.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at room temperature for 18 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WASH\", \"details\": \"washed with distilled water and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"The resulting residue was purified by silica gel column chromatography (Kanto silica gel 60N, 40 to 50 \\u03bcm, ethyl acetate:hexane=1:4 to 1:2)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 18.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 35.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 66.0}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e01391e70a804871a7ea396c6d1ed86d",
    "procedure_text": "69.1 g (0.5 mol) of p-hydroxybenzoic acid were dissolved in 400 ml of ethanol and treated with a solution of 56.1 g (1 mol) of KOH in 250 ml of water. The reaction batch was heated under reflux. While so doing 74.26 g (0.55 mol) of 4-bromo-1-butene were slowly added dropwise. After 5 hours the ethanol was removed on a rotary evaporator. The aqueous phase was brought to a pH value of 10 with NaOH and extracted repeatedly with diethyl ether. The aqueous phase was poured into a mixture of 46 ml of concentrated HCl and 500 ml of ice-water. The separated acid was filtered off, washed with a small amount of water and recrystallized from methanol/water (2:1). After drying at 60\u00b0 C. in a water-jet vacuum 40 g of 4-(but-3-enyloxy)-benzoic acid remained behind as a white powder; phase succession (\u00b0 C.): C 120 N 141 I.",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"p-hydroxybenzoic acid\"}], \"amount\": {\"mass\": {\"value\": 69.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 400.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"KOH\"}], \"amount\": {\"mass\": {\"value\": 56.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-bromo-1-butene\"}], \"amount\": {\"mass\": {\"value\": 74.26, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The reaction batch was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"under reflux\"}, {\"type\": \"ADDITION\", \"details\": \"were slowly added dropwise\"}, {\"type\": \"CUSTOM\", \"details\": \"After 5 hours the ethanol was removed on a rotary evaporator\", \"duration\": {\"value\": 5.0, \"units\": \"HOUR\"}, \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted repeatedly with diethyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"The aqueous phase was poured into a mixture of 46 ml of concentrated HCl and 500 ml of ice-water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 46.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"The separated acid was filtered off\"}, {\"type\": \"WASH\", \"details\": \"washed with a small amount of water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"recrystallized from methanol/water (2:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"After drying at 60\\u00b0 C. in a water-jet vacuum 40 g of 4-(but-3-enyloxy)-benzoic acid\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(but-3-enyloxy)-benzoic acid\"}], \"amount\": {\"mass\": {\"value\": 40.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}]}, \"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(But-3-enyloxy)-benzoic acid\"}]}]}]}"
  },
  {
    "reaction_id": "ord-f718c57d28cc41cb84c76a30f3485482",
    "procedure_text": "Methyl 4-bromobenzoate (0.96 g, 4.46 mmol) was added to a mixture of 1-naphthaleneboronic acid (0.73 g, 4.25 mmol) and sodium carbonate (0.075 g, 7.08 mmol) in toluene (30 mL), ethanol (6 mL) and water (12 mL). The resultant solution was purged with nitrogen for 10 minutes before tetrakis(triphenylphosphine) palladium(0) (0.10 g, 0.09 mmol) was added. The reaction mixture was heated to reflux for 65 hours. The solution was cooled to ambient temperature, then filtered through a pad of Celite, which was subsequently rinsed with ethyl acetate. The combined filtrate was diluted to 100 mL with water/ethyl acetate (1:1, v/v). The aqueous layer was extracted with ethyl acetate, and the combined extracts were dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness to yield the title compound as a gold oil (1.09 g). This material was used without further purification in the next step.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m5_m6_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Methyl 4-bromobenzoate\"}], \"amount\": {\"mass\": {\"value\": 0.96, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-naphthaleneboronic acid\"}], \"amount\": {\"mass\": {\"value\": 0.73, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium carbonate\"}], \"amount\": {\"mass\": {\"value\": 0.075, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 6.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 12.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"resultant solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrakis(triphenylphosphine) palladium(0)\"}], \"amount\": {\"mass\": {\"value\": 0.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The reaction mixture was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to reflux for 65 hours\", \"duration\": {\"value\": 65.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"filtered through a pad of Celite, which\"}, {\"type\": \"WASH\", \"details\": \"was subsequently rinsed with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"The combined filtrate was diluted to 100 mL with water/ethyl acetate (1:1\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The aqueous layer was extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"the combined extracts were dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated to dryness\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.09, \"units\": \"GRAM\"}}}], \"isolated_color\": \"gold\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-870d116c69d04e60bb832d34c8b07902",
    "procedure_text": "A solution of 82 (250 mg, 0.43 mmol) in DCM (5 mL) was treated with TFA (1 mL) at room temperature. After 2 h, the reaction mixture was concentrated, diluted with EtOAc, washed with 1N aqueous NaOH and brine, dried over Na2SO4, filtered and concentrated to afford 210 mg (100%) of 83 as a light yellow wax. The product was used without further purification.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"82\"}], \"amount\": {\"mass\": {\"value\": 250.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TFA\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"the reaction mixture was concentrated\"}, {\"type\": \"ADDITION\", \"details\": \"diluted with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with 1N aqueous NaOH and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"83\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 210.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 100.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-191c9910a17e4385b9f1d7eca4509ab0",
    "procedure_text": "(4-Chloro-3-hydroxy-phenyl)-acetic acid ethyl ester was reacted with 2-fluoro-5-nitrobenzaldehyde as outlined in Example 21, Step 5, to provide [4-chloro-3-(2-formyl-4-nitro-phenoxy)-phenyl]-acetic acid ethyl ester.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(4-Chloro-3-hydroxy-phenyl)-acetic acid ethyl ester\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-fluoro-5-nitrobenzaldehyde\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"[4-chloro-3-(2-formyl-4-nitro-phenoxy)-phenyl]-acetic acid ethyl ester\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-05240dce866d4786a7afb779990a33ef",
    "procedure_text": "To the solution of 2-(5-{4-bromo-3-[(tert-butoxycarbonyl-methyl-amino)-methyl]-phenyl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (142 mg, 0.27 mmol) and 2-{5-[3-Methoxycarbonyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester (125 mg, 0.25 mmol) in 1,2-dimethoxyether (2.3 ml) and water (0.7 ml) was added sodium bicarbonate (63 mg, 0.75 mmol), followed by Pd(PPh3)4 (12 mg) and PdCl2(dppf)CH2Cl2 (12 mg). The mixture was heated at 80\u00b0 C. for 20 hours. The mixture was diluted with EtOAc, and was washed with water and brine, and was dried with sodium sulfate. Concentration and purification by flash column chromatography (hexanes/EtOAc) gave 4,4\u2032-bis-[2-(1-tert-butoxycarbonyl-pyrrolidin-2-yl)-3H-imidazol-4-yl]-biphenyl-2-[(tert-butoxycarbonyl-methyl-amino)-2\u2032-carboxylic acid dimethyl ester (82 mg). m/z: 826 (M+H)+, 413.6 (M+2H)+/2.",
    "reference_string": "{\"inputs\": {\"m1_m2_m5_m6_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(5-{4-bromo-3-[(tert-butoxycarbonyl-methyl-amino)-methyl]-phenyl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester\"}], \"amount\": {\"mass\": {\"value\": 142.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-{5-[3-Methoxycarbonyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester\"}], \"amount\": {\"mass\": {\"value\": 125.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"amount\": {\"mass\": {\"value\": 63.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,2-dimethoxyether\"}], \"amount\": {\"volume\": {\"value\": 2.3, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 0.7, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"PdCl2(dppf)CH2Cl2\"}], \"amount\": {\"mass\": {\"value\": 12.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd(PPh3)4\"}], \"amount\": {\"mass\": {\"value\": 12.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 80.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WASH\", \"details\": \"was washed with water and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"was dried with sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"Concentration and purification by flash column chromatography (hexanes/EtOAc)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4,4\\u2032-bis-[2-(1-tert-butoxycarbonyl-pyrrolidin-2-yl)-3H-imidazol-4-yl]-biphenyl\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 82.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-9e27475635f240bfa6158d208f924b5b",
    "procedure_text": "Acetyl chloride (1.71 mL, 24.0 mmol) was added to a solution of crude tert-butyl 4-{2-[(1S)-1-aminoethyl]-4-chlorophenyl}piperidine-1-carboxylate (3-7) (5.42 g of \u02dc70% pure material, 11.2 mmol) and triethylamine (6.69 mL, 48.0 mmol) in dichloromethane at approximately 0\u00b0 C. After 2 h, the reaction mixture was poured into water and extracted three times with ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel (gradient elution; 35 to 50% ethyl acetate/hexanes as eluent) provided tert-butyl 4-{2-[(1S)-1-(acetylamino)ethyl]-4-chlorophenyl}piperidine-1-carboxylate (3-8) as a pale yellow foam (4.1 g). If desired, traces of the minor R-enantiomer could be removed using preparative chiral high pressure liquid chromatography on CHIRALPAK AD Phase, (7.5% ethano/heptanes as eluent) to give in order of elution: R-enantiomer as a colorless solid followed by the S-enantiomer as a colorless solid.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Acetyl chloride\"}], \"amount\": {\"volume\": {\"value\": 1.71, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl 4-{2-[(1S)-1-aminoethyl]-4-chlorophenyl}piperidine-1-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 5.42, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 6.69, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted three times with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined organic extracts were washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification of the crude residue by flash chromatography on silica gel (gradient elution; 35 to 50% ethyl acetate/hexanes as eluent)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude residue\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl 4-{2-[(1S)-1-(acetylamino)ethyl]-4-chlorophenyl}piperidine-1-carboxylate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 4.1, \"units\": \"GRAM\"}}}], \"isolated_color\": \"pale yellow\", \"texture\": {\"type\": \"FOAM\", \"details\": \"foam\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-bbf0ce0686a94d969f9dad2854850836",
    "procedure_text": "To a solution of ethyl trifluoroacetate (0.12 mL, 1.00 mmol) in 4.0 mL of dry tetrahydrofuran was added anhydrous hydrazine (25 mL, 0.80 mmol), and the resultant solution was heated to reflux. After one hour, the solution was cooled to room temperature and was added via syringe to a mixture of the amidine hydrochloride (283 mg, 1.00 mmol) from Step B and solid sodium hydroxide (50 mg) in 3.0 mL of dry tetrahydrofuran. The reaction mixture was warmed at reflux for 3 h, and was then allowed to cool to room temperature overnight. The precipitated solids were removed by filtration, and the filtrate was concentrated under reduced pressure to afford a yellow gum, which was partitioned between ethyl acetate and water. The organic layer was washed with saturated aqueous brine, dried (magnesium sulfate) and concentrated under reduced pressure to provide the crude product, which was purified by flash chromatography (silica gel, step gradient, 0 to 20% ethyl acetate/hexanes) to afford the product as a white solid. LC/MS 339.8 (M+1).",
    "reference_string": "{\"inputs\": {\"m1_m6_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl trifluoroacetate\"}], \"amount\": {\"volume\": {\"value\": 0.12, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrazine\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4_m5_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"amidine hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 283.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"resultant solution\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The reaction mixture was warmed\"}, {\"type\": \"TEMPERATURE\", \"details\": \"at reflux for 3 h\", \"duration\": {\"value\": 3.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"to cool to room temperature overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The precipitated solids were removed by filtration\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate was concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"to afford a yellow gum, which\"}, {\"type\": \"CUSTOM\", \"details\": \"was partitioned between ethyl acetate and water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with saturated aqueous brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (magnesium sulfate)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"to provide the crude product, which\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"was purified by flash chromatography (silica gel, step gradient, 0 to 20% ethyl acetate/hexanes)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-ee3b9f20858c42269d47e19521e262ea",
    "procedure_text": "A stream of CH3SH gas was bubbled through a solution of 162 mg (3 mmoles) of sodium methoxide in 5 ml of methanol for 10 min. with cooling in an ice bath. The solution was allowed to warm to room temperature and 332 mg (1 mmole) of Z-8-bromo-2-(2,2-dimethylcyclopropanecarboxamido)-2-octenoic acid was added. The solution was heated under reflux for 30 min. in a N2 atmosphere. Most of the methanol was evaporated under reduced pressure, the residue 2.5 N HCl. The precipitated oil was extracted with ether (3\u00d7). The ether extracts were washed with water, saturated brine and dried over MgSO4. Removal of the ether under reduced pressure gave a colorless oil that crystallized upon standing. It was recrystallized from ether-hexane to give 178 mg of Z-2-(2,2-dimethylcyclopropanecarboxamido)-8-methylthio-2-octenoic acid, m.p. 82\u00b0-84\u00b0 C. Homogeneous by TLC (toluene-acetic acid, 4:1). The NMR spectrum was in accord with the desired structure",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N2\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH3SH\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium methoxide\"}], \"amount\": {\"mass\": {\"value\": 162.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Z-8-bromo-2-(2,2-dimethylcyclopropanecarboxamido)-2-octenoic acid\"}], \"amount\": {\"mass\": {\"value\": 332.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"with cooling in an ice bath\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The solution was heated\"}, {\"type\": \"CUSTOM\", \"details\": \"Most of the methanol was evaporated under reduced pressure\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The precipitated oil was extracted with ether (3\\u00d7)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The ether extracts were washed with water, saturated brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Removal of the ether under reduced pressure\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"gave a colorless oil that\"}, {\"type\": \"CUSTOM\", \"details\": \"crystallized\"}, {\"type\": \"CUSTOM\", \"details\": \"It was recrystallized from ether-hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether-hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Z-2-(2,2-dimethylcyclopropanecarboxamido)-8-methylthio-2-octenoic acid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 178.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-70807f05420e4b6193a45e87f1d14980",
    "procedure_text": "A mixture prepared from 4-[[(dimethylamino)methylene]amino]-3-pyridinol N,N-dimethylcarbamate (7.4 g), trifluoroacetic acid (30 mL) and water (15 mL) was refluxed for a half hour. The reaction mixture was concentrated, filtered over a pad of basic alumina (CH2Cl2, 30% ethyl acetate/CH2Cl2, ethyl acetate), recrystallized from methanol/diethyl ether, and dried under high vacuum and refluxing ethanol to yield 4.97 g of microcrystals, m.p. 159\u00b0-160\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-[[(dimethylamino)methylene]amino]-3-pyridinol N,N-dimethylcarbamate\"}], \"amount\": {\"mass\": {\"value\": 7.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trifluoroacetic acid\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"was refluxed for a half hour\"}, {\"type\": \"CONCENTRATION\", \"details\": \"The reaction mixture was concentrated\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered over a pad of basic alumina (CH2Cl2, 30% ethyl acetate/CH2Cl2, ethyl acetate)\"}, {\"type\": \"CUSTOM\", \"details\": \"recrystallized from methanol/diethyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol diethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried under high vacuum\"}, {\"type\": \"TEMPERATURE\", \"details\": \"refluxing ethanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"to yield 4.97 g of microcrystals, m.p. 159\\u00b0-160\\u00b0 C.\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-67b75ec7c6eb4356a43db8564c15da3d",
    "procedure_text": "Prepared analogously to Compound 3C substituting 7-amino-4-bromo-5-fluoro-2-methyl-2,3-dihydro-1H-isoindol-1-one (Compound 31D) for 2-amino-5-bromo-N,N-diethylbenzamide (Compound 3D). 1H NMR (CDCl3, 400 MHz): \u03b4 7.75 (d, J=4.5 Hz, 2H), 6.41 (d, J=13.1 Hz, 1H), 4.46 (t, J=6.1 Hz, 2H), 4.39 (s, 2H), 3.70 (t, J=5.6 Hz, 2H), 3.17 (s, 3H), 2.20-2.09 (m, 3H). MS (ESI): m/z=305.14 [M+H]+. UPLC: tR=0.95 min (UPLC-TOF: polar\u20143 min).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Compound 3D\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Compound 3C\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Compound 31D\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-amino-5-bromo-N,N-diethylbenzamide\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"tR=0.95 min (UPLC-TOF: polar\\u20143 min)\", \"duration\": {\"value\": 3.0, \"units\": \"MINUTE\"}}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-87df338463cf4ff9b0aae301b7d4b2ce",
    "procedure_text": "3,5-Dimethyl-indene-2-carboxylic acid (37.3 g) is converted to its acid chloride by treatment with thionyl chloride (580 ml). Excess thionyl chloride is distilled off. Yield 40.5 g, 99%.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,5-Dimethyl-indene-2-carboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 37.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acid chloride\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"thionyl chloride\"}], \"amount\": {\"volume\": {\"value\": 580.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"DISTILLATION\", \"details\": \"Excess thionyl chloride is distilled off\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"thionyl chloride\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-53ca006744664867a2a8c57b2bbd5abc",
    "procedure_text": "Procedure B was performed using N-(4-Chloro-3-iodophenyl)-6-(trifluoromethyl)-2-methylpyridine-3-carboxamide (88 mg, 0.2 mmol) with 2-pyridylzinc bromide (1 mL, 0.5 mmol, 0.5 M in THF). Purified by silica gel chromatography (10-80% ethyl acetate/hexanes) to yield N-(4-chloro-3-(pyridin-2-yl)phenyl)-6-(trifluoromethyl)-2-methylpyridine-3-carboxamide as a yellow solid: TLC Rf=0.28 (35% ethyl acetate/hexanes); TLC Rf=0.28 (35% ethyl acetate/hexanes); 1H NMR (CDCl3, 400 MHz) 8.88 (bs, 1H), 8.41 (d, 1H), 7.96 (dd, 1H), 7.74 (m, 4H), 7.52 (d, 1H), 7.22 (m, 1H), 2.75 (s, 3H); MS (Q1) 392 (M)+.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(4-Chloro-3-iodophenyl)-6-(trifluoromethyl)-2-methylpyridine-3-carboxamide\"}], \"amount\": {\"mass\": {\"value\": 88.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-pyridylzinc bromide\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Purified by silica gel chromatography (10-80% ethyl acetate/hexanes)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(4-chloro-3-(pyridin-2-yl)phenyl)-6-(trifluoromethyl)-2-methylpyridine-3-carboxamide\"}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-34836e8a1f394dddabf709136239da58",
    "procedure_text": "3-Cyanobenzenesulfonyl chloride (53 mg, 0.26 mmol) was added to a solution of 3-chloro-6,7,8,9-tetrahydro-5H-dipyrido[2,3-b;3\u2032,4\u2032-d]pyrrole (50 mg, 0.24 mmol) in pyridine (2 mL), and the reaction was stirred overnight at room temperature. The reaction mixture was added to water (20 mL), and the resulting precipitate was filtered and dried under vacuum to provide 40 (68 mg, 76% yield) as a yellow solid. LC-MS (M+H=373, obsd.=373).",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-Cyanobenzenesulfonyl chloride\"}], \"amount\": {\"mass\": {\"value\": 53.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-chloro-6,7,8,9-tetrahydro-5H-dipyrido[2,3-b;3\\u2032,4\\u2032-d]pyrrole\"}], \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction was stirred overnight at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"the resulting precipitate was filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"dried under vacuum\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"40\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 68.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 76.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 76.0}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-ffaa0625b1ec4a96828ad553d5a135fb",
    "procedure_text": "In the same reaction apparatus as in Example 4, a mixture of 50 g of 25% fuming sulfuric acid and 1.75 g of sodium borofluoride was dropwise added to 250 g of tetrahydrofuran at 0\u00b0 C. over a period of one hour, and they were subjected to reaction at the same temperature for 2 hours. The final conversion was 66%, and the reaction system was solidified to form a wax-like mass. This product was then treated similarly to Example 4 to obtain colorless PTMG. The results of the analyses of the thus obtained PTMG and the catalytic efficiency \u03b1 were as shown in Table 1.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sulfuric acid\"}], \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium borofluoride\"}], \"amount\": {\"mass\": {\"value\": 1.75, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"mass\": {\"value\": 250.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"they were subjected to reaction at the same temperature for 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"to form a wax-like mass\"}, {\"type\": \"ADDITION\", \"details\": \"This product was then treated similarly to Example 4\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"PTMG\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b387fcd5fdd241abbd2cbb1f1ff13196",
    "procedure_text": "To a suspension of 6-((2-chloropyrimidin-4-yl)amino)hexahydrofuro[3,2-b]furan-3-ol (354 mg, 1.37 mmol) in n-BuOH (3 mL) were added 1-methyl-1H-pyrazol-4-amine (220 mg, 1.65 mmol) and DIPEA (531 mg, 4.11 mmol). Then the mixture was stirred under nitrogen atmosphere at 150\u00b0 C. overnight and concentrated in vacuo. The residue was purified by silica gel column chromatography (DCM/MeOH (v/v)=30/1) to give the title compound as a yellow solid (120 mg, 22%).",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-((2-chloropyrimidin-4-yl)amino)hexahydrofuro[3,2-b]furan-3-ol\"}], \"amount\": {\"mass\": {\"value\": 354.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-BuOH\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-methyl-1H-pyrazol-4-amine\"}], \"amount\": {\"mass\": {\"value\": 220.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DIPEA\"}], \"amount\": {\"mass\": {\"value\": 531.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 150.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"Then the mixture was stirred under nitrogen atmosphere at 150\\u00b0 C. overnight\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by silica gel column chromatography (DCM/MeOH (v/v)=30/1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM MeOH\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 120.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 22.0}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-77d3f67b18c24bbbb40cb6af408abb5a",
    "procedure_text": "To (R)-benzyl 3-oxocyclopentanecarboxylate (0.5 g, 2.291 mmol) in ethanol (5 mL) were sequentially added sodium cyanide (0.281 g, 5.73 mmol), ammonium carbonate (2.86 g, 29.8 mmol) and water (5.00 mL) at room temperature. The contents were heated at 70\u00b0 C. (oil bath temp.) for 3 hours. The reaction mixture was kept at room temperature for 10 min. Solid separates out. The solid was filtered and washed with water (3\u00d710 mL). The solid was dried overnight under vacuum (155 mg, 0.538 mmol, 23.5%) and used as such for the subsequent step without further purification. MS (ESI) m/z 289.16 (M+H)+",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-benzyl 3-oxocyclopentanecarboxylate\"}], \"amount\": {\"mass\": {\"value\": 0.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium cyanide\"}], \"amount\": {\"mass\": {\"value\": 0.281, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium carbonate\"}], \"amount\": {\"mass\": {\"value\": 2.86, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 70.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"at room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"The solid was filtered\"}, {\"type\": \"WASH\", \"details\": \"washed with water (3\\u00d710 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The solid was dried overnight under vacuum (155 mg, 0.538 mmol, 23.5%)\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"without further purification\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 10.0, \"units\": \"MINUTE\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-d15ef826fc124f6eb8736dfd9be215f1",
    "procedure_text": "79.7 mg (0.2 mmol) of 5'-[(2-naphthyl)methylthio]-5'-deoxythymidine [prepared as described in step (a) above] were dried by azeotropic distillation with pyridine and then dissolved in 2.5 ml of tetrahydrofuran. 0.084 ml (0.48 mmol) of diisopropylamine was then added to the solution. 54 \u03bcl (0.24 mmol) of 2-cyanoethyl N,N-diisopropylchlorophosphoramidite were then added dropwise to the mixture, under an atmosphere of argon. The resulting mixture was stirred at room temperature for 1.75 hours under the same atmosphere. The tetrahydrofuran was then removed by distillation under reduced pressure. The resulting residue was dissolved in 10 ml of ethyl acetate, and the solution was washed with a 10% w/v aqueous solution of sodium carbonate and with a saturated aqueous solution of sodium chloride, in that order. The solution was then dried over anhydrous magnesium sulfate, after which the solvent was distilled off under reduced pressure, and the residue was purified by column chromatography through 10 g of silica gel (70-230 mesh), using ethyl acetate as the eluent, to give 67 mg (yield 56%) of the title compound as a foam-like substance.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-cyanoethyl N,N-diisopropylchlorophosphoramidite\"}], \"amount\": {\"volume\": {\"value\": 54.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5'-[(2-naphthyl)methylthio]-5'-deoxythymidine\"}], \"amount\": {\"mass\": {\"value\": 79.7, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 2.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropylamine\"}], \"amount\": {\"volume\": {\"value\": 0.084, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The resulting mixture was stirred at room temperature for 1.75 hours under the same atmosphere\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The tetrahydrofuran was then removed by distillation under reduced pressure\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISSOLUTION\", \"details\": \"The resulting residue was dissolved in 10 ml of ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"the solution was washed with a 10% w/v aqueous solution of sodium carbonate and with a saturated aqueous solution of sodium chloride, in that order\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium carbonate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The solution was then dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"after which the solvent was distilled off under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was purified by column chromatography through 10 g of silica gel (70-230 mesh)\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.75, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 67.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 56.0}}], \"texture\": {\"type\": \"FOAM\", \"details\": \"foam-like\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-50f09c057d634610aa68ce540db392a6",
    "procedure_text": "To a solution of 1.04 g (2.37 mmol) of {[4-(4-fluorobutoxy)-benzenesulfonyl]-(4-methoxybenzyl)-amino}-acetic acid methyl ester in 15 ml of THF, 15 ml of MeOH and 7 ml of H2O, 0.24 g (5.7 mmol) of LiOH mono-hydrate is added in portions and the mixture is stirred for 30 min at 0\u20135\u00b0 C. After stirring for additional 3.5 h, the reaction mixture is acidified with 1 N aqueous HCl and extracted with AcOEt. The combined extracts are washed with brine, dried over MgSO4 and concentrated under reduced pressure to give ([4-(4-fluoro-butoxy)-benzenesulfonyl]-(4-methoxy-benzyl)-amino)-acetic acid; NMR (CDCl3): 1.86\u20131.96 (m, 4H), 3.79 (s, 3H), 3.90 (s, 2H), 4.08 (t, 2H, J=5.52 Hz), 4.38 (s, 2H), 4.48 (t, 1H, J=6.04 Hz), 4.55\u20134.65 (m, 1H), 6.84 (d, 2H, J=8.56 Hz), 6.98 (d, 2H, J=9.08 Hz), 7.14 (d, 2H, J=8.56 Hz), 7.81 (d, 2H, J=9.08 Hz).",
    "reference_string": "{\"inputs\": {\"m1_m4_m5_m6_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"{[4-(4-fluorobutoxy)-benzenesulfonyl]-(4-methoxybenzyl)-amino}-acetic acid methyl ester\"}], \"amount\": {\"mass\": {\"value\": 1.04, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"LiOH mono-hydrate\"}], \"amount\": {\"mass\": {\"value\": 0.24, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"amount\": {\"volume\": {\"value\": 7.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture is stirred for 30 min at 0\\u20135\\u00b0 C\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"After stirring for additional 3.5 h\", \"duration\": {\"value\": 3.5, \"units\": \"HOUR\"}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with AcOEt\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"AcOEt\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined extracts are washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"([4-(4-fluoro-butoxy)-benzenesulfonyl]-(4-methoxy-benzyl)-amino)-acetic acid\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-1f7b4d946cf540da806a36f0e3f9640b",
    "procedure_text": "A suspension of 2-oxo-1,2-dihydroquinoline-3-carboxylic acid 1-1 (500 mg, 2.64 mmol, 1 equiv, prepared by the method of Marsais, F; Godard, A.; Queguiner, G. J. Heterocyclic Chem. 1989, 26,1589) and 1,2-phenylenediamine (344 mg, 3.18 mmol, 1.20 equiv) in polyphosphoric acid (15 mL) was heated under argon at 200\u00b0 C. for 4.5 h. The hot reaction mixture was poured over ice (200 g), and the resulting mixture was allowed to stand overnight (20 h). The precipitate was filtered, washed with water (200 mL), and air dried to give the title compound as an olive-colored solid. 1H NMR (400 MHz, (CD3)2SO) \u03b4 12.58 (s, 1H), 9.15 (s, 1H), 7.94 (br d, 1H, J=7.5 Hz), 7.78 (dd, 2H, J=5.6, 2.9), 7.63 (br t, 1H, J=7.5 Hz), 7.42 (br d, 1H, J=8.2 Hz), 7.33 (dd, 2H, J=5.9, 2.9), 7.25 (br t, 1H, J=7.5 Hz); HRMS (electrospray FT/ICR) calculated for C16H12N3O [M+H]+ 262.0975, found 262.0981; anal. calcd for C16H11N3O+1.10 H3PO4+0.75 H2O: C, 50.23; H, 4.16; N, 10.98. Found C, 50.24; H, 4.21; N, 10.93.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,2-phenylenediamine\"}], \"amount\": {\"mass\": {\"value\": 344.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"polyphosphoric acid\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-oxo-1,2-dihydroquinoline-3-carboxylic acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Heterocyclic\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"prepared by the method of Marsais, F\"}, {\"type\": \"CUSTOM\", \"details\": \"(20 h)\", \"duration\": {\"value\": 20.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"The precipitate was filtered\"}, {\"type\": \"WASH\", \"details\": \"washed with water (200 mL), and air\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"isolated_color\": \"olive-colored\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-861a5fc947844df6a5feefe5ab58db20",
    "procedure_text": "N\u2032-(3,4-Dichlorophenyl)hydrazine was liberated from its hydrochloride (10.0 g, 46.8 mmol) by partitioning the solid between diluted Na2CO3 solution (10 ml saturated solution and 40 ml water) and AcOEt. The aqueous layer was extracted two more times with AcOEt, the organic extracts were dried (Na2SO4), the solvent was removed in vacuo, and the residue was taken up in dry toluene (100 ml). To this solution acetic anhydride (4.78 g, 46.8 mmol) was slowly added, and the reaction mixture was stirred at room temperature for 15 min. Light petroleum (50 ml) was added, the mixture was cooled in the refrigerator (\u221220\u00b0 C.), and the resulting crystals were collected on a sintered glass funnel and washed with cold petrol ether. Recrystallization from MeOH yielded (V) (8.30 g, 81%) as shiny white crystals, mp 179-182\u00b0 C. (lit. 168-171\u00b0 C.). TLC CHCl3/MeOH 9:1.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Light petroleum\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N\\u2032-(3,4-Dichlorophenyl)hydrazine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 10.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic anhydride\"}], \"amount\": {\"mass\": {\"value\": 4.78, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture was stirred at room temperature for 15 min\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"by partitioning the solid between diluted Na2CO3 solution (10 ml saturated solution and 40 ml water) and AcOEt\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2CO3\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"AcOEt\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The aqueous layer was extracted two more times with AcOEt\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"AcOEt\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"the organic extracts were dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was removed in vacuo\"}, {\"type\": \"TEMPERATURE\", \"details\": \"the mixture was cooled in the refrigerator (\\u221220\\u00b0 C.)\", \"temperature\": {\"setpoint\": {\"value\": -20.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"the resulting crystals were collected on a sintered glass funnel\"}, {\"type\": \"WASH\", \"details\": \"washed with cold petrol ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"petrol ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Recrystallization from MeOH\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{\"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 8.3, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 81.0}}], \"isolated_color\": \"shiny white\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c41c172606ab4c4f887573ae6fdcce6d",
    "procedure_text": "Into 2.0 liters of ethanol, previously saturated with ammonia, was added 378 g of 2-cyano-3,3-bis(ethylthio)propenenitrile. The mildly exothermic reaction warmed the mixture to 38\u00b0. The mixture was stirred at ambient temperature for 0.5 hour, then heated under reflux (ca 55\u00b0) for 1.0 hour. The mixture was concentrated by distillation of about one liter of solvent. To the mixture was added 1.5 liters of ice-water and the mixture was cooled in an ice-bath. The yellow solid was isolated and dried to give 223 g of 3-amino-2-cyano-3-(ethylthio)propenenitrile, m.p. 180\u00b0-182\u00b0. The nmr spectrum was consistent with the assigned structure.",
    "reference_string": "{\"inputs\": {\"m3_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonia\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-cyano-3,3-bis(ethylthio)propenenitrile\"}], \"amount\": {\"mass\": {\"value\": 378.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"LITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at ambient temperature for 0.5 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The mildly exothermic reaction\"}, {\"type\": \"TEMPERATURE\", \"details\": \"warmed the mixture to 38\\u00b0\"}, {\"type\": \"TEMPERATURE\", \"details\": \"heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"under reflux (ca 55\\u00b0) for 1.0 hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"CONCENTRATION\", \"details\": \"The mixture was concentrated by distillation of about one liter of solvent\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solvent\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"LITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"To the mixture was added 1.5 liters of ice-water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"amount\": {\"volume\": {\"value\": 1.5, \"units\": \"LITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"the mixture was cooled in an ice-bath\"}, {\"type\": \"CUSTOM\", \"details\": \"The yellow solid was isolated\"}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 0.5, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-amino-2-cyano-3-(ethylthio)propenenitrile\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 223.0, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-07d8eb95f8f440d49edfa421b09b5d09",
    "procedure_text": "To a cooled (5-6\u00b0 C.), stirred suspension of crude potassium 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carboxylate (21.9 g, 115 mmol) in dichloromethane (180 mL) containing N,N-dimethylformamide (2.5 mL, 32.3 mmol), is added, dropwise, oxalyl chloride (19.0 mL, 218 mmol) over a period of 10 minutes. The reaction is exothermic with gas evolution. After the addition, the ice-bath is removed and the reaction mixture stirred at room temperature. After 5 hours, the solution is added to a cooled, stirred (10-12\u00b0 C.) suspension of N,O-dimethylhydroxylamine hydrochloride (17.6 g, 180 mmol) in dichloromethane (80 mL) containing N,N-diisopropylethyamine (100 mL, 574 mmol). After 18 hours at room temperature, water (150 mL) is added. The two layers are separated. The organic layer is extracted with water (3\u00d7150 mL), and the organic layer dried over anhydrous sodium sulfate, filtered and concentrated under diminished pressure to give a brown solid which is recrystallized from ether (35 mL) to give 15.6 g (69%) of N-methoxy-N-methyl-5,6-dihydro-4H-pyrrolo[1,2-b]-pyrazole-2-carboxamide as a brown solid having HPLC purity, 91.3% (HPLC conditions described in Example 17).",
    "reference_string": "{\"inputs\": {\"m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,O-dimethylhydroxylamine hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 17.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 80.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 21.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 180.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 2.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-diisopropylethyamine\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"oxalyl chloride\"}], \"amount\": {\"volume\": {\"value\": 19.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 5.5, \"precision\": 0.5, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"is added\"}, {\"type\": \"ADDITION\", \"details\": \"After the addition\"}, {\"type\": \"CUSTOM\", \"details\": \"the ice-bath is removed\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"STIRRING\", \"details\": \"the reaction mixture stirred at room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"ADDITION\", \"details\": \"the solution is added to a cooled\"}, {\"type\": \"STIRRING\", \"details\": \"stirred\"}, {\"type\": \"WAIT\", \"details\": \"After 18 hours at room temperature\", \"duration\": {\"value\": 18.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The two layers are separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"The organic layer is extracted with water (3\\u00d7150 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"the organic layer dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under diminished pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a brown solid which\"}, {\"type\": \"CUSTOM\", \"details\": \"is recrystallized from ether (35 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"amount\": {\"volume\": {\"value\": 35.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 5.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-methoxy-N-methyl-5,6-dihydro-4H-pyrrolo[1,2-b]-pyrazole-2-carboxamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 15.6, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 69.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 69.5}}], \"isolated_color\": \"brown\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4215c71e68a3464d8800e1014729793f",
    "procedure_text": "A cooled (\u221278\u00b0 C.) solution of commercially available 3-bromo-2,4-dimethoxypyridine (1.390 g; 5.74 mmol) in anh. THF (70 ml), under nitrogen, was treated dropwise with a solution of 1.6 M n-BuLi in hexanes (3.60 ml; 5.74 mmol). The resulting solution was further stirred at \u221278\u00b0 C. for 15 min. A solution of ethyl 4-((tert-butylsulfinyl)imino)-2-methylbutanoate (1.290 g; 5.22 mmol) in anh. THF (5 ml) was then added to the cooled reaction mixture, and stirring at \u221278\u00b0 C. was continued for 30 min. The resulting reaction mixture was treated successively with aq. sat. NH4Cl (35 ml), Et2O (75 ml) and water (20 ml). The separated organic layer was then washed with brine (30 ml), dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH=30/1) afforded ethyl 4-(2,4-dimethoxypyridin-3-yl)-4-(1,1-dimethylethylsulfinamido)-2-methylbutanoate as a yellow oil. LC-MS (conditions B): tR=0.78 min. and [M+H]+: 386.68 g/mol; tR=0.80 min. and [M+H]+: 386.76 g/mol (mixture of diastereoisomers).",
    "reference_string": "{\"inputs\": {\"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-BuLi\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"amount\": {\"volume\": {\"value\": 3.6, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-bromo-2,4-dimethoxypyridine\"}], \"amount\": {\"mass\": {\"value\": 1.39, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 70.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5_m9_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH4Cl\"}], \"amount\": {\"volume\": {\"value\": 35.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Et2O\"}], \"amount\": {\"volume\": {\"value\": 75.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 4-((tert-butylsulfinyl)imino)-2-methylbutanoate\"}], \"amount\": {\"mass\": {\"value\": 1.29, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -78.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The resulting solution was further stirred at \\u221278\\u00b0 C. for 15 min\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"stirring at \\u221278\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": -78.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"WAIT\", \"details\": \"was continued for 30 min\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}}, {\"type\": \"CUSTOM\", \"details\": \"The resulting reaction mixture\"}, {\"type\": \"WASH\", \"details\": \"The separated organic layer was then washed with brine (30 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anh. MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated to dryness under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification by FC (DCM/MeOH=30/1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM MeOH\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 4-(2,4-dimethoxypyridin-3-yl)-4-(1,1-dimethylethylsulfinamido)-2-methylbutanoate\"}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-cd2cb52a429549f7a2c90d8c160c7f39",
    "procedure_text": "(R)-3-{4-[3-[3-(tert-Butyldimethylsilanyloxymethyl)-4-trifluoromethoxyphenyl]-1-(4-cyclohexylphenyl)ureidomethyl]benzoylamino}-2-hydroxypropionic acid (17 mg, 0.023 mmol) was dissolved in acetonitrile:water (9:1) (2 mL) and caesium fluoride (35 mg, 0.35 mmol) added. The reaction mixture was stirred at 80\u00b0 C. for 6 hours and additional amounts of caesium fluoride (35 mg) added. The mixture was stirred at 60\u00b0 C. overnight, concentrated in vacuo and diluted with ethyl acetate (10 mL) and water (5 mL). The organic phase was washed with water (3\u00d75 mL) and dried with magnesium sulphate and concentrated in vacuo. The residue was purified by preparative HPLC affording the title compound.",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-3-{4-[3-[3-(tert-Butyldimethylsilanyloxymethyl)-4-trifluoromethoxyphenyl]-1-(4-cyclohexylphenyl)ureidomethyl]benzoylamino}-2-hydroxypropionic acid\"}], \"amount\": {\"mass\": {\"value\": 17.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile water\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"caesium fluoride\"}], \"amount\": {\"mass\": {\"value\": 35.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"caesium fluoride\"}], \"amount\": {\"mass\": {\"value\": 35.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 80.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred at 80\\u00b0 C. for 6 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"The mixture was stirred at 60\\u00b0 C. overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"ADDITION\", \"details\": \"diluted with ethyl acetate (10 mL) and water (5 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic phase was washed with water (3\\u00d75 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried with magnesium sulphate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulphate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by preparative HPLC\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 6.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b221295cc29747928e2b5e4962a4d7fe",
    "procedure_text": "A solution of but-3-ynyl 4-methylbenzenesulfonate (2.0 mL) and piperazine (2.0 g) in EtOH (6 mL) was heated to reflux for 30 min. The mixture was concentrated, diluted with NaOH 2 M (8 mL) and extracted with Et2O (50 mL). Evaporation of the organic layer gave a 2:1 mixture of mono and bis-alkylated piperazine (450 mg) which was discarded. The aqueous layer was further extracted with DCM (100 mL) to give of 1-(but-3-ynyl)piperazine (640 mg).",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"but-3-ynyl 4-methylbenzenesulfonate\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"piperazine\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOH\"}], \"amount\": {\"volume\": {\"value\": 6.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"mono and bis-alkylated piperazine\"}], \"amount\": {\"mass\": {\"value\": 450.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"to reflux for 30 min\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}}, {\"type\": \"CONCENTRATION\", \"details\": \"The mixture was concentrated\"}, {\"type\": \"ADDITION\", \"details\": \"diluted with NaOH 2 M (8 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"amount\": {\"volume\": {\"value\": 8.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with Et2O (50 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Et2O\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Evaporation of the organic layer\"}, {\"type\": \"CUSTOM\", \"details\": \"gave\"}, {\"type\": \"EXTRACTION\", \"details\": \"The aqueous layer was further extracted with DCM (100 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(but-3-ynyl)piperazine\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 640.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-404c63211b7144929ca611adc56a4c94",
    "procedure_text": "4'-(2-Benzylaminoethyl)methanesulfonanilide (XXIX.HCl) (8.0 g) and 20% Pd/C (0.5 g) were combined in MeOH (200 ml) and heated at 40\u00b0 for 18 hours in a Parr hydrogenator under an average hydrogen pressure of 3 atmospheres. The catalyst was filtered off. Concentration of the filtrate caused precipitation of Compound (XXVIII).HCl, 5.5 g as a white solid, m.p. 244\u00b0-246\u00b0 (decomp.), whose elemental analysis for C, H, and N, and NMR spectrum were consistent with the structure indicated.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4'-(2-Benzylaminoethyl)methanesulfonanilide\"}], \"amount\": {\"mass\": {\"value\": 8.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd/C\"}], \"amount\": {\"mass\": {\"value\": 0.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"heated at 40\\u00b0 for 18 hours in a Parr hydrogenator under an average hydrogen pressure of 3 atmospheres\", \"duration\": {\"value\": 18.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"The catalyst was filtered off\"}, {\"type\": \"CUSTOM\", \"details\": \"precipitation of Compound (XXVIII)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Compound ( XXVIII )\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-b02d7a18b47c44c2aedcc487094f59b2",
    "procedure_text": "A solution of 3-(4-hydroxyphenyl)-1-propanol (20 g, 13.1 mmole) in DMF (5 mL) was added to a solution of DMF (35 mL) containing NaH (1.31 g, 60% in mineral oil) at 0\u00b0 C. under nitrogen atmosphere. The reaction mixture was slowly warmed to 80\u00b0 C. After stirring for 1 h at 80\u00b0 C., the reaction mixture was cooled to 0\u00b0 C., and 6-bromohexanenitrile (5.78 g, 32.83 mmole) was added. The final mixture was re-heated to 80\u00b0 C., and stirred for 24 h. The reaction mixture was quenched with saturated NaCl solution (200 mL), and the product was extracted with EtOAc (300 mL). The organic layer was washed with brine solution, dried with Na2SO4, and evaporated to dryness, yielding a pale yellow solid. Purification of the crude product by flash silica column chromatography: 4/1 to 1/1 hexane/EtOAc provided 6-{3-[4-(5-cyanopentyloxy)phenyl]propoxy}hexanenitrile in 30% yield (1.33 g). Rf=0.63 in 1/1 EtOAc/hexane. 1H-NMR (CDCl3, 299.96 MHz): \u03b4 (ppm) 7.09\u20137.07 (d, 2H), 6.81\u20136.78 (d, 2H), 3.96\u20133.92 (t, 2H), 3.42\u20133.37 (m, 4H), 2.64\u20132.58 (t, 2H), 2.39\u20132.32 (m, 4H), 1.87\u20131.52 (m, 14H).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"final mixture\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(4-hydroxyphenyl)-1-propanol\"}], \"amount\": {\"mass\": {\"value\": 20.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 35.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaH\"}], \"amount\": {\"mass\": {\"value\": 1.31, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-bromohexanenitrile\"}], \"amount\": {\"mass\": {\"value\": 5.78, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 80.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring for 1 h at 80\\u00b0 C.\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"the reaction mixture was cooled to 0\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"STIRRING\", \"details\": \"stirred for 24 h\", \"duration\": {\"value\": 24.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was quenched with saturated NaCl solution (200 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaCl\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"the product was extracted with EtOAc (300 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 300.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with brine solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried with Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated to dryness\"}, {\"type\": \"CUSTOM\", \"details\": \"yielding a pale yellow solid\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification of the crude product by flash silica column chromatography\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-{3-[4-(5-cyanopentyloxy)phenyl]propoxy}hexanenitrile\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 30.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-9f266ffc4c04449da14457a0ed194621",
    "procedure_text": "To a 1000 mL four-necked flask equipped with a mechanical stirrer, a dropping funnel and a thermometer, 496.8 g (1.37 mole) of 25% sodium chlorite aqueous solution, and then 26 mL (0.46 mole) acetic acid were slowly added. The pH in the reaction system was pH 4.4. Furthermore, 100 g (0.62 mole) of diethyl malonate was slowly added under room temperature, and then the mixture was stirred under room temperature for 3 hours, and then 490 mL ethyl acetate was added to the reaction system to separate the liquids. The organic layer was separated, and ethyl acetate was distilled off under reduced pressure. Toluene was added thereto to perform azeotropic dehydration and the toluene was distilled off under reduced pressure, to give 105 g of diethyl ketomalonate as an oily substance (97 yield rate).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 490.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium chlorite\"}], \"amount\": {\"mass\": {\"value\": 496.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 26.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl malonate\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred under room temperature for 3 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"To a 1000 mL four-necked flask equipped with a mechanical stirrer, a dropping funnel\"}, {\"type\": \"CUSTOM\", \"details\": \"to separate the liquids\"}, {\"type\": \"CUSTOM\", \"details\": \"The organic layer was separated\"}, {\"type\": \"DISTILLATION\", \"details\": \"ethyl acetate was distilled off under reduced pressure\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"Toluene was added\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Toluene\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"the toluene was distilled off under reduced pressure\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ketomalonate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 105.0, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-03c7c1c2b95d4be3935fc50dc2649c79",
    "procedure_text": "To a solution of 200 ml. of piperidone in 500 ml. of tetrahydrofuran were added 33.5 g (0.1 mole) of 2,7-bis(2-chloroacetyl)xanthene and 2 g of potassium iodide with warming. The reaction mixture was allowed to stand for 7 days, filtered and the filtrate evaporated to dryness, leaving a residue which was treated with dilute acid and filtered. The filtrate was made alkaline, and the resulting oily product was extracted with methylene chloride. The methylene chloride solution was acidified with ethereal HCl which gave an oily product that was recrystallized from methanol-diethyl ether then vacuum dried to give the desired product. M.P. 260\u00b0-262\u00b0C.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"piperidone\"}], \"reaction_role\": \"REACTANT\"}]}, \"m4_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,7-bis(2-chloroacetyl)xanthene\"}], \"amount\": {\"mass\": {\"value\": 33.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium iodide\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"with warming\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"the filtrate evaporated to dryness\"}, {\"type\": \"CUSTOM\", \"details\": \"leaving a residue which\"}, {\"type\": \"ADDITION\", \"details\": \"was treated\"}, {\"type\": \"ADDITION\", \"details\": \"with dilute acid\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"EXTRACTION\", \"details\": \"the resulting oily product was extracted with methylene chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"gave an oily product that\"}, {\"type\": \"CUSTOM\", \"details\": \"was recrystallized from methanol-diethyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol diethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"vacuum dried\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 7.0, \"units\": \"DAY\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-193815c939704bd49830b06765e62cda",
    "procedure_text": "A solution of 7.2 mg (0.3 mmol) LiOH in 1 mL water was added to a solution of 140 mg (0.18 mmol) ethyl 1\u2032-{(R)-3-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carbonyloxy]-propionyl}-1,4\u2032-bipiperidinyl-4-carboxylate in 1 mL THF and the reaction mixture was stirred for 3 h at RT. 1 mL HCl (1 M) was added and the crude product was purified by HPLC. The fractions containing the product were combined and freeze-dried.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"LiOH\"}], \"amount\": {\"mass\": {\"value\": 7.2, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 1\\u2032-{(R)-3-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carbonyloxy]-propionyl}-1,4\\u2032-bipiperidinyl-4-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 140.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture was stirred for 3 h at RT\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the crude product was purified by HPLC\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"The fractions containing the product\"}, {\"type\": \"CUSTOM\", \"details\": \"freeze-dried\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-68cffc05b64c425c9733ef06bd7449d1",
    "procedure_text": "A solution of (E)-2-[2-(1H-indazol-3-yl)vinyl]benzoic acid (30 mg, 0.11 mmol) obtained in Step 1 of Example 47 in THF (0.50 mL) was sequentially added with 4-methylmorpholine (25 \u03bcL, 0.23 mmol), 3-amino-1,2,4-triazole (14 mg, 0.17 mmol), EDC (31 mg, 0.16 mmol) and 1-hydroxybenzotriazole monohydrate (20 mg, 0.15 mmol) followed by stirring at room temperature for 2.0 hours. The reaction mixture was added organic layer and aqueous layer and the organic layer was with water and ethyl acetate to separate the mixture into concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol=100/0 to 90/10) to obtain Compound 139 (17 mg, 45%).",
    "reference_string": "{\"inputs\": {\"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m6_m2_m3_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(E)-2-[2-(1H-indazol-3-yl)vinyl]benzoic acid\"}], \"amount\": {\"mass\": {\"value\": 30.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-methylmorpholine\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-amino-1,2,4-triazole\"}], \"amount\": {\"mass\": {\"value\": 14.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EDC\"}], \"amount\": {\"mass\": {\"value\": 31.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-hydroxybenzotriazole monohydrate\"}], \"amount\": {\"mass\": {\"value\": 20.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 0.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"by stirring at room temperature for 2.0 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"The reaction mixture was added organic layer and aqueous layer\"}, {\"type\": \"CUSTOM\", \"details\": \"to separate the mixture\"}, {\"type\": \"CONCENTRATION\", \"details\": \"into concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by silica gel column chromatography (chloroform/methanol=100/0 to 90/10)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Compound 139\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 17.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 45.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-1fa6a6ac64514bfd91a5361fad248254",
    "procedure_text": "To the methyl 4-{2-[2-(2-aminoethyl)-1-benzhydryl-5-chloro-1H-indol-3-yl]ethoxy}benzoate (Step 5, Example 1)was added 3,4-dichlorobenzenesulfonyl chloride according to the procedure in Example 1 Step 7 to generate the product in 60% yield.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 4-{2-[2-(2-aminoethyl)-1-benzhydryl-5-chloro-1H-indol-3-yl]ethoxy}benzoate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,4-dichlorobenzenesulfonyl chloride\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 60.0}}]}]}]}"
  },
  {
    "reaction_id": "ord-8c0c705e0225498792a77c2a834aeeea",
    "procedure_text": "To 3-hydroxymethyl-1,2,3,4-tetrahydroquinoxalin-2-one (IV, EXAMPLE 286, 1.35 g), 1.00 g of carbonyldiimidazole, and 30 ml of THF are added 1.64 ml of triethylamine. The reaction is stirred at 20\u00b0-25\u00b0 for 6 hr, then at 80\u00b0 for 18 hr, at which time an additional 0.11 g carbonyldiimidazole are added. Heating is continued for another 6 hr, at which time the reaction mixture is cooled and the solvent is removed under reduced pressure. The residue is partitioned between methylene chloride and water, the organic layers are dried over sodium sulfate and concentrated. The residue is crystallized from methanol/dichloromethane to give the title compound, mp 230\u00b0-231\u00b0; MS (m/z) at 204; NMR (CDCl3) 4.60, 4.78, 6.93, 7.19, 7.82 and 8.48 \u03b4.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"carbonyldiimidazole\"}], \"amount\": {\"mass\": {\"value\": 0.11, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-hydroxymethyl-1,2,3,4-tetrahydroquinoxalin-2-one\"}], \"amount\": {\"mass\": {\"value\": 1.35, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"carbonyldiimidazole\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 1.64, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction is stirred at 20\\u00b0-25\\u00b0 for 6 hr\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WAIT\", \"details\": \"at 80\\u00b0 for 18 hr\", \"duration\": {\"value\": 18.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"Heating\"}, {\"type\": \"WAIT\", \"details\": \"is continued for another 6 hr, at which time\", \"duration\": {\"value\": 6.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"the reaction mixture is cooled\"}, {\"type\": \"CUSTOM\", \"details\": \"the solvent is removed under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue is partitioned between methylene chloride and water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"the organic layers are dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue is crystallized from methanol/dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 6.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-68fb4e95b7464fc9add72fb075b7ef28",
    "procedure_text": "3-(1H-Indol-6-yl)-3-pyridin-3-yl-acrylic acid ethyl ester CLVII was prepared from 6-bromo-1H-indole and 3-pyridin-3-yl-acrylic acid ethyl ester using the procedure described above for preparation of 3-(3-Cyano-1H-Indol-4-yl)-3-phenyl-acrylic acid ethyl ester LVIII (Example 14).",
    "reference_string": "{\"inputs\": {\"m0_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-bromo-1H-indole\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-pyridin-3-yl-acrylic acid ethyl ester\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(3-Cyano-1H-Indol-4-yl)-3-phenyl-acrylic acid ethyl ester\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(1H-Indol-6-yl)-3-pyridin-3-yl-acrylic acid ethyl ester\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2caf2a55e53e4d129929a31f4b98c726",
    "procedure_text": "The title compound was prepared from 0.3 g of 6-(2,3,5,6-tetramethyl-phenyl)-pyrido[2,3-d]pyrimidine-2,7-diamine from Example 98 and 0.125 mL of tert-butyl isocyanate according to Example 2. The product was purified by medium pressure liquid chromatography eluting with 1:1 CHCl3 :EtOAc; mp >300\u00b0 C.; CIMS (1% ammonia in methane): m/z (relative intensity) 393 (MH+, 55), 394 (MH+ +1, 13), 84 (100).",
    "reference_string": "{\"inputs\": {\"m0_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-(2,3,5,6-tetramethyl-phenyl)-pyrido[2,3-d]pyrimidine-2,7-diamine\"}], \"amount\": {\"mass\": {\"value\": 0.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl isocyanate\"}], \"amount\": {\"volume\": {\"value\": 0.125, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The product was purified by medium pressure liquid chromatography\"}, {\"type\": \"WASH\", \"details\": \"eluting with 1:1 CHCl3\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CHCl3\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-cf42e1c3c252406f96f3ed982b503b07",
    "procedure_text": "m-Chloroperbenzoic acid (MCPBA), a mixture of sodium borate and trifluoroacetic acid or a mixture of acetic anhydride and H2O2 is preferably used for the oxidation. If desired, a commercially available wetting agent can additionally be added to the oxidizing agent. The reaction times lie in a wide range and range from about 0.5 to about 15 hours, preferably 1 to 8 hours. The reaction temperature ranges from \u221220 to about 100\u00b0 C., preferably from 0 to about 85\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"m-Chloroperbenzoic acid\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium borate\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trifluoroacetic acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic anhydride\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O2\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"a commercially available wetting agent can additionally be added to the oxidizing agent\"}, {\"type\": \"CUSTOM\", \"details\": \"The reaction times\"}, {\"type\": \"CUSTOM\", \"details\": \"ranges from \\u221220 to about 100\\u00b0 C., preferably from 0 to about 85\\u00b0 C.\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 4.5, \"precision\": 3.5, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"perbenzoic acid\"}]}]}]}"
  },
  {
    "reaction_id": "ord-dfa883a8947146d0a3519bd8d60be686",
    "procedure_text": "4-Nitrophenylhydrazine (15.0 g, 0.10 mole) and acetic acid (24.0 g, 0.40 mole) were mixed in a flask equipped with a stirrer and reflux condenser and heated at about 90\u00b0 C for one hour. The solid mass was collected, washed with water, and then dissolved in hot ethanol. The resulting solution was chilled in ice to give tan needles. Yield 14.4 g (74%), mp 207\u00b0-209\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-Nitrophenylhydrazine\"}], \"amount\": {\"mass\": {\"value\": 15.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"mass\": {\"value\": 24.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 90.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"equipped with a stirrer\"}, {\"type\": \"TEMPERATURE\", \"details\": \"reflux condenser\"}, {\"type\": \"CUSTOM\", \"details\": \"The solid mass was collected\"}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISSOLUTION\", \"details\": \"dissolved in hot ethanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"The resulting solution was chilled in ice\"}, {\"type\": \"CUSTOM\", \"details\": \"to give tan needles\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-5333bca35d7e449eacd86c6aae418ef4",
    "procedure_text": "A solution of triflic anhydride (42.8 g, 0.15 mol) in CH2Cl2 (100 mL) was added dropwise to a 0\u00b0 C. solution of 6-hydroxyquinoline (20.00 g, 0.138 mol) and pyridine (23 g, 0.277 mol) in CH2Cl2 (500 mL). The cooling bath was removed and the resulting solution was stirred at RT for 4 h. The reaction mixture was washed with water (3\u00d7300 mL) and the organic phase was dried (MgSO4) and concentrated under vacuum to afford crude quinolin-6-yl trifluoromethanesulfonate (40 g, >100% yield) as an oil. 1H-NMR (400 MHz, DMSO-d6) \u03b4 9.00 (d, 1H, J=2.8 Hz), 8.50 (d, 1H, J=8.0 Hz), 8.21 (d, J=2.8 Hz, 1H), 8.18 (d, J=9.2 Hz, 1H), 7.80 (m, 1H), 7.64 (m, 1H); MS (ESI) m/z: 277.9 (M+H+).",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triflic anhydride\"}], \"amount\": {\"mass\": {\"value\": 42.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-hydroxyquinoline\"}], \"amount\": {\"mass\": {\"value\": 20.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"amount\": {\"mass\": {\"value\": 23.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the resulting solution was stirred at RT for 4 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The cooling bath was removed\"}, {\"type\": \"WASH\", \"details\": \"The reaction mixture was washed with water (3\\u00d7300 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 300.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"the organic phase was dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under vacuum\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"quinolin-6-yl trifluoromethanesulfonate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 40.0, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 100.0}}], \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-5fe6025313db441eb2d02197eab1cf91",
    "procedure_text": "Tris(dibenzylideneacetone)dipalladium (141 mg, 0.154 mM) and triphenylarsine (188 mg, 0.616 mM) were dissolved in degassed N-methylpyrrolidone (40 ml) under nitrogen, and stirred for 15 minutes. (5RS)-3-(3-Fluoro-4-iodophenyl)-5-(N-(t-butoxycarbonyl)isoxazol-3-ylaminomethyl)-4,5-dihydro-isoxazole (1.5 g, 3.08 mM) and 1-t-butoxycarbonyl-4-trimethylstannyl-1,2,5,6-tetrahydropyridine (1.99 g, 4.62 mM) were added, and the reaction heated at 70\u201380\u00b0 for 18 hours. The mixture was filtered through celite and evaporated to dryness, and the residue chromatographed on a 40 g silica Biotage column, eluting with 25% ethyl acetate in isohexane. Relevant fractions were combined to give the desired product (817 mg).",
    "reference_string": "{\"inputs\": {\"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(5RS)-3-(3-Fluoro-4-iodophenyl)-5-(N-(t-butoxycarbonyl)isoxazol-3-ylaminomethyl)-4,5-dihydro-isoxazole\"}], \"amount\": {\"mass\": {\"value\": 1.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-t-butoxycarbonyl-4-trimethylstannyl-1,2,5,6-tetrahydropyridine\"}], \"amount\": {\"mass\": {\"value\": 1.99, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5_m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triphenylarsine\"}], \"amount\": {\"mass\": {\"value\": 188.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-methylpyrrolidone\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Tris(dibenzylideneacetone)dipalladium\"}], \"amount\": {\"mass\": {\"value\": 141.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred for 15 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"the reaction heated at 70\\u201380\\u00b0 for 18 hours\", \"duration\": {\"value\": 18.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"The mixture was filtered through celite\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated to dryness\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue chromatographed on a 40 g silica Biotage column\"}, {\"type\": \"WASH\", \"details\": \"eluting with 25% ethyl acetate in isohexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isohexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 817.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-cba379e2ae724ecfa262f7164f228183",
    "procedure_text": "Following General Procedure A above using N-(3,5-difluorophenylacetyl)-L-alanine (Example B) and 3-amino-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one (General Procedure 6-B), the title compound was prepared. The reaction was monitored by tlc on silica gel (Rf=0.15 in 12% methanol/dichloromethane) and purification was by flash chromatography using 12% methanol/dichloromethane as the eluant.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(3,5-difluorophenylacetyl)-L-alanine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-amino-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The reaction was monitored by tlc on silica gel (Rf=0.15 in 12% methanol/dichloromethane) and purification\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a4f86bd6b3a24d18bc77b7ba9a4c71b2",
    "procedure_text": "A mixture of 3.0 g (8.6 mmol) of [5-chloro-1-(4-ethylphenyl)-2-(prop-2-ylthio)-imidazol-4-yl]-2-methyl-2-propen-1-one and 2.3 g (11 mmol) of sodium metaperiodate was heated at 50\u00b0 C. for 3 hours in 30 ml of 90% aqueous methanol. The mixture was cooled and poured into water. Extraction with dichloromethane yielded an oil which was purified by flash chromatography on silica (20% ethyl acetate in petroleum ether) to obtain 1.3 g (41%) of [5-chloro-1-(4-ethylphenyl)-2-(prop-2-ylsulfinyl)-imidazol-4-yl]-2-methyl-2-propen-1-one as cream-colored crystals melting at 83\u00b0-4\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"[5-chloro-1-(4-ethylphenyl)-2-(prop-2-ylthio)-imidazol-4-yl]-2-methyl-2-propen-1-one\"}], \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium metaperiodate\"}], \"amount\": {\"mass\": {\"value\": 2.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The mixture was cooled\"}, {\"type\": \"EXTRACTION\", \"details\": \"Extraction with dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"yielded an oil which\"}, {\"type\": \"CUSTOM\", \"details\": \"was purified by flash chromatography on silica (20% ethyl acetate in petroleum ether)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"petroleum ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"[5-chloro-1-(4-ethylphenyl)-2-(prop-2-ylsulfinyl)-imidazol-4-yl]-2-methyl-2-propen-1-one\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.3, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 41.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 41.4}}], \"isolated_color\": \"cream-colored\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f1b2698498544723962efca050a4bbda",
    "procedure_text": "The title compound was prepared from commercially available 4,5-difluoro-1,2-phenylendiamine (144 mg, 1.0 mmol) and 3-oxo-3-(3-pyridin-3-yl-phenyl)-propionic acid tert-butyl ester (Example K1) (297 mg, 1.0 mmol) in xylene (6 ml) under reflux conditions for 1.5 h according to the general procedure M. Obtained as an off-white solid (224 mg, 64%).",
    "reference_string": "{\"inputs\": {\"m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4,5-difluoro-1,2-phenylendiamine\"}], \"amount\": {\"mass\": {\"value\": 144.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-oxo-3-(3-pyridin-3-yl-phenyl)-propionic acid tert-butyl ester\"}], \"amount\": {\"mass\": {\"value\": 297.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"xylene\"}], \"amount\": {\"volume\": {\"value\": 6.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 224.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 64.0}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0595045c329042d7b4f039ada9af541a",
    "procedure_text": "CuCN (3.7 g, 40.70 mmol) was added to a solution of 5-bromo-1H-indole (5 g, 25.26 mmol) in 1-methylpyrrolidin-2-one (25 mL), and the resulting solution was stirred at reflux for 18 hours. The reaction mixture was then added to 200 g of ice and the mixture was filtered. The filter cake was washed with ammonium hydroxide (3\u00d750 mL). The residue was dissolved in chloroform (600 mL) and then filtered. The organic layer was washed with water (200 mL), and dried (MgSO4). After a further filtration, the filtrate was concentrated to yield 3.7 g (82%) of 1H-indole-5-carbonitrile as brown oil.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CuCN\"}], \"amount\": {\"mass\": {\"value\": 3.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-bromo-1H-indole\"}], \"amount\": {\"mass\": {\"value\": 5.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-methylpyrrolidin-2-one\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the resulting solution was stirred\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"at reflux for 18 hours\", \"duration\": {\"value\": 18.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"the mixture was filtered\"}, {\"type\": \"WASH\", \"details\": \"The filter cake was washed with ammonium hydroxide (3\\u00d750 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium hydroxide\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue was dissolved in chloroform (600 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"amount\": {\"volume\": {\"value\": 600.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with water (200 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"After a further filtration\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate was concentrated\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1H-indole-5-carbonitrile\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 3.7, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 82.0}}], \"isolated_color\": \"brown\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3b840fe3600b463a9c64f485a30401ed",
    "procedure_text": "A solution of 2-amino-5-bromo-3-(hydroxymethyl)pyridine (34.6 g, 170.0 mmol) in hydrobromic acid (48% in H2O, 93 mL) was stirred at reflux overnight. The reaction mixture was cooled to room temperature, the precipitated product filtered and washed with H2O (100 mL) and dried. The title product was obtained as a light yellow solid (36.1 g, 56%, py 96.5%).",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-amino-5-bromo-3-(hydroxymethyl)pyridine\"}], \"amount\": {\"mass\": {\"value\": 34.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrobromic acid\"}], \"amount\": {\"volume\": {\"value\": 93.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"at reflux overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"the precipitated product filtered\"}, {\"type\": \"WASH\", \"details\": \"washed with H2O (100 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title product\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2946c9d438cb4f04bb885094c294531a",
    "procedure_text": "The 4-Bromo-3-chloro-phenol (24 mmol, 5 g) in anhydrous THF (50 mL) was added to a stirred solution of NaH (60% in mineral oil, 120 mmol, 4.8 g) in THF (100 mL) and DMF (42 mL) under N2 at room temperature. This solution stirred for 30 minutes. The iodoethane (240 mmol, 19.2 mL) was then added. The solution was stirred and was refluxed overnight. The reaction was cooled and quenched with 1 N HCl (150 mL), extracted into CH2Cl2 (2\u00d7150 mL), dried over MgSO4, concentrated in vacuo, and distilled under vacuum yielding 1-bromo-2-chloro-4-ethoxybenzene as a brown oil (4.59 g, 81%). 1H NMR (CDCl3, 300 MHz): \u03b47.42 (1H, d, J 8.7 Hz), 6.96 (1H, d, J 2.9 Hz), 6.64 (1H, dd, J 8.8 and 2.5 Hz), 3.95 (2H, q, J 7.0 Hz), 1.39 (3H, t, J 7.0 Hz.)",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-Bromo-3-chloro-phenol\"}], \"amount\": {\"mass\": {\"value\": 5.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaH\"}], \"amount\": {\"mass\": {\"value\": 4.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 42.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"iodoethane\"}], \"amount\": {\"volume\": {\"value\": 19.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"This solution stirred for 30 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"The solution was stirred\"}, {\"type\": \"TEMPERATURE\", \"details\": \"was refluxed overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"The reaction was cooled\"}, {\"type\": \"CUSTOM\", \"details\": \"quenched with 1 N HCl (150 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted into CH2Cl2 (2\\u00d7150 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"DISTILLATION\", \"details\": \"distilled under vacuum\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-bromo-2-chloro-4-ethoxybenzene\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 4.59, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 81.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 81.2}}], \"isolated_color\": \"brown\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0b22bc81df154ef6963841d46d4949aa",
    "procedure_text": "A solution of 4-(methylthio)phenol (2.80 g) in dry 1,2-dimethoxyethane was added slowly to a stirred suspension of sodium hydride (0.87 g) in dry 1,2-dimethoxyethane (50 ml). The mixture was stirred for 30 minutes, then a solution of 7-(1-bromoethyl)-1,2,4-triazolo[1,5-a]pyrimidine (4.54 g, prepared in a similar manner to that described in Example 6 above) in dry 1,2-dimethoxyethane (150 ml) was added dropwise. The reaction mixture was stirred overnight at room temperature. The sodium bromide was removed from the mixture by filtration. The solvent was evaporated from the mixture and the residue was dissolved in dichloromethane and washed with 200 ml of a 5% aqueous solution of sodium hydroxide followed by water. The organic layer was dried over magnesium sulphate. Evaporation of the solvent afforded a crude product which was purified by column chromatography on silica gel using as eluent a mixture of ethyl acetate and petroleum ether (in the ratio 4:6 respectively), followed by recrystallisation from a mixture of ethyl acetate and hexane, to give 7-{1-[4-(methylthio)phenoxy]ethyl}-1,2,4-triazolo[1,5-a]pyrimidine. Yield 3.66 g, (m.p. 84\u00b0-86\u00b0 C.).",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,2-dimethoxyethane\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m4_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(methylthio)phenol\"}], \"amount\": {\"mass\": {\"value\": 2.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydride\"}], \"amount\": {\"mass\": {\"value\": 0.87, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,2-dimethoxyethane\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,2-dimethoxyethane\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-(1-bromoethyl)-1,2,4-triazolo[1,5-a]pyrimidine\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred for 30 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added dropwise\"}, {\"type\": \"STIRRING\", \"details\": \"The reaction mixture was stirred overnight at room temperature\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The sodium bromide was removed from the mixture by filtration\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bromide\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The solvent was evaporated from the mixture\"}, {\"type\": \"DISSOLUTION\", \"details\": \"the residue was dissolved in dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with 200 ml of a 5% aqueous solution of sodium hydroxide\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aqueous solution\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layer was dried over magnesium sulphate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulphate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Evaporation of the solvent\"}, {\"type\": \"CUSTOM\", \"details\": \"afforded a crude product which\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"was purified by column chromatography on silica gel using as eluent\"}, {\"type\": \"ADDITION\", \"details\": \"a mixture of ethyl acetate and petroleum ether (in the ratio 4:6 respectively),\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"petroleum ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"followed by recrystallisation from a mixture of ethyl acetate and hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-{1-[4-(methylthio)phenoxy]ethyl}-1,2,4-triazolo[1,5-a]pyrimidine\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-22a0fe8105ec413985180111a7946a5c",
    "procedure_text": "A 4 ml vial was charged with crude (R)-4-(3-iodo-2-methyl-propyl]-4H-benzo[1,4]oxazin-3-one (108LM46-43) (0.312 g) and 4-butyl-piperidine (0.210 g, 1.49 mmol) in dry MeCN (\u00bd ml) and shaken at 60\u00b0 C. for 3 days. The reaction mixture was quenched with water (1 ml), and the product extracted into EtOAc (2\u00d71 ml). The combined organic layers were added a cation exchange column. The column was washed with MeOH (2 column volumes) then the product was eluded of the column using 8% ammonium hydroxide in MeOH (2 column volumes). The product was purified by flash CC (SiO2; MeOH/DCM 1:20) to give the title compound (108LM53-50) (0.193 g, 17% -3 steps). 1H.NMR (CDCl3) \u03b4 7.18 (d, J=7.8 Hz, 1H), 7.03-6.96 (m, 3H), 4.58 (ABq, J=14.3 Hz, J=33.9 Hz, CH2), 4.05-3.90 (m, 2H), 2.88 (bd, J=10.4 Hz, 1H), 2.71 (bd, J=10.4 Hz, 1H), 2.25-2.01 (m, 3H), 2.00-1.92 (m, 1H), 1.83-1.75 (m, 1H), 1.68-1.56 (m, 2H), 1.33-1.12 (m, 9H), 0.95-0.85 (m, 6H); 13C NMR (CDCl3) \u03b4 164.9, 145.7, 128.9, 123.8, 122.7, 117.2, 115.8, 67.8, 64.2, 55.8, 54.4, 45.4, 36.6, 36.1, 33.0, 32.8, 29.3, 23.2, 17.1, 14.4; HPLC-MS (ammonium acetate) [M+H]+=345.3.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-4-(3-iodo-2-methyl-propyl]-4H-benzo[1,4]oxazin-3-one\"}], \"amount\": {\"mass\": {\"value\": 0.312, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-butyl-piperidine\"}], \"amount\": {\"mass\": {\"value\": 0.21, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeCN\"}], \"amount\": {\"volume\": {\"value\": 0.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"shaken at 60\\u00b0 C. for 3 days\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was quenched with water (1 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"the product extracted into EtOAc (2\\u00d71 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"The combined organic layers were added a cation exchange column\"}, {\"type\": \"WASH\", \"details\": \"The column was washed with MeOH (2 column volumes)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The product was purified by flash CC (SiO2; MeOH/DCM 1:20)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH DCM\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"DAY\"}, \"products\": [{\"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.193, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 17.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-56a3117fab404cd69be75e08df15c134",
    "procedure_text": "132.5 Parts of 2-chloropropionic acid (98% strength) and 199 parts of 50% sodium hydroxide solution are added simultaneously but separately at 110\u00b0-115\u00b0 C. to a solution of 254 parts of 4-(4'-trifluoromethylphenoxy)-phenol in 1,000 parts of xylene. During the addition, the reaction temperature is maintained by azeotropic distillation of water in a water trap. The addition being complete, stirring is continued for 15 minutes at 110\u00b0-115\u00b0 C., the batch is cooled to 90\u00b0 C. and after addition of 400 parts of water, it is stirred for a further 10 minutes at 85\u00b0 C., then acidified at this temperature with 120 parts of phosphoric acid, and stirred for a further 10 minutes. After elimination of the water phase, xylene is distilled off in a water jet vacuum, and the solids are dried at 60\u00b0 C. and 250 mbar. 326 parts of 2-[4'-(4\" -trifluoromethylphenoxy)-phenoxy]-propionic acid are obtained. The content of pure final product is 99.6% corresponding to a yield of 99.6% of theory. The residual content of 4-(4'-trifluoromethyl-phenoxy)-phenol is 0.35%.",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"phosphoric acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m5_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"400\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3_m4_m9\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloropropionic acid\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"254\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(4'-trifluoromethylphenoxy)-phenol\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"xylene\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 90.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirring\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"During the addition\"}, {\"type\": \"ADDITION\", \"details\": \"The addition\"}, {\"type\": \"STIRRING\", \"details\": \"is stirred for a further 10 minutes at 85\\u00b0 C.\", \"duration\": {\"value\": 10.0, \"units\": \"MINUTE\"}, \"temperature\": {\"setpoint\": {\"value\": 85.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"STIRRING\", \"details\": \"stirred for a further 10 minutes\", \"duration\": {\"value\": 10.0, \"units\": \"MINUTE\"}}, {\"type\": \"DISTILLATION\", \"details\": \"After elimination of the water phase, xylene is distilled off in a water jet vacuum\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"xylene\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solids are dried at 60\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-[4'-(4\\\" -trifluoromethylphenoxy)-phenoxy]-propionic acid\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a2c1eb71dd4e4193b13a5e9c9371cdd3",
    "procedure_text": "Prepared from methyl (5R)-3-(4-fluoro-3-isopropyl-2-oxo-2,3-dihydro-6-benzoxazolyl)-2-oxo-5-oxazolidinecarboxylate (Step 4, 0.250 g, 7.39 mmol) and ammonia in methanol (5 ml) according to the method of EXAMPLE 86, Step 10 (0.14 g, 59%); MS for C14H14FN3O5 m/z 324 (M+H)+; 1H NMR (DMSO-d6, 300 Mhz) \u03b4 7.88 (br s, 1H), 7.63 (br s, 1H), 7.53 (d, 1H), 7.44 (dd, 1H), 5.04 (dd, 1H), 4.55 (m, 1H), 4.26 (t, 1H), 4.02 (dd, 1H), 1.41 (dd, 6H).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl (5R)-3-(4-fluoro-3-isopropyl-2-oxo-2,3-dihydro-6-benzoxazolyl)-2-oxo-5-oxazolidinecarboxylate\"}], \"amount\": {\"mass\": {\"value\": 0.25, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonia\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-471ec68d71cd44ec9d7cd447d827b676",
    "procedure_text": "To a solution, cooled to 0\u00b0 C., of 5.20 g (21.0 mmol) of 6-chloro-2-(4-fluorophenyl)imidazo[1,2-b]pyridazine (CAS No.: 244081-70-7) in 130 mL of chloroform is rapidly added dropwise a solution of 6.61 g (40.9 mmol) of iodine monochloride in 40 mL of chloroform. After cooling to room temperature and stirring for 4 hours, the mixture is treated with aqueous 5% sodium thiosulfate solution. The product is extracted with dichloromethane. The organic phase is dried by filtration through a hydrophobic filter cartridge and concentrated under reduced pressure. The residue is triturated in acetonitrile, and the solid is isolated after filtering off and rinsing with diisopropyl ether. 5.7 g of a beige-colored powder are isolated after drying under vacuum.",
    "reference_string": "{\"inputs\": {\"m4_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"iodine monochloride\"}], \"amount\": {\"mass\": {\"value\": 6.61, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"amount\": {\"volume\": {\"value\": 130.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-chloro-2-(4-fluorophenyl)imidazo[1,2-b]pyridazine\"}], \"amount\": {\"mass\": {\"value\": 5.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium thiosulfate\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirring for 4 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"The product is extracted with dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The organic phase is dried by filtration through a hydrophobic filter cartridge\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue is triturated in acetonitrile\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solid is isolated\"}, {\"type\": \"FILTRATION\", \"details\": \"after filtering off\"}, {\"type\": \"WASH\", \"details\": \"rinsing with diisopropyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"beige-colored powder\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 5.7, \"units\": \"GRAM\"}}}], \"isolated_color\": \"beige-colored\", \"texture\": {\"type\": \"POWDER\", \"details\": \"powder\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-844d2b3fb12a496ba7f77aef44116cd8",
    "procedure_text": "8.04 g (0.0389 mol) of 2,4-di-tert-butylphenol and 4.13 g (0.0408 mol) of triethylamine were dissolved in 15 mL of toluene followed by dropping in 5.01 g (0.0389 mol) of ethanesulfonyl chloride over the course of 30 minutes at 10\u00b0 C. Following completion of dropping, the mixture was stirred for 2 hours at 25\u00b0 C. and the 2,4-di-tert-butylphenol was confirmed to no longer be present. The reaction liquid was placed in 3% aqueous hydrochloric acid solution and following separation of the organic layer, was washed once with saturated aqueous NaHCO3 solution and twice with saturated brine followed by drying with MgSO4 and concentrating. The resulting crude crystals were purified by crystallization with n-heptane to obtain 8.14 g (yield: 70%) of 2,4-di-tert-butylphenyl ethanesulfonate (white crystals, melting point: 76\u00b0 C.).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,4-di-tert-butylphenol\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,4-di-tert-butylphenol\"}], \"amount\": {\"mass\": {\"value\": 8.04, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"mass\": {\"value\": 4.13, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanesulfonyl chloride\"}], \"amount\": {\"mass\": {\"value\": 5.01, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 25.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred for 2 hours at 25\\u00b0 C.\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The reaction liquid\"}, {\"type\": \"CUSTOM\", \"details\": \"separation of the organic layer\"}, {\"type\": \"WASH\", \"details\": \"was washed once with saturated aqueous NaHCO3 solution and twice with saturated brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"by drying with MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrating\"}, {\"type\": \"CUSTOM\", \"details\": \"The resulting crude crystals were purified by crystallization with n-heptane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-heptane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,4-di-tert-butylphenyl ethanesulfonate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 8.14, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 70.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 70.1}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-80158afda2ff4b538477de4458713c4b",
    "procedure_text": "A mixture of t-butyl bromoacetate (2 g, 10 mmol), 3-hydroxypyridine (1.5 g, 15 mmol), and K2CO3 (2.9 g, 21 mmol) in THF (20 mL) is stirred at 60\u00b0 C. After 0.5 h, the reaction mixture is cooled down at room temperature and diluted with H2O, then extracted with EtOAc. The organic phase is washed with H2O, and brine, then dried over Na2SO4. The solution is filtered and the solvent is evaporated in vacuo. The residue is purified by silica gel column chromatography to give the title compound MS: 210 [M+H]+; tR (HPLC, ACQUITY UPLC\u2122 BEH C18 1.7 \u03bcm, 50\u00d72.1 mm; 5% CH3CN+0.1% TFA/H2O+0.1% TFA for 0.5 min then 5-100% CH3CN+0.1% TFA/H2O+0.1% TFA for 5 min then 100% CH3CN+0.1% TFA for 1.5 min, flow 0.5 ml/min): 1.85 min.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"t-butyl bromoacetate\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-hydroxypyridine\"}], \"amount\": {\"mass\": {\"value\": 1.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"K2CO3\"}], \"amount\": {\"mass\": {\"value\": 2.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"is stirred at 60\\u00b0 C\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"the reaction mixture is cooled down at room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic phase is washed with H2O, and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"The solution is filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"the solvent is evaporated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue is purified by silica gel column chromatography\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 0.5, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a4b8e94ff9b544f7b4fcb9b31d7dbeff",
    "procedure_text": "A suspension of 5-carbomethoxy-1,2-dihydro-2-methyl-9H-carbazol-4(3H)-one (1.0 g, 3.89 mM), 3-fluorobenzyl bromide (0.48 ml, 3.97 mM), and potassium carbonate (1.07 g, 7.78 mM) in 20 mL DMF was stirred at room temperature for 22 hours. The mixture was diluted with EtOAc and 1N HCl. The layers were separated and the aqueous extracted with EtOAc. The combined EtOAc layers were extracted with 1N HCl, water, then brine. After drying (Na2SO4), evaporation in vacuo afforded 1.38 g (97%) of the 9-[(3-fluorophenyl)methyl]-5-carbomethoxy-2-methyl-1,2-dihydrocarbazol-4(3H)-one. 1H NMR (CDCl3) \u03b47.4-7.2 (m, 5H), 7.0 (m, 1H), 6.75 (m, 2H), 5.4 (s, 2H), 4.05 (s, 3H), 3.0 (m, 1H), 2.65-2.45 (m, 3H), 2.3 (dd, J=15 and 9 Hz, 1H), 1.1 (d, J=7 Hz, 3H). MS (ES) m/e 334, 366.",
    "reference_string": "{\"inputs\": {\"m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-carbomethoxy-1,2-dihydro-2-methyl-9H-carbazol-4(3H)-one\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-fluorobenzyl bromide\"}], \"amount\": {\"volume\": {\"value\": 0.48, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 1.07, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at room temperature for 22 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The layers were separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"the aqueous extracted with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The combined EtOAc layers were extracted with 1N HCl, water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"After drying\"}, {\"type\": \"CUSTOM\", \"details\": \"(Na2SO4), evaporation in vacuo\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 22.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"9-[(3-fluorophenyl)methyl]-5-carbomethoxy-2-methyl-1,2-dihydrocarbazol-4(3H)-one\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.38, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 97.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-436d933d57a249bcaa38a223e34be616",
    "procedure_text": "To a solution of methyl 3-methyl-2-(5-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl) oxazole-2-carboxamido)butanoate (Example 1, 150 mg) in THF (3 ml) was added 1 M aqueous solution of Lithium hydroxide monohydrate (0.6 ml) and the mixture was stirred for 4 hours at RT. The reaction mixture was acidified with dilute HCl and extracted with EtOAc. The organic layer was separated, dried over Na2SO4, concentrated under reduced pressure and then crystallized in EtOAc to give the title compound. Yield: 125 mg (85%); 1H NMR (DMSO-d6, 300 MHz): \u03b4 12.93 (bs, 1H), 9.14 (s, 1H), 9.06 (s, 1H), 8.64 (d, 1H), 8.03 (d, 1H), 7.81 (s, 1H), 7.8 (d, 2H), 7.64 (d, 2H), 7.58 (dd, 1H), 7.52 (dd, 1H), 7.34 (m, 1H), 4.28, (m, 1H), 2.26 (m, 1H), 0.95 (d, 6H); MS (ES+) m/z 491 (M+1).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m5_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 3-methyl-2-(5-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl) oxazole-2-carboxamido)butanoate\"}], \"amount\": {\"mass\": {\"value\": 150.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aqueous solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Lithium hydroxide monohydrate\"}], \"amount\": {\"volume\": {\"value\": 0.6, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred for 4 hours at RT\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The organic layer was separated\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"crystallized in EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-61396e39260f489fbc6b50b15e85a3f5",
    "procedure_text": "Ethyl 2-(2-nitroanilino)benzo[b]thiophene-3-carboxylate (6.0 g) was dissolved in N,N-dimethylformamide (120 ml) and the mixture was stirred at 0\u00b0 C., during which potassium tert-butoxide (3.0 g) was added portionwise. Methyl iodide (12.4 g) was added dropwise under ice-cooling and the mixture was stirred at 0\u00b0 C. for 5 min and heated to room temperature. The reaction mixture was extracted with ethyl acetate, washed with saturated brine and dried over anhydrous magnesium sulfate. After natural filtration, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (hexane:ethyl acetate=4:1) to give crude crystals (2.8 g) of ethyl 2-(N-methyl-2-nitroanflino)benzo[b]thiophene-3-carboxylate. Without purification, the crystals were treated in the same manner as in Starting Material Synthesis Example 21 using ethanol (50 ml), 18% hydrochloric acid (50 ml) and tin(II) chlorihe.dihydrate (12.6 g) to give ethyl 2-(2-amino-N-methylanilino)benzo[b]thiophene-3-carboxylate (3.2 g).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Methyl iodide\"}], \"amount\": {\"mass\": {\"value\": 12.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ethyl 2-(2-nitroanilino)benzo[b]thiophene-3-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 6.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 120.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium tert-butoxide\"}], \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at 0\\u00b0 C. for 5 min\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"was added portionwise\"}, {\"type\": \"TEMPERATURE\", \"details\": \"cooling\"}, {\"type\": \"TEMPERATURE\", \"details\": \"heated to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"The reaction mixture was extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with saturated brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"After natural filtration\"}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was evaporated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was separated by silica gel column chromatography (hexane:ethyl acetate=4:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"to give crude crystals (2.8 g) of ethyl 2-(N-methyl-2-nitroanflino)benzo[b]thiophene-3-carboxylate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude crystals\"}], \"amount\": {\"mass\": {\"value\": 2.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 2-(N-methyl-2-nitroanflino)benzo[b]thiophene-3-carboxylate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Without purification\"}, {\"type\": \"ADDITION\", \"details\": \"the crystals were treated in the same manner as\"}, {\"type\": \"CUSTOM\", \"details\": \"Material Synthesis Example 21 using ethanol (50 ml), 18% hydrochloric acid (50 ml) and tin(II) chlorihe\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tin(II)\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 5.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dihydrate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 12.6, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 2-(2-amino-N-methylanilino)benzo[b]thiophene-3-carboxylate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 3.2, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-cc215d8a50ad418c8e0934f7e847e458",
    "procedure_text": "Prepared by Procedure T and Scheme AD using N-(3-{1-[4-(3,4-dimethylphenyl)-4-oxobutyl]-4-piperidinyl}phenyl)-2-methylpropanamide and methyl iodide: 1H NMR (400 MHz, CDCl3) \u03b4 7.76 (s, 1H), 7.72 (dd, 1H, J=1.8, 7.7 Hz), 7.33 (t, 1H, J=8.8 Hz), 7.22 (d, 1H, J=7.8 Hz), 7.18 (d, 1H, J=8.8 Hz), 7.01 (m, 2H), 3.24 (s, 3H), 3.10 (d, 1H, J=10.6 Hz), 3.00 (t, 1H, J=7.6 Hz), 2.49 (m, 4H), 2.33 (s, 6H), 2.11 (m, 3H), 1.99 (m, 1H), 1.79 (m, 4H), 1.26 (t, 2H, J=7.6 Hz), 1.02 (d, 6H, J=7.6 Hz); ESMS m/e: 435.2 (M+H)+.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(3-{1-[4-(3,4-dimethylphenyl)-4-oxobutyl]-4-piperidinyl}phenyl)-2-methylpropanamide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl iodide\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Prepared by Procedure T and Scheme AD\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-92bfbd42dcc745f28111fc60cbae7d4a",
    "procedure_text": "N,N'-Bis(2-acetoxypropionyl)-3,5-diamino-2,4,6-triiodobenzylacetate (0.16 g, 0.2 mmol) was dissolved in a mixture of methanol (5 ml) and water (5 ml) and the pH was adjusted to 12 using a 1M aqueous solution of NaOH. After stirring for 15 h, the solution was neutralized with 1M HCl and the solvents were removed by evaporation. Purification by preparative HPLC gave 61 mg (46%) of the pure product.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N'-Bis(2-acetoxypropionyl)-3,5-diamino-2,4,6-triiodobenzylacetate\"}], \"amount\": {\"mass\": {\"value\": 0.16, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aqueous solution\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring for 15 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the solvents were removed by evaporation\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification by preparative HPLC\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pure product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 61.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 46.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d54a00cbb60c4c57bb0975f2edfc08d4",
    "procedure_text": "To a solution of tert-butyl 2-chlorothiazole-5-carboxylate (100 mg, 0.455 mmol) in MeCN (880 \u03bcl) and MeOH (880 ul) was added 5.4M NaOMe in MeOH (337 \u03bcl, 1.821 mmol) followed by 2M NaOH (881 \u03bcl, 1.762 mmol). The reaction mixture was heated to 80\u00b0 C. overnight and, after cooling to RT, the mixture was evaporated under reduced pressure. The residue was acidified with a minimal volume of 6M aqueous hydrochloric acid. The resulting precipitate was filtered, washed with water and dried in a high vacuum oven overnight to afford the title compound;",
    "reference_string": "{\"inputs\": {\"m1_m4_m5_m2_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl 2-chlorothiazole-5-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOMe\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeCN\"}], \"amount\": {\"volume\": {\"value\": 880.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"amount\": {\"volume\": {\"value\": 880.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"amount\": {\"volume\": {\"value\": 337.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"amount\": {\"volume\": {\"value\": 881.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 80.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"after cooling to RT\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"the mixture was evaporated under reduced pressure\"}, {\"type\": \"FILTRATION\", \"details\": \"The resulting precipitate was filtered\"}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried in a high vacuum oven overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-cb03e62ad0b64a9d826739bbf163214e",
    "procedure_text": "In 65 ml of dimethylsulfoxide were dissolved 20.01 g of the 4'-benzyloxy-2'-hydroxy-3'-(3-methyl-2-butenyl)acetophenone obtained in Production Example 15 and 15.00 g of the 4-benzyloxybenzaldehyde obtained in Production Example 27, and 130 ml of a saturated ethanol solution of potassium hydroxide was added to the solution and the mixture was stirred at room temperature in a nitrogen current for 2.5 hours. After the reaction, the reaction liquid was diluted with water and was gradually made acidic by addition of 3N hydrochloric acid under cooling. The formed precipitate was recovered by filtration and recrystallized from a mixed solvent of benzene and ethanol to obtain 23.64 g (yield =72.7%) of 4,4'-dibenzyloxy-2'-hydroxy-3'-(3-methyl-2-butenyl)chalcone in the form of a yellow needle.",
    "reference_string": "{\"inputs\": {\"m2_m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4'-benzyloxy-2'-hydroxy-3'-(3-methyl-2-butenyl)acetophenone\"}], \"amount\": {\"mass\": {\"value\": 20.01, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylsulfoxide\"}], \"amount\": {\"volume\": {\"value\": 65.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-benzyloxybenzaldehyde\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 15.0, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c1112000371a4f79b250af02077581ad",
    "procedure_text": "Following a similar procedure to that described in Example 8, but using N-(2-t-butyl-5-carboxyphenyl)-3-(2,6-dimethoxyphenyl)octanamide (prepared as described in Preparation 74E) and 4-aminopyridine, the title compound was obtained as colorless crystals, melting at 169-172\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(2-t-butyl-5-carboxyphenyl)-3-(2,6-dimethoxyphenyl)octanamide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-aminopyridine\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-5d4cd55e8bcb4eba81382997411fbf1a",
    "procedure_text": "To a solution of (S)-methyl 2-(methylsulfonyloxy)-2-phenylacetate (I5) (520 mg, 2.13 mmol) in CH3CN (10 mL), is added 4-fluoroaniline (473 mg, 4.26 mmol) and the mixture is heated at 120\u00b0 C. for 5 minutes under MW irradiation (UPLC-MS: complete conversion). Acetonitrile was evaporated and the resulting crude is dissolved in 1N HCl and extracted several times with EtOAc. The combined organic phase is dried over Na2SO4, filtered and evaporated to dryness to obtain intermediate I254 as a pale yellow oil (520 mg, 94% yield).",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(S)-methyl 2-(methylsulfonyloxy)-2-phenylacetate\"}], \"amount\": {\"mass\": {\"value\": 520.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-fluoroaniline\"}], \"amount\": {\"mass\": {\"value\": 473.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH3CN\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 120.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Acetonitrile was evaporated\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Acetonitrile\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISSOLUTION\", \"details\": \"the resulting crude is dissolved in 1N HCl\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted several times with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic phase is dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated to dryness\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"oil\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 520.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 94.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 94.2}}], \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-99668b8e2fbe4bc38bc5f73c97125451",
    "procedure_text": "To a stirred solution of 7-azaindole (1.18 g, 10.0 mmol) in anhydrous dimethylformamide (10 mL) cooled to 0\u00b0 C. was added NaH [60% dispersion in mineral oil] (0.480 g, 12.0 mmol) in portions over 15 min. The resulting mixture was allowed to stir for 1 hr at 0\u00b0 C., after which (2-(chloromethoxy)ethyl)trimethylsilane [SEM-Cl] (2.12 mL, 12.0 mmol) was added over 15 min. The resulting mixture was stirred for 1 hr, after which it was quenched with H2O (50 mL), and partioned between EtOAc and H2O. The organic layer was separated, washed with brine, dried over MgSO4, filtered, and evaporated in vacuo to yield a yellow oil (2.50 g, 100%). HPLC retention time: 2.66 minutes; MS ESI (m/z): 249.4 (M+1)+, calc. 248.",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-azaindole\"}], \"amount\": {\"mass\": {\"value\": 1.18, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaH\"}], \"amount\": {\"mass\": {\"value\": 0.48, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(2-(chloromethoxy)ethyl)trimethylsilane\"}], \"amount\": {\"volume\": {\"value\": 2.12, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"to stir for 1 hr at 0\\u00b0 C.\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"The resulting mixture was stirred for 1 hr\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"after which it was quenched with H2O (50 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The organic layer was separated\"}, {\"type\": \"WASH\", \"details\": \"washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"oil\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.5, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 100.0}}], \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-06a0866fb0ad4a07b10854d2759a82f4",
    "procedure_text": "A solution of 2-chloro-4-(3-methyl-1H-pyrazol-1-yl)-benzoic acid methyl ester of Step A (1.42 g, 5.6 mmol) in 20 mL of tetrahydrofuran containing 6 mL of 1 M aqueous lithium hydroxide was stirred overnight at ambient temperature. The reaction mixture was partitioned between ethyl acetate and 1 N hydrochloric acid. The organic layer was washed with water and brine, and dried over sodium sulfate. Evaporation of the solvent afforded the title compound (1.05 g ), m.p. 192-193\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloro-4-(3-methyl-1H-pyrazol-1-yl)-benzoic acid methyl ester\"}], \"amount\": {\"mass\": {\"value\": 1.42, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium hydroxide\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was partitioned between ethyl acetate and 1 N hydrochloric acid\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with water and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Evaporation of the solvent\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.05, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-aa72221a92b14bb09df7e7b47b44f883",
    "procedure_text": "A solution of 2-((1-benzyl-1H-pyrazol-4-yl)(hydroxy)methylene)malononitrile (26.5 g, 106 mmol) in CH(OMe)3 (250 mL) was heated to 75\u00b0 C. for 16 hr. Then the solution was concentrated. The residue was washed with MeOH (50 mL) to give 14.5 g (51.8%) of 2-((1-benzyl-1H-pyrazol-4-yl)(methoxy)methylene)malononitrile as an off-white solid. 1H NMR (DMSO-d6) \u03b4 8.71 (s, 1H), 8.08 (s, 1H), 7.42-7.24 (m, 5H), 5.46 (s, 2H), 4.12 (s, 3H). MS (ESI) m/e [M+1]+ 264.9.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-((1-benzyl-1H-pyrazol-4-yl)(hydroxy)methylene)malononitrile\"}], \"amount\": {\"mass\": {\"value\": 26.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH(OMe)3\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"Then the solution was concentrated\"}, {\"type\": \"WASH\", \"details\": \"The residue was washed with MeOH (50 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-((1-benzyl-1H-pyrazol-4-yl)(methoxy)methylene)malononitrile\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 14.5, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 51.8}}], \"isolated_color\": \"off-white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0b6aa9e0b63d4942a59ece033a458622",
    "procedure_text": "Prepared by proceeding in a similar manner to Intermediate 18, starting from methyl 7-amino-1,2-dihydrofuro[2,3-c]quinoline-6-carboxylate (Intermediate 23) and 2-bromo-4-fluorobenzenesulfonyl chloride and stirring at room temperature for 3 days.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-bromo-4-fluorobenzenesulfonyl chloride\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Intermediate 18\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 7-amino-1,2-dihydrofuro[2,3-c]quinoline-6-carboxylate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Intermediate 23\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirring at room temperature for 3 days\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Prepared\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"DAY\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-61407ac0d4724b6e936ac46ea9f803fc",
    "procedure_text": "Using the same method as for COMPOUND 17 and using INTERMEDIATE 5a (205 mg, 0.44 mmol), 4-(3-pyridinyl)benzaldehyde (88.7 mg, 0.48 mmol), and decaborane (16.4 mg, 0.13 mmol) afforded COMPOUND 52 (266 mg, 61% yield) as its TFA salt. This material was lyophilized from CH3CN/H2O to produce a slightly yellow solid.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"decaborane\"}], \"amount\": {\"mass\": {\"value\": 16.4, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"COMPOUND 17\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"INTERMEDIATE 5a\"}], \"amount\": {\"mass\": {\"value\": 205.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m0_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TFA\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(3-pyridinyl)benzaldehyde\"}], \"amount\": {\"mass\": {\"value\": 88.7, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"COMPOUND 52\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 266.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 61.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d1edc047765948a3941283abebe1d577",
    "procedure_text": "To a solution of tert-butyl 4-(2-(1-oxo-3-phenyl-2-(pyridin-3-yl)-1H-inden-6-yloxy)ethyl)piperazine-1-carboxylate (0.38 mmol, 200 mg) obtained in Step 2 of Example 44 in CH2Cl2 (0.3M) was added TFA (20 eq). The resulting mixture was stirred at room temperature for 40 min and diluted with CH2Cl2. The solution was basicified to pH 9 by the addition of 3N NaOH. The mixture was washed with H2O, dried over MgSO4, and concentrated in vacuo. The residue was purified by silica gel column chromatography (acetone/hexanes=1:1) to obtain the title compound (75%).",
    "reference_string": "{\"inputs\": {\"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl 4-(2-(1-oxo-3-phenyl-2-(pyridin-3-yl)-1H-inden-6-yloxy)ethyl)piperazine-1-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TFA\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The resulting mixture was stirred at room temperature for 40 min\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WASH\", \"details\": \"The mixture was washed with H2O\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by silica gel column chromatography (acetone/hexanes=1:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 40.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 75.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-53f705ab13db4d52b1223e99ce7b3f5e",
    "procedure_text": "To a solution of benzylamine (10.7 g, 100 mmol) in methanol (100 mL) was added methyl methacrylate (10 g, 100 mmol). The reaction solution was stirred at room temperature for 12 hours. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=1:1) to give methyl 3-(benzylamino)-2-methylpropanoate as a light yellow oil (12 g, 57%).",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzylamine\"}], \"amount\": {\"mass\": {\"value\": 10.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl methacrylate\"}], \"amount\": {\"mass\": {\"value\": 10.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction solution was stirred at room temperature for 12 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"The reaction mixture was concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=1:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"petroleum ether ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 12.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 3-(benzylamino)-2-methylpropanoate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 12.0, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 57.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 57.9}}], \"isolated_color\": \"light yellow\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-66812808f29d49579c398d7b84bfc254",
    "procedure_text": "By the method of Example 2, 1,2,3,4,7,8,9,10-octahydro-6-methyl-phenanthridine is reacted with n-butyl-lithium solution and the resulting anion is reacted with trimethylsilyl isothiocyanate to give 1,2,3,4,7,8,9,10-octahydro-6-methylphenanthridine-4-thiocarboxamide.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,2,3,4,7,8,9,10-octahydro-6-methyl-phenanthridine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-butyl-lithium\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trimethylsilyl isothiocyanate\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,2,3,4,7,8,9,10-octahydro-6-methylphenanthridine-4-thiocarboxamide\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a14299d1add9429195bbc83639b72c11",
    "procedure_text": "Following general procedure F and using 8-cyclopropyl-6-ethynyl-2,2,4,4-tetramethylchroman (Intermediate 34, 0.096 g, 0.38 mmol), methyl-4-iodo phenyl acetate (Reagent B, 0.094 g, 0.34 mmol), triethyl amine (3 mL), tetrahydrofuiran (3 mL), copper(I)iodide (0.025 g, 0.13 mmol) and dichlorobis(triphenylphosphine)palladium(II) (0.075 g, 0.11 mmol) the title compound was obtained (0.137 g, 90%). 1H NMR (300 MHz, CDCl3): \u03b4 7.47 (d, 2H, J=7.9 Hz), 7.29 (d, 1H, J=1.8 Hz), 7.24 (d, 2H, J=7.9 Hz), 6.82 (d, 1H, J=2.1 Hz), 3.70 (s, 3H), 3.63 (s, 2H), 2.22-2.13 (m, 1H), 1.85 (s, 2H), 1.38 (s, 6H), 1.36 (s, 6H), 0.94-0.86 (m, 2H), 0.68-0.63 (m, 2H).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"8-cyclopropyl-6-ethynyl-2,2,4,4-tetramethylchroman\"}], \"amount\": {\"mass\": {\"value\": 0.096, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"copper(I)iodide\"}], \"amount\": {\"mass\": {\"value\": 0.025, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl-4-iodo phenyl acetate\"}], \"amount\": {\"mass\": {\"value\": 0.094, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Reagent B\"}], \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichlorobis(triphenylphosphine)palladium(II)\"}], \"amount\": {\"mass\": {\"value\": 0.075, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethyl amine\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Intermediate 34\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-825cef61c5cc4ab9a371de940b3a9004",
    "procedure_text": "n-Butyllithium (1.6M in hexane, 330 ml) was added dropwise with stirring to a solution of 2,6-dichloro-4-trifluoromethylbromobenzene (163.3 g) in ether while maintaining the temperature below -70\u00b0 C. The mixture was stirred for 1 hour at -78\u00b0 C. then ethyl chloroformate (61.7 g) was added while maintaining the temperature below -70\u00b0 C. The mixture was stirred at room temperature overnight. It was cooled to 0\u00b0 C. and a saturated aqueous solution of ammonium chloride was added. The layers were separated and the organic layer was washed with water, dried (Na2SO4) and filtered. The filtrate was evaporated to dryness and the residue was distilled to give ethyl 2,6-dichloro-4-trifluoromethylbenzoate (123.9 g) as a colourless liquid bp 90\u00b0-96\u00b0 C. at 5 mmHg.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium chloride\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-Butyllithium\"}], \"amount\": {\"volume\": {\"value\": 330.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,6-dichloro-4-trifluoromethylbromobenzene\"}], \"amount\": {\"mass\": {\"value\": 163.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl chloroformate\"}], \"amount\": {\"mass\": {\"value\": 61.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -78.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred for 1 hour at -78\\u00b0 C.\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"while maintaining the temperature below -70\\u00b0 C\"}, {\"type\": \"TEMPERATURE\", \"details\": \"while maintaining the temperature below -70\\u00b0 C\"}, {\"type\": \"STIRRING\", \"details\": \"The mixture was stirred at room temperature overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"It was cooled to 0\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The layers were separated\"}, {\"type\": \"WASH\", \"details\": \"the organic layer was washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"The filtrate was evaporated to dryness\"}, {\"type\": \"DISTILLATION\", \"details\": \"the residue was distilled\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 2,6-dichloro-4-trifluoromethylbenzoate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 123.9, \"units\": \"GRAM\"}}}], \"isolated_color\": \"colourless\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"liquid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-285f929e1d7740bcb9c1e9b9361a3547",
    "procedure_text": "20.2 g. of 2,4-dichloropyridin-5-methanol (0.11 mol.) and 150 ml. of phosphorus oxychloride are refluxed for 19 hours. Then the excess phosphorus oxychloride is removed in vacuo and ice is added to the residue. 5-Chloromethyl-2,4-dichloropyridine is filtered off, washed with water, dried in the desiccator over P2O5 and recrystallized from hexane; yield 17.95 g. (83%), m.p. 55\u00b0-56\u00b0.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,4-dichloropyridin-5-methanol\"}], \"amount\": {\"moles\": {\"value\": 0.11, \"units\": \"MOLE\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"phosphorus oxychloride\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Then the excess phosphorus oxychloride is removed in vacuo and ice\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"phosphorus oxychloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"is added to the residue\"}, {\"type\": \"FILTRATION\", \"details\": \"5-Chloromethyl-2,4-dichloropyridine is filtered off\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-Chloromethyl-2,4-dichloropyridine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried in the desiccator over P2O5\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"P2O5\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"recrystallized from hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-Chloromethyl-2,4-dichloropyridine\"}]}]}]}"
  },
  {
    "reaction_id": "ord-f79dbd5a05f64c40838cd993c3b0f486",
    "procedure_text": "A stirred solution of 15.0 grams (0.0062 mole) of 1-methylsulfonyloxy-5-phenylpentane and 9.1 grams (0.190 mole) of sodium cyanide in 150 mL of N,N-dimethylformamide was heated at 50\u00b0 C. to 55\u00b0 C. for about 60 hours. After this time the reaction mixture was poured into 400 mL of water. The mixture was extracted with three 250 mL portions of diethyl ether. The combined extracts were then washed with three 200 mL portions of water and 200 mL of an aqueous solution saturated with sodium chloride. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, yielding 10.2 grams of 6-phenylhexanenitrile. The NMR spectrum was consistent with the proposed structure.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-methylsulfonyloxy-5-phenylpentane\"}], \"amount\": {\"mass\": {\"value\": 15.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium cyanide\"}], \"amount\": {\"mass\": {\"value\": 9.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 400.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"The mixture was extracted with three 250 mL portions of diethyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"three\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined extracts were then washed with three 200 mL portions of water and 200 mL of an aqueous solution saturated with sodium chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"three\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aqueous solution\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layer was dried with magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"The filtrate was concentrated under reduced pressure\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-phenylhexanenitrile\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 10.2, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-817680bc6c86447aa7f08b5fb6db08de",
    "procedure_text": "Prepared according to the coupling procedure for Example 17 from 6-bromo-4,4-dimethyl-2-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazine and 3-chlorophenyl boronic acid. A yellowish solid: mp 108-109\u00b0 C.; 1H-NMR (DMSO-d6) \u03b4 7.69 (t, 1H, J=1.7 Hz), 7.59 (d, 1H, J=7.8 Hz), 7.35-7.50 (m, 3H), 7.32 (dt, 1H, J=8.1, 1.1 Hz), 6.91 (s, 1H), 6.87 (d, 1H, J=8.4 Hz), 5.35 (m, 1H), 1.60 (s, 3H), 1.59 (s, 3H); MS (ESI) m/z 340 [M\u2212H]\u2212.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-bromo-4,4-dimethyl-2-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-chlorophenyl boronic acid\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Prepared\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-e73170a92bec467fbfc7829ad381e853",
    "procedure_text": "A mixture of ethyl 3-(1-boc-1,2,3,4-tetrahydro-quinolin-6-yl)crotonate [9 g, Reference Example 7(c)] and 5% palladium on charcoal (2.5 g) in ethanol (250 ml) was hydrogenated at room temperature and pressure overnight. The spent catalyst was removed by filtration through Celite and the filtrate was evaporated to give the title compound (9.1 g) as a colourless oil.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 3-(1-boc-1,2,3,4-tetrahydro-quinolin-6-yl)crotonate\"}], \"amount\": {\"mass\": {\"value\": 9.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"palladium on charcoal\"}], \"amount\": {\"mass\": {\"value\": 2.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"was hydrogenated at room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"pressure overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The spent catalyst was removed by filtration through Celite\"}, {\"type\": \"CUSTOM\", \"details\": \"the filtrate was evaporated\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 9.1, \"units\": \"GRAM\"}}}], \"isolated_color\": \"colourless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-02c8cdbd48cc48c288390aefb00e3f8c",
    "procedure_text": "2 Parts of \u03b1,\u03b1-bis[2-(diisopropylamino)ethyl]-\u03b1-phenylacetonitrile is dissolved in 20 parts by volume of concentrated sulfuric acid and the resulting solution heated on a steam bath for about 90 minutes. The solution is then cooled to about 0\u00b0 C. and made alkaline by the addition of dilute sodium hydroxide. The alkaline solution is extracted with ether, the ether extract dried over calcium sulfate and stripped of solvent to afford \u03b1,\u03b1-bis[2-(diisopropylamino)ethyl]-\u03b1-phenylacetamide, melting at about 102\u00b0-103\u00b0 C. after crystallization from hexane. This compound has the following structural formula ##STR13##",
    "reference_string": "{\"inputs\": {\"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"\\u03b1,\\u03b1-bis[2-(diisopropylamino)ethyl]-\\u03b1-phenylacetonitrile\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sulfuric acid\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"the resulting solution heated on a steam bath for about 90 minutes\", \"duration\": {\"value\": 90.0, \"units\": \"MINUTE\"}}, {\"type\": \"EXTRACTION\", \"details\": \"The alkaline solution is extracted with ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"the ether extract\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over calcium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"calcium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"\\u03b1,\\u03b1-bis[2-(diisopropylamino)ethyl]-\\u03b1-phenylacetamide\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-5f2b64f2bb804757a467e50c3f744d9e",
    "procedure_text": "The title compound was prepared from 1-(4-benzenesulfonyl-4-methylpentyl)-3-hydroxypiperidine and benzyl bromide.",
    "reference_string": "{\"inputs\": {\"m0_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(4-benzenesulfonyl-4-methylpentyl)-3-hydroxypiperidine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzyl bromide\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4a1c3d4552874a0f82597bf9a8da0c1a",
    "procedure_text": "A solution of 1,5-dimethyl-1,3,4,5-tetrahydropyrano[4,3-b]indole-1-acetic acid ethyl ester (17.0 g), described in Example 916, in tetrahydrofuran (200 ml) is added dropwise to a suspension of lithium aluminium hydride (5.0 g) in tetrahydrofuran (150 ml). The mixture is heated at reflux for 2.5 hr. and then cooled and treated with a mixture of water-tetrahydrofuran (30 ml - 150 ml). The mixture is filtered through celite and the filtrate is evaporated. The residue is purified by chromatography on silica gel. Elution with chloroform gives 1,5-dimethyl-1,3,4,5-tetrahydropyrano[4,3-b]indole-1-ethanol.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,5-dimethyl-1,3,4,5-tetrahydropyrano[4,3-b]indole-1-acetic acid ethyl ester\"}], \"amount\": {\"mass\": {\"value\": 17.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium aluminium hydride\"}], \"amount\": {\"mass\": {\"value\": 5.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water tetrahydrofuran\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The mixture is heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"at reflux for 2.5 hr\", \"duration\": {\"value\": 2.5, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"and then cooled\"}, {\"type\": \"FILTRATION\", \"details\": \"The mixture is filtered through celite\"}, {\"type\": \"CUSTOM\", \"details\": \"the filtrate is evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue is purified by chromatography on silica gel\"}, {\"type\": \"WASH\", \"details\": \"Elution with chloroform\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,5-dimethyl-1,3,4,5-tetrahydropyrano[4,3-b]indole-1-ethanol\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-601dbf55b4fc4544b90b83b6507824e5",
    "procedure_text": "3.60 g (9.88 mmole) of 1-amino-4-t-butyldimethylsilyloxy-(2R)-(3,4-dichlorophenyl)-2-butanol [prepared as described in Example 1(e)], 1.64 ml (11.8 mmole) of triethylamine and 121 mg (0.99 mmole) of 4-dimethylaminopyridine were dissolved in 100 ml of methylene chloride, and 0.94 ml (11.8 mmole) of chloroacetyl chloride were added dropwise, whilst ice-cooling. The mixture was then stirred at the same temperature for 2 hours. At the end of this time, 100 ml of methylene chloride were added to the reaction mixture, and the resulting mixture was washed with ice-cooled 10% w/v aqueous hydrochloric acid, with a saturated aqueous solution of sodium hydrogencarbonate and with a saturated aqueous solution of sodium chloride, in that order. It was then dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure, and the resulting residue was purified by silica gel flash column chromatography, using a gradient elution method, with mixtures of ethyl acetate and hexane ranging from 1:5 to 1:2 by volume as the eluent, to obtain 3.32 g (yield 76%) of the title compound as a colorless oil.",
    "reference_string": "{\"inputs\": {\"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m5_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-amino-4-t-butyldimethylsilyloxy-(2R)-(3,4-dichlorophenyl)-2-butanol\"}], \"amount\": {\"mass\": {\"value\": 3.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 1.64, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-dimethylaminopyridine\"}], \"amount\": {\"mass\": {\"value\": 121.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4_m8_m0\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroacetyl chloride\"}], \"amount\": {\"volume\": {\"value\": 0.94, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was then stirred at the same temperature for 2 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooling\"}, {\"type\": \"WASH\", \"details\": \"the resulting mixture was washed with ice-\"}, {\"type\": \"TEMPERATURE\", \"details\": \"cooled 10%\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"It was then dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The solvent was then removed by distillation under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"the resulting residue was purified by silica gel flash column chromatography\"}, {\"type\": \"WASH\", \"details\": \"a gradient elution method\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 3.32, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 76.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 76.2}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b81bc1f050e4493c97a057ede4be5ac1",
    "procedure_text": "Under a nitrogen atmosphere, 2-chloro-N-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-5,6-dimethyl-3-nitropyridin-4-amine (25.00 g, 66.35 mmol), toluene (250 mL), triethylamine (11.1 mL, 79.6 mmol), and N,N-bis(4-methoxybenzyl)amine (18.8 g, 73.0 mmol) were combined and heated at reflux for three days. The volatiles were removed under reduced pressure, and the residue was partitioned between ethyl acetate and saturated aqueous potassium carbonate. The ethyl acetate layer was separated and concentrated under reduced pressure. The residue was dissolved in dichloromethane, and the resulting solution was washed sequentially with water and brine. The combined aqueous fractions were extracted with ethyl acetate. The combined organic fractions were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude solid was triturated with ethanol, isolated by filtration, and washed with diethyl ether to provide 37.29 g of N4-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-N2,N2-bis(4-methoxybenzyl)-5,6-dimethyl-3-nitropyridin-2,4-diamine as an orange solid.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloro-N-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-5,6-dimethyl-3-nitropyridin-4-amine\"}], \"amount\": {\"mass\": {\"value\": 25.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 11.1, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-bis(4-methoxybenzyl)amine\"}], \"amount\": {\"mass\": {\"value\": 18.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"at reflux for three days\", \"duration\": {\"value\": 3.0, \"units\": \"DAY\"}}, {\"type\": \"CUSTOM\", \"details\": \"The volatiles were removed under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was partitioned between ethyl acetate and saturated aqueous potassium carbonate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The ethyl acetate layer was separated\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue was dissolved in dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"the resulting solution was washed sequentially with water and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The combined aqueous fractions were extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic fractions were dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude solid was triturated with ethanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"isolated by filtration\"}, {\"type\": \"WASH\", \"details\": \"washed with diethyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N4-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-N2,N2-bis(4-methoxybenzyl)-5,6-dimethyl-3-nitropyridin-2,4-diamine\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 37.29, \"units\": \"GRAM\"}}}], \"isolated_color\": \"orange\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-9a082a5a7beb47e5986a4caef0260ff6",
    "procedure_text": "A 200 mL round bottom flask is charged with 1,4-bis(bromomethyl)naphthalene (Example 26(b), 2.07 g, 6.6 mmol) and toluene (75 mL). The flask is equipped with a Dean-Stark trap, condenser, and nitrogen inlet. The mixture is heated to reflux temperature to dry the toluene and starting material. A total of 25 mL of toluene is collected in the Dean-Stark trap and then discarded. The mixture is cooled to room temperature and then trimethyl-phosphite (4 mL, 34 mmol) is added and the reaction is heated at a gentle reflux overnight. The reaction is checked by TLC after 24 hours and found to be complete. The toluene and excess trimethylphosphite are removed at a reduced pressure to yield an oil. The product is chromatographed on 400 g of 40-63 \u03bcm silica gel. The sample is applied in ethyl acetate and elution is with 10% methanol-ethyl acetate. Fractions which contained 50 mL each are collected. The desired product (2.01 g, 0.00542 mole, 81%) is eluted in fractions 60-80 and is a viscous oil.",
    "reference_string": "{\"inputs\": {\"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,4-bis(bromomethyl)naphthalene\"}], \"amount\": {\"mass\": {\"value\": 2.07, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 75.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trimethyl-phosphite\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The flask is equipped with a Dean-Stark trap, condenser, and nitrogen inlet\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The mixture is heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to reflux temperature\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"to dry the toluene\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"A total of 25 mL of toluene is collected in the Dean-Stark trap\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"the reaction is heated at\"}, {\"type\": \"TEMPERATURE\", \"details\": \"a gentle reflux overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The toluene and excess trimethylphosphite are removed at a reduced pressure\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trimethylphosphite\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"to yield an oil\"}, {\"type\": \"CUSTOM\", \"details\": \"The product is chromatographed on 400 g of 40-63 \\u03bcm silica gel\"}, {\"type\": \"WASH\", \"details\": \"elution\"}, {\"type\": \"CUSTOM\", \"details\": \"are collected\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 24.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 0.00542, \"units\": \"MOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.01, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 81.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f67684f9f97940a5abcdcacea1dd932a",
    "procedure_text": "A process for preparing 2(4-fluorophenyl)\u03b1-methyl-5-benzoxazole acetic acid starting from 4-hydroxy-3-amino-phenylacetic acid, which is firstly reacted with 4-fluorobenzoyl chloride, and the product obtained is reacted with phosphoric acid; the 2(4-fluorophenyl)5-benzoxazole acetic acid obtained in this manner is esterified with ethyl alcohol, and the ester is treated with diethyloxalate; the ethyl 2(4-fluorophenyl)5-benzoxazole oxalacetate obtained is reacted with formaldehyde and potassium carbonate to obtain ethyl 2(4-fluorophenyl)5-benzoxazole acrylate, which is hydrolysed to obtain the corresponding acid, from which the 2(4-fluorophenyl)\u03b1-methyl-5-benzoxazole acetic acid is obtained by hydrogenation.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"phosphoric acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2(4-fluorophenyl)\\u03b1-methyl-5-benzoxazole acetic acid\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-hydroxy-3-amino-phenylacetic acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-fluorobenzoyl chloride\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the product obtained\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2(4-fluorophenyl)5-benzoxazole acetic acid\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-962367940dee4c08b8d39c8d1c496bbe",
    "procedure_text": "Ethyl-[2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-5-trifluoromethyl-benzyl]-carbamic acid benzyl ester and (5-bromo-6-methoxy-pyridin-3-yl)-acetic acid ethyl ester were reacted as described in Example 3, Step 6 to provide (5-{2-[(N-benzyloxycarbonyl-N-ethyl-amino)-methyl]-4-trifluoromethyl-phenyl}-6-methoxy-pyridin-3-yl)-acetic acid ethyl ester.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ethyl-[2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-5-trifluoromethyl-benzyl]-carbamic acid benzyl ester\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(5-bromo-6-methoxy-pyridin-3-yl)-acetic acid ethyl ester\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(5-{2-[(N-benzyloxycarbonyl-N-ethyl-amino)-methyl]-4-trifluoromethyl-phenyl}-6-methoxy-pyridin-3-yl)-acetic acid ethyl ester\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2699ebc1d3e4428c805c1f8985b50352",
    "procedure_text": "2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yl trifluoromethanesulfonate (0.100 g, 0.25 mmol), tert-butyl 4-aminopiperidine-1-carboxylate (0.102 g, 0.51 mmol), Pd2 dba3 (0.023 g, 0.025 mmol), BINAP (0.032 g, 0.05 mmol) and cesium carbonate (0.124 g, 0.38 mmol) were combined in a capped vial and stirred at 100\u00b0 C. for 16 hours. The cooled mixture was filtered through GF paper and the filtrate partitioned between saturated NaHCO3 and EtOAc. The aqueous phase was extracted with EtOAc and the combined organic phases were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography (CH2Cl2 followed by 1% MeOH/CH2Cl2) to provide 0.107 g (95%) of desired product as an orange foam.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"cesium carbonate\"}], \"amount\": {\"mass\": {\"value\": 0.124, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yl trifluoromethanesulfonate\"}], \"amount\": {\"mass\": {\"value\": 0.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl 4-aminopiperidine-1-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 0.102, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd2 dba3\"}], \"amount\": {\"mass\": {\"value\": 0.023, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"BINAP\"}], \"amount\": {\"mass\": {\"value\": 0.032, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred at 100\\u00b0 C. for 16 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The cooled mixture was filtered through GF paper\"}, {\"type\": \"CUSTOM\", \"details\": \"the filtrate partitioned between saturated NaHCO3 and EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The aqueous phase was extracted with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"the combined organic phases were washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by flash column chromatography (CH2Cl2 followed by 1% MeOH/CH2Cl2)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH CH2Cl2\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.107, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 95.0}}], \"isolated_color\": \"orange\", \"texture\": {\"type\": \"FOAM\", \"details\": \"foam\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-adf97076cf8c426ba714eca51f9b1f46",
    "procedure_text": "3-[7-(2,4-Dimethoxyphenyl)-2,3,6,7-tetrahydro-[1,4]thiazepin-5-yl]-4-hydroxy-6-methyl-pyran-2-one (150 mg, 0.39 mmol), prepared as in Reference 5, was dissolved in toluene (2 ml) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (0.3 mL, 35 wt % in water) was added to the solution. The mixture was stirred at 80\u00b0 C. The reaction was monitored by analytical HPLC and after reaction was complete (20 minutes) the solvent was then removed in vacuo. Product was purified by preparative HPLC (RPC18 column, 2-80% acetonitrile/water containing 0.1% HCl) to provide 3-[7-(2,4-dimethoxy-phenyl)-2,3-dihydro-[1,4]thiazepin-5-yl]-4-hydroxy-6-methyl-pyran-2-one (35 mg) as an orange powder. LCMS: MH+ 373.0.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-[7-(2,4-Dimethoxyphenyl)-2,3,6,7-tetrahydro-[1,4]thiazepin-5-yl]-4-hydroxy-6-methyl-pyran-2-one\"}], \"amount\": {\"mass\": {\"value\": 150.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,3-dichloro-5,6-dicyano-1,4-benzoquinone\"}], \"amount\": {\"volume\": {\"value\": 0.3, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 80.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at 80\\u00b0 C\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"after reaction\"}, {\"type\": \"CUSTOM\", \"details\": \"(20 minutes)\", \"duration\": {\"value\": 20.0, \"units\": \"MINUTE\"}}, {\"type\": \"CUSTOM\", \"details\": \"was then removed in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"Product was purified by preparative HPLC (RPC18 column, 2-80% acetonitrile/water containing 0.1% HCl)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile water\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-[7-(2,4-dimethoxy-phenyl)-2,3-dihydro-[1,4]thiazepin-5-yl]-4-hydroxy-6-methyl-pyran-2-one\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 35.0, \"units\": \"MILLIGRAM\"}}}], \"isolated_color\": \"orange\", \"texture\": {\"type\": \"POWDER\", \"details\": \"powder\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f338593bb42141e5a94468c5d011ca54",
    "procedure_text": "A mixture of 0.1 mol of p-cyanobenzaldehyde, 0.1 mol of 3-hydroxymethyl-2-octanol, 200 ml of benzene and 150 mg of p-toluenesulfonic acid is boiled under a water separator until the reaction is complete. Usual working-up gives 2-p-cyanophenyl-5-n-pentyl-4-methyl-1,3-dioxane.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"p-cyanobenzaldehyde\"}], \"amount\": {\"moles\": {\"value\": 0.1, \"units\": \"MOLE\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-hydroxymethyl-2-octanol\"}], \"amount\": {\"moles\": {\"value\": 0.1, \"units\": \"MOLE\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"p-toluenesulfonic acid\"}], \"amount\": {\"mass\": {\"value\": 150.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzene\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-p-cyanophenyl-5-n-pentyl-4-methyl-1,3-dioxane\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-43d732d3f95e4666bb8a5b3221c2df18",
    "procedure_text": "5-Amino-2-chloropyridine (3.0 g) was dissolved in DMF (40 mL), N-iodosuccinimide (5.25 g) was added and the reaction mixture was stirred at room temperature for 3 hours. Water and MTB-ether were added to the reaction mixture, the layers were separated and the organic layer was washed 3\u00d7 with water, washed with brine, dried over MgSO4 and concentrated in vacuum. The residue was purified by column chromatography (silica 60, hexane/ethyl acetate=3:1, Rf=0.30) to afford 4.80 g of the title compound of the formula",
    "reference_string": "{\"inputs\": {\"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-iodosuccinimide\"}], \"amount\": {\"mass\": {\"value\": 5.25, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-Amino-2-chloropyridine\"}], \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Water\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture was stirred at room temperature for 3 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the layers were separated\"}, {\"type\": \"WASH\", \"details\": \"the organic layer was washed 3\\u00d7 with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuum\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by column chromatography (silica 60, hexane/ethyl acetate=3:1, Rf=0.30)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 4.8, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 80.8}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-cf82d9fb5a754ed2877e7e081d14bac3",
    "procedure_text": "To a solution of 4-(1,4-dimethyl-1H-pyrazol-5-yl)-5-ethyl-2-thiophenecarboxylic acid (130 mg, 0.52 mmol), 2-{(2S)-2-amino-3-[2-(trifluoromethyl)phenyl]propyl}-1H-isoindole-1,3(2H)-dione (200 mg, 0.52 mmol) [prepared according to Preparation 6] and diisopropylethylamine (0.45 ml, 2.60 mmol) in DCM at 25\u00b0 C. was added bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (267 mg, 0.57 mmol) in one portion. The solution stirred at 25\u00b0 C. for 12 h and was then dry loaded onto silica and purified via column chromatography (silica, 30-70% EtOAc in hexanes) yielding 4-(1,4-dimethyl-1H-pyrazol-5-yl)-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-5-ethyl-2-thiophenecarboxamide (278 mg, 0.43 mmol, 82% yield) as a yellow oil: LCMS (ES) m/e 581 (M+H)+.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m5_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(1,4-dimethyl-1H-pyrazol-5-yl)-5-ethyl-2-thiophenecarboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 130.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-{(2S)-2-amino-3-[2-(trifluoromethyl)phenyl]propyl}-1H-isoindole-1,3(2H)-dione\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropylethylamine\"}], \"amount\": {\"volume\": {\"value\": 0.45, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"bromo-tris-pyrrolidino-phosphonium hexafluorophosphate\"}], \"amount\": {\"mass\": {\"value\": 267.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 25.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The solution stirred at 25\\u00b0 C. for 12 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"was then dry\"}, {\"type\": \"CUSTOM\", \"details\": \"purified via column chromatography (silica, 30-70% EtOAc in hexanes)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 12.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(1,4-dimethyl-1H-pyrazol-5-yl)-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-5-ethyl-2-thiophenecarboxamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 0.43, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 278.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 82.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 82.7}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3135daf03cb84048a57f502366deb3ed",
    "procedure_text": "A solution of 290 mg (0.93 mmole) of (3R, 5S)-5-[(1S)-1-(t-butoxycarbonyl)amino-2-cyclohexylethyl]-3-methyldihydrofuran-2(3H)-one (prepared as described in Preparation 2) in 3 ml of methanol was mixed with 3 ml of isobutylamine, and the mixture was allowed to stand overnight at room temperature. At the end of this time, the reaction mixture was concentrated by distillation under reduced pressure, and the residue was triturated with hexane to afford 340 mg of the title compound as colorless crystals, melting at 125\u00b0-126\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(3R, 5S)-5-[(1S)-1-(t-butoxycarbonyl)amino-2-cyclohexylethyl]-3-methyldihydrofuran-2(3H)-one\"}], \"amount\": {\"mass\": {\"value\": 290.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isobutylamine\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"At the end of this time, the reaction mixture was concentrated by distillation under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was triturated with hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 340.0, \"units\": \"MILLIGRAM\"}}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d5ed7ce04f444b6cb76b1b007b13c19a",
    "procedure_text": "A mixture of (R)-2-(6-chloro-5-cyanopyrazin-2-ylamino)-4-methylpentanamide (70 mg, 0.261 mmol), 3-aminoquinoline (60 mg, 0.416 mmol), K2CO3 (60 mg, 0.434 mmol), BINAP (25 mg, 0.040 mmol) and Pd(OAc)2 (10 mg, 0.044 mmol) in dioxane (2 mL) was degassed with Ar, then was stirred at 100 C for 20 h. Water and EtOAc were added. Organic phase was separated, dried over Na2SO4, concentrated in vacuo to give (R)-2-(5-cyano-6-(quinolin-3-ylamino)pyrazin-2-ylamino)-4-methylpentanamide as a crude residue (131 mg). The crude (R)-2-(5-cyano-6-(quinolin-3-ylamino)pyrazin-2-ylamino)-4-methylpentanamide (131 mg) was dissolved in EtOH (2 mL) and DMSO (1 mL), aq. 1N NaOH (1.0 mL) and aq. H2O2 (50%, 1.0 mL) were added. The mixture was stirred at room temperature for 30 min. HOAc (0.5 mL) was added. The mixture was then concentrated in vacuo. The residue was purified by HPLC to give the titled compound (30 mg). MS 394.4 (M+H); UV 201.1, 247.4, 297.8, 352.3 nm; t 0.476 min.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HOAc\"}], \"amount\": {\"volume\": {\"value\": 0.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m6_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O2\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMSO\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-2-(5-cyano-6-(quinolin-3-ylamino)pyrazin-2-ylamino)-4-methylpentanamide\"}], \"amount\": {\"mass\": {\"value\": 131.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOH\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at room temperature for 30 min\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"The mixture was then concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by HPLC\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"titled compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 30.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-50451163a4734bf08f200b54f9d5fef2",
    "procedure_text": "As in Example 115, (E,E)-5-(3,4-dimethoxyphenyl)-2,4-decadienoic acid (3.08 g) and 4-nitrophenol (2.75 g) in 20 mL of dichloromethane was treated with 1,3-dicyclohexylcarbodiimide (2.11 g). The mixture was stirred at room temperature for 3 days and after the usual work up, crystallization of the crude ester from 2-propanol-hexane gave 2.98 g of (E,E)-5-(3,4-dimethoxyphenyl)-2,4-decadienoic acid 4-nitrophenyl ester, mp 95\u00b0-96.5\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(E,E)-5-(3,4-dimethoxyphenyl)-2,4-decadienoic acid\"}], \"amount\": {\"mass\": {\"value\": 3.08, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-nitrophenol\"}], \"amount\": {\"mass\": {\"value\": 2.75, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,3-dicyclohexylcarbodiimide\"}], \"amount\": {\"mass\": {\"value\": 2.11, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at room temperature for 3 days\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"after the usual work up, crystallization of the crude ester from 2-propanol-hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ester\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-propanol hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"DAY\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(E,E)-5-(3,4-dimethoxyphenyl)-2,4-decadienoic acid 4-nitrophenyl ester\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.98, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a4648e85d6d94be588e55164e6e9a00f",
    "procedure_text": "To a mixture of (1RS,2SR,6RS,7SR)-10-oxatricyclo[5.2.1.02,6]decane-3,5-dione (166 mg, 1 mmol) and 4-dimethylaminopyridine (610 mg, 5 mmol) under an atmosphere of nitrogen is added dry chloroform (5.6 ml), and the mixture is stirred at room temperature until all the solids are dissolved. To this solution is then added dry toluene (2 ml), and 3,5-dimethylbiphen-4-yllead triacetate (0.5 M solution in dry chloroform, 2.4 ml, 1.2 mmol). The reaction mixture is heated at reflux for 1 hour, then cooled to room temperature, acidified to pH1 with 2N aqueous hydrochloric acid, filtered and extracted with dichloromethane. The organic extracts are combined, dried over anhydrous magnesium sulfate, filtered and the filtrate evaporated under reduced pressure. The crude product is purified by column chromatography on silica gel to give (1RS,2SR,6RS,7SR)-4-(3,5-dimethylbiphen-4-yl)-10-oxa-tricyclo[5.2.1.02,6]decane-3,5-dione.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m6_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,5-dimethylbiphen-4-yllead triacetate\"}], \"amount\": {\"volume\": {\"value\": 2.4, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"amount\": {\"volume\": {\"value\": 5.6, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(1RS,2SR,6RS,7SR)-10-oxatricyclo[5.2.1.02,6]decane-3,5-dione\"}], \"amount\": {\"mass\": {\"value\": 166.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-dimethylaminopyridine\"}], \"amount\": {\"mass\": {\"value\": 610.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture is stirred at room temperature until all the solids\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"DISSOLUTION\", \"details\": \"are dissolved\"}, {\"type\": \"TEMPERATURE\", \"details\": \"The reaction mixture is heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"at reflux for 1 hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"cooled to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"the filtrate evaporated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude product is purified by column chromatography on silica gel\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(1RS,2SR,6RS,7SR)-4-(3,5-dimethylbiphen-4-yl)-10-oxa-tricyclo[5.2.1.02,6]decane-3,5-dione\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-6795b49bb9d349daa4b75417eb06291c",
    "procedure_text": "(COCl)2 (560 \u03bcL, 6.39 mmol) was added dropwise to a stirred solution of 3,4-bis(benzyloxy)-5-(dimethylcarbamoyl)-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylic acid (7) (1.6 g, 3.20 mmol) in DCM (20 mL) at 0\u00b0 C., followed by 2 drops of DMF. The reaction mixture was stirred at RT for 5 h, concentrated in vacuo and the resulting residue was dissolved in DCM (15 mL). N,O-dimethylhydroxylamine was added (215 mg, 3.52 mmol) followed by pyridine (620 \u03bcL, 7.67 mmol), and the reaction allowed to stir at RT for 18 h. The mixture was diluted with DCM (25 mL) and water (50 mL), the organic layer was separated and washed with water (2\u00d725 mL), brine (25 mL), dried (MgSO4), filtered and concentrated in vacuo. The product was purified by silica gel chromatography (40 g, 0-80% EtOAc in isohexane) to afford 3,4-bis(benzyloxy)-N2-methoxy-1-(4-methoxyphenyl)-N2,N5,N5-trimethyl-1H-pyrrole-2,5-dicarboxamide (33) (505 mg, 22%) as a colourless oil. m/z 544 (M+H)+ (ES+).",
    "reference_string": "{\"inputs\": {\"m6_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(COCl)2\"}], \"amount\": {\"volume\": {\"value\": 560.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,4-bis(benzyloxy)-5-(dimethylcarbamoyl)-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 1.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"reaction_role\": \"CATALYST\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"amount\": {\"volume\": {\"value\": 620.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred at RT for 5 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"DISSOLUTION\", \"details\": \"the resulting residue was dissolved in DCM (15 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"N,O-dimethylhydroxylamine was added (215 mg, 3.52 mmol)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,O-dimethylhydroxylamine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"STIRRING\", \"details\": \"to stir at RT for 18 h\", \"duration\": {\"value\": 18.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"the organic layer was separated\"}, {\"type\": \"WASH\", \"details\": \"washed with water (2\\u00d725 mL), brine (25 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The product was purified by silica gel chromatography (40 g, 0-80% EtOAc in isohexane)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"mass\": {\"value\": 40.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isohexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 5.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,4-bis(benzyloxy)-N2-methoxy-1-(4-methoxyphenyl)-N2,N5,N5-trimethyl-1H-pyrrole-2,5-dicarboxamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 505.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 22.0}}], \"isolated_color\": \"colourless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b44152434d224f93bfe06f55a5021c99",
    "procedure_text": "A solution of (R)-1-(tert-butoxycarbonyl)piperidine-2-carboxylic acid (Example 15 g. 18.5 g, 80.7 mmol) in anhydrous THF (44.4 mL) was cooled to 0\u00b0 C. BH3Me2S (44.4 mL, 88.8 mmol) was added drop wise over 15 minutes. After complete addition, the mixture was allowed to warm to room temperature, and stirring was continued for 18 hours. The mixture was quenched with water, and extracted with ethyl acetate. The organic extract was dried over anhydrous Na2SO4, filtered, and concentrated. The resulting residue was flash chromatographed on silica gel (35% ethyl acetate in hexanes) to provide (R)-tert-butyl-2-(hydroxymethyl)piperidine-1-carboxylate as a white solid (14.2 g, 82%). MS116 (MH+-boc)",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-1-(tert-butoxycarbonyl)piperidine-2-carboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 15.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 44.4, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirring\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"was cooled to 0\\u00b0 C\", \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"ADDITION\", \"details\": \"BH3Me2S (44.4 mL, 88.8 mmol) was added drop wise over 15 minutes\", \"duration\": {\"value\": 15.0, \"units\": \"MINUTE\"}}, {\"type\": \"ADDITION\", \"details\": \"After complete addition\"}, {\"type\": \"CUSTOM\", \"details\": \"The mixture was quenched with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The organic extract\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"was dried over anhydrous Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"chromatographed on silica gel (35% ethyl acetate in hexanes)\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 18.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-tert-butyl-2-(hydroxymethyl)piperidine-1-carboxylate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 14.2, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 82.0}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-25f78a7186094550abf658c010be3cc3",
    "procedure_text": "A mixture of 1.92 g of 5-[6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1H-imidazo[4,5-c]pyridin-1-yl]-3-{[-1-(2-chlorophenyl)propyl]oxy}thiophene-2-carboxamide in 35 ml THF is cooled to 0\u00b0 C. At 0\u00b0 C. 1.25 ml tetra-n-butylammonium fluoride (\u02dc75% in H20) are added. The reaction mixture is allowed to warm to room temperature and stirred for 90 minutes.",
    "reference_string": "{\"inputs\": {\"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-[6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1H-imidazo[4,5-c]pyridin-1-yl]-3-{[-1-(2-chlorophenyl)propyl]oxy}thiophene-2-carboxamide\"}], \"amount\": {\"mass\": {\"value\": 1.92, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 35.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetra-n-butylammonium fluoride\"}], \"amount\": {\"volume\": {\"value\": 1.25, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred for 90 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"At 0\\u00b0 C\", \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"to warm to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}], \"outcomes\": [{\"reaction_time\": {\"value\": 90.0, \"units\": \"MINUTE\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-be4a94ff7a074ec3b50b59fe8168cdd2",
    "procedure_text": "A solution of 3.0 g (11.8 mmol) of 2,5-diphenylpentane carboxylic acid and 1.91 9 (11.8 mmol) of carbonyldiimidazole is stirred at ambient temperature for one hour and then mixed with a solution of 2.13 g (11.8 mmol) of 2-(3,4-dimethylethoxyphenyl)ethylamine in 20 ml of tetrahydrofuran, stirred overnight at ambient temperature and, after the solvent has been distilled off, the residue is dissolved in ethyl acetate. The organic phase is washed twice with 15 ml of 1N HCl, twice with 20 ml of saturated NaHCO3 solution and then with a saturated NaCl solution. After drying over MgSO4 and distilling off the solvent, 4.9 g (100% of theory) of the desired end product are left, and this end product is further processed in the form of an oil without any more purification.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,5-diphenylpentane carboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"9\"}], \"amount\": {\"moles\": {\"value\": 11.8, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"carbonyldiimidazole\"}], \"reaction_role\": \"REACTANT\"}]}, \"m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(3,4-dimethylethoxyphenyl)ethylamine\"}], \"amount\": {\"mass\": {\"value\": 2.13, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred overnight at ambient temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"DISTILLATION\", \"details\": \"after the solvent has been distilled off\"}, {\"type\": \"DISSOLUTION\", \"details\": \"the residue is dissolved in ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic phase is washed twice with 15 ml of 1N HCl, twice with 20 ml of saturated NaHCO3 solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"After drying over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"distilling off the solvent, 4.9 g (100% of theory) of the desired end product\"}, {\"type\": \"WAIT\", \"details\": \"are left\"}, {\"type\": \"CUSTOM\", \"details\": \"this end product is further processed in the form of an oil without any more purification\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-b93493bd349c4f4c8bd9a86574c0494e",
    "procedure_text": "Analogously to Method I, 9.170 g of benzyl 3-hydroxy-4-(4-hydroxyphenyl)piperidinecarboxylate and 11.00 g of tertbutyl 3-toluenesulphonyloxy)azetidine-1-carboxylate are reacted. The title compound is obtained as a yellow oil. Rf=023 (3:1 EtOAc-heptane); Rt=5.01.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzyl 3-hydroxy-4-(4-hydroxyphenyl)piperidinecarboxylate\"}], \"amount\": {\"mass\": {\"value\": 9.17, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"azetidine-1-carboxylate\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-1228e7b16ac947da8049e41440d813b5",
    "procedure_text": "From trifluoromethanesulfonic acid 6-amino-3-cyano-2-furan-2-yl-pyridin-4-yl ester and 2-(aminomethyl)quinoline in DME. ES-MS m/e (%): 342 (M+H+, 100).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trifluoromethanesulfonic acid 6-amino-3-cyano-2-furan-2-yl-pyridin-4-yl ester\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(aminomethyl)quinoline\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DME\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-d6db3cd14b5845dd9533a61955c6d031",
    "procedure_text": "The title compound was made in a similar way as that of the compound of example 52 from 3-(1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-phenyl-1H-isochromen-1-one (intermediate D2a, 50 mg, 0.098 mmol), and 4-(trimethylstannyl)-1H-indazole (Intermediate G19, 41.4 mg, 0,147 mmol) to give the title compound (19 mg, 39%).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-phenyl-1H-isochromen-1-one\"}], \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(trimethylstannyl)-1H-indazole\"}], \"amount\": {\"mass\": {\"value\": 41.4, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 19.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 39.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-8dfb2164dc544dc8997b75eee5b226a1",
    "procedure_text": "In 5 ml of THF were dissolved 63 mg of 3-(methylthio)-1-propanol and 100 mg of methyl 2-(3-cyano-4-hydroxyphenyl)isonicotinate, and the resulting solution was heated at 0\u00b0 C. for 10 minutes in the presence of 0.15 ml of tributylphosphine and 149 mg of 1,1\u2032-(azodicarbonyl)dipiperidine. Then, the reaction solution was warmed to room temperature and stirred all day and night. After removal of the solvent, water was added and extraction with ethyl acetate was performed. The resulting organic layer is washed with brine and then dried and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform:methanol=95:5) to obtain 92 mg of methyl 2-{3-cyano-4-[3-(methylthio)propoxy]phenyl}isonicotinate. (2) Then, 92 mg of the compound was dissolved in a mixed solution of 3 ml of methanol and 3 ml of THF, and 0.32 ml of a 1M aqueous sodium hydroxide solution was added thereto, followed by heating at 60\u00b0 C. for 1 hour. After being cooled, the reaction solution was diluted with diisopropyl ether and an aqueous layer was separated. The aqueous layer was neutralized with 1M hydrochloric acid and then extracted with ethyl acetate. After washing with brine, the organic layer was dried and concentrated under reduced pressure to obtain 81 mg of 2-{3-cyano-4-[3-(methylthio)propoxy]phenyl}isonicotinic acid.",
    "reference_string": "{\"inputs\": {\"m5_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(methylthio)-1-propanol\"}], \"amount\": {\"mass\": {\"value\": 63.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 2-(3-cyano-4-hydroxyphenyl)isonicotinate\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tributylphosphine\"}], \"amount\": {\"volume\": {\"value\": 0.15, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,1\\u2032-(azodicarbonyl)dipiperidine\"}], \"amount\": {\"mass\": {\"value\": 149.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred all day and night\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"After removal of the solvent, water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"EXTRACTION\", \"details\": \"extraction with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The resulting organic layer is washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The resulting residue was purified by silica gel column chromatography (chloroform:methanol=95:5)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 2-{3-cyano-4-[3-(methylthio)propoxy]phenyl}isonicotinate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 92.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0acf2824452747efb84a9da23a52d6f2",
    "procedure_text": "The compound obtained in Step 2 of Example 59 (100 mg) was dissolved in chloroform (10 ml). Triethylamine (0.128 ml) and methanesulfonyl chloride (0.036 ml) were added dropwise under ice-cooling, and the mixture was stirred at the same temperature for 10 minutes and then stirred at room temperature for 1.5 hours. The reaction solution was concentrated, and the residue was purified by silica gel column chromatography (developed with methanol-chloroform) to give the title compound (82 mg) as a colorless solid.",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Triethylamine\"}], \"amount\": {\"volume\": {\"value\": 0.128, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanesulfonyl chloride\"}], \"amount\": {\"volume\": {\"value\": 0.036, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at the same temperature for 10 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooling\"}, {\"type\": \"STIRRING\", \"details\": \"stirred at room temperature for 1.5 hours\", \"duration\": {\"value\": 1.5, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CONCENTRATION\", \"details\": \"The reaction solution was concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was purified by silica gel column chromatography (developed with methanol-chloroform)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 10.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 82.0, \"units\": \"MILLIGRAM\"}}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a91480c239384beeb71acf9b41b56d98",
    "procedure_text": "Ethyl 3-(3-chloro-2-thienyl)-3-oxopropanoate (1.26 g, 5.42 mmol) was dissolved in anhydrous acetonitrile (10 mL), treated with triethylamine (0.63 mL, 6.2 mmol, 1.15 equiv) and cooled to 0\u00b0 C. To the mixture was added 4-acetamidobenzenesulfonyl azide (1.43 g, 6.0 mmol, 1.1 equiv) and after 10 minutes at 0\u00b0 C., the mixture was warmed to ambient temperature. To the mixture, additional acetonitrile (20 mL) was added and the mixture was stirred at ambient temperature for an additional 45 minutes. The mixture was treated with sodium hydroxide (10 mL, 1 N aqueous), sodium carbonate (25 mL, aqueous saturated) and water (75 mL) and then extracted with ethyl acetate (2\u00d7150 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 70:30; hexanes:ethyl acetate), providing the titled compound.",
    "reference_string": "{\"inputs\": {\"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4_m5_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium carbonate\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 75.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ethyl 3-(3-chloro-2-thienyl)-3-oxopropanoate\"}], \"amount\": {\"mass\": {\"value\": 1.26, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 0.63, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-acetamidobenzenesulfonyl azide\"}], \"amount\": {\"mass\": {\"value\": 1.43, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at ambient temperature for an additional 45 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"the mixture was warmed to ambient temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate (2\\u00d7150 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic extracts were dried with sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by silica gel gradient chromatography (100:0 to 70:30; hexanes:ethyl acetate)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 10.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"titled compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-2037c9c108ac45baa65f71caf36f56b2",
    "procedure_text": "Reaction of formylphosphonic acid and glycine was carried out in the manner described in Example 16 except that the catalyst was 1% palladium on alumina (0.5 g, 3.2 mm pellets). A 34% yield of glyphosate was obtained.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"formylphosphonic acid\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"glycine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"palladium on alumina\"}], \"amount\": {\"mass\": {\"value\": 0.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"glyphosate\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 34.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-7611a6ea622f406a99ad5d5f8f59f140",
    "procedure_text": "Compound 137 (50 mg, 0.16 mmol), (5-tert-butyl-2-m-tolyl-2H-pyrazol-3-yl)-carbamic acid 2,2,2-trichloro-ethyl ester (80 mg, 0.20 mmol), and DIEA (0.08 mL, 0.49 mmol) were suspended in DMSO (2 mL), and stirred overnight at 60\u00b0 C. The reaction solution was diluted with H2O/EtOAc, and filtered through an Extrelut column. The column was washed with EtOAc, and the filtrate was concentrated. The crude product was purified via Biotage eluting with a gradient of 25 to 100% EtOAc in hexanes to provide 230 (22 mg, 24% yield) as a tan solid. LC-MS (M+H=559, obsd.=559).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMSO\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Compound 137\"}], \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(5-tert-butyl-2-m-tolyl-2H-pyrazol-3-yl)-carbamic acid 2,2,2-trichloro-ethyl ester\"}], \"amount\": {\"mass\": {\"value\": 80.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O EtOAc\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DIEA\"}], \"amount\": {\"volume\": {\"value\": 0.08, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred overnight at 60\\u00b0 C\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"filtered through an Extrelut column\"}, {\"type\": \"WASH\", \"details\": \"The column was washed with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate was concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude product was purified via Biotage\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"eluting with a gradient of 25 to 100% EtOAc in hexanes\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"230\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 22.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 24.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 24.6}}], \"isolated_color\": \"tan\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-0a16bb1b5fcb4ca8ba63a277dff6e8c0",
    "procedure_text": "From the broth 3.7 g pravastatin dibenzylamine salt crude product was produced by the method given in Example 4, from which after recrystallization 2.9 g pravastatin dibenzylamine salt was obtained. The recrystallized pravastatin dibenzylamine salt was suspended in 45 ml ethanol, then under stirring 110 mole % sodium hydroxide was added by the feeding of 1M ethanolic sodium hydroxide solution. Stirring of the solution is continued for half an hour, then 0.3 g charcoal was added into it and stirred for another half an hour. The solution was filtered, and the filtrate was concentrated to 15 ml. Then 60 ml acetone was added to the concentrate at 56-60\u00b0 C. The solution obtained was cooled to room temperature, then kept overnight at +5\u00b0 C. Subsequently, the precipitate was filtered, then washed with 2\u00d720 ml acetone, 2\u00d720 ml ethyl acetate and 2\u00d720 ml n-hexane, and finally dried in vacuum. The resulting 1.7 g crude pravastatin was dissolved in ethanol, then clarified with charcoal and crystallized from an ethanol-ethyl acetate mixture. In this way 1.54 g pravastatin was obtained that was identical with the product of Example 2.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"charcoal\"}], \"amount\": {\"mass\": {\"value\": 0.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pravastatin dibenzylamine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 45.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"Stirring of the solution\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"after recrystallization 2.9 g pravastatin dibenzylamine salt\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pravastatin dibenzylamine\"}], \"amount\": {\"mass\": {\"value\": 2.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"was obtained\"}, {\"type\": \"WAIT\", \"details\": \"is continued for half an hour\"}, {\"type\": \"STIRRING\", \"details\": \"stirred for another half an hour\"}, {\"type\": \"FILTRATION\", \"details\": \"The solution was filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate was concentrated to 15 ml\"}, {\"type\": \"ADDITION\", \"details\": \"Then 60 ml acetone was added to the\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrate at 56-60\\u00b0 C\", \"temperature\": {\"setpoint\": {\"value\": 58.0, \"precision\": 2.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"The solution obtained\"}, {\"type\": \"FILTRATION\", \"details\": \"Subsequently, the precipitate was filtered\"}, {\"type\": \"WASH\", \"details\": \"washed with 2\\u00d720 ml acetone, 2\\u00d720 ml ethyl acetate and 2\\u00d720 ml n-hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-hexane\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"finally dried in vacuum\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The resulting 1.7 g crude pravastatin was dissolved in ethanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pravastatin\"}], \"amount\": {\"mass\": {\"value\": 1.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"crystallized from an ethanol-ethyl acetate mixture\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pravastatin\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.54, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f74788854af1427cb03d3fb12ca9a353",
    "procedure_text": "To a solution of 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid ethyl ester (0.40 g, 1.3 mmol) (as prepared in the previous step) in ethanol (3 mL) was added a solution of 6M KOH (0.2 mL, 1.2 mmol) and the reaction was stirred for 10 min and then concentrated to give 0.40 g (100%) of the title compound as a yellow solid. 1H-NMR (CD3OD; 400 MHz) \u03b4 7.98 (s, 1H), 5.92 (s, 2H), 3.62 (m, 2H), 0.94 (m, 2H), 0.00 (s, 9H). Mass spectrum (ESI-neg, m/z): Calcd. for C11H16KN3O3Si, 266.1 (M-K). found 266.0.",
    "reference_string": "{\"inputs\": {\"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid ethyl ester\"}], \"amount\": {\"mass\": {\"value\": 0.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"KOH\"}], \"amount\": {\"volume\": {\"value\": 0.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction was stirred for 10 min\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 10.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.4, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 100.0}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-456ef6d6316c4ca5b1b551c7b9244f70",
    "procedure_text": "1,1-Dimethylethyl 7-amino-8-hydroxy-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate (3.6 mmol) and potassium [(ethyloxy)carbonothioyl]sulfide (3.96 mmol) were suspended in pyridine (6 ml) and the reaction mixture was heated at 70\u00b0 C. for 3 h. The solvent was removed under reduced pressure providing a crude product that after dissolution in ethyl acetate, washing with water and evaporation of the organic phase under reduced pressure gave the title compound as a yellow solid (2.5 mmol, 69% yield).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,1-Dimethylethyl 7-amino-8-hydroxy-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate\"}], \"amount\": {\"moles\": {\"value\": 3.6, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium [(ethyloxy)carbonothioyl]sulfide\"}], \"amount\": {\"moles\": {\"value\": 3.96, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"amount\": {\"volume\": {\"value\": 6.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 70.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The solvent was removed under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"providing a crude product that\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washing with water and evaporation of the organic phase under reduced pressure\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 2.5, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 69.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 69.4}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-6ac5d6538ee14f36b628bcf23de42c35",
    "procedure_text": "To a solution of the product (4.5 g, 2.48 mmol) from Step 2 in dioxane (2 mL) was added 4M HCl in dioxane (8 mL) at rt and the resulting mixture was stirred for 1 h at that temperature. The solvent was removed in vacuo to obtain a thick oil. The oil was triturated with ether to obtain a white solid (2.5 g). The solid was recrystallized with toluene (20 mL) to obtain the title product (1.8 g, 53%) as a crystalline solid: MS; m/z 268 (M+H): 1H NMR (400 MHz, DMSO-d6); \u03b4 1.73 (m, 1H), 1.89 (m, 1H), 1.98 (m, 1H), 2.09 (m, 1H), 3.18 (m, 2H), 3.87 (m, 1H), 3.88 (s, 2H), 4.13 (dd, 1H, J1=7.2 Hz, J2=6.4 Hz), 4.19 (dd, 1H, J1=8.8, J2=3.2 Hz), 6.91 (d, 2H, J=6.8 Hz), 7.15-7.20 (m, 5H), 7.27 (m, 2H): HPLC (UV); 97.4%.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"amount\": {\"mass\": {\"value\": 4.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dioxane\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dioxane\"}], \"amount\": {\"volume\": {\"value\": 8.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the resulting mixture was stirred for 1 h at that temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The solvent was removed in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"to obtain a thick oil\"}, {\"type\": \"CUSTOM\", \"details\": \"The oil was triturated with ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.5, \"units\": \"GRAM\"}}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-1ca2664e99204126ab2b62c4df37e9a7",
    "procedure_text": "To a solution of ethyl 2-thienyloxyacetate (1.1 g, 5.9 mmol) in acetic acid (15 mL) is added N-chlorosuccinimide (0.78 g, 5.9 mmol). The solution is stirred for 1.5 hour. After this time the solution is concentrated. The resulting oil is dissolved in ether and washed with 1N NaOH, water and sat. NaCl. The organic layer is dried over MgSO4, filtered and concentrated under vacuum. The title compound (1.26 g, 5.7 mmol) is obtained as an oil. 1H NMR (CDCl3, 300 MHz) \u03b46.52 (d, 1H), 6.06 (d, 1H), 4.60 (s, 2H), 4.24 (q, 2H), 1.31 (t, 3H).",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 2-thienyloxyacetate\"}], \"amount\": {\"mass\": {\"value\": 1.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-chlorosuccinimide\"}], \"amount\": {\"mass\": {\"value\": 0.78, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The solution is stirred for 1.5 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"After this time the solution is concentrated\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The resulting oil is dissolved in ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with 1N NaOH, water and sat. NaCl\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaCl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layer is dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under vacuum\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.5, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 5.7, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.26, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4c3f6478250949da9bfa436d823abd7a",
    "procedure_text": "Further, the suspension of 80 g of polyphosphoric acid and 80 ml of toluene was stirred at 100\u00b0 C., 20 ml of toluene solution of above-mentioned compound (methyl 2-[4-(2-carboxyethylamino)-3-chlorophenyl]propionate) were added thereto and stirred for further 1 hour. After cooling, ice-water was added to the reaction mixture, then the mixture was poured into an aqueous solution of sodium hydroxide to adjust the pH to 9 to 10, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was subjected to column chromatography on silica gel, eluted with a mixture of ether and hexane to give 6.4 g of methyl 2-(8-chloro-1,2,3,4-tetrahydro-4-oxoquinolin-6-yl)propionate (Compound 32).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 2-[4-(2-carboxyethylamino)-3-chlorophenyl]propionate\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"polyphosphoric acid\"}], \"amount\": {\"mass\": {\"value\": 80.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"toluene\"}], \"amount\": {\"volume\": {\"value\": 80.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 100.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at 100\\u00b0 C.\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"stirred for further 1 hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"After cooling\"}, {\"type\": \"EXTRACTION\", \"details\": \"followed by extraction with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with water and saturated aqueous solution of sodium chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"The solvent was distilled off\"}, {\"type\": \"WASH\", \"details\": \"eluted with a mixture of ether and hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 2-(8-chloro-1,2,3,4-tetrahydro-4-oxoquinolin-6-yl)propionate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 6.4, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f7b391a96eda4ccd934740ade256eed1",
    "procedure_text": "To a solution of Example 37 (10 mg, 0.024 mmol) and excess potassium carbonate in DMF (0.5 mL) was added 3 drops of iodomethane. The reaction was stirred at rt for 1 h, before filtering and subjecting to purification via reverse phase HPLC. The fractions containing the major product were collected, diluted with ethyl acetate, and washed with aqueous sodium bicarbonate, water, and brine. The organic layer was dried (MgSO4), filtered, and concentrated to afford the title compound. 1H NMR (500 MHz), [CD3OD]: 8.38 (s, 1H), 7.78 (d, 2H), 7.76 (br, 3H), 7.30 (br, 3H), 3.83 (s, 3H), 3.66 (s, 3H), 2.66 (m, 1H), 2.45 (m, 1H), 1.85-1.72 (br, 2H). LCMS: [M+1]+=424. Human FAAH lysate assay: IC50=37 nM",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"amount\": {\"mass\": {\"value\": 10.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 0.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"iodomethane\"}], \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction was stirred at rt for 1 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"before filtering\"}, {\"type\": \"CUSTOM\", \"details\": \"subjecting to purification via reverse phase HPLC\"}, {\"type\": \"ADDITION\", \"details\": \"The fractions containing the major product\"}, {\"type\": \"CUSTOM\", \"details\": \"were collected\"}, {\"type\": \"ADDITION\", \"details\": \"diluted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"washed with aqueous sodium bicarbonate, water, and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layer was dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-10c123996df84035831a42c218e977c3",
    "procedure_text": "To a suspension of 5-methylpyrazin-2-amine (1.09 g, 10 mmol) in chloroform (100 mL) was added pyridine (0.85 mL, 10.5 mmol). The mixture was stirred in a foil-wrapped flask fitted with an addition funnel, and a solution of bromine (0.54 mL, 10.5 mmol) in chloroform (10 mL) was added dropwise over 10 min. The mixture was allowed to react an additional 20 minutes after addition was complete and then poured into a separatory funnel containing 10 mL water. The phases were separated and the organics washed again with water, dried over sodium sulfate, filtered and concentrated in vacuo. The resulting red oil was purified by silica gel chromatography with 12-100% EtOAc/hexanes. The major UV active peak was collected to give 3-bromo-5-methylpyrazin-2-amine (1.06 g, 5.64 mmol, 56.4% yield) as a cream-colored solid. 1H NMR (500 MHz, DMSO-d6) \u03b4 ppm 7.85 (s, 1H) 6.42 (br. s., 2H) 2.25 (s, 3H). MS (LC/MS) R.T.=0.93; [M+H]+=189.9.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"amount\": {\"volume\": {\"value\": 0.85, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-methylpyrazin-2-amine\"}], \"amount\": {\"mass\": {\"value\": 1.09, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"bromine\"}], \"amount\": {\"volume\": {\"value\": 0.54, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred in a foil-wrapped flask\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"fitted with an addition funnel\"}, {\"type\": \"CUSTOM\", \"details\": \"to react an additional 20 minutes\", \"duration\": {\"value\": 20.0, \"units\": \"MINUTE\"}}, {\"type\": \"ADDITION\", \"details\": \"after addition\"}, {\"type\": \"ADDITION\", \"details\": \"poured into a separatory funnel\"}, {\"type\": \"CUSTOM\", \"details\": \"The phases were separated\"}, {\"type\": \"WASH\", \"details\": \"the organics washed again with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The resulting red oil was purified by silica gel chromatography with 12-100% EtOAc/hexanes\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The major UV active peak was collected\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-bromo-5-methylpyrazin-2-amine\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 5.64, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.06, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 56.4}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 56.4}}], \"isolated_color\": \"cream-colored\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-12647d25d5e1446f9c54102c02b5077b",
    "procedure_text": "To a mixture of 5 g (0.024 mol) of p-trifluoromethylbenzoyl chloride in 100 mL of THF was added in portions 3 g (0.027 mol) of LAH, stirred at room temperature for 2 h, then refluxed for 2 h and cooled. To the reaction mixture was added 3 mL of water, 3 mL of 15% NaOH solution, and 9 mL of water and the resulting mixture was refluxed for 10 min, cooled, and filtered. The filtrate was concentrated in vacuo to afford 5.5 g (100%) of p-trifluoromethyl-benzyl alcohol, as a clear oil.",
    "reference_string": "{\"inputs\": {\"m3_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 9.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"p-trifluoromethylbenzoyl chloride\"}], \"amount\": {\"mass\": {\"value\": 5.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"LAH\"}], \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred at room temperature for 2 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"refluxed for 2 h\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"cooled\"}, {\"type\": \"TEMPERATURE\", \"details\": \"the resulting mixture was refluxed for 10 min\", \"duration\": {\"value\": 10.0, \"units\": \"MINUTE\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"cooled\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"The filtrate was concentrated in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"p-trifluoromethyl-benzyl alcohol\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 5.5, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 100.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-be13fb66d06d4810a82631cc0442e4d7",
    "procedure_text": "To a stirred solution of tert-butyl 4-({6-[1-(phenylsulfonyl)-5-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3-yl]pyrazin-2-yl}oxy)piperidine-1-carboxylate (0.075 g, 0.13 mmol) and iodoethane (11 pt, 0.14 mmol) in DMF (1.3 mL) at 0\u00b0 C. was added sodium hydride (60% mineral oil dispersion; 6.0 mg, 0.15 mmol). The reaction mixture was stirred at 0\u00b0 C. for 1 h then quenched with aqueous saturated sodium bicarbonate (5 mL). The reaction mixture was extracted with EtOAc (3\u00d710 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated. The crude residue was purified by silica gel chromatography (EtOAc/Hexanes gradient) to afford tert-butyl 4-({6-[5-(1-ethyl-1H-pyrazol-4-yl)-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine-3-yl]pyrazin-2-yl}oxy)piperidine-1-carboxylate as a yellow oil. LRMS (ESI) calculated for C32H35N7O5S [M+H]+, 630.2; found 630.2.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl 4-({6-[1-(phenylsulfonyl)-5-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3-yl]pyrazin-2-yl}oxy)piperidine-1-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 0.075, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"iodoethane\"}], \"amount\": {\"moles\": {\"value\": 0.14, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydride\"}], \"amount\": {\"mass\": {\"value\": 6.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 1.3, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred at 0\\u00b0 C. for 1 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"then quenched with aqueous saturated sodium bicarbonate (5 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The reaction mixture was extracted with EtOAc (3\\u00d710 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic layers were dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude residue was purified by silica gel chromatography (EtOAc/Hexanes gradient)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude residue\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc Hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl 4-({6-[5-(1-ethyl-1H-pyrazol-4-yl)-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine-3-yl]pyrazin-2-yl}oxy)piperidine-1-carboxylate\"}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-bae9925ceb90400983885ac9b1584879",
    "procedure_text": "207.7 mg of 2-(difluoromethoxy)benzyl bromide is added to a mixture of 200 mg of methyl 3-hydroxy-5-(3H-imidazo[4,5-c]pyridin-3-yl)thiophene-2-carboxylate and 110.9 mg of potassium carbonate in 6 ml anhydrous DMF. The mixture is stirred for 14 h at room temperature. Additional 207.7 mg of 2-(Difluoromethoxy)benzyl bromide and 110.9 mg of potassium carbonate are added and the mixture is stirred at 75\u00b0 C. for 3 h. Ice water is added to the mixture at room temperature and the organic phase is extracted with dichloromethane. The organic phase is poured on a phase separator and the solvent is removed under vacuum. The residue is dissolved in ethyl acetate and purified by flash column chromatography (eluent: hexane/ethyl acetate 1/1 (v/v) to 0/100 (v/v)) to yield the title compound.",
    "reference_string": "{\"inputs\": {\"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ice water\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m3_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(difluoromethoxy)benzyl bromide\"}], \"amount\": {\"mass\": {\"value\": 207.7, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 3-hydroxy-5-(3H-imidazo[4,5-c]pyridin-3-yl)thiophene-2-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 110.9, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 6.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(Difluoromethoxy)benzyl bromide\"}], \"amount\": {\"mass\": {\"value\": 207.7, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 110.9, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture is stirred for 14 h at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"the mixture is stirred at 75\\u00b0 C. for 3 h\", \"duration\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 75.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"the organic phase is extracted with dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"The organic phase is poured on a phase separator\"}, {\"type\": \"CUSTOM\", \"details\": \"the solvent is removed under vacuum\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue is dissolved in ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"purified by flash column chromatography (eluent: hexane/ethyl acetate 1/1 (v/v) to 0/100 (v/v))\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 14.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-90065dde628948169b93512d3c393401",
    "procedure_text": "A mixture of 1-(4-chlorophenyl)-2-aminopropiophenone hydrochloride (365 mg, 1.66 mmol), 2-(2,6-dichlorophenyl)-3H-benzimidazole-5-carbonyl chloride hydrochloride (600 mg, 1.66 mmol) (from Example 1-13) and triethylamine (924 \u03bcL, 671 mg, 6.63 mmol) in THF (25 mL) was stirred at ambient temperature for 18 h. The solution was then poured into ethyl acetate and extracted with water and brine. The organic layer was dried, filtered, and the solvent was removed under reduced pressure. The residue was purified by chromatography using a gradient of 50-90% heptane/ethyl acetate to give 2-(2,6-dichlorophenyl)-3H-benzimidazole-5-carboxylic acid [2-(4-chlorophenyl)-1-methyl-2-oxoethyl]-amide. 1H-NMR (acetone-d6, 400 MHz): \u03b4 8.57 (m, broad, 1H), 8.37 (m, 3H), 8.11 (m, broad, 1H), 7.83 (m, 5H), 5.92 (quintet, J=7.2 Hz, 1H), 1.75 (d, J=7.0 Hz, 3H). MS (ESI) m/z 473.9 (M+H).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(4-chlorophenyl)-2-aminopropiophenone hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 365.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(2,6-dichlorophenyl)-3H-benzimidazole-5-carbonyl chloride hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 600.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 924.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at ambient temperature for 18 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted with water and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The organic layer was dried\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was removed under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by chromatography\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 18.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(2,6-dichlorophenyl)-3H-benzimidazole-5-carboxylic acid [2-(4-chlorophenyl)-1-methyl-2-oxoethyl]-amide\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3bff4419c0e44de98d361cf0d8f27188",
    "procedure_text": "To a solution of 2-[4-(5,6,7,8-tetrahydro-quinoxalin-5-ylamino)-butyl]-isoindole-1,3-dione (298 mg, 0.850 mmol) in CH3CN (12 mL) was added 2-chloromethyl-benzoimidazole-1-carboxylic acid tert-butyl ester (295 mg, 1.11 mmol), potassium iodide (14 mg), and diisopropylethylamine (0.296 ml, 1.70 mmol). The reaction mixture was stirred at 60\u00b0 C. for 17 hours. Saturated sodium bicarbonate (15 mL) was added and the mixture was extracted with CH2Cl2 (3\u00d730 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated. Purification of the crude material by column chromatography on silica gel (1:10 EtOAc:hexanes then EtOAc then 1:10 McOH:EtOAc) provided the product as a clear oil (422 mg, 85%): 1H NMR (CDCl3): \u03b4 1.34-1.43 (m, 2H), 1.48-1.60 (m, 2H), 1.68 (s, 9H), 1.71-1.81 (m, 1H), 1.88-1.97 (m, 1H), 2.00-2.21 (m, 2H), 2.60-2.69 (m, 1H), 2.76-2.93 (m, 3H), 3.55 (t, 2H, J=6.9 Hz), 4.29 (dd, 1H, J=9.6, 5.4 Hz), 4.46 (d, 1H, J=15.3 Hz), 4.61 (d, 1H, J=15.3 Hz), 7.19-7.24 (m, 2H), 7.63-7.69 (m, 3H), 7.74-7.81 (m, 3H), 8.18 (d, 1H, J=2.1 Hz), 8.27 (d, 1H, J=2.1 Hz).",
    "reference_string": "{\"inputs\": {\"m1_m6_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-[4-(5,6,7,8-tetrahydro-quinoxalin-5-ylamino)-butyl]-isoindole-1,3-dione\"}], \"amount\": {\"mass\": {\"value\": 298.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloromethyl-benzoimidazole-1-carboxylic acid tert-butyl ester\"}], \"amount\": {\"mass\": {\"value\": 295.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium iodide\"}], \"amount\": {\"mass\": {\"value\": 14.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropylethylamine\"}], \"amount\": {\"volume\": {\"value\": 0.296, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH3CN\"}], \"amount\": {\"volume\": {\"value\": 12.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred at 60\\u00b0 C. for 17 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"the mixture was extracted with CH2Cl2 (3\\u00d730 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined organic extracts were dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification of the crude material by column chromatography on silica gel (1:10 EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude material\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 17.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 422.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 85.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 85.5}}], \"isolated_color\": \"clear\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-986e7356c4b346408530d035d1b301d8",
    "procedure_text": "A solution of ethyl 2-[4-(4-chlorophenyl)benzyloxy]-2-phenylpropionate (7.9 g.) in methanol (100 ml.) containing potassium hydroxide (11.0 g.) was heated under reflux for 2 hours and then evaporated. The residue was partitioned between water (100 ml.) and ether (30 ml.). The aqueous phase was separated and acidified with 4 N-hydrochloric acid to pH 2-3 and extracted with ether (3\u00d730 ml.). These ether extracts were washed with water, dried (MgSO4) and evaporated. The residue was crystallised by treatment with a mixture of ethyl acetate and hexane to give 2-[4-(4-chlorophenyl)-benzyloxy]-2-phenylpropionic acid, (3.5 g.), m.p. 125\u00b0-126\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 2-[4-(4-chlorophenyl)benzyloxy]-2-phenylpropionate\"}], \"amount\": {\"mass\": {\"value\": 7.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium hydroxide\"}], \"amount\": {\"mass\": {\"value\": 11.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"under reflux for 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was partitioned between water (100 ml.) and ether (30 ml.)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The aqueous phase was separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ether (3\\u00d730 ml.)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"These ether extracts were washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was crystallised by treatment with a mixture of ethyl acetate and hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-[4-(4-chlorophenyl)-benzyloxy]-2-phenylpropionic acid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 3.5, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-7c4d67e45c9340a4900940e7b2ef3bb6",
    "procedure_text": "C-[3-(2-Chloro-phenyl)-6-(2,4-difluoro-phenoxy)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-N,N-dimethyl-methanesulfonamide (273 mg, 0.447 mmol) was dissolved in 5 mL chloroform, and 2.5 mL of trifluoroacetic acid was added. The reaction mixture was stirred for 22 hours at room temperature, and was then concentrated to dryness under reduced pressure. The residue was dissolved in 7 mL of MeOH, and sodium borohydride (109 mg, 4.47 mmol) was added. The reaction mixture was stirred for 15 minutes, then concentrated under reduced pressure. The residue was partitioned between 100 mL EtOAc and 100 mL brine, and the organic layer was separated, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified via flash chromatography (0% to 40% EtOAc in hexanes) to yield 167 mg of C-[3-(2-Chloro-phenyl)-6-(2,4-difluoro-phenoxy)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-N,N-dimethyl-methanesulfonamide. Mass Spec. M+H=481.",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"C-[3-(2-Chloro-phenyl)-6-(2,4-difluoro-phenoxy)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-N,N-dimethyl-methanesulfonamide\"}], \"amount\": {\"mass\": {\"value\": 273.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trifluoroacetic acid\"}], \"amount\": {\"volume\": {\"value\": 2.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium borohydride\"}], \"amount\": {\"mass\": {\"value\": 109.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred for 22 hours at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"was then concentrated to dryness under reduced pressure\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue was dissolved in 7 mL of MeOH\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"amount\": {\"volume\": {\"value\": 7.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"STIRRING\", \"details\": \"The reaction mixture was stirred for 15 minutes\", \"duration\": {\"value\": 15.0, \"units\": \"MINUTE\"}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was partitioned between 100 mL EtOAc and 100 mL brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the organic layer was separated\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified via flash chromatography (0% to 40% EtOAc in hexanes)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 22.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"C-[3-(2-Chloro-phenyl)-6-(2,4-difluoro-phenoxy)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-N,N-dimethyl-methanesulfonamide\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 167.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-7a16a80309be49a386bd3f3d8860fd8b",
    "procedure_text": "A mixture of 3 g of 4-ethoxybutyl p-toluenesulfonate, 2.65 g of tert-butyl (3R)-3-methylpiperazine-1-carboxylate, 3.07 mL of triethylamine, and 30 mL of acetonitrile was stirred at 90\u00b0 C. for 3 hours. The reaction mixture was poured into a saturated aqueous sodium hydrogen carbonate solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (chloroform/methanol) to obtain 3.1 g of tert-butyl (3R)-4-(4-ethoxybutyl)-3-methylpiperazine-1-carboxylate.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydrogen carbonate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-ethoxybutyl p-toluenesulfonate\"}], \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl (3R)-3-methylpiperazine-1-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 2.65, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 3.07, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 90.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at 90\\u00b0 C. for 3 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"followed by extraction with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with saturated brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The solvent was evaporated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was purified by silica gel column chromatography (chloroform/methanol)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl (3R)-4-(4-ethoxybutyl)-3-methylpiperazine-1-carboxylate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 3.1, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-91ecc06887ee464a9ddcbdd53316a71b",
    "procedure_text": "To a solution of 25 g of ethyl 3,3-diethoxypropionate (131 mmol) in 79 mL of methanol there are added 13.1 mL of aqueous 35% sodium hydroxide solution (452 mmol). The reaction mixture is stirred at ambient temperature for 3 hours. The reaction mixture is then concentrated to remove the methanol. After dissolving the undissolved material by adding water, aqueous 5N HCl solution is added to obtain a pH of 5. Dichloromethane is added and then the organic phase is washed with brine. After drying over MgSO4 and concentrating to dryness, the title product is obtained in the form of an oil which is used in the next Step without being otherwise purified.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 3,3-diethoxypropionate\"}], \"amount\": {\"mass\": {\"value\": 25.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"moles\": {\"value\": 452.0, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 79.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Dichloromethane\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture is stirred at ambient temperature for 3 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"The reaction mixture is then concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"to remove the methanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISSOLUTION\", \"details\": \"After dissolving the undissolved material\"}, {\"type\": \"ADDITION\", \"details\": \"by adding water, aqueous 5N HCl solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"is added\"}, {\"type\": \"CUSTOM\", \"details\": \"to obtain a pH of 5\"}, {\"type\": \"WASH\", \"details\": \"the organic phase is washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"After drying over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrating to dryness\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title product\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f1700d0eeb994fb18ea79f6c3e24ee2c",
    "procedure_text": "To a solution of 3.09 g (0.01 mole) of 1-(hydroxymethyl)-9,10-dimethoxy-1,6,7,11b-tetrahydro-2H-[1,3]oxazino[4,3-a]isoquinoline-4-thione in 200 ml of dioxane 0.015 mole of HgO are added, and the mixture is reacted with 9.3 g (0.1 mole) of aniline. The reaction mixture is allowed to stand at room temperature for 24 hours, whereupon the HgS is filtered off, and the solvent and the excess of aniline are distilled off. The aimed compound is obtained in a yield of 45%.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HgS\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(hydroxymethyl)-9,10-dimethoxy-1,6,7,11b-tetrahydro-2H-[1,3]oxazino[4,3-a]isoquinoline-4-thione\"}], \"amount\": {\"mass\": {\"value\": 3.09, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dioxane\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aniline\"}], \"amount\": {\"mass\": {\"value\": 9.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"is filtered off\"}, {\"type\": \"DISTILLATION\", \"details\": \"the solvent and the excess of aniline are distilled off\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aniline\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aimed compound\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 45.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a1b52e426da543ab9767617419a2a9f1",
    "procedure_text": "The titled compound was prepared according to the procedure of Method C using N\u2032-hydroxynicotinimidamide (Tyger) and pyrimidine-5-carboxylic acid (Maybridge). 1H NMR (300 MHz, DMSO-d6) \u03b4 7.68 (ddd, J=8.0, 4.9, 1.0 Hz, 1H), 8.48 (dt, J=7.7, 2.1 Hz, 1H), 8.84 (dd, J=4.7, 1.7 Hz, 1H), 9.29 (dd, J=2.4, 1.0 Hz, 1H), 9.51 (s, 1H), 9.56 (s, 2H) ppm; MS (DCI/NH3) m/z=226 (M+H)+, 243 (M+NH4)+.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N\\u2032-hydroxynicotinimidamide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyrimidine-5-carboxylic acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH3\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"titled compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-6571cac3e2e840079c4fc68443eba744",
    "procedure_text": "To a mixture of 4-(2-fluoro-4-nitrophenoxy)-5-methyl-6-(2-(4-methylpiperazin-1-yl)ethoxy)pyrrolo[2,1-f][1,2,4]triazine (20 mg, 0.05 mmol) in anhydrous methanol (1 mL) and anhydrous THF (1 mL) at ambient temperature under nitrogen atmosphere was added zinc dust (33 mg, 50 mmol) and ammonium chloride (27 mg, 50 mmol). The reaction mixture was stirred for 7 h before the catalyst was filtered off and the filtrate was concentrated in vacuo to give a solid which was partitioned between chloroform and water. The aqueous phase was extracted twice with chloroform. The combined organic layers were washed with water, dried over anhydrous magnesium sulfate and concentrated in vacuo to give the desired compound (16 mg, 87%) as a solid. 1H NMR (CDCl3) \u03b4 7.86-7.83 (m, 1H), 7.50-7.38 (m, 2H), 7.09-7.00 (m, 1H), 6.56-6.45 (m, 1H), 4.14 (t, 2H, J=5.5 Hz), 2.99-2.38 (m, 18H); MS(ESI+) m/z 401.4 (M+H)+.",
    "reference_string": "{\"inputs\": {\"m1_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(2-fluoro-4-nitrophenoxy)-5-methyl-6-(2-(4-methylpiperazin-1-yl)ethoxy)pyrrolo[2,1-f][1,2,4]triazine\"}], \"amount\": {\"mass\": {\"value\": 20.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium chloride\"}], \"amount\": {\"mass\": {\"value\": 27.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"zinc\"}], \"amount\": {\"mass\": {\"value\": 33.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred for 7 h before the catalyst\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"was filtered off\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate was concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a solid which\"}, {\"type\": \"CUSTOM\", \"details\": \"was partitioned between chloroform and water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The aqueous phase was extracted twice with chloroform\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined organic layers were washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 7.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 16.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 87.0}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-806be3a6e32446999c248b72eac1798b",
    "procedure_text": "1,1\u2032-Carbonyldiimidazole (357 mg, 2.20 mmol) was added to a solution of 4-[(2S)-4-((1R)-1-phenylethyl)-morpholin-2-yl]-benzoic acid (623 mg, 2.00 mmol) in dichloromethane at 0\u00b0 C. After stirring for 2 hours, morpholine (0.35 ml, 4.0 mmol) was added to the reaction mixture. After stirring over night, the resulting suspension was concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to afford morpholin-4-yl-{4-[(2S)-4-((1R)-1-phenylethyl)-morpholin-2-yl]-phenyl}-methanone (465 mg, 60%.) as a colorless oil.",
    "reference_string": "{\"inputs\": {\"m1_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,1\\u2032-Carbonyldiimidazole\"}], \"amount\": {\"mass\": {\"value\": 357.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-[(2S)-4-((1R)-1-phenylethyl)-morpholin-2-yl]-benzoic acid\"}], \"amount\": {\"mass\": {\"value\": 623.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"morpholine\"}], \"amount\": {\"volume\": {\"value\": 0.35, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring for 2 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"After stirring over night\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the resulting suspension was concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by silica gel column chromatography (hexane/ethyl acetate)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"morpholin-4-yl-{4-[(2S)-4-((1R)-1-phenylethyl)-morpholin-2-yl]-phenyl}-methanone\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 465.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 60.0}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-def137155da94eccaf1fd18f4c149956",
    "procedure_text": "A mixture of 5-bromo-2-fluorobenzonitrile (25.0 g, 125 mmol), 4-methylimidazole (12.5 g, 152 mmol), potassium carbonate (34.55 g, 250 mmol) in DMSO (500 mL) was stirred at 90\u00b0 C. for 16 h. Water (1.5 L) was added and the resulting suspension was stirred with ice-bath cooling for 1 h. The precipitate was then filtered off, washed with water (0.5 L) and dried at 50\u00b0 C. over KOH. The resulting raw material (25.6 g) was dissolved in boiling ethyl acetate (300 mL). After addition of diisopropylether (300 mL) the solution was allowed to cool to room temperature. Filtration and drying afforded the title compound (19.35 g, 59%) as a white solid. Mp 166\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Water\"}], \"amount\": {\"volume\": {\"value\": 1.5, \"units\": \"LITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m3_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-bromo-2-fluorobenzonitrile\"}], \"amount\": {\"mass\": {\"value\": 25.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-methylimidazole\"}], \"amount\": {\"mass\": {\"value\": 12.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"potassium carbonate\"}], \"amount\": {\"mass\": {\"value\": 34.55, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMSO\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 90.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at 90\\u00b0 C. for 16 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"the resulting suspension was stirred with ice-bath\"}, {\"type\": \"TEMPERATURE\", \"details\": \"cooling for 1 h\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"The precipitate was then filtered off\"}, {\"type\": \"WASH\", \"details\": \"washed with water (0.5 L)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 0.5, \"units\": \"LITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried at 50\\u00b0 C. over KOH\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"KOH\"}], \"reaction_role\": \"WORKUP\"}]}, \"temperature\": {\"setpoint\": {\"value\": 50.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"DISSOLUTION\", \"details\": \"The resulting raw material (25.6 g) was dissolved\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"raw material\"}], \"amount\": {\"mass\": {\"value\": 25.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"After addition of diisopropylether (300 mL) the solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropylether\"}], \"amount\": {\"volume\": {\"value\": 300.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"to cool to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"Filtration\"}, {\"type\": \"CUSTOM\", \"details\": \"drying\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 19.35, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 59.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 59.1}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a2b81c40e0c84beea2c1a8fa53119db9",
    "procedure_text": "To crude methyl 4-cyclobutyl-2-methyl-5-(4H-1,2,4-triazol-3-yl)benzoate (compound 202.2, 0.24 mmol, 1.0 equiv) from the previous step in a 4-mL vial was added methanol (1.5 mL) and water (0.5 mL) and lithium hydroxide monohydrate (20 mg, 0.48 mmol, 2.0 equiv), The resulting mixture was stirred at 40\u00b0 C. for 42 hours. The reaction mixture was diluted into water (5 mL), acidified to pH 3 with 1M H3PO4 and extracted with DCM (3\u00d75 mL). The organics were dried (Na2SO4), filtered and concentrated in vacuo to obtain the title compound as a white solid (61 mg, 98% over 2 steps). m/z (ES+) 258 (M+H)+.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m7_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 4-cyclobutyl-2-methyl-5-(4H-1,2,4-triazol-3-yl)benzoate\"}], \"amount\": {\"moles\": {\"value\": 0.24, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound 202.2\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 1.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"lithium hydroxide monohydrate\"}], \"amount\": {\"mass\": {\"value\": 20.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 0.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H3PO4\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 40.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The resulting mixture was stirred at 40\\u00b0 C. for 42 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted with DCM (3\\u00d75 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DCM\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organics were dried (Na2SO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 42.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 61.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 98.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 98.8}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-ca0f60e986f145b78bb282d29ae2f8b0",
    "procedure_text": "To a solution of 232a (1.2 g, 5.8 mmol) in CH3OH (25 mL) was added HCHO (1 mL, 35 mmol) and acetic acid (1 mL), followed by the addition of NaBHCN3 (1.0 g, 12 mmol). The mixture was stirred at room temperature for 2 h. It was then evaporated under reduced pressure and the residue was purified by reverse-phase Combiflush eluting with 0.3% NH4HCO3 in water/acetonitrile to afford 232b as a yellow solid (1.0 g, 78%). MS-ESI: [M+H]+ 220.",
    "reference_string": "{\"inputs\": {\"m1_m4_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"232a\"}], \"amount\": {\"mass\": {\"value\": 1.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCHO\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH3OH\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at room temperature for 2 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"followed by the addition of NaBHCN3 (1.0 g, 12 mmol)\"}, {\"type\": \"CUSTOM\", \"details\": \"It was then evaporated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was purified by reverse-phase Combiflush\"}, {\"type\": \"WASH\", \"details\": \"eluting with 0.3% NH4HCO3 in water/acetonitrile\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NH4HCO3\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water acetonitrile\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"232b\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 78.0}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-286b610a16d14b3d844cf9152162ad65",
    "procedure_text": "7.2 g (19.4 mmol) of N-(4-benzenesulphonyl-2-nitro-phenyl)-N-methyl-methanesulphonamide are heated to 130\u00b0 C. in 70 ml conc. sulphuric acid for 15 minutes. Then the mixture is poured onto ice water, the precipitate formed is suction filtered, washed with water and dried.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(4-benzenesulphonyl-2-nitro-phenyl)-N-methyl-methanesulphonamide\"}], \"amount\": {\"mass\": {\"value\": 7.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sulphuric acid\"}], \"amount\": {\"volume\": {\"value\": 70.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"Then the mixture is poured onto ice water\"}, {\"type\": \"CUSTOM\", \"details\": \"the precipitate formed\"}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-3665cdef00b04a4db3c1ec76ae6b43f1",
    "procedure_text": "A solution of 30 g of 7-chloro-2-(3,3-diethoxy-1-hydroxy-2-propyl-amino)-5-(2-fluorophenyl)-3H-1,4-benzodiazepine in 300 ml of glacial acetic acid was heated to reflux temperature for 5 h. After cooling the solvent was removed in a vacuum, the residue was taken up in 300 ml of ethanol, the solution was treated with 150 ml of 2N aqueous sodium hydroxide solution and left te stand at room temperature for 2 h. Then, about 200 ml of ethanol were distilled off at 30\u00b0 C. in a vacuum. The solution remaining behind was extracted three times with chloroform. The chloroform extracts were washed with saturated sodium chloride solution, then dried over sodium sulphate and evaporated to dryness in a vacuum. The residue (20.5 g) was dissolved in chloroform and chromatographed over 500 g of silica gel. Byproducts (total 4.1 g) were eluted with chloroform containing 0.2% to 1.6% ethanol. 13.0 g of the desired product were eluted with chloroform containing 2.4 to 20% ethanol. After recrystallization from ethyl acetate/diethyl ether there were obtained 11.6 g of 8-chloro-6-(2-fluorophenyl)-4H-imidazo[1,2-a][1,4]benzodiazepine-2-methanol of m.p. 196-199.5\u00b0 C. After repeated recrystallization from ethyl acetate the m.p. lay at 199-201\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7-chloro-2-(3,3-diethoxy-1-hydroxy-2-propyl-amino)-5-(2-fluorophenyl)-3H-1,4-benzodiazepine\"}], \"amount\": {\"mass\": {\"value\": 30.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 300.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"to reflux temperature for 5 h\", \"duration\": {\"value\": 5.0, \"units\": \"HOUR\"}}, {\"type\": \"TEMPERATURE\", \"details\": \"After cooling the solvent\"}, {\"type\": \"CUSTOM\", \"details\": \"was removed in a vacuum\"}, {\"type\": \"ADDITION\", \"details\": \"the solution was treated with 150 ml of 2N aqueous sodium hydroxide solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"Then, about 200 ml of ethanol were distilled off at 30\\u00b0 C. in a vacuum\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}, \"temperature\": {\"setpoint\": {\"value\": 30.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"The solution remaining behind was extracted three times with chloroform\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The chloroform extracts were washed with saturated sodium chloride solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulphate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulphate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated to dryness in a vacuum\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue (20.5 g) was dissolved in chloroform\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"residue\"}], \"amount\": {\"mass\": {\"value\": 20.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"chromatographed over 500 g of silica gel\"}, {\"type\": \"WASH\", \"details\": \"Byproducts (total 4.1 g) were eluted with chloroform containing 0.2% to 1.6% ethanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"13.0 g of the desired product were eluted with chloroform containing 2.4 to 20% ethanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"amount\": {\"mass\": {\"value\": 13.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"After recrystallization from ethyl acetate/diethyl ether there\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate diethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"8-chloro-6-(2-fluorophenyl)-4H-imidazo[1,2-a][1,4]benzodiazepine-2-methanol\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 11.6, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-8936ecbb8154402d9657a89966333bad",
    "procedure_text": "In 800 ml of methanol was dissolved 15.9 g of [(1S)-1-[(2R)-2-(2,4-difluorophenyl)-2-oxiranyl]ethyl]benzoate. To the solution was added 28% methanolic solution (12.9 ml) of sodium methylate with ice cooling and the reaction mixture was stirred at room temperature for 6 hours. To the reaction mixture was added 63.2 ml of 1N aqueous solution of hydrochloric acid and the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (gradient eluent; hexane:ethyl acetate=6:1\u21922:1) to give 9.7 g of (1S)-1-[(2R)-2-(2,4-difluorophenyl)-2-oxiranyl]ethanol as a colorless oil.",
    "reference_string": "{\"inputs\": {\"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanolic solution\"}], \"amount\": {\"volume\": {\"value\": 12.9, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium methylate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aqueous solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m6_m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"[(1S)-1-[(2R)-2-(2,4-difluorophenyl)-2-oxiranyl]ethyl]benzoate\"}], \"amount\": {\"mass\": {\"value\": 15.9, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 800.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture was stirred at room temperature for 6 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"DISTILLATION\", \"details\": \"the solvent was distilled off under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by silica gel chromatography (gradient eluent; hexane:ethyl acetate=6:1\\u21922:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 6.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(1S)-1-[(2R)-2-(2,4-difluorophenyl)-2-oxiranyl]ethanol\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 9.7, \"units\": \"GRAM\"}}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-589896f253964c8bb0a858c114933e6f",
    "procedure_text": "Sodium borohydride [1.89 g (50 mmol)] was added to a solution of 2.82 g (10.0 mmol) of 4-(3-phthalimidopropyloxy)pyridine in 150 ml of ethanol. The mixture was stirred at room temperature for 15 minutes. After the solvent was distilled off, brine was added to the residue. The mixture was extracted with chloroform and dried over anhydrous magnesium sulfate, and then the solvent was distilled off. The residue was purified by column chromatography (eluent: ethanol/ethyl acetate=1:10), and then recrystallized from ethyl acetate to obtain 1.54 g of the desired compound (yield: 54.2%, colorless crystals)",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Sodium borohydride\"}], \"amount\": {\"mass\": {\"value\": 1.89, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(3-phthalimidopropyloxy)pyridine\"}], \"amount\": {\"mass\": {\"value\": 2.82, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at room temperature for 15 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"DISTILLATION\", \"details\": \"After the solvent was distilled off\"}, {\"type\": \"ADDITION\", \"details\": \"brine was added to the residue\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The mixture was extracted with chloroform\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"the solvent was distilled off\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by column chromatography (eluent: ethanol/ethyl acetate=1:10)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"recrystallized from ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.54, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 54.2}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 54.2}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-21f5d4985c1d4d7683b8f00c5eaa4437",
    "procedure_text": "From styrene oxide and 6-amino-1-hexanol. Yield after chromatography (methanol): 30% (oil).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"styrene oxide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-amino-1-hexanol\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-7ab3f6dd0f6c40abadaef1706102c314",
    "procedure_text": "To a solution of 6-methoxycarbonylmethoxy-5-nitro-nicotinic acid ethyl ester (3.271 g) in acetic acid (25 ml) was added iron powder (9.64 g). The mixture was stirred for 2 h at 60\u00b0 C. The mixture was filtered and the filter cake was washed with acetic acid, EtOAc, EtOH, dichloromethane and with MeOH. The filtrate was concentrated. The residue was suspended in CH2Cl2/MeOH 9:1 and passed with more of the same solvent mixture over silica gel to give the title compound (1.52 g) as a light brown solid. MS (m/e)=223.1 [M+H+].",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6-methoxycarbonylmethoxy-5-nitro-nicotinic acid ethyl ester\"}], \"amount\": {\"mass\": {\"value\": 3.271, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"iron\"}], \"amount\": {\"mass\": {\"value\": 9.64, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 60.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred for 2 h at 60\\u00b0 C\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The mixture was filtered\"}, {\"type\": \"WASH\", \"details\": \"the filter cake was washed with acetic acid, EtOAc, EtOH, dichloromethane and with MeOH\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOH\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"The filtrate was concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.52, \"units\": \"GRAM\"}}}], \"isolated_color\": \"light brown\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b6cbab7848254a1999677e2bd4498c36",
    "procedure_text": "In a manner similar to the method described in example 4a, 5-bromosalicylaldehyde (3 g, 15 mmol) (Aldrich) reacted with methanesulfonic acid tetrahydropyran-4-yl ester (4 g, 22 mmol) prepared in Example 32a and K2CO3 in N,N-dimethylformamide to give 5-bromo-2-(tetrahydro-pyran-4-yloxy)-benzaldehyde as a yellow solid (Yield 2.86 g, 67%).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-bromosalicylaldehyde\"}], \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanesulfonic acid tetrahydropyran-4-yl ester\"}], \"amount\": {\"mass\": {\"value\": 4.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"K2CO3\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-bromo-2-(tetrahydro-pyran-4-yloxy)-benzaldehyde\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.86, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 67.0}}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e9cff9277721458b8b5cff4952132e3b",
    "procedure_text": "Mon-ethyl methoxy(methyl)malonate (14.52 grams, 0.08 mole) was reacted with thionyl chloride (19.61 grams, 0.16 mole) at 50\u00b0 C. for a 13-hour reaction period with an additional holding period of approximately 32 hours at room temperature. Vacuum evaporation of the excess thionyl chloride gave 15.2 grams (0.08 mole) of ethyl 2-(chlorocarbonyl)-2-methoxypropionate. NMR analysis of the product indicated the following:",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl methoxy(methyl)malonate\"}], \"amount\": {\"mass\": {\"value\": 14.52, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"thionyl chloride\"}], \"amount\": {\"mass\": {\"value\": 19.61, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"reaction period with an additional holding period of approximately 32 hours at room temperature\", \"duration\": {\"value\": 32.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"Vacuum evaporation of the excess thionyl chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"thionyl chloride\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 2-(chlorocarbonyl)-2-methoxypropionate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 0.08, \"units\": \"MOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 15.2, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-8d6323aaf58642598ff88c32ae62ade8",
    "procedure_text": "A solution of dimethyl bicyclo[3.3.1]nonane-1,5-dicarboxylate (8.32 g, 36.8 mmol) and Ba(OH)2.8H2O (5.80 g, 18.4 mmol) in ethanol (40 mL) and H2O (10 mL) was refluxed overnight. After cooled to room temperature, the mixture was concentrated under reduced pressure. The resulting residue was added diluted with water (100 mL) and extracted with diethyl ether (3\u00d7200 mL). The combined organic layer was washed with brine (100 mL), dried over sodium sulfate and concentrated under reducer pressure to recover starting material as an orange oil. The aqueous phase was adjusted to pH 1\u02dc2 with 2N aq. HCl, and extracted with dichloromethane (3\u00d7100 mL). The combined organic layer was washed with brine (100 mL), dried over sodium sulfate and concentrated under reduced pressure to afford 1.8 g (67%) of 5-(methoxycarbonyl)bicyclo[3.3.1]nonane-1-carboxylic acid as a white solid. ESI-MS m/z: 213 (M+H)+.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethyl bicyclo[3.3.1]nonane-1,5-dicarboxylate\"}], \"amount\": {\"mass\": {\"value\": 8.32, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Ba(OH)2.8H2O\"}], \"amount\": {\"mass\": {\"value\": 5.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"the mixture was concentrated under reduced pressure\"}, {\"type\": \"ADDITION\", \"details\": \"The resulting residue was added\"}, {\"type\": \"ADDITION\", \"details\": \"diluted with water (100 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with diethyl ether (3\\u00d7200 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined organic layer was washed with brine (100 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reducer pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"to recover\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with dichloromethane (3\\u00d7100 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined organic layer was washed with brine (100 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-(methoxycarbonyl)bicyclo[3.3.1]nonane-1-carboxylic acid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.8, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 67.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 21.6}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4363dabc83874b53a061e880dad7c775",
    "procedure_text": "3-Nitrobenzaldehyde (3.0 g, 20 mmoles), ethyl 3-amino-2-butenoate (2.6 g, 20 mmoles) and ethyl 4,4,4-trifluoro-3-oxobutanoate (2.92 ml, 20 mmoles) were heated at reflux in ethanol (25 ml) for 6 hours. The solvent was removed in vacuo and the residue crystallised by the addition of ether/petroleum ether (60\u00b0-80\u00b0). The resulting solid was recrystallised from ether/petroleum ether (60\u00b0-80\u00b0) to give the title compound as colourless crystals (1.9 g) mp 120\u00b0-1\u00b0.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 25.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-Nitrobenzaldehyde\"}], \"amount\": {\"mass\": {\"value\": 3.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 3-amino-2-butenoate\"}], \"amount\": {\"mass\": {\"value\": 2.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 4,4,4-trifluoro-3-oxobutanoate\"}], \"amount\": {\"volume\": {\"value\": 2.92, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The solvent was removed in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue crystallised by the addition of ether/petroleum ether (60\\u00b0-80\\u00b0)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether petroleum ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The resulting solid was recrystallised from ether/petroleum ether (60\\u00b0-80\\u00b0)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether petroleum ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.9, \"units\": \"GRAM\"}}}], \"isolated_color\": \"colourless\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-14c211aee669485fb1646827e85b1ad9",
    "procedure_text": "In a 4 neck 5 L flask was added (R)-N-hydroxy-1,4-dioxaspiro[4.5]decane-2-carbimidoyl chloride (158 g, 719 mmol) in 2.5 L of THF. The material was cooled to 3\u00b0 C. and methanesulfonyl chloride (56.1 ml, 719 mmol) added in 10 mL portions over 10 minutes. N-ethyl-N-isopropylpropan-2-amine (126 ml, 719 mmol) was added through an addition funnel over 12 minutes. The reaction was stirred in the ice bath for 30 minutes and then at ambient temperature for 1 hour. The reaction was filtered and the solids washed with MTBE (about 3 L). The filtrate was concentrated and the residue was purified over silica gel (7:1 to 3:1 Hexanes/EtOAc) to afford an oil that slowly solidified under vacuum. The solids were ground using a mortar and pestle, washed with hexanes (about 1000 mL) and dried to afford (R)-N-(methylsulfonyloxy)-1,4-dioxaspiro[4.5]decane-2-carbimidoyl chloride (158 g, 531 mmol, 73.8% yield) as a white solid.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanesulfonyl chloride\"}], \"amount\": {\"volume\": {\"value\": 56.1, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-N-hydroxy-1,4-dioxaspiro[4.5]decane-2-carbimidoyl chloride\"}], \"amount\": {\"mass\": {\"value\": 158.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 2.5, \"units\": \"LITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-ethyl-N-isopropylpropan-2-amine\"}], \"amount\": {\"volume\": {\"value\": 126.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 3.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The reaction was filtered\"}, {\"type\": \"WASH\", \"details\": \"the solids washed with MTBE (about 3 L)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MTBE\"}], \"amount\": {\"volume\": {\"value\": 3.0, \"units\": \"LITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"The filtrate was concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was purified over silica gel (7:1 to 3:1 Hexanes/EtOAc)\"}, {\"type\": \"CUSTOM\", \"details\": \"to afford an oil that\"}, {\"type\": \"WASH\", \"details\": \"washed with hexanes (about 1000 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexanes\"}], \"amount\": {\"volume\": {\"value\": 1000.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-N-(methylsulfonyloxy)-1,4-dioxaspiro[4.5]decane-2-carbimidoyl chloride\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 531.0, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 158.0, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 73.8}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 73.9}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-27397a5e854945f7977fbcf252fb32aa",
    "procedure_text": "4-[4-(4-Trifluoromethyl-phenyl)-piperazin-1-yl]-butyric acid lithium salt (26 mg; 0.08 mmol, prepared in accordance with Example 3), diisopropylethyl amine (26 \u03bcL; 0.15 mmol) and tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (28 mg; 0.08 mmol) are diluted in a 2 to 1 mixture of dimethylformamide and tetrahydrofuran (1.5 mL) and the resulting solution is stirred for 5 minutes. A solution of piperidin-4-yl-(3-trifluoromethyl-phenyl)-amine hydrochloride (21 mg; 0.08 mmol, prepared in accordance with Example 80) in dimethylformamide (0.5 mL) is added and the reaction is then stirred for 4 hours at room temperature. Following dilution with dichloromethane (10 mL), the organic layer is sequentially washed with water (5 mL), aq. sat. sodium hydrogen carbonate (3\u00d75 mL), is dried over magnesium sulfate and concentrated under reduced pressure. The residue obtained is finally purified by preparative HPLC to deliver the desired product in pure form (14 mg; 0.03 mmol). The structure was confirmed using Protocol I-B. Calculated mass=543; observed mass=543; HPLC retention time=5.20 min.",
    "reference_string": "{\"inputs\": {\"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m2_m3_m6_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-[4-(4-Trifluoromethyl-phenyl)-piperazin-1-yl]-butyric acid lithium salt\"}], \"amount\": {\"mass\": {\"value\": 26.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropylethyl amine\"}], \"amount\": {\"volume\": {\"value\": 26.0, \"units\": \"MICROLITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate\"}], \"amount\": {\"mass\": {\"value\": 28.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 1.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"piperidin-4-yl-(3-trifluoromethyl-phenyl)-amine hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 21.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 0.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the resulting solution is stirred for 5 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"the reaction is then stirred for 4 hours at room temperature\", \"duration\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"WASH\", \"details\": \"the organic layer is sequentially washed with water (5 mL), aq. sat. sodium hydrogen carbonate (3\\u00d75 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydrogen carbonate\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"is dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue obtained\"}, {\"type\": \"CUSTOM\", \"details\": \"is finally purified by preparative HPLC\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 5.0, \"units\": \"MINUTE\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-847105c1692d455080369114984b6d46",
    "procedure_text": "A solution of (E)-4-methyl-3,5-dioxa-7-octadecen-9,12-diyne(3.76 g) in acetone (60 mL) was treated with aqueous sulfuric acid (0.2 N, 6 mL) and left at room temperature for 3 hours. Half of the acetone was removed in vacuo and the residual solution was poured into water, extracted with ether and the combined extracts were dried (MgSO4), concentrated and purified by liquid chromatography (4:1 parts by volume hexane-ethyl acetate) to yield pure material (E)-2-tridecen-4,7-diyn-1-ol (2.5 g).",
    "reference_string": "{\"inputs\": {\"m1_m3_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(E)-4-methyl-3,5-dioxa-7-octadecen-9,12-diyne\"}], \"amount\": {\"mass\": {\"value\": 3.76, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sulfuric acid\"}], \"amount\": {\"volume\": {\"value\": 6.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Half of the acetone was removed in vacuo\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetone\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"the residual solution was poured into water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"the combined extracts were dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"purified by liquid chromatography (4:1 parts by volume hexane-ethyl acetate)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 3.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(E)-2-tridecen-4,7-diyn-1-ol\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.5, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-317edc89f3fd4f2d953d65969a14c2bf",
    "procedure_text": "Trifluoroacetic acid (1.0 mL, 6.49 mmol) was added to a solution of (S)-methyl 6-(1-(1-(tert-butoxycarbonyl)azetidin-3-yl)-1H-pyrazol-4-yl)-5-(3-chloro-4-fluorophenoxy)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate (0.098 g, 0.033 mmol) in dichloromethane (1.0 mL) and the reaction mixture stirred at rt for 2 h. The mixture was then concentrated and the residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate solution. The organic phase was separated, dried over anhydrous sodium sulfate, filtered, and concentrated to afford methyl (S)-6-(1-(1-(tert-butoxycarbonyl)azetidin-3-yl)-1H-pyrazol-4-yl)-5-(4-fluorophenoxy)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate (0.105 g, 100%) as an off-white solid. MS (ESI, pos. ion) m/z 437 [M+H]+.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Trifluoroacetic acid\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(S)-methyl 6-(1-(1-(tert-butoxycarbonyl)azetidin-3-yl)-1H-pyrazol-4-yl)-5-(3-chloro-4-fluorophenoxy)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 0.098, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture stirred at rt for 2 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"The mixture was then concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The organic phase was separated\"}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl (S)-6-(1-(1-(tert-butoxycarbonyl)azetidin-3-yl)-1H-pyrazol-4-yl)-5-(4-fluorophenoxy)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.105, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 100.0}}], \"isolated_color\": \"off-white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f1ddca763a4149cfbb4553963d638397",
    "procedure_text": "To a solution of methyl 2-[4-(6-amino-5-nitro-2-pyridyl)-5-(2,4-difluorophenyl)-1H-imidazol-2-yl]-2-methyl-propanoate (56 g, 134.17 mmol) in dimethyl sulfoxide (DMSO, 400 mL) and water (320 mL), is added sulfuric acid 95-97% (80 mL) dropwise. Then the mixture is cooled to 0\u00b0 C. To the above mixture a solution of sodium nitrite (18.70 g, 268.35 mmol) in water (80 mL) is added dropwise over 15 min at 0\u00b0 C. The reaction mixture is stirred for 20 min at that temperature and then the cooling bath is removed and the temperature is allowed to rise to RT. To the reaction mixture is added a 0.8 M aqueous solution of buffered sodium phosphate monobasic (1200 mL, pH=6). A yellow suspension appears. This suspension is stirred at RT for 1 h. The solid is filtered, washed with water, and dried in the oven to afford the title compound as an orange solid (49.5 g, 88%). LC-ES/MS m/z 419 (M+1).",
    "reference_string": "{\"inputs\": {\"m1_m4_m5_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 2-[4-(6-amino-5-nitro-2-pyridyl)-5-(2,4-difluorophenyl)-1H-imidazol-2-yl]-2-methyl-propanoate\"}], \"amount\": {\"mass\": {\"value\": 56.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sulfuric acid\"}], \"amount\": {\"volume\": {\"value\": 80.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethyl sulfoxide\"}], \"amount\": {\"volume\": {\"value\": 400.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 320.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium nitrite\"}], \"amount\": {\"mass\": {\"value\": 18.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 80.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture is stirred for 20 min at that temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the cooling bath is removed\"}, {\"type\": \"CUSTOM\", \"details\": \"to rise to RT\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"ADDITION\", \"details\": \"To the reaction mixture is added a 0.8 M aqueous solution of buffered sodium phosphate monobasic (1200 mL, pH=6)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aqueous solution\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium phosphate monobasic\"}], \"amount\": {\"volume\": {\"value\": 1200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"STIRRING\", \"details\": \"This suspension is stirred at RT for 1 h\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"FILTRATION\", \"details\": \"The solid is filtered\"}, {\"type\": \"WASH\", \"details\": \"washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"dried in the oven\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 20.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 49.5, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 88.0}}], \"isolated_color\": \"orange\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-7c7873db9e3d4c059e5a71acc54e1d00",
    "procedure_text": "To a solution of 2-amino-4-methoxycarbonylphenyl trifluoromethanesulfonate (2.6 g) in a mixture of pyridine (5.6 ml) and dichloromethane (20 ml) was added benzyl chloroformate (2.08 ml) at 0\u00b0 C., and the mixture was stirred at 20\u00b0 C. for 4.5 hours. The mixture was diluted with dichloromethane and washed successively with diluted hydrochloric acid, aqueous sodium bicarbonate and brine. The organic layer was dried over sodium sulfate and evaporated in vacuo. The residue was chromatographed on silica gel eluting with dichloromethane to give 2-benzyloxycarbonylamino-4-methoxycarbonylphenyl trifluoromethanesulfonate (2.61 g) as colorless crystals.",
    "reference_string": "{\"inputs\": {\"m1_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-amino-4-methoxycarbonylphenyl trifluoromethanesulfonate\"}], \"amount\": {\"mass\": {\"value\": 2.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"amount\": {\"volume\": {\"value\": 5.6, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzyl chloroformate\"}], \"amount\": {\"volume\": {\"value\": 2.08, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 20.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at 20\\u00b0 C. for 4.5 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WASH\", \"details\": \"washed successively with diluted hydrochloric acid, aqueous sodium bicarbonate and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The organic layer was dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was chromatographed on silica gel eluting with dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 4.5, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-benzyloxycarbonylamino-4-methoxycarbonylphenyl trifluoromethanesulfonate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 2.61, \"units\": \"GRAM\"}}}], \"isolated_color\": \"colorless\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-f16b8076c9264cbebd15d232c40254b6",
    "procedure_text": "A mixed solution of 2 g of 1,6-dibromopyrene, 1 g of 4-t-butylphenylboronic acid, 2.4 g of tripotassium phosphate, 0.4 g of tetrabutylammonium bromide, 22 mg of palladium acetate and 60 ml of dimethylformamide was heated and stirred under a nitrogen gas stream at 130\u00b0 C. for 6 hours. The solution was cooled to room temperature and 30 ml of water was poured into the solution, followed by extraction with 100 ml of dichloromethane. The organic layer was washed twice with 50 ml of water, dried over magnesium sulfate and then evaporated. The concentrate was purified by silica gel column chromatography and then vacuum-dried to obtain 0.7 g of 1-bromo-6-(4-t-butylphenyl)pyrene.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m5_m6_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,6-dibromopyrene\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-t-butylphenylboronic acid\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tripotassium phosphate\"}], \"amount\": {\"mass\": {\"value\": 2.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrabutylammonium bromide\"}], \"amount\": {\"mass\": {\"value\": 0.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"palladium acetate\"}], \"amount\": {\"mass\": {\"value\": 22.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 130.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"stirred under a nitrogen gas stream at 130\\u00b0 C. for 6 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The solution was cooled to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"followed by extraction with 100 ml of dichloromethane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed twice with 50 ml of water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"The concentrate was purified by silica gel column chromatography\"}, {\"type\": \"CUSTOM\", \"details\": \"vacuum-dried\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 6.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-bromo-6-(4-t-butylphenyl)pyrene\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.7, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 30.5}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-64b645d960d245bb88cbc3c5b421da9c",
    "procedure_text": "At RT, 53.6 mg (0.2 mmol) of 2-amino-4-(4-hydroxyphenyl)-6-sulfanyl-3,5-pyridinedicarbonitrile and 58.2 mg (0.3 mmol) of N,N-diethylbromoacetamide are stirred in 0.5 ml of DMF together with 33.6 mg (0.4 mmol) of NaHCO3 for 4 hours. TLC (CH2Cl2/CH3OH 10:1) shows complete conversion. The entire mixture is diluted with water and ethyl acetate and the EA phase is dried with MgSO4 and concentrated under reduced pressure. The residue crystallizes from methanol.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2 CH3OH\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m5_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-amino-4-(4-hydroxyphenyl)-6-sulfanyl-3,5-pyridinedicarbonitrile\"}], \"amount\": {\"mass\": {\"value\": 53.6, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-diethylbromoacetamide\"}], \"amount\": {\"mass\": {\"value\": 58.2, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"amount\": {\"mass\": {\"value\": 33.6, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 0.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m6_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"the EA phase is dried with MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EA\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue crystallizes from methanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-3e60278ed3854d7c8b6769c0c673dab0",
    "procedure_text": "Isobutylchloroformate (0.575 ml) and triethylamine (0.63 ml) were added to a solution of 4-chloro-3-[[(tricyclo[3.3.1.13,7]dec-1-ylmethyl)amino]carbonyl]-benzenepropanoic acid (Example 6c, 1.64 g) in tetrahydrofuran (30 ml) at 0\u00b0 C. After 1 h the precipitates were removed by filtration and the filtrate added portionwise to a solution of sodium borohydride (0.18 g) in water (10 ml) at 0\u00b0 C. After a further 1 h the reaction mixture was poured onto dilute hydrochloric acid and extracted with ethyl acetate. The organic phase was extracted twice with dilute hydrochloric acid, twice with saturated sodium hydrogencarbonate solution and once with brine, dried over magnesium sulfate and concentrated under reduced pressure to give a residue. Purification by silica gel chromatography (eluting with dichloromethane/methanol 96:4); yielded the subtitled compound as a solid (1.3 g).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Isobutylchloroformate\"}], \"amount\": {\"volume\": {\"value\": 0.575, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 0.63, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-chloro-3-[[(tricyclo[3.3.1.13,7]dec-1-ylmethyl)amino]carbonyl]-benzenepropanoic acid\"}], \"amount\": {\"mass\": {\"value\": 1.64, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"After 1 h the precipitates were removed by filtration\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"ADDITION\", \"details\": \"the filtrate added portionwise to a solution of sodium borohydride (0.18 g) in water (10 ml) at 0\\u00b0 C\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium borohydride\"}], \"amount\": {\"mass\": {\"value\": 0.18, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}, \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"ADDITION\", \"details\": \"After a further 1 h the reaction mixture was poured onto dilute hydrochloric acid\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The organic phase was extracted twice with dilute hydrochloric acid, twice with saturated sodium hydrogencarbonate solution and once with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloric acid\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydrogencarbonate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a residue\"}, {\"type\": \"CUSTOM\", \"details\": \"Purification\"}, {\"type\": \"WASH\", \"details\": \"by silica gel chromatography (eluting with dichloromethane/methanol 96:4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"subtitled compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.3, \"units\": \"GRAM\"}}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-1eb21e8289b747389416286cf9c13e47",
    "procedure_text": "1-(4'-Chlorophenyl-amino)-2-(2',6'-dimethylphenylamino)-propane, applied as starting substance, is obtained with a yield of 50.9% by reacting N-(\u03b2-chloropropyl)-4-chloro-aniline, a compound prepared as described in Example 27, point (b), with 2,6-dimethylaniline according to the method given in Example 25, point (a). The hydrochloride of the product melts at 170\u00b0-178\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(4'-Chlorophenyl-amino)-2-(2',6'-dimethylphenylamino)-propane\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"( a )\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"( b )\"}], \"reaction_role\": \"REACTANT\"}]}, \"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,6-dimethylaniline\"}], \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrochloride\"}], \"reaction_role\": \"REACTANT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(\\u03b2-chloropropyl)-4-chloro-aniline\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"is obtained with a yield of 50.9%\"}, {\"type\": \"CUSTOM\", \"details\": \"a compound prepared\"}], \"outcomes\": [{\"products\": [{\"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 50.9}}]}]}]}"
  },
  {
    "reaction_id": "ord-a799f18a373b48f39c2713ea503cb4b6",
    "procedure_text": "To a suspension of sodium hydride (NaH) (0.69 g, 30 mmol) in dimethylformamide (DMF) (100 mL) was added 2-mercaptobenzimidazole (4.5 g, 10 mmol) in DMF (20 mL) at 0\u00b0 C. under N2. To the resultant solution was added geranyl chloride (5.16 g, 10 mmol) over 30 minutes. The reaction was stirred for five hours at ambient temperature under N2 then treated with 2N NaOH and extracted with diethyl ether (Et2O). The Et2O extract was washed with saturated NaCl, concentrated in vacuo, dissolved in methylene chloride, and dried over Na2SO4. Recrystallization from Et2O gave white crystalline 2-[(3,7-dimethyl-2,6(E)-octadienyl)-thio]-1H-1,3-benzimidazole (3.15 g, 36.6%). m.p. 98\u00b0-100\u00b0 C. NMR (CDCl3):\u03b47.4(m, 2H), 7.1(m, 2H) 5.3(t,J=8 Hz, 1H) 5.0(m 1H) , 3.90(d, J= 10 Hz, 2H , 2.00(m, 4H), 1.65(m, 9H).",
    "reference_string": "{\"inputs\": {\"m2_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-mercaptobenzimidazole\"}], \"amount\": {\"mass\": {\"value\": 4.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 20.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydride\"}], \"amount\": {\"mass\": {\"value\": 0.69, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"resultant solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"geranyl chloride\"}], \"amount\": {\"mass\": {\"value\": 5.16, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaOH\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction was stirred for five hours at ambient temperature under N2\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted with diethyl ether (Et2O)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The Et2O extract\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Et2O\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"was washed with saturated NaCl\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaCl\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"DISSOLUTION\", \"details\": \"dissolved in methylene chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"Recrystallization from Et2O\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Et2O\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 5.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-[(3,7-dimethyl-2,6(E)-octadienyl)-thio]-1H-1,3-benzimidazole\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 3.15, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 36.6}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-bb1302a16b5c402a92d0d948a20aac17",
    "procedure_text": "3,3-Dimethyl-dihydro-furan-2,5-dione (6.4 g) was heated at 50\u00b0 C. in ethanol (150 mL) overnight. The solvent was removed in vacuo and the residue triturated with hexane to yield 2,2-Dimethyl-succinic acid 4-ethyl ester (4.66 g) which was used without further purification. t-Butanol (7.5 mL) was added to a mixture of 2,2-Dimethyl-succinic acid 4-ethyl ester (2.74 g, 15.7 mmol) in dichloromethane (62 mL) containing magnesium sulfate (7.5 g) and conc. sulfuric acid (0.85 mL) and the mixture was stirred at room temperature overnight. Saturated sodium bicarbonate solution was added and the product was extracted into dichloromethane, washed with brine solution, dried and concentrated to yield the diested as a colorloess oil (1.89 g). The ethyl ester was hydrolyzed by trating the crude sample with potassium hydroxide (2.75 g) in a mixture of ethanol (50 mL) and water (25 mL) at room temperatire for 2 h. The reaction was acidified using 1N HCl (aq) and extracted into ether, dried and concentrated to yield 2,2-Dimethyl-succinic acid 1-tert-butyl ester (1.4 g). This acid was treated under the conditions of Example 320 (step 1) to yield 3-[3-(3-Chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-2,2-dimethyl-propionic acid tert-butyl ester (1.9 g). This t-Bu ester was deprotected using formic acid (19 mL) at 50\u00b0 C. for 20 min. The crude product was concentrated and triturated with a mixture of ether and hexane to yield 3-[3-(3-Chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-2,2-dimethyl-propionic acid (1.12 g). To a solution of 3-[3-(3-Chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-2,2-dimethyl-propionic acid (561 mg, 2 mmol) and triethylamine (1.1 mL, 8 mmol) in THF (9 ml), isobutyl chloroformate (0.31 mL, 2.4 mmol) was added dropwise at \u221278 \u00b0 C. After being stirred for 1 h, hydrazine hydrate (1 mL, 11 mmol) was added. The reaction mixture was stirred at room temperature for 1 h and concentrated. A small amount of ice was added to quence any excess reagent and precipitate the product, which was collected by filtration to give 482 mg of the title compound.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrazine hydrate\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m5_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-[3-(3-Chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-2,2-dimethyl-propionic acid\"}], \"amount\": {\"mass\": {\"value\": 561.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"volume\": {\"value\": 1.1, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isobutyl chloroformate\"}], \"amount\": {\"volume\": {\"value\": 0.31, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 9.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After being stirred for 1 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"The reaction mixture was stirred at room temperature for 1 h\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"ADDITION\", \"details\": \"A small amount of ice was added\"}, {\"type\": \"CUSTOM\", \"details\": \"precipitate the product, which\"}, {\"type\": \"FILTRATION\", \"details\": \"was collected by filtration\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 482.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fe76ff3d363e4b79bf049a21724fe2c3",
    "procedure_text": "Example 5 was prepared by coupling 4-fluoro-3-(4-pyridin-3-yl-[1,2,3]triazol-1-yl)-benzoic acid with N-(3-amino-5-tert-butyl-2-methoxy-phenyl)-methane-sulfonamide in the same manner as Example 1. ESI MS m/z 539 [C26H27FN6O4S+H]+.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-fluoro-3-(4-pyridin-3-yl-[1,2,3]triazol-1-yl)-benzoic acid\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(3-amino-5-tert-butyl-2-methoxy-phenyl)-methane-sulfonamide\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Example 5 was prepared\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-bf438f129d634d4c9cb247d55e48924b",
    "procedure_text": "Oxalyl chloride (0.35 ml) was added to a stirred suspension of 4-acetoxybenzoic acid (0.57 g) in methylene chloride (15 ml) which had been cooled to 0\u00b0 C. DMF (2 drops) was added and the mixture was stirred at ambient temperature for 4 hours. The mixture was evaporated to give 4-acetoxybenzoyl chloride which was used without further purification. A mixture of the acid chloride so obtained, N-(3-amino-4-chlorophenyl)-4-cyanobenzamide (0.813 g) and pyridine (15 ml) was stirred and heated at 100\u00b0 C. for 16 hours. The mixture was cooled to ambient temperature and poured into 2N aqueous hydrochloric acid solution (175 ml). The precipitate was isolated, washed with water and dried. The material so obtained was purified by column chromatography on silica using a 7:3 mixture of isohexane and ethyl acetate as eluent. There was thus obtained the title compound (0.74 g); m.p. 195-196\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"reaction_role\": \"CATALYST\"}]}, \"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Oxalyl chloride\"}], \"amount\": {\"volume\": {\"value\": 0.35, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-acetoxybenzoic acid\"}], \"amount\": {\"mass\": {\"value\": 0.57, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at ambient temperature for 4 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The mixture was evaporated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-acetoxybenzoyl chloride\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-ed77f7ac88fd42ecb5a82aed6d858fc8",
    "procedure_text": "A mixture of 2-quinolinecarboxylic acid (520 mg) and 1,1\u2032-carbonyldiimidazole (243 mg) in tetrahydrofuran (5 ml) was stirred at room temperature for 1.5 hours. A solution of 4-(3-aminophenyl)-3-oxo-2-benzyl-3,4-dihydropyrido[2,3-b]pyrazine (493 mg) in 1,4-dioxane (5 ml) was added to the mixture and stirring was continued for 5 days. The reaction mixture was poured into a mixture of ethyl acetate and an aqueous sodium bicarbonate solution. The organic phase was washed with brine, dried over magnesium sulfate, concentrated, and subjected to silica gel column chromatography (hexane-ethyl acetate, 1:1) to afford 2-benzyl-3-oxo-4-[3-(quinolin-2-yl)carbonylaminophenyl]-3,4-dihydropyrido[2,3-b]pyrazine (87 mg) as a solid.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-quinolinecarboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 520.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,1\\u2032-carbonyldiimidazole\"}], \"amount\": {\"mass\": {\"value\": 243.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(3-aminophenyl)-3-oxo-2-benzyl-3,4-dihydropyrido[2,3-b]pyrazine\"}], \"amount\": {\"mass\": {\"value\": 493.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,4-dioxane\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"was stirred at room temperature for 1.5 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"stirring\"}, {\"type\": \"WAIT\", \"details\": \"was continued for 5 days\", \"duration\": {\"value\": 5.0, \"units\": \"DAY\"}}, {\"type\": \"WASH\", \"details\": \"The organic phase was washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.5, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-benzyl-3-oxo-4-[3-(quinolin-2-yl)carbonylaminophenyl]-3,4-dihydropyrido[2,3-b]pyrazine\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 87.0, \"units\": \"MILLIGRAM\"}}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-725c4c95a5da404fbf418265cdd39b8a",
    "procedure_text": "To a stirring solution of diisopropylamine (56.4 g, 0.55 mol) in THF (500 mL) at \u221240\u00b0 C., n-butyl lithium (200 mL, 2.66 M hexane solution) was added dropwise. The mixture was stirred at \u221240\u00b0 C. for 1 hour and then cooled to \u221278\u00b0 C. Then, a solution of 4-fluorobromobenzene (87.5 g, 0.50 mol) in THF (100 mL) was slowly added dropwise thereto such that the inner temperature of the reaction solution did not exceed \u221270\u00b0 C. After the reaction solution was stirred at \u221278\u00b0 C. for 1 hour, a solution of ethyl trifluoroacetate (65.4 mL, 0.55 mol) in THF (100 mL) was added thereto at the same temperature. After the temperature of the reaction solution was raised to 0\u00b0 C. over 1 hour under stirring, a saturated aqueous ammonium chloride solution was added thereto, and the solution was diluted with ethyl acetate. The organic layer was separated and washed with saturated brine and then dried over magnesium sulfate. After the drying agent was removed by filtration, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=1/4), and the resulting yellow oily substance was purified again by distillation under reduced pressure (1 mmHg, 53\u00b0 C.), whereby the objective compound (83.8 g, 61.8%) was obtained as a yellow oily substance.",
    "reference_string": "{\"inputs\": {\"m1_m6_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diisopropylamine\"}], \"amount\": {\"mass\": {\"value\": 56.4, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-butyl lithium\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m4_m8\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl trifluoroacetate\"}], \"amount\": {\"volume\": {\"value\": 65.4, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m9\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m3_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-fluorobromobenzene\"}], \"amount\": {\"mass\": {\"value\": 87.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium chloride\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": -40.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred at \\u221240\\u00b0 C. for 1 hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooled to \\u221278\\u00b0 C\", \"temperature\": {\"setpoint\": {\"value\": -78.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"did not exceed \\u221270\\u00b0 C\", \"temperature\": {\"setpoint\": {\"value\": -70.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"STIRRING\", \"details\": \"After the reaction solution was stirred at \\u221278\\u00b0 C. for 1 hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": -78.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"After the temperature of the reaction solution was raised to 0\\u00b0 C. over 1 hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"STIRRING\", \"details\": \"under stirring\"}, {\"type\": \"CUSTOM\", \"details\": \"The organic layer was separated\"}, {\"type\": \"WASH\", \"details\": \"washed with saturated brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over magnesium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"magnesium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"After the drying agent was removed by filtration\"}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was evaporated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by silica gel column chromatography (ethyl acetate/hexane=1/4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate hexane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"the resulting yellow oily substance was purified again by distillation under reduced pressure (1 mmHg, 53\\u00b0 C.), whereby the objective compound (83.8 g, 61.8%)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound\"}], \"amount\": {\"mass\": {\"value\": 83.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"WORKUP\"}]}, \"temperature\": {\"setpoint\": {\"value\": 53.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"was obtained as a yellow oily substance\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-24073a779fb74aa1af56dda13a5722aa",
    "procedure_text": "To a solution of the N-{2-[(4-benzylpiperazin-1-yl)carbonyl]phenyl}-1H-indazol-5-amine (127 mg, 0.309 mmol) obtained in Example 515 in ethanol (5 ml) were added 10% Pd-C (20 mg) and ammonium formate (98 mg, 1.55 mmol), and the resulting mixture was heated under reflux for 2 hours. The solid was removed by filtration using Celite, and the solvent was distilled off under reduced pressure. The residue was extracted with ethyl acetate, and the extract solution was washed with a saturated aqueous sodium hydrogencarbonate solution and then a saturated aqueous sodium chloride solution, dried over sodium sulfate, and then distilled under reduced pressure to remove the solvent, whereby N-[2-(piperazin-1-ylcarbonyl)phenyl]-1H-indazol-5-amine (56 mg, 57%) was obtained.",
    "reference_string": "{\"inputs\": {\"m1_m3_m4_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-{2-[(4-benzylpiperazin-1-yl)carbonyl]phenyl}-1H-indazol-5-amine\"}], \"amount\": {\"mass\": {\"value\": 127.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonium formate\"}], \"amount\": {\"mass\": {\"value\": 98.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 5.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd-C\"}], \"amount\": {\"mass\": {\"value\": 20.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"the resulting mixture was heated\"}, {\"type\": \"TEMPERATURE\", \"details\": \"under reflux for 2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"The solid was removed by filtration\"}, {\"type\": \"DISTILLATION\", \"details\": \"the solvent was distilled off under reduced pressure\"}, {\"type\": \"EXTRACTION\", \"details\": \"The residue was extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"the extract solution was washed with a saturated aqueous sodium hydrogencarbonate solution\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydrogencarbonate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"a saturated aqueous sodium chloride solution, dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium chloride\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"distilled under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"to remove the solvent\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-[2-(piperazin-1-ylcarbonyl)phenyl]-1H-indazol-5-amine\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 56.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 57.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 56.4}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b681358ea0aa49b2860a89776dc4c0f3",
    "procedure_text": "50 mg (0.12 mmol) of 3-(2-{[(3R)-1-azabicyclo[2.2.2]oct-3-ylamino]carbonyl}-1-benzofuran-7-yl)benzoic acid hydrochloride (Example 149) and 24.2 mg (0.23 mmol) of 3-ethoxypropylamine are reacted together by general method E. 17.8 mg (28.9% of theory) of the title compound are obtained.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-(2-{[(3R)-1-azabicyclo[2.2.2]oct-3-ylamino]carbonyl}-1-benzofuran-7-yl)benzoic acid hydrochloride\"}], \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-ethoxypropylamine\"}], \"amount\": {\"mass\": {\"value\": 24.2, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d331f50568a647939281cd8e4687cb73",
    "procedure_text": "In a 500 ml round bottom flask, methyl 3-(dimethylamino)-2-((dimethylamino)methyleneamino)acrylate (1A, 12 g, 61 mmol) was dissolved in acetic acid (45 ml) and TFA (15 ml). 1,3-Dimethyl-1H-pyrrole (5.8 g, 61 mmol) was added and the mixture was stirred at room temperature for an hour and then at 110\u00b0 C. for 4 hours. Volatiles were then evaporated from the reaction mixture, the residue was cooled in an ice bath and ice cold saturated K2CO3 solution (200 ml) was slowly added to it. The mixture was extracted with EtOAc (3\u00d7250 ml). Combined organic layers were then washed with brine, dried over sodium sulfate, filtered and evaporated. The crude product was purified on a silica column using hexane-EtOAc (0-100%). Desired product methyl 1,3-dimethyl-1H-pyrrolo[3,2-c]pyridine-6-carboxylate (1J, 6.8 g, 55%) was obtained.",
    "reference_string": "{\"inputs\": {\"m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 3-(dimethylamino)-2-((dimethylamino)methyleneamino)acrylate\"}], \"amount\": {\"mass\": {\"value\": 12.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetic acid\"}], \"amount\": {\"volume\": {\"value\": 45.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TFA\"}], \"amount\": {\"volume\": {\"value\": 15.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,3-Dimethyl-1H-pyrrole\"}], \"amount\": {\"mass\": {\"value\": 5.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at room temperature for an hour\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Volatiles were then evaporated from the reaction mixture\"}, {\"type\": \"TEMPERATURE\", \"details\": \"the residue was cooled in an ice bath\"}, {\"type\": \"ADDITION\", \"details\": \"ice cold saturated K2CO3 solution (200 ml) was slowly added to it\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"The mixture was extracted with EtOAc (3\\u00d7250 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 250.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"Combined organic layers were then washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude product was purified on a silica column\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 4.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Desired product\"}], \"reaction_role\": \"PRODUCT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methyl 1,3-dimethyl-1H-pyrrolo[3,2-c]pyridine-6-carboxylate\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 6.8, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 55.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-621e0def98824858a359ec5271016cbe",
    "procedure_text": "To a solution of ethyl3-formyl-2-isopropyl-1H-indole-6-carboxylate (Compound 34, 1.22 g, 4.72 mmol) in DMF (10 ml) was added NaH (170 mg, 7.08 mmol) and 2-(chloromethyl)oxazole (1.10 g, 9.44 mmol). The reaction was stirred at 25\u00b0 C. for 12 h, diluted with EtOAc, washed with H2O, brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by chromatography on silica gel (0\u219250% EtOAc-hexanes) to yield the title compound as a yellow oil.",
    "reference_string": "{\"inputs\": {\"m1_m2_m5_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl3-formyl-2-isopropyl-1H-indole-6-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 1.22, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Compound 34\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaH\"}], \"amount\": {\"mass\": {\"value\": 170.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(chloromethyl)oxazole\"}], \"amount\": {\"mass\": {\"value\": 1.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 25.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction was stirred at 25\\u00b0 C. for 12 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WASH\", \"details\": \"washed with H2O, brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by chromatography on silica gel (0\\u219250% EtOAc-hexanes)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc-hexanes\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 12.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"isolated_color\": \"yellow\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b87d6d5f51034919b64a22853f73bcdc",
    "procedure_text": "A mixture of 3-fluoro-4-[5-methoxy-4-oxo-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-1(4H)-yl]phenyl trifluoromethanesulfonate (230 mg, 0.45 mmol); 3,5-dimethylisoxazole-4-boronic acid (70 mg, 0.50 mmol), Pd(PPh3)4 (29 mg, 0.025 mmol), Na2CO3 (106 mg, 1.0 mmol), DME (4 mL), and H2O (1 mL) was refluxed for 3 h under Ar atmosphere. After cooling to room temperature, the reaction mixture was poured into water and extracted with AcOEt. The extract was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography eluting with THF and recrystallized from MeOH/H2O to give the title compound (121 mg, 59% yield) as a white solid: mp 200-202\u00b0 C.; 1H NMR (300 MHz, CDCl3): \u03b4 ppm 2.27 (3H, s), 2.42 (3H, s), 3.92 (3H, s), 6.49 (1H, t, J=8.3 Hz), 6.89 (1H, ddd, J=0.8, 1.9, 8.3 Hz), 7.08 (1H, dd, J=1.9, 12.1 Hz), 7.32 (1H, d, J=1.9 Hz), 7.35-7.47 (5H, m), 7.79 (1H, d, J=1.9 Hz), 7.85 (1H, d, J=2.3 Hz). LC-MS (ESI) m/z 458 [M+H]+. Anal. Calcd for C25H20FN5O3: C, 65.64; H, 4.41; N, 15.31. Found: C, 65.55; H, 4.32; N, 15.33.",
    "reference_string": "{\"inputs\": {\"m2_m5_m3_m4_m7\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,5-dimethylisoxazole-4-boronic acid\"}], \"amount\": {\"mass\": {\"value\": 70.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2CO3\"}], \"amount\": {\"mass\": {\"value\": 106.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DME\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd(PPh3)4\"}], \"amount\": {\"mass\": {\"value\": 29.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-fluoro-4-[5-methoxy-4-oxo-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-1(4H)-yl]phenyl trifluoromethanesulfonate\"}], \"amount\": {\"mass\": {\"value\": 230.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted with AcOEt\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"AcOEt\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The extract was washed with brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by basic silica gel column chromatography\"}, {\"type\": \"WASH\", \"details\": \"eluting with THF\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"recrystallized from MeOH/H2O\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH H2O\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 121.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 59.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 58.8}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-7c65f689581e428da4ad2323a74d0556",
    "procedure_text": "4-Ethoxy-2-(4-methylphenyl)-3-oxobutanenitrile (1.493 g) is dissolved in ethanol (50 mL). After adding hydrazine 2HCl (1.10 g), TEA (0.85 mL) and molecular sieve, the reaction mixture is heated to 80\u00b0 C. After stirring for 15 hours and cooling to room temperature, the molecular sieve is removed by filtering. The reaction solvent is removed under reduced pressure. After the reaction is terminated by adding saturated aq. NaHCO3, the reaction mixture is extracted 3 times with ethyl acetate. The organic layer is washed with water and dehydrated with MgSO4. After concentration under reduced pressure, the produced solid is recrystallized to obtain the target compound (90%). 1H NMR (CDCl3, 300 MHz): \u03b4 7.26 (m, 2H), 7.02 (m, 2H), 6.80 (br, 2H), 4.20 (s, 2H), 3.38 (m, 2H), 2.24 (s, 3H), 1.06 (t, 3H).",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-Ethoxy-2-(4-methylphenyl)-3-oxobutanenitrile\"}], \"amount\": {\"mass\": {\"value\": 1.493, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrazine 2HCl\"}], \"amount\": {\"mass\": {\"value\": 1.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TEA\"}], \"amount\": {\"volume\": {\"value\": 0.85, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 80.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring for 15 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooling to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"the molecular sieve is removed\"}, {\"type\": \"FILTRATION\", \"details\": \"by filtering\"}, {\"type\": \"CUSTOM\", \"details\": \"The reaction solvent is removed under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"After the reaction is terminated\"}, {\"type\": \"ADDITION\", \"details\": \"by adding saturated aq. NaHCO3\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"the reaction mixture is extracted 3 times with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer is washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"After concentration under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"the produced solid is recrystallized\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 90.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-a40d9e1625fd4ebcb16a1195d112489d",
    "procedure_text": "Step (b) of Example 92 was repeated, except that the compound prepared in step (b) of Example 114 and the compound prepared in step (c) of Example 143 were used as the starting compounds. Thus, the title compound was obtained.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"compound\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-b6261fcfc4be4eb4867d929b71a6a458",
    "procedure_text": "Pd/C (10 wt %, 8.7 \u03bcg) and azide 8 (18.0 mg, 0.0247 mmol) were added to a 0.20 M solution of 18 (0.0988 mmol) in 0.40 mL of EtOAc (filtered through activated alumina). The reaction mixture was stirred under a hydrogen atmosphere for 26 h and then filtered through a plug of Celite with washing of the filter pad with EtOAc. The filtrate was concentrated, and a 1:1 mixture of deoxygenated H2O/dioxane (4.0 mL) was added. The mixture was stirred for 20 h at rt and concentrated. Reverse-phase HPFC (20:80 to 100:0 MeCN:H2O) followed by lyophilization afforded 9.3 mg (48%) of 6 as an amorphous solid. [\u03b1]D23=\u22122.0 (c=0.6, MeOH). IR: 1226, 1496, 1542, 1741, 2964 cm\u22121. 1H NMR (500 MHz, MeOD): \u03b4 0.81 (d, 3H, J=6.5 Hz), 0.87 (d, 3H, J=6.5 Hz), 0.89 (d, 3H, J=7.0 Hz), 0.92 (t, 3H, J=7.5 Hz), 0.98 (d, 3H, J=6.5 Hz), 1.06 (d, 3H, J=6.5 Hz), 1.12-1.21 (m, 1H), 1.17 (d, 3H, J=7.0 Hz), 1.58-1.70 (m, 2H), 1.77-1.91 (m, 2H), 1.92-2.05 (m, 3H), 2.06-2.17 (m, 2H), 2.16 (s, 3H), 2.35 (s, 6H), 2.46-2.57 (m, 2H), 2.92 (d, 2H, J=5.5 Hz), 3.11 (q, 2H, J=16.2 Hz), 4.28-4.50 (br s, 1H), 4.32-4.38 (m, 1H), 4.70 (d, 1H, J=8.5 Hz), 5.46 (d, 1H, J=12.0 Hz), 5.87 (d, 1H, J=11.0 Hz), 6.05 (d, 1H, J=12.0 Hz), 7.12-7.18 (m, 1H), 7.19-7.26 (m, 4H), 8.09 (s, 1H). 13C NMR (125 MHz, MeOD) \u03b4 11.1, 16.6, 19.0, 20.3, 20.8, 20.9, 22.9, 25.5, 26.2, 26.9, 32.4, 35.9, 37.6, 39.1, 39.7, 42.1, 44.5, 45.8, 51.2, 55.2, 62.7, 70.8, 125.6, 127.5, 129.4, 130.6, 139.7, 150.9, 162.7, 170.8, 171.7, 172.0, 173.3, 176.5, 181.8. HRMS (FAB) calcd for C40H62N5O9S (M+H): 788.4268. Found: 788.4256.",
    "reference_string": "{\"inputs\": {\"m5_m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"azide\"}], \"amount\": {\"mass\": {\"value\": 18.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"18\"}], \"amount\": {\"moles\": {\"value\": 0.0988, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 0.4, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Pd/C\"}], \"amount\": {\"mass\": {\"value\": 8.7, \"units\": \"MICROGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred under a hydrogen atmosphere for 26 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"filtered through a plug of Celite\"}, {\"type\": \"WASH\", \"details\": \"with washing of the filter pad with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"The filtrate was concentrated\"}, {\"type\": \"ADDITION\", \"details\": \"a 1:1 mixture of deoxygenated H2O/dioxane (4.0 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O dioxane\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"was added\"}, {\"type\": \"STIRRING\", \"details\": \"The mixture was stirred for 20 h at rt\", \"duration\": {\"value\": 20.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 26.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"6\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 9.3, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 48.0}}, {\"type\": \"YIELD\", \"details\": \"CALCULATEDPERCENTYIELD\", \"percentage\": {\"value\": 47.8}}], \"isolated_color\": \"amorphous\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c3fde617594e4c0b8c61f3c9fdd37d95",
    "procedure_text": "[1,1\u2032-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (17 mg, 0.24 mmol) was added to a stirred solution of 10a (50 mg, 0.114 mmol) and 3-methoxyphenylboronic acid (21 mg, 0.140 mmol) in dioxane (0.6 mL) and saturated aqueous sodium bicarbonate (0.125 mL) at rt. The resulting solution was irradiated in a microwave reactor at 120\u00b0 C. for 10 min. After cooling to rt, the reaction mixture was filtered through a short column of CELITE\u00ae eluting with EtOAc. The resulting crude oil was purified by preparative reversed phase HPLC on YMC Pack Pro C18 stationary phase (CH3CN/H2O as eluent, 0.05% TFA as modifier), followed by lyophilization of the purified fractions to afford the title compound 78. m/z (ES) 465 (MH)+; IP=C rating.",
    "reference_string": "{\"inputs\": {\"m5_m1_m2_m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"10a\"}], \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-methoxyphenylboronic acid\"}], \"amount\": {\"mass\": {\"value\": 21.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dioxane\"}], \"amount\": {\"volume\": {\"value\": 0.6, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"amount\": {\"volume\": {\"value\": 0.125, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"[1,1\\u2032-Bis(diphenylphosphino)ferrocene]dichloropalladium(II)\"}], \"amount\": {\"mass\": {\"value\": 17.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The resulting solution was irradiated in a microwave reactor at 120\\u00b0 C. for 10 min\", \"duration\": {\"value\": 10.0, \"units\": \"MINUTE\"}, \"temperature\": {\"setpoint\": {\"value\": 120.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"FILTRATION\", \"details\": \"the reaction mixture was filtered through a short column of CELITE\\u00ae\"}, {\"type\": \"WASH\", \"details\": \"eluting with EtOAc\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The resulting crude oil was purified by preparative reversed phase HPLC on YMC Pack Pro C18 stationary phase (CH3CN/H2O as eluent, 0.05% TFA as modifier)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH3CN H2O\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"TFA\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound 78\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-56ce66e72e984e86a4c202acdde71ffd",
    "procedure_text": "Starting from 2-amino-4-methoxybenzothiazole (1.5 g) and trifluoroacetic acid (5.5 ml), without 1,2 dichlorobenzene. Purification by flash chromatography (eluent 20% ethyl acetate/hexane) yielded the title compound as a light brown oil (0.74 g). TLC Rf 0.70 (50% ethyl acetate in hexane)",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-amino-4-methoxybenzothiazole\"}], \"amount\": {\"mass\": {\"value\": 1.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trifluoroacetic acid\"}], \"amount\": {\"volume\": {\"value\": 5.5, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,2 dichlorobenzene\"}], \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Purification by flash chromatography (eluent 20% ethyl acetate/hexane)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"eluent\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.74, \"units\": \"GRAM\"}}}], \"isolated_color\": \"light brown\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4a4a230aa3ed43b9a6490d7361835e53",
    "procedure_text": "2 g Trans,trans-6,6-dimethyl-2,4-heptadienal are dissolved in ethanol and reacted at room temperature with 275 mg NaBH4 in successive portions. After stirring for ca. 1 hour at room temperature the mixture is concentrated on a rotary evaporator, the residue partitioned between ethyl acetate and saturated aqueous NaHCO3 and the organic phase dried and concentrated under vacuum. The oily crude product is further reacted directly.",
    "reference_string": "{\"inputs\": {\"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Trans,trans-6,6-dimethyl-2,4-heptadienal\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaBH4\"}], \"amount\": {\"mass\": {\"value\": 275.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"After stirring for ca. 1 hour at room temperature the mixture\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"is concentrated on a rotary evaporator\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue partitioned between ethyl acetate and saturated aqueous NaHCO3\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaHCO3\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the organic phase dried\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated under vacuum\"}, {\"type\": \"CUSTOM\", \"details\": \"The oily crude product is further reacted directly\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-fa5b09b24dba42f1bbcdaec160dd76b1",
    "procedure_text": "(Step 1) To 50 g of 2,4,6-trichloro-1,3,5-triazine was added 300 ml of dry tetrahydrofuran and while the mixture was stirred at room temperature, 150 ml of 2M phenylmagnesium bromide-tetrahydrofuran was added dropwise over about 30 minutes. After completion of dropwise addition, the mixture was stirred at room temperature for 1 hour, and then concentrated. To the residue was added iced water and the resultant was extracted with ether. The extract was washed with water, dried over MgSO4, and concentrated. The resulting crystal crop was recrystallized from isopropyl alcohol to provide 21.1 g of 2,4-dichloro-6-phenyl-1,3,5-triazine as pale yellow crystals.",
    "reference_string": "{\"inputs\": {\"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,4,6-trichloro-1,3,5-triazine\"}], \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 300.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"phenylmagnesium bromide tetrahydrofuran\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"while the mixture was stirred at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"ADDITION\", \"details\": \"After completion of dropwise addition\"}, {\"type\": \"STIRRING\", \"details\": \"the mixture was stirred at room temperature for 1 hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"ADDITION\", \"details\": \"To the residue was added iced water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"the resultant was extracted with ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The extract was washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The resulting crystal crop was recrystallized from isopropyl alcohol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"isopropyl alcohol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,4-dichloro-6-phenyl-1,3,5-triazine\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 21.1, \"units\": \"GRAM\"}}}], \"isolated_color\": \"pale yellow\", \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-bcfbc1fc0abc4946859fee9b240a5d38",
    "procedure_text": "The reaction is performed under the conditions of Example 16, but starting with 7,8-difluoro-1-methyl-4-oxo-1,4-dihydrobenzo[b][1,8]-naphthyridine-3-carboxylic acid (1.3 g) and (RS)-2-(3-fluorophenyl)piperazine (1.8 g). After 1 recrystallization in dimethylformamide (50 cc) containing ethanol (50%), (RS)-7-fluoro-8-[3-(3-fluorophenyl)-1-piperazinyl]-1-methyl-4-oxo -1,4-dihydrobenzo[b][1,8]naphthyridine-3-carboxylic acid (1.74 g) is obtained in the form of a yellow solid, m.p. 254\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"7,8-difluoro-1-methyl-4-oxo-1,4-dihydrobenzo[b][1,8]-naphthyridine-3-carboxylic acid\"}], \"amount\": {\"mass\": {\"value\": 1.3, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(RS)-2-(3-fluorophenyl)piperazine\"}], \"amount\": {\"mass\": {\"value\": 1.8, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"After 1 recrystallization in dimethylformamide (50 cc)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"ADDITION\", \"details\": \"containing ethanol (50%)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(RS)-7-fluoro-8-[3-(3-fluorophenyl)-1-piperazinyl]-1-methyl-4-oxo -1,4-dihydrobenzo[b][1,8]naphthyridine-3-carboxylic acid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 1.74, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-d94c0d6f20cb4319aff7be92655579bc",
    "procedure_text": "To a solution of 2.884 g (0.01 mol) of testosterone in 30 ml of dry benzene was added 1.008 g (0.012 mol) of sodium bicarbonate; then, while stirring, there were introduced dropwise 1.888 g (0.012 mol) of bromoacetyl chloride over a 5 minute period. The reaction mixture was then stirred under reflux for 6 hours until no testosterone could be traced by TLC. (Plates of Silica Gel G and a CHCH3 /CH3OH system were used.) The inorganic residue was filtered while hot, the filtrate was evaporated in vacuo and the residue was recrystallized from methanol, m.p. 144\u00b0-145\u00b0 C., yield 3.2 g (78%). IR (KBr) 1735 (C=O), 1660 (C=O) cm-1. PMR as expected. The product has the formula: ##STR1520##",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"testosterone\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m6_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"testosterone\"}], \"amount\": {\"mass\": {\"value\": 2.884, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium bicarbonate\"}], \"amount\": {\"mass\": {\"value\": 1.008, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzene\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CHCH3 CH3OH\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"bromoacetyl chloride\"}], \"amount\": {\"mass\": {\"value\": 1.888, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"then, while stirring\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"The reaction mixture was then stirred\"}, {\"type\": \"FILTRATION\", \"details\": \") The inorganic residue was filtered while hot, the filtrate\"}, {\"type\": \"CUSTOM\", \"details\": \"was evaporated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"the residue was recrystallized from methanol, m.p. 144\\u00b0-145\\u00b0 C., yield 3.2 g (78%)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-2f5c5eab6ad440deacf29542f6e304bd",
    "procedure_text": "Similarly prepared to Intermediate 26 from 2,6-dibromo-4-methylbenzaldehyde phenylhydrazone (Intermediate 32).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Intermediate 26\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,6-dibromo-4-methylbenzaldehyde phenylhydrazone\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Intermediate 32\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-33d88bb151324943a1aa15a625eddc0c",
    "procedure_text": "In 30 ml of N,N-dimethylformamide were dissolved 2.2 g (0.01 mol) of 2-tert.-butyl-4-chloro-5-mercapto-3(2H)-pyridazinone and 3.5 g (0.0105 mol) of 4-(4'-trifluoromethylphenoxy) benzyl bromide, and thereto was added 2.1 g (0.02 mol) of anhydrous sodium carbonate to effect reaction at 85\u00b0 to 90\u00b0 C. for 4 hours. After the reaction, the reaction liquid was allowed to cool, poured into water and then extracted with benzene. The benzene layer was washed with 5% aqueous solution of sodium hydroxide and then with water, dried over anhydrous sodium sulfate and then freed of benzene by distillation under reduced pressure. The oily residue was incorporated with n-hexane and the precipitated crystals were filtered off to obtain white crystals (yield: 85.5%).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5_m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-tert.-butyl-4-chloro-5-mercapto-3(2H)-pyridazinone\"}], \"amount\": {\"mass\": {\"value\": 2.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(4'-trifluoromethylphenoxy) benzyl bromide\"}], \"amount\": {\"mass\": {\"value\": 3.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 30.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium carbonate\"}], \"amount\": {\"mass\": {\"value\": 2.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"reaction at 85\\u00b0 to 90\\u00b0 C. for 4 hours\", \"duration\": {\"value\": 4.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"After the reaction\"}, {\"type\": \"CUSTOM\", \"details\": \"the reaction liquid\"}, {\"type\": \"TEMPERATURE\", \"details\": \"to cool\"}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with benzene\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzene\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The benzene layer was washed with 5% aqueous solution of sodium hydroxide\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzene\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"aqueous solution\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydroxide\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"with water, dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"freed of benzene by distillation under reduced pressure\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzene\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"the precipitated crystals were filtered off\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crystals\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 85.5}}], \"texture\": {\"type\": \"CRYSTAL\", \"details\": \"crystals\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-775767fa8d2f4a399ca91925cf401ba2",
    "procedure_text": "A solution of 2,5-difluorobenzophenone (0.655 g, 3.0 mmol) and hydrazine (1.0 mL) in dried pyridine (10 mL) was heated at 130\u00b0 C. for 5 hours and then concentrated and purified by chromatography (SiO2, 15-30% ethyl acetate/hexane) to provide the title compound (0.254 g, 40% yield): mp 124-125\u00b0 C.; 1H NMR (CDCl3) \u03b4 10.89 (br s, 1H), 7.94 (d, 2H), 7.65 (dd, 1H), 7.42-7.54 (m, 3H), 7.33 (dd, 1H), 7.21 (dt, 1H); EL-MS (m/z) 212 [M]+.",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2,5-difluorobenzophenone\"}], \"amount\": {\"mass\": {\"value\": 0.655, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrazine\"}], \"amount\": {\"volume\": {\"value\": 1.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"pyridine\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"purified by chromatography (SiO2, 15-30% ethyl acetate/hexane)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.254, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 40.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-03630a330bcf4de8b1c6b7578dbcf72e",
    "procedure_text": "It is prepared by BOC-cleavage of tert-butyl ester 59 (0.666 g, 1.95 mmol) with 4M-HCl in dioxane (2.93 ml, 11.72 mmol) as described for amine 7.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"amine\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"tert-butyl ester\"}], \"amount\": {\"mass\": {\"value\": 0.666, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"HCl\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dioxane\"}], \"amount\": {\"volume\": {\"value\": 2.93, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-7d4ea64c9bf14de2a878977329e6dc72",
    "procedure_text": "To a solution of triphenylphosphine (1.73 g, 6.6 mmol) in THF (26 mL) was added diethyl azodicarboxylate (1.04 mL, 6.6 mmol) at 0\u00b0 C., and the reaction mixture was stirred for 15 minutes. 1-BOC-2-(S)-azetidinemethanol (1.03 g, 5.5 mmol) and 2-chloro-3-pyridinol (785 mg, 6.0 mmol, Aldrich Chemical Co.) were then added. The reaction mixture was allowed to warm slowly to room temperature and stir overnight. Solvent was removed, and the residue was dissolved in ethyl acetate. The solution was washed with saturated aqueous K2CO3 and brine, dried over MgSO4 and concentrated. The residue was chromatographed on a silica gel column, eluting with ethyl acetate:hexane (1:4 to 1:1) to afford the title compound (611 mg). MS (DCI/NH3) m/z 299 (M+H)+.",
    "reference_string": "{\"inputs\": {\"m3_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-BOC-2-(S)-azetidinemethanol\"}], \"amount\": {\"mass\": {\"value\": 1.03, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloro-3-pyridinol\"}], \"amount\": {\"mass\": {\"value\": 785.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triphenylphosphine\"}], \"amount\": {\"mass\": {\"value\": 1.73, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl azodicarboxylate\"}], \"amount\": {\"volume\": {\"value\": 1.04, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 26.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the reaction mixture was stirred for 15 minutes\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"STIRRING\", \"details\": \"stir overnight\", \"duration\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}}, {\"type\": \"CUSTOM\", \"details\": \"Solvent was removed\"}, {\"type\": \"DISSOLUTION\", \"details\": \"the residue was dissolved in ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The solution was washed with saturated aqueous K2CO3 and brine\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"K2CO3\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was chromatographed on a silica gel column\"}, {\"type\": \"WASH\", \"details\": \"eluting with ethyl acetate:hexane (1:4 to 1:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 15.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 611.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c590acba076f44329984d03a91994eeb",
    "procedure_text": "The 4-hydroxy-3-methylbenzoic acid (10.1 g, 66.38 mmole) was suspended in methanesulfonic acid (50 mL) and cooled to 0\u00b0 C. (ice bath). Hexamethylenetetramine (18.6 g, 132.75 mmole) was added portionwise over 1 hour. The reaction was warmed to room temperature followed by heating to 90\u00b0 C. (oil bath) for 5 hours. The reaction was allowed to cool to room temperature and stired for 18 hours. The contents were poured into water (100 mL) and extracted with EtOAc (2\u00d7100 mL). The combined extracts were washed with brine (50 mL), dried over MgSO4, filtered and concentrated in vacuo to give an off-white solid (9.0 g, 75%). 1H NMR (DMSO/400 MHz) 12.84 (brs, 1H), 11.40 (s, 1H), 10.09 (s, 1H), 8.20 (s, 1H), 7.98 (s, 1H), 2.21 (s, 3H).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanesulfonic acid\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-hydroxy-3-methylbenzoic acid\"}], \"amount\": {\"mass\": {\"value\": 10.1, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Hexamethylenetetramine\"}], \"amount\": {\"mass\": {\"value\": 18.6, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"The reaction was warmed to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"by heating to 90\\u00b0 C. (oil bath) for 5 hours\", \"duration\": {\"value\": 5.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 90.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"to cool to room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with EtOAc (2\\u00d7100 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"EtOAc\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The combined extracts were washed with brine (50 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"brine\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over MgSO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"concentrated in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 18.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solid\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 9.0, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 75.0}}], \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-da4e96b7c5644984bc51574f01bf31ff",
    "procedure_text": "By use of the process of either Example 1(B) or 10(D), 1-bromo-7-methoxy-3,7-dimethyloctane is reacted with 4-(methylsulfonyl)phenol to yield 1-(7'-methoxy-3',7'-dimethyloctyloxy)-4-(methylsulfonyl)benzene. ##STR16##",
    "reference_string": "{\"inputs\": {\"m1_m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"10(D)\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-bromo-7-methoxy-3,7-dimethyloctane\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(methylsulfonyl)phenol\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-(7'-methoxy-3',7'-dimethyloctyloxy)-4-(methylsulfonyl)benzene\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-47ae621101b443629c79ff0558628c65",
    "procedure_text": "The crude product 2-ethyl-2-methyl-5-{4-(methylthio)phenyl}-3(2H)-furanone from the previous Step 3 was dissolved in 50 ml ethanol, 50 ml THF and 50 ml water, and 10 g of OXONE was added thereto. The reaction mixture was stirred overnight at room temperature. Then the insoluble materials were removed by filtration and the filtrate was concentrated in vacuo. The resulting aqueous layer was extracted with dichloromethane (100 ml\u00d71 and 50 ml\u00d72). The organic layer was concentrated under reduced pressure and the resulting residue was purified by column chromatography (hexane/ethylacetate=2:1) to yield 4.5 g of 2-ethyl-2-methyl-5-{4-(methylsufonyl)phenyl}-3(2H)-furanone. NMR: \u03b40.89 (t, J=7.2 Hz, 3H), 1.48 (s, 3H), 1.91 (q, J=7.2 Hz, 2H), 3.11 (s, 3H), 6.13 (s, 1H), 8.07 (m, 4H).",
    "reference_string": "{\"inputs\": {\"m1_m2_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-ethyl-2-methyl-5-{4-(methylthio)phenyl}-3(2H)-furanone\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3_m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"THF\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"OXONE\"}], \"amount\": {\"mass\": {\"value\": 10.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred overnight at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Then the insoluble materials were removed by filtration\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate was concentrated in vacuo\"}, {\"type\": \"EXTRACTION\", \"details\": \"The resulting aqueous layer was extracted with dichloromethane (100 ml\\u00d71 and 50 ml\\u00d72)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dichloromethane\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"The organic layer was concentrated under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"the resulting residue was purified by column chromatography (hexane/ethylacetate=2:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane ethylacetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-ethyl-2-methyl-5-{4-(methylsufonyl)phenyl}-3(2H)-furanone\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 4.5, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-e84eb261d0174a0dbc16f09413d0d274",
    "procedure_text": "To a suspension of NaH (60%, 2.0 g, 51 mmol) in dry DMF (125 ml) cooled at 0\u00b0 C., a solution of 2-(3-butoxyphenyl)-(tert-butoxycarbonyl)ethylamine (7.5 g, 25.5 mmol) in dry DMF (125 ml) was added dropwise. After 1 h at room temperature, 2-chloro-N,N-dimethylacetamide (5.2 ml, 51 mmol) was added and the mixture was stirred for 16 h at room temperature. H2O (10 ml) was added and the solvent was evaporated under reduced pressure. The residue was dissolved in H2O (150 ml) and extracted with CH2Cl2 (2\u00d7150 ml). The collected organic phases were dried over Na2SO4, filtered and evaporated. The crude was purified by flash chromatography (petroleum ether/EtOAc 4:6) affording the title compound (7.2 g, 75%) as light yellow oil.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaH\"}], \"amount\": {\"mass\": {\"value\": 2.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 125.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-(3-butoxyphenyl)-(tert-butoxycarbonyl)ethylamine\"}], \"amount\": {\"mass\": {\"value\": 7.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF\"}], \"amount\": {\"volume\": {\"value\": 125.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-chloro-N,N-dimethylacetamide\"}], \"amount\": {\"volume\": {\"value\": 5.2, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred for 16 h at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"the solvent was evaporated under reduced pressure\"}, {\"type\": \"DISSOLUTION\", \"details\": \"The residue was dissolved in H2O (150 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"H2O\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"EXTRACTION\", \"details\": \"extracted with CH2Cl2 (2\\u00d7150 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"amount\": {\"volume\": {\"value\": 150.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The collected organic phases were dried over Na2SO4\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Na2SO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CUSTOM\", \"details\": \"evaporated\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude was purified by flash chromatography (petroleum ether/EtOAc 4:6)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"petroleum ether EtOAc\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 7.2, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 75.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-55cc73cf521149e091891a97668c18b0",
    "procedure_text": "4-Formylimidazole (20.0 g, 208.14 mmol) and p-toluenesulfonyl chloride (43.7 g, 229.0 mmol) were suspended in N,N-dimethylacetamide (200 mL). To the obtained suspension was added dropwise triethylamine (23.2 g, 229.0 mmol) at 10\u00b0 C. or below, and the mixture was stirred at 10\u00b0 C. or below for 1 hr or more. To the reaction mixture was added n-heptane (60 mL) at 30\u00b0 C. or below. To the obtained solution was added dropwise water (240 mL) at 30\u00b0 C. or below for crystallization. The mixture was stirred at room temperature for 1 hr or more to give crystals. The obtained crystals were collected by filtration, and washed with water (300 mL) to give wet crystals. The obtained wet crystals were dried under reduced pressure at an outside temperature of 50\u00b0 C. to give 1-tosyl-4-formyl-1H-imidazole (44.2 g, 176.6 mmol). yield 85%.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-heptane\"}], \"amount\": {\"volume\": {\"value\": 60.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 240.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-Formylimidazole\"}], \"amount\": {\"mass\": {\"value\": 20.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"p-toluenesulfonyl chloride\"}], \"amount\": {\"mass\": {\"value\": 43.7, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N,N-dimethylacetamide\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"mass\": {\"value\": 23.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred at 10\\u00b0 C. or below for 1 hr or more\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"for crystallization\"}, {\"type\": \"STIRRING\", \"details\": \"The mixture was stirred at room temperature for 1 hr or more\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"CUSTOM\", \"details\": \"to give crystals\"}, {\"type\": \"FILTRATION\", \"details\": \"The obtained crystals were collected by filtration\"}, {\"type\": \"WASH\", \"details\": \"washed with water (300 mL)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"amount\": {\"volume\": {\"value\": 300.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"to give wet crystals\"}, {\"type\": \"CUSTOM\", \"details\": \"The obtained wet crystals were dried under reduced pressure at an outside temperature of 50\\u00b0 C.\", \"temperature\": {\"setpoint\": {\"value\": 50.0, \"units\": \"CELSIUS\"}}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-tosyl-4-formyl-1H-imidazole\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"AMOUNT\", \"amount\": {\"moles\": {\"value\": 176.6, \"units\": \"MILLIMOLE\"}}}, {\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 44.2, \"units\": \"GRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 85.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c2cdce0bfcd242c092bbc9b6cdab22de",
    "procedure_text": "According to the method of Example 1, Step C, deprotection was performed (50\u00b0 C., 2 hours) by using Intermediate 71 (123 mg) and 10% hydrogen chloride/methanol solution (6 ml). The reaction mixture was cooled to room temperature, and then the solvent was evaporated under reduced pressure. The residue was added with methanol (2 ml) and diethyl ether (6 ml). The deposited precipitates were collected by filtration and washed with diethyl ether to obtain the title compound (52 mg) as light yellow powdery solid.",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Intermediate 71\"}], \"amount\": {\"mass\": {\"value\": 123.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrogen chloride methanol\"}], \"amount\": {\"volume\": {\"value\": 6.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"(50\\u00b0 C., 2 hours)\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"temperature\": {\"setpoint\": {\"value\": 50.0, \"units\": \"CELSIUS\"}}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was evaporated under reduced pressure\"}, {\"type\": \"ADDITION\", \"details\": \"The residue was added with methanol (2 ml) and diethyl ether (6 ml)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"amount\": {\"volume\": {\"value\": 6.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The deposited precipitates\"}, {\"type\": \"FILTRATION\", \"details\": \"were collected by filtration\"}, {\"type\": \"WASH\", \"details\": \"washed with diethyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 52.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3cf1cf431d5b482eb804bdc75085585f",
    "procedure_text": "A portion (470 mg) of the crude compound obtained in Example 126 was suspended in methylene chloride (4 ml) and to the suspension was added trifluoroacetic acid (4 ml). The mixture was stirred for 1 hour at room temperature. The reaction mixture was made basic with saturated aqueous solution of sodium hydrogencarbonate and extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. Then, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate-ethyl acetate/methanol=9:1) to yield 100 mg (41%) of the titled compound.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methylene chloride\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude compound\"}], \"amount\": {\"mass\": {\"value\": 470.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trifluoroacetic acid\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydrogencarbonate\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture was stirred for 1 hour at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted with ethyl acetate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The organic layer was washed with water and saturated aqueous solution of sodium chloride\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium chloride\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over anhydrous sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DISTILLATION\", \"details\": \"Then, the solvent was distilled off under reduced pressure\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by silica gel column chromatography (ethyl acetate-ethyl acetate/methanol=9:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate ethyl acetate methanol\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 1.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"titled compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 41.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-ed7995cf24204eb79f422cb3910969a8",
    "procedure_text": "To a stirred solution 0.81 mmol 5-chloro-6-(3,6-dihydro-2H-pyran-4-yl)-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (Example A61(a)) in 40 ml methanol was added 0.41 mmol platinum(IV) oxide and the mixture was stirred under an atmosphere of hydrogen for 16 h. The reaction mixture was then filtered and the filtrate was concentrated in vacuo. The residue was purified by chromatography (SiO2, heptane/ethyl acetate) to yield the title compound as a white solid (38% yield). MS (m/e): 284.3 ({37Cl}[M+H\u2212Me2C\u2550CH2]+, 49%), 282.3 ({35Cl} [M+H\u2212Me2C\u2550CH2]+, 100%).",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"platinum(IV) oxide\"}], \"amount\": {\"moles\": {\"value\": 0.41, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"CATALYST\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"solution\"}], \"amount\": {\"moles\": {\"value\": 0.81, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"5-chloro-6-(3,6-dihydro-2H-pyran-4-yl)-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 40.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"the mixture was stirred under an atmosphere of hydrogen for 16 h\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"FILTRATION\", \"details\": \"The reaction mixture was then filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"the filtrate was concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was purified by chromatography (SiO2, heptane/ethyl acetate)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"heptane ethyl acetate\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 16.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 38.0}}], \"isolated_color\": \"white\", \"texture\": {\"type\": \"CUSTOM\", \"details\": \"solid\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-3d7b5aea4dc24ef5aa244cf7a9e8030a",
    "procedure_text": "To a solution of 2.76 g of 2-fluoroacetophenone in 50 ml of ether is added dropwise over 30 minutes a solution of 3.2 g of bromine in 10 ml of chloroform. Evaporation of the reaction mixture under reduced pressure affords \u03b1-bromo-2-fluoroacetophenone.",
    "reference_string": "{\"inputs\": {\"m1_m3_m2_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-fluoroacetophenone\"}], \"amount\": {\"mass\": {\"value\": 2.76, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"bromine\"}], \"amount\": {\"mass\": {\"value\": 3.2, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"chloroform\"}], \"amount\": {\"volume\": {\"value\": 10.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"Evaporation of the reaction mixture under reduced pressure\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"\\u03b1-bromo-2-fluoroacetophenone\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-beaed38ce4454432a427603f2ea74704",
    "procedure_text": "To a mixture of 3-amino-5-(2-methylphenyl)-1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-one obtained in Step E (200 mg) and acetonitrile (6 mL) was slowly added a solution of N-bromosuccinimide (163 mg) in acetonitrile (2 mL) under ice-cooling. The reaction mixture was stirred overnight at room temperature, and the resulting solid was collected by filtration, and washed with acetonitrile. The obtained solid was purified by silica gel chromatography (methanol/dichloromethane) to give the title compound (127 mg).",
    "reference_string": "{\"inputs\": {\"m1_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3-amino-5-(2-methylphenyl)-1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-one\"}], \"amount\": {\"mass\": {\"value\": 200.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 6.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-bromosuccinimide\"}], \"amount\": {\"mass\": {\"value\": 163.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"amount\": {\"volume\": {\"value\": 2.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred overnight at room temperature\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"TEMPERATURE\", \"details\": \"cooling\"}, {\"type\": \"FILTRATION\", \"details\": \"the resulting solid was collected by filtration\"}, {\"type\": \"WASH\", \"details\": \"washed with acetonitrile\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"acetonitrile\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The obtained solid was purified by silica gel chromatography (methanol/dichloromethane)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol dichloromethane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 8.0, \"precision\": 8.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 127.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-ae7595a7da9b49159daa3683a7a72637",
    "procedure_text": "Following the procedure as described in Example 5, making variations to replace benzyl bromide with 1-iodobutane to react with ethyl 4-methyl-2-(2-oxoimidazolidin-1-yl)thiazole-5-carboxylate, the title compound was obtained in 73% yield: NMR (300 MHZ, CDCl3) \u03b4 4.08 (q, J=7.2 Hz, 2H), 3.99-3.85 (m, 2H), 3.47-3.33 (m, 2H), 3.11 (t, J=7.5 Hz, 2H), 2.38 (s, 3H), 1.41-1.22 (m, 7H), 0.74 (t, J=7.2 Hz, 3H); MS (ES+) m/z 312.3 (M+1).",
    "reference_string": "{\"inputs\": {\"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzyl bromide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1-iodobutane\"}], \"reaction_role\": \"REACTANT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl 4-methyl-2-(2-oxoimidazolidin-1-yl)thiazole-5-carboxylate\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 73.0}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-fc8d26a399404f3784b9ec097faeec07",
    "procedure_text": "Methyl 6-acetyl-4-ethylthio-7-hydroxy-8-propylquinoline-2-carboxylate (1.0 g), was added to Raney Nickel (16 g wet wt; previously washed with ethanol) in dry ethanol (100 mls), and reflux for 11/2 hours. The catalyst was filtered off, and the filtrate evaporated to dryness. The residue was triturated with 40\u00b0-60\u00b0 petroleum ether and the yellow solid collected by filtration to give 0.6 g of the sub-title product. A recrystallisation from ethanol gave 0.2 g, mp 110\u00b0-111\u00b0.",
    "reference_string": "{\"inputs\": {\"m1_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Methyl 6-acetyl-4-ethylthio-7-hydroxy-8-propylquinoline-2-carboxylate\"}], \"amount\": {\"mass\": {\"value\": 1.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"Raney Nickel\"}], \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"WASH\", \"details\": \"previously washed with ethanol) in dry ethanol (100 mls)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethanol\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"reflux for 11/2 hours\", \"duration\": {\"value\": 2.0, \"units\": \"HOUR\"}}, {\"type\": \"FILTRATION\", \"details\": \"The catalyst was filtered off\"}, {\"type\": \"CUSTOM\", \"details\": \"the filtrate evaporated to dryness\"}, {\"type\": \"CUSTOM\", \"details\": \"The residue was triturated with 40\\u00b0-60\\u00b0 petroleum ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"petroleum ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"the yellow solid collected by filtration\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sub-title product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 0.6, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-c04d2627863340efb56aee924cea524f",
    "procedure_text": "Reaction of 4-(3-(methylamino)pyridin-4-yl)cyclohexanone (prepared by the reaction of 4-bromo-N-methylpyridin-3-amine with 8-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,4-dioxa-spiro[4.5]dec-7-ene using the sequence described in Example 1 Step A-C) with N-(azetidin-3-yl)-2-((6-(trifluoromethyl)quinazolin-4-yl)amino)acetamide (as prepared in Example 1 Step G) in the presence of TEA and NaBH(OAc)3 as described in Example 1, Step H afforded the product.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"N-(azetidin-3-yl)-2-((6-(trifluoromethyl)quinazolin-4-yl)amino)acetamide\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-(3-(methylamino)pyridin-4-yl)cyclohexanone\"}], \"reaction_role\": \"REACTANT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"4-bromo-N-methylpyridin-3-amine\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"8-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,4-dioxa-spiro[4.5]dec-7-ene\"}], \"reaction_role\": \"REACTANT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"NaBH(OAc)3\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"afforded the product\"}], \"outcomes\": [{\"products\": [{}]}]}"
  },
  {
    "reaction_id": "ord-26eb8c4a49ec4c398b26c834d3071124",
    "procedure_text": "Through a solution of 3,4-difluorobenzaldehyde (25.0 g, 0.176 mol) in MeOH (500 mL) in a round bottom flask, was bubbled ammonia gas for two hours at room temperature. The flask was then cooled to 0\u00b0 C. and trimethylsilyl cyanide was then added slowly. The reaction mixture was stirred for 2 h, at which time TLC analysis indicated that the reaction was complete (Rf=0.35, 3:2 hexane/EtOAc). The solvent was removed in vacuo and the residue was subjected to flash column chromatography on silica gel to obtain the desired product, which was used in the next step without purification.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane EtOAc\"}], \"reaction_role\": \"REACTANT\"}]}, \"m1_m5_m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"3,4-difluorobenzaldehyde\"}], \"amount\": {\"mass\": {\"value\": 25.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ammonia\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MeOH\"}], \"amount\": {\"volume\": {\"value\": 500.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"trimethylsilyl cyanide\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 0.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred for 2 h, at which time TLC analysis\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The solvent was removed in vacuo\"}], \"outcomes\": [{\"reaction_time\": {\"value\": 2.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"desired product\"}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-4a8d7a0eca5349c2b12420a87cc284dc",
    "procedure_text": "(R)-8-Fluoro-3-(N,N-di-n-propylamino)-5-trifloromethanesulfonyloxychroman (0.95 g, 2.4 mmol), triethylamine (0.53 g, 5.2 mmol), 1,3-bis(diphenylphosphino)propane (100 mg, catalytic amount), palladium(II)acetate (50 mg, catalytic amount) and DMF/MeOH (18 mL, 6:2) were mixed in a 50 mL three necked round bottom flask. The flask was evacuated followed by the inlet of CO (repeated three times). The reaction mixture was stirred at 70\u00b0 C. for 7 hours. The solvent was removed in vacuo and the residue was dissolved in diethyl ether/2M NH3. The layers were separated and the water phase was extracted once with ether. The combined ether layers were dried (MgSO4) and the solvent was removed in vacuo to give a brown oily residue which was purified by flash chromatography (SiO2, CH2Cl2 /EtOAC, 20:1) to give 650 mg of the title compound as a clear oil (87% yield). [\u03b1]D21 -92\u00b0 (c 10 mg/mL MeOH). Mass spectrum (70 eV) m/Z (relative intensity) 309(20, M+), 281(18), 280(100), 56(10), 43(22), 42(12), 41(16).",
    "reference_string": "{\"inputs\": {\"m1_m2_m3_m6_m5_m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"(R)-8-Fluoro-3-(N,N-di-n-propylamino)-5-trifloromethanesulfonyloxychroman\"}], \"amount\": {\"mass\": {\"value\": 0.95, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"triethylamine\"}], \"amount\": {\"mass\": {\"value\": 0.53, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"1,3-bis(diphenylphosphino)propane\"}], \"amount\": {\"mass\": {\"value\": 100.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"three\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"DMF MeOH\"}], \"amount\": {\"volume\": {\"value\": 18.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"palladium(II)acetate\"}], \"amount\": {\"mass\": {\"value\": 50.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"CATALYST\"}]}}, \"conditions\": {\"temperature\": {\"setpoint\": {\"value\": 70.0, \"units\": \"CELSIUS\"}}, \"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The reaction mixture was stirred at 70\\u00b0 C. for 7 hours\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The flask was evacuated\"}, {\"type\": \"CUSTOM\", \"details\": \"The solvent was removed in vacuo\"}, {\"type\": \"DISSOLUTION\", \"details\": \"the residue was dissolved in diethyl ether/2M NH3\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The layers were separated\"}, {\"type\": \"EXTRACTION\", \"details\": \"the water phase was extracted once with ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"The combined ether layers were dried (MgSO4)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ether\"}], \"reaction_role\": \"WORKUP\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"MgSO4\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"the solvent was removed in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"to give a brown oily residue which\"}, {\"type\": \"CUSTOM\", \"details\": \"was purified by flash chromatography (SiO2, CH2Cl2 /EtOAC, 20:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"CH2Cl2\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 7.0, \"units\": \"HOUR\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"title compound\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 650.0, \"units\": \"MILLIGRAM\"}}}, {\"type\": \"YIELD\", \"details\": \"PERCENTYIELD\", \"percentage\": {\"value\": 87.0}}], \"isolated_color\": \"clear\", \"texture\": {\"type\": \"OIL\", \"details\": \"oil\"}, \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-57841952ef7c4e039428cfe553c1fad0",
    "procedure_text": "To a solution of 400 mg of 2-methyl-4-isopropyl-5-phenylselenyl-imidazole (1.4 mmol) in 4 ml of dry dimethylformamide is added 70 mg of 60% oil suspension of sodium hydride (1.8 mmol) under ice cooling and the mixture is allowed to stand for 5 minutes followed by the addition of 270 mg of benzyloxymethyl chloride (1.7 mmol). The mixture is stirred for 30 minutes under ice cooling, mixed with ice water and extracted with diethyl ether. The extract is washed with water, dried over sodium sulfate and filtered. The filtrate is concentrated in vacuo. The crude product is chromatographed on a column of silica gel, eluting with ethyl acetate/n-hexane (1:1). The product is recrystallized from n-hexane to give 297 mg of the objective 2-methyl-4-phenylselenyl-5-isopropyl-imidazole (I-87 ) and 1-benzyloxymethyl-4-isopropyl-2-methyl-5-phenyl-selenyl-imidazole (I-37). Yield, 52%; mp. 94\u00b0-96\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m4\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"benzyloxymethyl chloride\"}], \"amount\": {\"mass\": {\"value\": 270.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m2_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"oil\"}], \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium hydride\"}], \"amount\": {\"moles\": {\"value\": 1.8, \"units\": \"MILLIMOLE\"}}, \"reaction_role\": \"REACTANT\"}]}, \"m1_m6\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-methyl-4-isopropyl-5-phenylselenyl-imidazole\"}], \"amount\": {\"mass\": {\"value\": 400.0, \"units\": \"MILLIGRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"dimethylformamide\"}], \"amount\": {\"volume\": {\"value\": 4.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ice water\"}], \"reaction_role\": \"REACTANT\"}]}}, \"conditions\": {\"stirring\": {\"type\": \"CUSTOM\", \"details\": \"The mixture is stirred for 30 minutes under ice cooling\"}, \"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"EXTRACTION\", \"details\": \"extracted with diethyl ether\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"diethyl ether\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"The extract is washed with water\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"water\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"DRY_WITH_MATERIAL\", \"details\": \"dried over sodium sulfate\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"sodium sulfate\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"FILTRATION\", \"details\": \"filtered\"}, {\"type\": \"CONCENTRATION\", \"details\": \"The filtrate is concentrated in vacuo\"}, {\"type\": \"CUSTOM\", \"details\": \"The crude product is chromatographed on a column of silica gel\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"crude product\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"WASH\", \"details\": \"eluting with ethyl acetate/n-hexane (1:1)\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"ethyl acetate n-hexane\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The product is recrystallized from n-hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"n-hexane\"}], \"reaction_role\": \"WORKUP\"}]}}], \"outcomes\": [{\"reaction_time\": {\"value\": 5.0, \"units\": \"MINUTE\"}, \"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"2-methyl-4-phenylselenyl-5-isopropyl-imidazole\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 297.0, \"units\": \"MILLIGRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  },
  {
    "reaction_id": "ord-523d7966cb5445e38f9bced2848f4a13",
    "procedure_text": "A suspension of 25.0 g (0.055 mol) of [2-(2-nitro-5-trifluoromethylphenyl)-1-(4-methoxyphenyl)ethyl]propanedioic acid, dimethyl ester (see Example 4A) in 200 ml of methanol was treated with a cold suspension of 2.5 g of 5% palladium on charcoal in 50 ml of methanol (under nitrogen) and placed on the Parr apparatus at 58 lbs. of hydrogen. The theoretical amount of hydrogen was consumed in about 30 minutes and this mixture was then heated at 50\u00b0-55\u00b0 C. for one hour to assure that all of the nitro compound had dissolved. The mixture was removed from the Parr and allowed to stand at room temperature overni-ght. The flask was heated to dissolve the crystallized product, and the hot solution was filtered through Celite (under nitrogen) and washed with hot methanol. The colorless filtrate was concentrated on a rotary evaporator to give 22.2 g of a nearly colorless solid. The latter was triturated with 100 ml of hexane and then with 50 ml of hexane. The solvent was decanted and the entrained solvent removed on a rotary evaporator to give 21.3 g of product, melting point 124\u00b0-127\u00b0 C. A sample of this material, after crystallization from methanol, melted at 125\u00b0-127\u00b0 C.",
    "reference_string": "{\"inputs\": {\"m1_m3\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"[2-(2-nitro-5-trifluoromethylphenyl)-1-(4-methoxyphenyl)ethyl]propanedioic acid, dimethyl ester\"}], \"amount\": {\"mass\": {\"value\": 25.0, \"units\": \"GRAM\"}}, \"reaction_role\": \"REACTANT\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 200.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}, \"m2\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrogen\"}], \"reaction_role\": \"REACTANT\"}]}, \"m4_m5\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"palladium on charcoal\"}], \"amount\": {\"mass\": {\"value\": 2.5, \"units\": \"GRAM\"}}, \"reaction_role\": \"CATALYST\"}, {\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"amount\": {\"volume\": {\"value\": 50.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"SOLVENT\"}]}}, \"conditions\": {\"conditions_are_dynamic\": true}, \"workups\": [{\"type\": \"CUSTOM\", \"details\": \"The theoretical amount of hydrogen was consumed in about 30 minutes\", \"duration\": {\"value\": 30.0, \"units\": \"MINUTE\"}, \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hydrogen\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"TEMPERATURE\", \"details\": \"this mixture was then heated at 50\\u00b0-55\\u00b0 C. for one hour\", \"duration\": {\"value\": 1.0, \"units\": \"HOUR\"}}, {\"type\": \"DISSOLUTION\", \"details\": \"had dissolved\"}, {\"type\": \"CUSTOM\", \"details\": \"The mixture was removed from the Parr\"}, {\"type\": \"CUSTOM\", \"details\": \"to stand at room temperature\", \"temperature\": {\"control\": {\"type\": \"AMBIENT\"}}}, {\"type\": \"TEMPERATURE\", \"details\": \"The flask was heated\"}, {\"type\": \"DISSOLUTION\", \"details\": \"to dissolve the crystallized product\"}, {\"type\": \"FILTRATION\", \"details\": \"the hot solution was filtered through Celite (under nitrogen)\"}, {\"type\": \"WASH\", \"details\": \"washed with hot methanol\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"methanol\"}], \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CONCENTRATION\", \"details\": \"The colorless filtrate was concentrated on a rotary evaporator\"}, {\"type\": \"CUSTOM\", \"details\": \"to give 22.2 g of a nearly colorless solid\"}, {\"type\": \"CUSTOM\", \"details\": \"The latter was triturated with 100 ml of hexane\", \"input\": {\"components\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"hexane\"}], \"amount\": {\"volume\": {\"value\": 100.0, \"units\": \"MILLILITER\"}}, \"reaction_role\": \"WORKUP\"}]}}, {\"type\": \"CUSTOM\", \"details\": \"The solvent was decanted\"}, {\"type\": \"CUSTOM\", \"details\": \"the entrained solvent removed on a rotary evaporator\"}], \"outcomes\": [{\"products\": [{\"identifiers\": [{\"type\": \"NAME\", \"value\": \"product\"}], \"measurements\": [{\"type\": \"AMOUNT\", \"details\": \"MASS\", \"amount\": {\"mass\": {\"value\": 21.3, \"units\": \"GRAM\"}}}], \"reaction_role\": \"PRODUCT\"}]}]}"
  }
]