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Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: Palladium acetate (45 mg, 0.2 mmol), BINAP (62 mg, 0.1 mmol) and cesium carbonate (650 mg, 2 mmol) were suspended in anhydrous 1,4-dioxane (3 ml) under an argon atmosphere and sonicated for 45 minutes. 2-Bromo-4-methylpyrimidine (173 mg, 1 mmol) and tert-butyl piperazine-1-carboxylate (208 mg, 1.3 mmol) were dissolved in 3 ml anhydrous 1,4-dioxane and the resulting solution was added to the catalyst-containing mixture. The resulting mixture was stirred at 110° C. overnight, afterwards diluted with ethyl acetate and filtered. The filtrate was evaporated to dryness under reduced pressure and the residue was purified by column chromatography (silica, gradient from DCM to DCM/ethyl acetate 8/2) to yield 120 mg of a brown oil (0.43 mmol, 43%) MS (APCI) m/z=279.2 [M+1]+. ### ORD JSON:

{"inputs": {"m7": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl acetate"}], "reaction_role": "SOLVENT"}]}, "m8": {"components": [{"identifiers": [{"type": "NAME", "value": "Palladium acetate"}], "amount": {"mass": {"value": 45.0, "units": "MILLIGRAM"}}, "reaction_role": "CATALYST"}]}, "m1": {"components": [{"identifiers": [{"type": "NAME", "value": "BINAP"}], "amount": {"mass": {"value": 62.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "cesium carbonate"}], "amount": {"mass": {"value": 650.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}]}, "m3_m4_m6": {"components": [{"identifiers": [{"type": "NAME", "value": "2-Bromo-4-methylpyrimidine"}], "amount": {"mass": {"value": 173.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "tert-butyl piperazine-1-carboxylate"}], "amount": {"mass": {"value": 208.0, "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": "1,4-dioxane"}], "amount": {"volume": {"value": 3.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"temperature": {"setpoint": {"value": 110.0, "units": "CELSIUS"}}, "stirring": {"type": "CUSTOM", "details": "The resulting mixture was stirred at 110\u00b0 C. overnight"}, "conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "sonicated for 45 minutes", "duration": {"value": 45.0, "units": "MINUTE"}}, {"type": "ADDITION", "details": "the resulting solution was added to the catalyst-containing mixture"}, {"type": "FILTRATION", "details": "filtered"}, {"type": "CUSTOM", "details": "The filtrate was evaporated to dryness under reduced pressure"}, {"type": "CUSTOM", "details": "the residue was purified by column chromatography (silica, gradient from DCM to DCM/ethyl acetate 8/2)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "DCM"}], "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "DCM ethyl acetate"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"reaction_time": {"value": 8.0, "precision": 8.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "brown oil"}], "measurements": [{"type": "AMOUNT", "details": "AMOUNT", "amount": {"moles": {"value": 0.43, "units": "MILLIMOLE"}}}, {"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 120.0, "units": "MILLIGRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 43.0}}, {"type": "YIELD", "details": "CALCULATEDPERCENTYIELD", "percentage": {"value": 43.0}}], "isolated_color": "brown", "texture": {"type": "OIL", "details": "oil"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: In a flask equipped with a stirring blade and a dropping funnel were charged 100 parts of dry methylene chloride and 60 parts of ethylenediamine, and the mixture was stirred in an ice bath. To the solution was slowly added 105 parts of methacrylic chloride through the dropping funnel. After the addition, the mixture was allowed to react at room temperature for 5 hours. The white precipitate thus formed was collected by filtration, thoroughly washed with dry methylene chloride, and dried to obtain aminoethylmethacrylamide hydrochloride. Then, 600 parts of ion-exchanged water, 10 parts of the resulting aminoethylmethacrylamide hydrochloride, and 1.0 part of an anionic surface active agent ("Perex OTP" produced by Kao Co., Ltd.) were charged in a flask equipped with a stirring blade and a tube for nitrogen introduction, followed by stirring. To the mixture was added 70 parts of methyl methacrylate to form an emulsion. To the emulsion was added 200 parts of a 3% aqueous solution of potassium persulfate, and the system was heated to 50° C., at which the emulsion was allowed to react for 24 hours. There were obtained fine particles of an aminoethylmethacrylamide hydrochloride/methyl methacrylate copolymer having an average particle size of 0.2 μm. The polymer particles were washed with water by means of a centrifugal separator. Then, 50.0 parts of the polymer particles was washed with a 5% sodium hydroxide aqueous solution to obtain fine particles of a methyl methacrylate copolymer having an amino group on the surface thereof. ### ORD JSON:

{"inputs": {"m5_m1": {"components": [{"identifiers": [{"type": "NAME", "value": "aminoethylmethacrylamide hydrochloride"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "water"}], "reaction_role": "SOLVENT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "methyl methacrylate"}], "reaction_role": "REACTANT"}]}, "m3_m4": {"components": [{"identifiers": [{"type": "NAME", "value": "aqueous solution"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "potassium persulfate"}], "reaction_role": "REACTANT"}]}}, "conditions": {"temperature": {"setpoint": {"value": 50.0, "units": "CELSIUS"}}, "stirring": {"type": "CUSTOM", "details": "by stirring"}, "conditions_are_dynamic": true}, "workups": [{"type": "ADDITION", "details": "were charged in a flask"}, {"type": "CUSTOM", "details": "equipped with a stirring blade and a tube for nitrogen introduction"}, {"type": "CUSTOM", "details": "to form an emulsion"}, {"type": "CUSTOM", "details": "to react for 24 hours", "duration": {"value": 24.0, "units": "HOUR"}}], "outcomes": [{"products": [{"reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: To methanol add 4-(3-aminophenyl)-1-(phenylmethyl)-2-piperazinecarboxamide and Pd(OH)2. Place the reaction on a Parr hydrogenator at 50 psi of H2 and shake. Monitor the progress of the reaction by thin-layer chromatography. Upon completion of the reaction, remove the catalyst by suction filtration through celite. Remove solvent in vacuo to obtain the title compound. ### ORD JSON:

{"inputs": {"m3_m1_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "4-(3-aminophenyl)-1-(phenylmethyl)-2-piperazinecarboxamide"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "Pd(OH)2"}], "reaction_role": "CATALYST"}, {"identifiers": [{"type": "NAME", "value": "methanol"}], "reaction_role": "SOLVENT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "the reaction on a Parr hydrogenator at 50 psi of H2 and shake"}, {"type": "CUSTOM", "details": "Monitor the progress of the reaction by thin-layer chromatography"}, {"type": "CUSTOM", "details": "Upon completion of the reaction"}, {"type": "CUSTOM", "details": "remove the catalyst"}, {"type": "FILTRATION", "details": "by suction filtration through celite"}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: Aluminium(III)chloride (0.666 mol) was added portionwise at RT to a solution of N-phenyl-2-benzothiazolylamine (0.222 mol) and 1,2dichloro-1-propanone (0.233 mol) in 1,2-dichloroethane (500 ml) and the mixture was stirred and heated at 80° C. for 2 hours. The mixture was poured into ice and extracted with CH2Cl2. The organic layer was decanted, dried filtered and the solvent was evaporated, yielding 68 g of (±)-1-[4-(2-benzothiazolylamino)phenyl]-2-chloro-1-propanone (95.7%) (interm. 22). ### ORD JSON:

{"inputs": {"m1_m2_m3_m4": {"components": [{"identifiers": [{"type": "NAME", "value": "Aluminium(III)chloride"}], "amount": {"moles": {"value": 0.666, "units": "MOLE"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "N-phenyl-2-benzothiazolylamine"}], "amount": {"moles": {"value": 0.222, "units": "MOLE"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "1,2dichloro-1-propanone"}], "amount": {"moles": {"value": 0.233, "units": "MOLE"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "1,2-dichloroethane"}], "amount": {"volume": {"value": 500.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"temperature": {"setpoint": {"value": 80.0, "units": "CELSIUS"}}, "stirring": {"type": "CUSTOM", "details": "the mixture was stirred"}, "conditions_are_dynamic": true}, "workups": [{"type": "ADDITION", "details": "The mixture was poured into ice"}, {"type": "EXTRACTION", "details": "extracted with CH2Cl2", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "CH2Cl2"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "The organic layer was decanted"}, {"type": "CUSTOM", "details": "dried"}, {"type": "FILTRATION", "details": "filtered"}, {"type": "CUSTOM", "details": "the solvent was evaporated"}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "(\u00b1)-1-[4-(2-benzothiazolylamino)phenyl]-2-chloro-1-propanone"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 68.0, "units": "GRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 95.7}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: A stirred solution of 4-[2-(2-carbamoyl-ethyl)-5-phenylpyrrol-1-yl]-benzoic acid tert-butyl ester (3.92 mmol, 1.0 eq.) in dioxane and pyridine was cooled in an ice bath. To the mixture was added Trifluoroacetic anhydride (TFA, 7.84 mmol, 2.0 eq.). After 10 minutes the ice bath was removed and the reaction was allowed to warm to room temperature overnight. The solvent was evaporated in vacuo and the residue treated with EtOAc (250 mL) and saturated NaHCO3 (150 mL). The organic layer was separated, dried (Na2SO4) and the solvent evaporated in vacuo. The residue was loaded onto a 40 g RediSep silica-gel column for purification. Gradient elution with ethyl acetate/hexane (0% to 10% ethyl acetate in hexane over 25 minutes) gave the product as a yellow solid after combination of the appropriate fractions and evaporation of the solvent in vacuo, 62% yield. ### ORD JSON:

{"inputs": {"m1_m3_m4": {"components": [{"identifiers": [{"type": "NAME", "value": "4-[2-(2-carbamoyl-ethyl)-5-phenylpyrrol-1-yl]-benzoic acid tert-butyl ester"}], "amount": {"moles": {"value": 3.92, "units": "MILLIMOLE"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "dioxane"}], "reaction_role": "SOLVENT"}, {"identifiers": [{"type": "NAME", "value": "pyridine"}], "reaction_role": "SOLVENT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "Trifluoroacetic anhydride"}], "amount": {"moles": {"value": 7.84, "units": "MILLIMOLE"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"temperature": {"control": {"type": "AMBIENT"}}, "conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "After 10 minutes the ice bath was removed", "duration": {"value": 10.0, "units": "MINUTE"}, "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ice"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "The solvent was evaporated in vacuo"}, {"type": "ADDITION", "details": "the residue treated with EtOAc (250 mL) and saturated NaHCO3 (150 mL)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "EtOAc"}], "amount": {"volume": {"value": 250.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "NaHCO3"}], "amount": {"volume": {"value": 150.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "The organic layer was separated"}, {"type": "DRY_WITH_MATERIAL", "details": "dried (Na2SO4)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "Na2SO4"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "the solvent evaporated in vacuo"}, {"type": "CUSTOM", "details": "The residue was loaded onto a 40 g RediSep silica-gel column for purification"}, {"type": "WASH", "details": "Gradient elution with ethyl acetate/hexane (0% to 10% ethyl acetate in hexane over 25 minutes)", "duration": {"value": 25.0, "units": "MINUTE"}, "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl acetate hexane"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "product"}], "measurements": [{"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 62.0}}], "isolated_color": "yellow", "texture": {"type": "CUSTOM", "details": "solid"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: The title compound (12 mg) was prepared using 130 mg (0.39 mmol) of 4-benzothiazol-2-yl-5-(3-bromopropyl)-2H-pyrazol-3-ylamine, which was derived from 3-(5-amino-4-benzothiazol-2-yl-1H-pyrazol-3-yl)-propan-1-ol, and a saturated solution of ammonia gas in ethanol. MS (m/z, ES+): 274.2 (M+1, 100%), 257.2 (M-NH2, 70%). ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "ethanol"}], "reaction_role": "SOLVENT"}]}, "m1": {"components": [{"identifiers": [{"type": "NAME", "value": "4-benzothiazol-2-yl-5-(3-bromopropyl)-2H-pyrazol-3-ylamine"}], "amount": {"mass": {"value": 130.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "3-(5-amino-4-benzothiazol-2-yl-1H-pyrazol-3-yl)-propan-1-ol"}], "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "ammonia"}], "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 12.0, "units": "MILLIGRAM"}}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: Using the general method of Example 10, 2-propylthiazolo[4,5-c]quinolin4-amine (1.75 g) was reacted with 1 equivalent of concentrated hydrochloric acid to provide 2-propylthiazolo[4,5-c]quinolin-4-amine hydrochloride as an off-white crystalline solid, m.p. 234-237° C. Analysis: Calculated for C13H13N3S HCl: %C, 55.81; %H, 5.04; %N, 15.02; Found: %C, 55.86; %H, 5.02; %N, 14.99. ### ORD JSON:

{"inputs": {"m1": {"components": [{"identifiers": [{"type": "NAME", "value": "2-propylthiazolo[4,5-c]quinolin4-amine"}], "amount": {"mass": {"value": 1.75, "units": "GRAM"}}, "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "hydrochloric acid"}], "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "2-propylthiazolo[4,5-c]quinolin-4-amine hydrochloride"}], "isolated_color": "off-white crystalline", "texture": {"type": "CUSTOM", "details": "solid"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: Except for using 4-formylbenzoic acid (112 mg) in place of 4-(diethoxymethyl)benzaldehyde and using 8-cyclohexyl-2,8-diazaspiro[4.5]decane (170 mg) in place of 8-isobutyl-2,8-diazaspiro[4.5]decane, the same operation as in Example 26 was performed to obtain the title compound (450 mg) having the following physical properties. ### ORD JSON:

{"inputs": {"m1": {"components": [{"identifiers": [{"type": "NAME", "value": "4-formylbenzoic acid"}], "amount": {"mass": {"value": 112.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "8-cyclohexyl-2,8-diazaspiro[4.5]decane"}], "amount": {"mass": {"value": 170.0, "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": 450.0, "units": "MILLIGRAM"}}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: Bromine (4.62 g) was added in one portion to a stirred solution of 4-trifluoromethylpyrimidin-6-one (4.3 g) and sodium acetate (10.53 g) in acetic acid (43 ml). After stirring for 2 hours, the reaction mixture was left to stand for a period of 3 days, after which time it was heated to 80° C. for 1 hour. After cooling to the ambient temperature (ca 22° C.), the solvent was evaporated under reduced pressure. The resultant orange solid was dissolved in ethyl acetate, and washed several times with water. The combined agueous washings were extracted with ethylacetate, and the combined organic layers were washed with aqueous sodium thiosulphate solution, followed by aqueous sodium bicarbonate solution and brine. After drying over magnesium sulphate, evaporation of the solvent under reduced pressure gave 5-bromo-4-trifluoromethylpyrimidin-6-one as white solid (4.8 g, mpt 226-227° C.); H NMR (CDC13), 8.05(s); 19 NMR (CDC13), -67.4(s). Preparation 4 ### ORD JSON:

{"inputs": {"m1_m2_m3_m4": {"components": [{"identifiers": [{"type": "NAME", "value": "Bromine"}], "amount": {"mass": {"value": 4.62, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "4-trifluoromethylpyrimidin-6-one"}], "amount": {"mass": {"value": 4.3, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "sodium acetate"}], "amount": {"mass": {"value": 10.53, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "acetic acid"}], "amount": {"volume": {"value": 43.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"temperature": {"setpoint": {"value": 80.0, "units": "CELSIUS"}}, "stirring": {"type": "CUSTOM", "details": "After stirring for 2 hours"}, "conditions_are_dynamic": true}, "workups": [{"type": "WAIT", "details": "the reaction mixture was left"}, {"type": "WAIT", "details": "to stand for a period of 3 days", "duration": {"value": 3.0, "units": "DAY"}}, {"type": "TEMPERATURE", "details": "After cooling to the ambient temperature (ca 22\u00b0 C.)", "temperature": {"control": {"type": "AMBIENT"}}}, {"type": "CUSTOM", "details": "the solvent was evaporated under reduced pressure"}, {"type": "DISSOLUTION", "details": "The resultant orange solid was dissolved in ethyl acetate", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl acetate"}], "reaction_role": "WORKUP"}]}}, {"type": "WASH", "details": "washed several times with water", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "water"}], "reaction_role": "WORKUP"}]}}, {"type": "EXTRACTION", "details": "The combined agueous washings were extracted with ethylacetate", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethylacetate"}], "reaction_role": "WORKUP"}]}}, {"type": "WASH", "details": "the combined organic layers were washed with aqueous sodium thiosulphate solution", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "sodium thiosulphate"}], "reaction_role": "WORKUP"}]}}, {"type": "DRY_WITH_MATERIAL", "details": "After drying over magnesium sulphate, evaporation of the solvent under reduced pressure", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "magnesium sulphate"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"reaction_time": {"value": 2.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "5-bromo-4-trifluoromethylpyrimidin-6-one"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 4.8, "units": "GRAM"}}}], "isolated_color": "white", "texture": {"type": "CUSTOM", "details": "solid"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: 5-[N-(2-Butyl)-sulfamoyl]-isatoic anhydride, which is to be used as the starting material, can be obtained, for example, in a manner analogous to that described in Example 1, using 2-chloro-5-chlorosulfonylbenzoic acid as the starting material, the product being obtained via 5-[N-(2-butyl)-sulfamoyl]-2-chloro-benzoic acid with a melting point of 118°-123° and 5-[N-(2-butyl)-sulfamoyl]-anthranilic acid with a melting point of 187°-188°. It melts at 228°-229°. ### ORD JSON:

{"inputs": {"m2": {"components": [{"identifiers": [{"type": "NAME", "value": "5-[N-(2-Butyl)-sulfamoyl]-isatoic anhydride"}], "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "2-chloro-5-chlorosulfonylbenzoic acid"}], "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "5-[N-(2-butyl)-sulfamoyl]-2-chloro-benzoic acid"}], "reaction_role": "PRODUCT"}, {"identifiers": [{"type": "NAME", "value": "5-[N-(2-butyl)-sulfamoyl]-anthranilic acid"}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: Following the procedure described in EXAMPLE 10.47, and making non-critical variations using spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one to replace 4′-bromospiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one, and 3-(chloromethyl)-1,2,4-oxadiazole to replace 2-(bromomethyl)-5-(trifluoromethyl)furan, the title compound was obtained (36%)) as a colorless solid: mp 160-162° C.; 1H NMR (300 MHz, CDCl3) δ 7.39 (dt, 1H), 7.20-7.13 (m, 3H), 7.05 (d, 1H), 6.50 (s, 1H), 6.12 (s, 1H), 5.86 (dd, 2H), 4.78 (ABq, 2H), 4.68 (s, 2H); 13C NMR (75 MHz, CDCl3) δ 176.7, 156.0, 149.3, 142.5, 139.6, 131.6, 129.4, 124.8, 124.5, 118.4, 113.6, 108.7, 103.0, 101.7, 93.7, 80.3, 58.2, 29.7, 28.0; MS (ES+) m/z 365.2 (M+1). ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "2-(bromomethyl)-5-(trifluoromethyl)furan"}], "reaction_role": "REACTANT"}]}, "m1": {"components": [{"identifiers": [{"type": "NAME", "value": "spiro[furo[2,3-f][1,3]benzodioxole-7,3\u2032-indol]-2\u2032(1\u2032H)-one"}], "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "4\u2032-bromospiro[furo[2,3-f][1,3]benzodioxole-7,3\u2032-indol]-2\u2032(1\u2032H)-one"}], "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "3-(chloromethyl)-1,2,4-oxadiazole"}], "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: The title compound was prepared according to the procedure of Intermediate 24 from 2.28 g (15.6 mmol) of 1,4-dioxa-8-aza-spiro[4.5]decane and 2.85 g (13.0 mmol) of 4-fluoro-N-(2-hydroxyethyl)-benzenesulfonamide, yielding 3.0 g of a colorless gum; MS (ES) m/z 343.2 (MH+); HRMS (EI) Calcd. for C15H22N2O5S (M+): 342.1249, Found: 342.1235. ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "4-fluoro-N-(2-hydroxyethyl)-benzenesulfonamide"}], "amount": {"mass": {"value": 2.85, "units": "GRAM"}}, "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "Intermediate 24"}], "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "1,4-dioxa-8-aza-spiro[4.5]decane"}], "amount": {"mass": {"value": 2.28, "units": "GRAM"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "reaction_role": "PRODUCT"}, {"identifiers": [{"type": "NAME", "value": "colorless gum"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 3.0, "units": "GRAM"}}}], "isolated_color": "colorless", "texture": {"type": "CUSTOM", "details": "gum"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: A modification of the general method described in Part C of Example 3 was used to treat 7-benzyloxy-2-butyl-5-oxido-1-(2-phenoxyethyl)-1H-imidazo[4,5-c]quinoline (1.0 g, 2.1 mmol). An analysis by TLC indicated that the reaction with trichloroacetyl isocyanate (1.35 mL, 11.3 mmol) was incomplete after two hours, and additional trichloroacetyl isocyanate (1 mL) was added and stirred for one hour. Following the reaction with sodium methoxide, a tan precipitate formed, and the mixture was stirred over two days. The precipitate was isolated by filtration, recrystallized from ethanol, isolated by filtration, washed with hexanes, and dried overnight in a vacuum oven to provide 0.63 g of 7-benzyloxy-2-butyl-1-(2-phenoxyethyl)-1H-imidazo[4,5-c]quinolin-4-amine as a white, crystalline solid, mp 188.0-189.0° C. ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "sodium methoxide"}], "reaction_role": "REACTANT"}]}, "m1": {"components": [{"identifiers": [{"type": "NAME", "value": "7-benzyloxy-2-butyl-5-oxido-1-(2-phenoxyethyl)-1H-imidazo[4,5-c]quinoline"}], "amount": {"mass": {"value": 1.0, "units": "GRAM"}}, "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "trichloroacetyl isocyanate"}], "amount": {"volume": {"value": 1.35, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "trichloroacetyl isocyanate"}], "amount": {"volume": {"value": 1.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"stirring": {"type": "CUSTOM", "details": "stirred for one hour"}, "conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "a tan precipitate formed"}, {"type": "STIRRING", "details": "the mixture was stirred over two days", "duration": {"value": 2.0, "units": "DAY"}}, {"type": "CUSTOM", "details": "The precipitate was isolated by filtration"}, {"type": "CUSTOM", "details": "recrystallized from ethanol", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethanol"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "isolated by filtration"}, {"type": "WASH", "details": "washed with hexanes", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "hexanes"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "dried overnight in a vacuum oven", "duration": {"value": 8.0, "precision": 8.0, "units": "HOUR"}}], "outcomes": [{"reaction_time": {"value": 2.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "7-benzyloxy-2-butyl-1-(2-phenoxyethyl)-1H-imidazo[4,5-c]quinolin-4-amine"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 0.63, "units": "GRAM"}}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: A solution of ethyl N-(b-ethoxycarbonylethyl)-N-(4-methoxyphenyl)glycinate (106.7 g, 0.345 mol) in dry benzene (400 mL) is added to a mixture of ethanolic sodium ethoxide in benzene (prepared by dissolving 13.1 g of sodium metal in 300 mL of ethanol and then the ethanolic sodium ethoxide solution is diluted with 500 mL of benzene) at room temperature over a period of 90 minutes. The mixture is heated at reflux for 30 minutes and then is cooled to room temperature. The solid is collected by filtration, and then is suspended in an ice-water mixture (1 L). The mixture, after being neutralized with 1 N hydrochloric acid, is extracted with diethyl ether (3×500 mL). The combined extracts are washed with water, dried over sodium sulfate, concentrated, and the residue is crystallized from n-hexane-diethyl ether to afford 1-(4-methoxyphenyl)-4-ethoxycarbonylpyrrolidine-3-one (87.4 g, 64%), mp 58°-60° C. 1H NMR (CDCl3) d 1.34 (3H, dt, CH2Me), 3.76 (3H, s, OMe), 3.75 (2H, dq, CH2Me), 4.14 (2H, s, 2-CH2), 4.12-4.39 (3H, m, H-4 and 5-CH2), 6.46 and 6.86 (each 2H, m, Ph). ### ORD JSON:

{"inputs": {"m1_m5_m2_m6": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl N-(b-ethoxycarbonylethyl)-N-(4-methoxyphenyl)glycinate"}], "amount": {"mass": {"value": 106.7, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "sodium ethoxide"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "benzene"}], "amount": {"volume": {"value": 400.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}, {"identifiers": [{"type": "NAME", "value": "benzene"}], "reaction_role": "SOLVENT"}]}, "m4_m8": {"components": [{"identifiers": [{"type": "NAME", "value": "sodium ethoxide"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "benzene"}], "amount": {"volume": {"value": 500.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m3_m7": {"components": [{"identifiers": [{"type": "NAME", "value": "sodium"}], "amount": {"mass": {"value": 13.1, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "ethanol"}], "amount": {"volume": {"value": 300.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"temperature": {"control": {"type": "AMBIENT"}}, "conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "prepared"}, {"type": "TEMPERATURE", "details": "The mixture is heated"}, {"type": "TEMPERATURE", "details": "at reflux for 30 minutes", "duration": {"value": 30.0, "units": "MINUTE"}}, {"type": "FILTRATION", "details": "The solid is collected by filtration"}, {"type": "EXTRACTION", "details": "is extracted with diethyl ether (3\u00d7500 mL)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "diethyl ether"}], "amount": {"volume": {"value": 500.0, "units": "MILLILITER"}}, "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 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 n-hexane-diethyl ether", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "n-hexane diethyl ether"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "1-(4-methoxyphenyl)-4-ethoxycarbonylpyrrolidine-3-one"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 87.4, "units": "GRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 64.0}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: A solution of L-tyrosyl-N-methyl-N-(3-phenylpropyl)-D-methioninamide monohydrochloride (1.3 g.) and aqueous hydrogen peroxide (3%, 2.7 ml.) in acetic acid (10 ml.) was stirred at room temperature for two hours, the concentrated. The residue was evaporated twice from ethyl acetate then purified by reverse phase high pressure liquid chromatography on octadecylsilated silica gel (350 g.) using ammonium acetate (0.15%) in methanol-water (3:2) as the eluant (200 ml./min.). A solution of the product (1.0 g.), which appeared in fraction 2 (k'=1.4-3.0), in hydrochloric acid (0.0936N, 30 ml.) and water (30 ml.) was lyophilized, affording L-tyrosyl-N-methyl-N-(3-phenylpropyl)-D-methioninamide S-oxide monohydrochloride monohydrate ([α]D25 +61.4°, c=1, methanol), whose free base is the compound of Formula II wherein Q is Met(O), R1 and R2 are each hydrogen, R4 is (CH2)nY wherein n is 3 and Y is phenyl and R5 is methyl. ### ORD JSON:

{"inputs": {"m1_m2_m3": {"components": [{"identifiers": [{"type": "NAME", "value": "L-tyrosyl-N-methyl-N-(3-phenylpropyl)-D-methioninamide monohydrochloride"}], "amount": {"mass": {"value": 1.3, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "hydrogen peroxide"}], "amount": {"volume": {"value": 2.7, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "acetic acid"}], "amount": {"volume": {"value": 10.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "The residue was evaporated twice from ethyl acetate", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl acetate"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "then purified by reverse phase high pressure liquid chromatography on octadecylsilated silica gel (350 g.)"}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "L-tyrosyl-N-methyl-N-(3-phenylpropyl)-D-methioninamide S-oxide monohydrochloride monohydrate"}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: Prepared as described for 4-hydroxy-6-(2-phenethyl)pyridazin-3(2H)-one (Example 1) from 3,4-bis(benzyloxy)-6-[(3-chloromethyl)phenyl)ethynyl]pyridazine (Intermediate 24) except that the reaction was carried out in ethyl acetate. The crude material was purified by reverse phase chromatography (50 g C18) cartridge eluting with 5-100% acetonitrile/water with acidic modifier and the appropriate fractions combined to give an orange solid. This was recrystallised from ethyl acetate to give a white solid (yield=32%). ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl acetate"}], "reaction_role": "SOLVENT"}]}, "m1": {"components": [{"identifiers": [{"type": "NAME", "value": "4-hydroxy-6-(2-phenethyl)pyridazin-3(2H)-one"}], "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "pyridazine"}], "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "Intermediate 24"}], "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "Prepared"}, {"type": "CUSTOM", "details": "The crude material was purified by reverse phase chromatography (50 g C18) cartridge", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "crude material"}], "reaction_role": "WORKUP"}]}}, {"type": "WASH", "details": "eluting with 5-100% acetonitrile/water with acidic modifier", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "acetonitrile water"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "to give an orange solid"}, {"type": "CUSTOM", "details": "This was recrystallised from ethyl acetate", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl acetate"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "solid"}], "measurements": [{"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 32.0}}], "texture": {"type": "CUSTOM", "details": "solid"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: To a solution of 500 mg of sodium 7-[2-(2-aminothiazol-4-yl)-2-ethoxyiminoacetamido]-3-methoxymethyl-3-cephem-4-carboxylate in 5 ml of N,N-dimethylacetamide were added, with ice-cooling, 395 mg of 1-iodoethyl ethylcarbonate, and then the mixture was stirred at room temperature for 30 minutes. At the end of this time, 50 ml of ethyl acetate were added to the reaction mixture, which was then washed with, in turn, 20 ml of water, 20 ml of a saturated aqueous solution of sodium bicarbonate and 20 ml of an aqueous solution of sodium chloride. The mixture was then dried over anhydrous magnesium sulphate and the solvent was removed by distillation under reduced pressure, giving a residue, which was chromatographed through 20 g silica gel eluted with ethyl acetate, to afford 460 mg of the title compound. ### ORD JSON:

{"inputs": {"m1_m4": {"components": [{"identifiers": [{"type": "NAME", "value": "sodium 7-[2-(2-aminothiazol-4-yl)-2-ethoxyiminoacetamido]-3-methoxymethyl-3-cephem-4-carboxylate"}], "amount": {"mass": {"value": 500.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "N,N-dimethylacetamide"}], "amount": {"volume": {"value": 5.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "1-iodoethyl ethylcarbonate"}], "amount": {"mass": {"value": 395.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl acetate"}], "amount": {"volume": {"value": 50.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "TEMPERATURE", "details": "cooling"}, {"type": "WASH", "details": "was then washed with, in turn, 20 ml of water, 20 ml of a saturated aqueous solution of sodium bicarbonate and 20 ml of an aqueous solution of sodium chloride", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "water"}], "amount": {"volume": {"value": 20.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "saturated aqueous solution"}], "amount": {"volume": {"value": 20.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "sodium bicarbonate"}], "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "aqueous solution"}], "amount": {"volume": {"value": 20.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "sodium chloride"}], "reaction_role": "WORKUP"}]}}, {"type": "DRY_WITH_MATERIAL", "details": "The mixture was then dried over anhydrous magnesium sulphate", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "magnesium sulphate"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "the solvent was removed by distillation under reduced pressure"}, {"type": "CUSTOM", "details": "giving a residue, which"}, {"type": "CUSTOM", "details": "was chromatographed through 20 g silica gel"}, {"type": "WASH", "details": "eluted 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": 460.0, "units": "MILLIGRAM"}}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: 4-Chloro-6,7-dimethoxyquinoline (111 mg), 5-tert-butyl-2-hydroxybenzaldehyde (356 mg), and 4-dimethylaminopyridine (244 mg) were suspended in monochlorobenzene (2 ml), and the suspension was stirred at 130° C. overnight. The reaction solution was cooled to room temperature, water was then added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was then washed with water and saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed therefrom by distillation under the reduced pressure, and the residue was purified by chromatography on silica gel using ethyl acetate-hexane for development to give 5-(tert-butyl)-2-[(6,7-dimethoxy-4-quinolyl)oxy]benzaldehyde. ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "4-dimethylaminopyridine"}], "amount": {"mass": {"value": 244.0, "units": "MILLIGRAM"}}, "reaction_role": "CATALYST"}]}, "m1": {"components": [{"identifiers": [{"type": "NAME", "value": "4-Chloro-6,7-dimethoxyquinoline"}], "amount": {"mass": {"value": 111.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "5-tert-butyl-2-hydroxybenzaldehyde"}], "amount": {"mass": {"value": 356.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}]}, "m5": {"components": [{"identifiers": [{"type": "NAME", "value": "monochlorobenzene"}], "amount": {"volume": {"value": 2.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "water"}], "reaction_role": "REACTANT"}]}}, "conditions": {"temperature": {"setpoint": {"value": 130.0, "units": "CELSIUS"}}, "stirring": {"type": "CUSTOM", "details": "the suspension was stirred at 130\u00b0 C. overnight"}, "conditions_are_dynamic": true}, "workups": [{"type": "TEMPERATURE", "details": "The reaction solution was cooled 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 ethyl acetate layer was then washed with water and saturated brine", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl acetate"}], "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "water"}], "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "brine"}], "reaction_role": "WORKUP"}]}}, {"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 removed"}, {"type": "DISTILLATION", "details": "by distillation under the reduced pressure"}, {"type": "CUSTOM", "details": "the residue was purified by chromatography on silica gel"}], "outcomes": [{"reaction_time": {"value": 8.0, "precision": 8.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "5-(tert-butyl)-2-[(6,7-dimethoxy-4-quinolyl)oxy]benzaldehyde"}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: To a solution of 1-[2-(tertbutyldimethylsilanyloxy)ethyl]-N-(4-(2-fluoro-4-iodophenylamino)-1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)cyclopropanesulfonamide (20 mg, 0.032 mmol) in THF (2 mL) at 0° C. is added 1N HCl (0.128 mL. 0.128 mmol). The ice-bath is removed after 30 minutes and the solution stirred at room temperature for 45 minutes. Then the solution is cooled to 0° C., saturated NaHCO3 (3 mL) solution is added, and extracted with ethyl acetate (3×5 mL). The combined organic layers are concentrated under reduced pressure to give the title compound. ### ORD JSON:

{"inputs": {"m1_m3_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "1-[2-(tertbutyldimethylsilanyloxy)ethyl]-N-(4-(2-fluoro-4-iodophenylamino)-1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)cyclopropanesulfonamide"}], "amount": {"mass": {"value": 20.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "HCl"}], "amount": {"volume": {"value": 0.128, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "THF"}], "amount": {"volume": {"value": 2.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"temperature": {"control": {"type": "AMBIENT"}}, "stirring": {"type": "CUSTOM", "details": "the solution stirred at room temperature for 45 minutes"}, "conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "The ice-bath is removed after 30 minutes", "duration": {"value": 30.0, "units": "MINUTE"}, "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ice"}], "reaction_role": "WORKUP"}]}}, {"type": "TEMPERATURE", "details": "Then the solution is cooled to 0\u00b0 C.", "temperature": {"setpoint": {"value": 0.0, "units": "CELSIUS"}}}, {"type": "ADDITION", "details": "saturated NaHCO3 (3 mL) solution is added", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "NaHCO3"}], "amount": {"volume": {"value": 3.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}]}}, {"type": "EXTRACTION", "details": "extracted with ethyl acetate (3\u00d75 mL)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl acetate"}], "amount": {"volume": {"value": 5.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}]}}, {"type": "CONCENTRATION", "details": "The combined organic layers are concentrated under reduced pressure"}], "outcomes": [{"reaction_time": {"value": 45.0, "units": "MINUTE"}, "products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: 100 ml of methanol, 80 ml of acetone and 0.3 ml of concentrated hydrochloric acid were added to 5.5 g (10.0 mmol) of N1-(4-sulfamoylbenzyl)-N5-dodecyl-biguanide dihydrochloride. The mixture was refluxed for 22 hours, and the solvent was distilled off under reduced pressure. To the residue were added 60 ml of ethanol, 40 ml of water and 6.2 ml of 5N sodium hydroxide, and the mixture was refluxed for 1 hour, concentrated under reduced pressure, and extracted with ethyl acetate. The extract was washed with 10% aqueous sodium acetate, washed with water, and concentrated under reduced pressure to remove the solvent. The residue was recrystallized repeatedly from a mixture of methyl ethyl ketone and ethanol (8:2) and then from ethanol to obtain 1.4 g of colorless crystals having a melting point of 188 to 191° C. ### ORD JSON:

{"inputs": {"m1_m4_m2_m3": {"components": [{"identifiers": [{"type": "NAME", "value": "methanol"}], "amount": {"volume": {"value": 100.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "hydrochloric acid"}], "amount": {"volume": {"value": 0.3, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "N1-(4-sulfamoylbenzyl)-N5-dodecyl-biguanide dihydrochloride"}], "amount": {"mass": {"value": 5.5, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "acetone"}], "amount": {"volume": {"value": 80.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "TEMPERATURE", "details": "The mixture was refluxed for 22 hours", "duration": {"value": 22.0, "units": "HOUR"}}, {"type": "DISTILLATION", "details": "the solvent was distilled off under reduced pressure"}, {"type": "ADDITION", "details": "To the residue were added 60 ml of ethanol, 40 ml of water and 6.2 ml of 5N sodium hydroxide", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethanol"}], "amount": {"volume": {"value": 60.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "water"}], "amount": {"volume": {"value": 40.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "sodium hydroxide"}], "amount": {"volume": {"value": 6.2, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}]}}, {"type": "TEMPERATURE", "details": "the mixture was refluxed for 1 hour", "duration": {"value": 1.0, "units": "HOUR"}}, {"type": "CONCENTRATION", "details": "concentrated under reduced pressure"}, {"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 10% aqueous sodium acetate", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "sodium acetate"}], "reaction_role": "WORKUP"}]}}, {"type": "WASH", "details": "washed with water", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "water"}], "reaction_role": "WORKUP"}]}}, {"type": "CONCENTRATION", "details": "concentrated under reduced pressure"}, {"type": "CUSTOM", "details": "to remove the solvent"}, {"type": "CUSTOM", "details": "The residue was recrystallized repeatedly from a mixture of methyl ethyl ketone and ethanol (8:2)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "methyl ethyl ketone"}], "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "ethanol"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "colorless crystals"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 1.4, "units": "GRAM"}}}], "isolated_color": "colorless", "texture": {"type": "CRYSTAL", "details": "crystals"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: A mixture of Hunig's base (286 μl, 1637 μmol), HATU (830 mg, 2182 μmol) and cyclohexanecarboxylic acid (147 mg, 1146 μmol) was dissolved in 2.0 mL CH2Cl2 and stirred at room temperature for 10 min. 6-bromobenzo[d]thiazol-2-amine (250 mg, 1091 μmol) was added, and stirring was continued overnight. The solids were filtered and washed with CH2Cl2. The filtrate was concentrated, dissolved in CH2Cl2 and purified by silica gel chromatography using 100% CH2Cl2 to provide N-(6-bromobenzo[d]thiazol-2-yl)cyclohexanecarboxamide (290 mg, 78% yield) as a white solid. MS (ESI pos. ion) m/z calc'd for C14H15BrN2OS: 339.3/341.3. found 339.0/341.0. ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "6-bromobenzo[d]thiazol-2-amine"}], "amount": {"mass": {"value": 250.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}]}, "m1_m2_m3": {"components": [{"identifiers": [{"type": "NAME", "value": "Hunig's base"}], "amount": {"volume": {"value": 286.0, "units": "MICROLITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "HATU"}], "amount": {"mass": {"value": 830.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "cyclohexanecarboxylic acid"}], "amount": {"mass": {"value": 147.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}]}, "m5": {"components": [{"identifiers": [{"type": "NAME", "value": "CH2Cl2"}], "amount": {"volume": {"value": 2.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"temperature": {"control": {"type": "AMBIENT"}}, "stirring": {"type": "CUSTOM", "details": "stirred at room temperature for 10 min"}, "conditions_are_dynamic": true}, "workups": [{"type": "STIRRING", "details": "stirring"}, {"type": "WAIT", "details": "was continued overnight", "duration": {"value": 8.0, "precision": 8.0, "units": "HOUR"}}, {"type": "FILTRATION", "details": "The solids were filtered"}, {"type": "WASH", "details": "washed with CH2Cl2", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "CH2Cl2"}], "reaction_role": "WORKUP"}]}}, {"type": "CONCENTRATION", "details": "The filtrate was concentrated"}, {"type": "DISSOLUTION", "details": "dissolved in CH2Cl2", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "CH2Cl2"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "purified by silica gel chromatography"}], "outcomes": [{"reaction_time": {"value": 10.0, "units": "MINUTE"}, "products": [{"identifiers": [{"type": "NAME", "value": "N-(6-bromobenzo[d]thiazol-2-yl)cyclohexanecarboxamide"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 290.0, "units": "MILLIGRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 78.0}}, {"type": "YIELD", "details": "CALCULATEDPERCENTYIELD", "percentage": {"value": 78.4}}], "isolated_color": "white", "texture": {"type": "CUSTOM", "details": "solid"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: 2-(6-Chloropyridin-3-yl)-N-(5-(3-fluorophenyl)pyridin-2-yl)acetamide 140-1 (100 mg, 0.29 mmol) was heated with 1-(piperazin-1-yl)ethanone (0.8 ml) at 108° C. for 4 hours. The mixture was dissolved in EtOAc (30 ml), washed with water (40 mL), and dried over Na2SO4. After concentration by evaporation, the residue was subjected to reverse phase HPLC to afford 2-(6-(4-acetylpiperazin-1-yl)pyridin-3-yl)-N-(5-(3-fluorophenyl)pyridin-2-yl)acetamide 140 as solid. ### ORD JSON:

{"inputs": {"m1_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "2-(6-Chloropyridin-3-yl)-N-(5-(3-fluorophenyl)pyridin-2-yl)acetamide"}], "amount": {"mass": {"value": 100.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "1-(piperazin-1-yl)ethanone"}], "amount": {"volume": {"value": 0.8, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "EtOAc"}], "amount": {"volume": {"value": 30.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "WASH", "details": "washed with water (40 mL)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "water"}], "amount": {"volume": {"value": 40.0, "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": "After concentration"}, {"type": "CUSTOM", "details": "by evaporation"}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "2-(6-(4-acetylpiperazin-1-yl)pyridin-3-yl)-N-(5-(3-fluorophenyl)pyridin-2-yl)acetamide"}], "texture": {"type": "CUSTOM", "details": "solid"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: A mixture of 11.37 g (50 mmol) of (Z)-N,N-diethyl-3,7-dimethyl-2,6-octadienylamine, 101.5 mg (0.25 mmol) of bis[η4 -(Z,Z)-1,5-cyclooctadiene]rhodium(I) tetrafluoroborate, 160 mg (0.275 mmol) of (R)-(6,6'-dimethoxybiphenyl-2,2'-diyl)bis(diphenylphosphine) and 25 ml of tetrahydrofuran was heated to 65° C. while stirring for 20 hours. The brownish-red reaction mixture was evaporated and the residue was distilled in a bulb-tube at about 150° C./0.2 mbar, whereby 10.7 g of (1E,3R)-N,N-diethyl-3,7-dimethyl-1,6-octadienylamine were obtained as a light yellowish oil. The distillate was diluted with 20 ml of hexane, treated with 50 ml of 50% acetic acid and the two-phase mixture was stirred vigorously for 1 hour. After working-up in an analogous manner to Example 14 and distillation in a bulb-tube at 140° C./15 mbar there were obtained 7.18 g of (R)-citronellal as a colourless liquid: e.e=98.6% ### ORD JSON:

{"inputs": {"m1_m2_m3_m4": {"components": [{"identifiers": [{"type": "NAME", "value": "(Z)-N,N-diethyl-3,7-dimethyl-2,6-octadienylamine"}], "amount": {"mass": {"value": 11.37, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "bis[\u03b74 -(Z,Z)-1,5-cyclooctadiene]rhodium(I) tetrafluoroborate"}], "amount": {"mass": {"value": 101.5, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "(R)-(6,6'-dimethoxybiphenyl-2,2'-diyl)bis(diphenylphosphine)"}], "amount": {"mass": {"value": 160.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "tetrahydrofuran"}], "amount": {"volume": {"value": 25.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"temperature": {"setpoint": {"value": 65.0, "units": "CELSIUS"}}, "stirring": {"type": "CUSTOM", "details": "while stirring for 20 hours"}, "conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "The brownish-red reaction mixture was evaporated"}, {"type": "DISTILLATION", "details": "the residue was distilled in a bulb-tube at about 150\u00b0 C./0.2 mbar", "temperature": {"setpoint": {"value": 150.0, "units": "CELSIUS"}}}], "outcomes": [{"reaction_time": {"value": 20.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "(1E,3R)-N,N-diethyl-3,7-dimethyl-1,6-octadienylamine"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 10.7, "units": "GRAM"}}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: The title compound was synthesized in analogy to (4-cyclopropylbenzyl)-[2-(4-fluoro-3-trifluoromethylphenyl)-ethyl]-amine (described in example S53) using 1,1-dimethylindan-5-carbaldehyde (prepared as described in example S100) (197 mg, 0.56 mmol), phenethylamine (67 mg, 0.56 mmol) and sodium borohydride (32 mg, 0.84 mmol). The desired product (129 mg, 83%) was isolated without further purification as a colorless oil. MS (ISP) 280.2 (M+H)+. ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "sodium borohydride"}], "amount": {"mass": {"value": 32.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}]}, "m1": {"components": [{"identifiers": [{"type": "NAME", "value": "(4-cyclopropylbenzyl)-[2-(4-fluoro-3-trifluoromethylphenyl)-ethyl]-amine"}], "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "1,1-dimethylindan-5-carbaldehyde"}], "amount": {"mass": {"value": 197.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "phenethylamine"}], "amount": {"mass": {"value": 67.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "desired product"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 129.0, "units": "MILLIGRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 83.0}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: To a stirred solution of 500 mg of 10,11-dihydro-10-(4-aminobenzoyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine in 3 ml of methylene chloride, cooled to 0° C., under argon, is added 346 μl of triethylamine followed by the addition of 340 mg of 2-methyl-5-fluorobenzoyl chloride in 2 ml of methylene chloride. The cooling bath is removed and stirring continued for 18 hours. After cooling to 0° C., an additional 342 mg of 2-methyl-5-fluorobenzoyl chloride in 2 ml of methylene chloride is added. The cooling bath is removed and stirring continued for 18 hours. The volatiles are removed in vacuo to a residue which is dissolved in 50 ml of methylene chloride and washed with 20 ml each of water, 2N citric acid, 1M sodium bicarbonate and brine. The organic layer is dried over Na2SO4 and passed through a pad of hydrous magnesium silicate. The filtrate is evaporated in vacuo to a residue which is crystallized from ethyl acetatehexane to give 295 mg of the desired product as a white solid, m.p. 170°-180° C. ### ORD JSON:

{"inputs": {"m3_m5": {"components": [{"identifiers": [{"type": "NAME", "value": "2-methyl-5-fluorobenzoyl chloride"}], "amount": {"mass": {"value": 340.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "methylene chloride"}], "amount": {"volume": {"value": 2.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m1_m4": {"components": [{"identifiers": [{"type": "NAME", "value": "10,11-dihydro-10-(4-aminobenzoyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine"}], "amount": {"mass": {"value": 500.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "methylene chloride"}], "amount": {"volume": {"value": 3.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "triethylamine"}], "amount": {"volume": {"value": 346.0, "units": "MICROLITER"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"temperature": {"setpoint": {"value": 0.0, "units": "CELSIUS"}}, "stirring": {"type": "CUSTOM", "details": "stirring"}, "conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "The cooling bath is removed"}, {"type": "ADDITION", "details": "an additional 342 mg of 2-methyl-5-fluorobenzoyl chloride in 2 ml of methylene chloride is added", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "2-methyl-5-fluorobenzoyl chloride"}], "amount": {"mass": {"value": 342.0, "units": "MILLIGRAM"}}, "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "methylene chloride"}], "amount": {"volume": {"value": 2.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "The cooling bath is removed"}, {"type": "STIRRING", "details": "stirring"}, {"type": "WAIT", "details": "continued for 18 hours", "duration": {"value": 18.0, "units": "HOUR"}}, {"type": "CUSTOM", "details": "The volatiles are removed in vacuo to a residue which"}, {"type": "DISSOLUTION", "details": "is dissolved in 50 ml of methylene chloride", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "methylene chloride"}], "amount": {"volume": {"value": 50.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}]}}, {"type": "WASH", "details": "washed with 20 ml each of water, 2N citric acid, 1M sodium bicarbonate and brine", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "water"}], "amount": {"volume": {"value": 20.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "citric 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 is dried over Na2SO4", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "Na2SO4"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "The filtrate is evaporated in vacuo to a residue which"}, {"type": "CUSTOM", "details": "is crystallized from ethyl acetatehexane"}], "outcomes": [{"reaction_time": {"value": 18.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "desired product"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 295.0, "units": "MILLIGRAM"}}}, {"type": "YIELD", "details": "CALCULATEDPERCENTYIELD", "percentage": {"value": 40.7}}], "isolated_color": "white", "texture": {"type": "CUSTOM", "details": "solid"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: To a solution of 2,4-dichloropyrimidine (0.15 g, 1.0 mmol), benzylamine (0.109 ml, 1.0 mmol) in THF was added DIPEA (0.526ml, 3.0 mmol) and the reaction was heated at reflux for 2 hours resulting in formation of a 4:1 mixture of regioisomers (desired versus undesired) by TLC (5% Methanol:methylene chloride). The reaction was stripped down in vacuo and purified by silica column (eluent: 2% methanol:methylene chloride) giving 0.12 g (0.548 mmol) of desired product 10 in 54% yield. LC/MS (M+1)=220 ### ORD JSON:

{"inputs": {"m1_m2_m5_m3": {"components": [{"identifiers": [{"type": "NAME", "value": "2,4-dichloropyrimidine"}], "amount": {"mass": {"value": 0.15, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "benzylamine"}], "amount": {"volume": {"value": 0.109, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "DIPEA"}], "amount": {"volume": {"value": 0.526, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "THF"}], "reaction_role": "SOLVENT"}]}, "m4_m6": {"components": [{"identifiers": [{"type": "NAME", "value": "Methanol"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "methylene chloride"}], "reaction_role": "SOLVENT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "TEMPERATURE", "details": "the reaction was heated"}, {"type": "TEMPERATURE", "details": "at reflux for 2 hours", "duration": {"value": 2.0, "units": "HOUR"}}, {"type": "CUSTOM", "details": "purified by silica column (eluent: 2% methanol:methylene chloride)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "methanol"}], "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "methylene chloride"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "desired product 10"}], "measurements": [{"type": "AMOUNT", "details": "AMOUNT", "amount": {"moles": {"value": 0.548, "units": "MILLIMOLE"}}}, {"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 0.12, "units": "GRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 54.0}}, {"type": "YIELD", "details": "CALCULATEDPERCENTYIELD", "percentage": {"value": 54.8}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: 1,1-Dimethylethyl 4-{4-[(3-chloropropyl)oxy]phenyl}-1-piperazinecarboxylate (D9) (1.6 g), was dissolved in 2-butanone (10 ml). Potassium carbonate (1.38 g) and a catalytic amount of potassium iodide were added, followed by 2-methylpiperidine (0.99 g). The mixture was heated at reflux for 72 h under nitrogen. The reaction mixture was diluted with water and extracted with dichloromethane. The organic phases were separated using a hydrophobic frit, combined and evaporated in vacuo. The residue was purified on a 100 g silica SPE bond elut cartridge, eluting with a gradient of 0% to 20% [0.880 ammonia-methanol (1:9)]-dichloromethane mixtures, to give the title compound (1.66 g). LCMS RT=2.48 min. ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "2-methylpiperidine"}], "amount": {"mass": {"value": 0.99, "units": "GRAM"}}, "reaction_role": "REACTANT"}]}, "m6": {"components": [{"identifiers": [{"type": "NAME", "value": "water"}], "reaction_role": "SOLVENT"}]}, "m2_m3": {"components": [{"identifiers": [{"type": "NAME", "value": "Potassium carbonate"}], "amount": {"mass": {"value": 1.38, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "potassium iodide"}], "reaction_role": "REACTANT"}]}, "m1_m5": {"components": [{"identifiers": [{"type": "NAME", "value": "1,1-Dimethylethyl 4-{4-[(3-chloropropyl)oxy]phenyl}-1-piperazinecarboxylate"}], "amount": {"mass": {"value": 1.6, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "2-butanone"}], "amount": {"volume": {"value": 10.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "TEMPERATURE", "details": "The mixture was heated"}, {"type": "TEMPERATURE", "details": "at reflux for 72 h under nitrogen", "duration": {"value": 72.0, "units": "HOUR"}}, {"type": "EXTRACTION", "details": "extracted with dichloromethane", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "dichloromethane"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "The organic phases were separated"}, {"type": "CUSTOM", "details": "evaporated in vacuo"}, {"type": "CUSTOM", "details": "The residue was purified on a 100 g silica SPE bond elut cartridge"}, {"type": "WASH", "details": "eluting with a gradient of 0% to 20% [0.880 ammonia-methanol (1:9)]-dichloromethane mixtures", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ammonia methanol"}], "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "dichloromethane"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 1.66, "units": "GRAM"}}}, {"type": "YIELD", "details": "CALCULATEDPERCENTYIELD", "percentage": {"value": 88.2}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: Triphenylphosphine (6.5 g, 25 mmol) was added to a solution of 4-[[2-(1,1-dimethylethyl)-2H-tetrazol-5-yl]-methyl]benzenemethanol (3.0 g, 12.4 mmol) and carbon tetrabromide (8.3 g. 25 mmol) in diethyl ether (150 mL). After 3 hours the reaction mixture was concentrated and the residue purified by chromatography on silica gel eluting with a 9:1 mixture of hexane-ethyl acetate to give 5-[[4-(bromomethyl)phenyl]methyl]-2-(1,1-dimethylethyl)-2H-tetrazole (2.4 g. 7.8 mmol) in 63% yield, mp. 73°-74° C. ### ORD JSON:

{"inputs": {"m1_m2_m3_m4": {"components": [{"identifiers": [{"type": "NAME", "value": "Triphenylphosphine"}], "amount": {"mass": {"value": 6.5, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "4-[[2-(1,1-dimethylethyl)-2H-tetrazol-5-yl]-methyl]benzenemethanol"}], "amount": {"mass": {"value": 3.0, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "carbon tetrabromide"}], "amount": {"mass": {"value": 8.3, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "diethyl ether"}], "amount": {"volume": {"value": 150.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "CONCENTRATION", "details": "After 3 hours the reaction mixture was concentrated", "duration": {"value": 3.0, "units": "HOUR"}}, {"type": "CUSTOM", "details": "the residue purified by chromatography on silica gel eluting with a 9:1 mixture of hexane-ethyl acetate", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "hexane ethyl acetate"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "5-[[4-(bromomethyl)phenyl]methyl]-2-(1,1-dimethylethyl)-2H-tetrazole"}], "measurements": [{"type": "AMOUNT", "details": "AMOUNT", "amount": {"moles": {"value": 7.8, "units": "MILLIMOLE"}}}, {"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 2.4, "units": "GRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 63.0}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: To a stirred solution of 5-benzyloxy-6-hydroxy-2-(1-phenyl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-cyclopropyl-amide (284) (430 mg, 0.69 mmol) in tetrahydrofuran (20 mL) was added 1N HCl (3.5 mL. 3.48 mmol) at room temperature and the reaction mixture was stirred for 30 min. After completion of the reaction, solid NaHCO3 was added, basified up to pH 8. Water (10 mL) was added and the mixture was extracted with ethyl acetate (3×30 mL). The organic part was dried and concentrated to get 5-benzyloxy-6-hydroxy-2-(1-phenyl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid cyclopropyl-(2-hydroxyethyl)-amide (285) (300 mg, 88.4%) as a light yellow sticky mass. ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "Water"}], "amount": {"volume": {"value": 10.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}, "m1_m5_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "5-benzyloxy-6-hydroxy-2-(1-phenyl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-cyclopropyl-amide"}], "amount": {"mass": {"value": 430.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "HCl"}], "amount": {"volume": {"value": 3.5, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "tetrahydrofuran"}], "amount": {"volume": {"value": 20.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "NaHCO3"}], "reaction_role": "REACTANT"}]}}, "conditions": {"stirring": {"type": "CUSTOM", "details": "the reaction mixture was stirred for 30 min"}, "conditions_are_dynamic": true}, "workups": [{"type": "ADDITION", "details": "was added"}, {"type": "EXTRACTION", "details": "the mixture was extracted with ethyl acetate (3\u00d730 mL)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl acetate"}], "amount": {"volume": {"value": 30.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "The organic part was dried"}, {"type": "CONCENTRATION", "details": "concentrated"}], "outcomes": [{"reaction_time": {"value": 30.0, "units": "MINUTE"}, "products": [{"identifiers": [{"type": "NAME", "value": "5-benzyloxy-6-hydroxy-2-(1-phenyl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid cyclopropyl-(2-hydroxyethyl)-amide"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 300.0, "units": "MILLIGRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 88.4}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: A 7.48 g. (17.6 mM) quantity of (αS,5S) 2-[(benzyloxy)carbonyl]-3-oxo-α-phthalimido-5-isoxazolidine acetic acid is dissolved in 150 ml. of ethyl acetate and 75 ml. of 95% ethanol. The solution is treated with 1.5 g. of palladium black and hydrogenated at 25° C. and 1 atmosphere of pressure. The reaction is stopped after 165 minutes, filtered, and the filtrate is evaporated in vacuo to yield 3-oxo-α-phthalimido-5-isoxazolidine acetic acid as a residue. ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "ethanol"}], "reaction_role": "SOLVENT"}]}, "m1": {"components": [{"identifiers": [{"type": "NAME", "value": "(\u03b1S,5S) 2-[(benzyloxy)carbonyl]-3-oxo-\u03b1-phthalimido-5-isoxazolidine acetic acid"}], "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl acetate"}], "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "palladium black"}], "reaction_role": "CATALYST"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "ADDITION", "details": "The solution is treated with 1.5 g"}, {"type": "CUSTOM", "details": "hydrogenated at 25\u00b0 C.", "temperature": {"setpoint": {"value": 25.0, "units": "CELSIUS"}}}, {"type": "FILTRATION", "details": "filtered"}, {"type": "CUSTOM", "details": "the filtrate is evaporated in vacuo"}], "outcomes": [{"reaction_time": {"value": 165.0, "units": "MINUTE"}, "products": [{"identifiers": [{"type": "NAME", "value": "3-oxo-\u03b1-phthalimido-5-isoxazolidine acetic acid"}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: In methanol (284 ml) is suspended 2',3',4'-trichloroacetophenone (94.7 g), and thereto is added sodium borohydride (7.6 g) at 15° C.-25° C. The mixture is stirred at 25° C. for two hours, and evaporated to remove the methanol. To the residue is added 2N hydrochloric acid (110 ml), and the mixture is extracted with ethyl acetate. The organic layer is washed with water, dried, and evaporated to remove the solvent to give crude 1-(2,3,4-trichlorophenyl)ethanol (95 g). ### ORD JSON:

{"inputs": {"m1": {"components": [{"identifiers": [{"type": "NAME", "value": "2',3',4'-trichloroacetophenone"}], "amount": {"mass": {"value": 94.7, "units": "GRAM"}}, "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "sodium borohydride"}], "amount": {"mass": {"value": 7.6, "units": "GRAM"}}, "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "methanol"}], "amount": {"volume": {"value": 284.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"temperature": {"setpoint": {"value": 25.0, "units": "CELSIUS"}}, "stirring": {"type": "CUSTOM", "details": "The mixture is stirred at 25\u00b0 C. for two hours"}, "conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "evaporated"}, {"type": "CUSTOM", "details": "to remove the methanol", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "methanol"}], "reaction_role": "WORKUP"}]}}, {"type": "ADDITION", "details": "To the residue is added 2N hydrochloric acid (110 ml)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "hydrochloric acid"}], "amount": {"volume": {"value": 110.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}]}}, {"type": "EXTRACTION", "details": "the mixture is extracted 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": "CUSTOM", "details": "dried"}, {"type": "CUSTOM", "details": "evaporated"}, {"type": "CUSTOM", "details": "to remove the solvent"}], "outcomes": [{"reaction_time": {"value": 2.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "1-(2,3,4-trichlorophenyl)ethanol"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 95.0, "units": "GRAM"}}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: A mixture of 5 parts of 1-(3-methylphenyl)piperazine dihydrochloride, 10.6 parts of sodium carbonate and 180 parts of N,N-dimethylformamide was stirred for 1 hour at 65° C. Then there were added 7.2 parts of 3,6-dibromopyridazine and the whole was stirred overnight at about 65° C. The reaction mixture was poured into ice water. The product was filtered off and dissolved in dichloromethane. The solution was washed twice with water, dried, filtered and evaporated. The residue was crystallized from ethanol. The product was filtered off and dried, yielding 4.1 parts (61.5%) of 3-bromo-6-[4-(3-methylphenyl)-1-piperazinyl]pyridazine: mp. 145.7° C. (compound 136). ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "ice water"}], "reaction_role": "REACTANT"}]}, "m1_m2_m5": {"components": [{"identifiers": [{"type": "NAME", "value": "1-(3-methylphenyl)piperazine dihydrochloride"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "sodium carbonate"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "N,N-dimethylformamide"}], "reaction_role": "SOLVENT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "3,6-dibromopyridazine"}], "reaction_role": "REACTANT"}]}}, "conditions": {"temperature": {"setpoint": {"value": 65.0, "units": "CELSIUS"}}, "stirring": {"type": "CUSTOM", "details": "was stirred for 1 hour at 65\u00b0 C"}, "conditions_are_dynamic": true}, "workups": [{"type": "STIRRING", "details": "the whole was stirred overnight at about 65\u00b0 C", "duration": {"value": 8.0, "precision": 8.0, "units": "HOUR"}, "temperature": {"setpoint": {"value": 65.0, "units": "CELSIUS"}}}, {"type": "FILTRATION", "details": "The product was filtered off"}, {"type": "DISSOLUTION", "details": "dissolved in dichloromethane", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "dichloromethane"}], "reaction_role": "WORKUP"}]}}, {"type": "WASH", "details": "The solution was 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": "CUSTOM", "details": "The residue was crystallized from ethanol", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethanol"}], "reaction_role": "WORKUP"}]}}, {"type": "FILTRATION", "details": "The product was filtered off"}, {"type": "CUSTOM", "details": "dried"}], "outcomes": [{"reaction_time": {"value": 1.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "3-bromo-6-[4-(3-methylphenyl)-1-piperazinyl]pyridazine"}], "measurements": [{"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 61.5}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: Dinitrotetraphenylporphyrin (2.0 g 2.83 m mol) was added to a hydrogenation flask (500-ml) and dissolved in dry toluene (200-ml). To this solution was added the catalyst about 10% ruthenium on alumina pellets (4.0 g, from Engelhard Industries, Iselin, N.J.). After evacuation, and flushing with hydrogen, the reduction was performed at 70° at 60 psi for 8-hr. Next, the flask was cooled to ambient temperature, filtered in the dark to remove the catalyst. The solid catalyst was washed repeatedly with toluene to obtain the product. The organic solvent was removed under reduced pressure in the dark at 50° C. to produce the crude solid residue. This residue showed one spot above the two spots near the base line for the product. An additional brown spot very close to the starting material was also observed. The residue was 1.6 g. ### ORD JSON:

{"inputs": {"m1": {"components": [{"identifiers": [{"type": "NAME", "value": "Dinitrotetraphenylporphyrin"}], "amount": {"mass": {"value": 2.0, "units": "GRAM"}}, "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "toluene"}], "reaction_role": "SOLVENT"}]}, "m3_m4": {"components": [{"identifiers": [{"type": "NAME", "value": "catalyst"}], "reaction_role": "CATALYST"}, {"identifiers": [{"type": "NAME", "value": "ruthenium on alumina"}], "reaction_role": "CATALYST"}]}}, "conditions": {"temperature": {"control": {"type": "AMBIENT"}}, "conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "After evacuation, and flushing with hydrogen", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "hydrogen"}], "reaction_role": "WORKUP"}]}}, {"type": "WAIT", "details": "the reduction was performed at 70\u00b0 at 60 psi for 8-hr"}, {"type": "FILTRATION", "details": "filtered in the dark"}, {"type": "CUSTOM", "details": "to remove the catalyst"}, {"type": "WASH", "details": "The solid catalyst was washed repeatedly with toluene", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "toluene"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "to obtain the product"}, {"type": "CUSTOM", "details": "The organic solvent was removed under reduced pressure in the dark at 50\u00b0 C.", "temperature": {"setpoint": {"value": 50.0, "units": "CELSIUS"}}}, {"type": "CUSTOM", "details": "to produce the crude solid residue"}, {"type": "CUSTOM", "details": "An additional brown spot very close to the starting material"}], "outcomes": [{"products": [{}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: 2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-methylisoindoline-1,3-dione was prepared by the procedure of Example 8 from 1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethylamine (1.4 g, 5.0 mmol) and 3-methylphthalic anhydride (810 mg, 5.0 mmol) in acetic acid (15 mL) to afford 2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethylamine (1.0 g, 3.7 mmol) and 3-methylphthalic anhydride (590 mg, 3.7 mmol). The product was obtained as a white solid (1.78 g, 85% yield); mp, 143.0-145.0° C.; 1H NMR (CDCl3) δ 1.46 (t, J=7.0 Hz, 3H, CH3), 2.67 (s, 3H, CH3), 2.83 (s, 3H, CH3), 3.79 (dd, J=4.8, 14.5 Hz, 1H, CHH), 3.85 (s, CH, CH3), 4.11 (q, J=7.0 Hz, 2H, CH2), 4.54 (dd, J=9.8, 14.5 Hz, 1H, CHH), 5.89 (dd, J=4.8, 9.9 Hz, 1H, NCH), 6.81-6.85 (m, 1H, Ar), 7.65 (d, J=7.5 Hz, 1H, Ar); 13C NMR (CDCl3) δ 14.65, 17.54, 41.49, 48.63, 54.89, 55.89, 64.44, 111.36, 112.48, 120.44, 121.17, 128.24, 129.69, 132.00, 133.69, 136.63, 138.29, 148.51, 149.55, 167.99, 168.46; Anal Calcd for C21H23NO6S: C, 60.42; H, 5.55; N, 3.36. Found: C, 60.68; 11, 5.40; N, 3.15. ### ORD JSON:

{"inputs": {"m0_m3_m4_m5": {"components": [{"identifiers": [{"type": "NAME", "value": "1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethylamine"}], "amount": {"mass": {"value": 1.4, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "3-methylphthalic anhydride"}], "amount": {"mass": {"value": 810.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "acetic acid"}], "amount": {"volume": {"value": 15.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"conditions_are_dynamic": true}, "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-methylisoindoline-1,3-dione"}], "reaction_role": "PRODUCT"}, {"identifiers": [{"type": "NAME", "value": "1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethylamine"}], "measurements": [{"type": "AMOUNT", "details": "AMOUNT", "amount": {"moles": {"value": 3.7, "units": "MILLIMOLE"}}}, {"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 1.0, "units": "GRAM"}}}], "reaction_role": "PRODUCT"}, {"identifiers": [{"type": "NAME", "value": "3-methylphthalic anhydride"}], "measurements": [{"type": "AMOUNT", "details": "AMOUNT", "amount": {"moles": {"value": 3.7, "units": "MILLIMOLE"}}}, {"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 590.0, "units": "MILLIGRAM"}}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: By substituting methylthiomethyl chloride for the dimethylaminopropyl chloride in the procedure of Example 4 and substituting the 2-methyl-4H-pyrazolo[1,5-a]pyrazolo-[4',3':5,6]pyrido[3,4-e]pyrimidin-5(8H)-one obtained in Example 8 for the 8-ethyl-2-methyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]-pyrido[3,4-e]pyrimidin-5(8H)-one, 2-methyl-4-methylthiomethyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyrido[3,4-e]pyrimidin-5(8H)-one is obtained. ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "8-ethyl-2-methyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]-pyrido[3,4-e]pyrimidin-5(8H)-one"}], "reaction_role": "REACTANT"}]}, "m1": {"components": [{"identifiers": [{"type": "NAME", "value": "methylthiomethyl chloride"}], "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "dimethylaminopropyl chloride"}], "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "2-methyl-4H-pyrazolo[1,5-a]pyrazolo-[4',3':5,6]pyrido[3,4-e]pyrimidin-5(8H)-one"}], "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "2-methyl-4-methylthiomethyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyrido[3,4-e]pyrimidin-5(8H)-one"}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: N-[2-(3amino-4-methoxyphenyl]ethyl]-2,2,2-trifluoro acetamide (26.2 g., 0.1 mole) and iodomethane (14.0 g., 6.2 ml , 0.1 mole) in dry dimethylformamide (500 ml) were stirred under nitrogen for 3 hr. The solution was poured into water and the suspension extracted with ethyl acetate. Evaporation of the extracts afforded an oil which was separated by high pressure liquid chromatography on silica using 1% methanol in dichloromethane as eluant. Evaporation of the fractions containing the major bond afforded the sub-title compound (6.1 g) as a white solid mp 65°-67°. The hydrochloride, prepared in the usual way, had mp 153°-155°. ### ORD JSON:

{"inputs": {"m1_m2_m4": {"components": [{"identifiers": [{"type": "NAME", "value": "N-[2-(3amino-4-methoxyphenyl]ethyl]-2,2,2-trifluoro acetamide"}], "amount": {"mass": {"value": 26.2, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "iodomethane"}], "amount": {"volume": {"value": 6.2, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "dimethylformamide"}], "amount": {"volume": {"value": 500.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "water"}], "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "EXTRACTION", "details": "the suspension extracted with ethyl acetate", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl acetate"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "Evaporation of the extracts"}, {"type": "CUSTOM", "details": "afforded an oil which"}, {"type": "CUSTOM", "details": "was separated by high pressure liquid chromatography on silica using 1% methanol in dichloromethane as eluant", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "dichloromethane"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "Evaporation of the fractions"}, {"type": "ADDITION", "details": "containing the major bond"}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "sub-title compound"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 6.1, "units": "GRAM"}}}], "isolated_color": "white", "texture": {"type": "CUSTOM", "details": "solid"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: To a solution of methyl 2-methyl-2-(6-methyl-5-phenyl-2, 3-dihydro-4-oxo-4 H-1,3-oxazin-3-yl)-butyrate (1.91 g) in 20 ml of ethanol was added at room temperature 30 ml of aq. NaOH (0.3N). After stirring for 24 h, ethanol was evaporated, and the mixture was acidified by hydrochloric acid. The precipitate was filtered off and dried to get the captioned compound (1.36 g). ### ORD JSON:

{"inputs": {"m1_m3_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "methyl 2-methyl-2-(6-methyl-5-phenyl-2, 3-dihydro-4-oxo-4 H-1,3-oxazin-3-yl)-butyrate"}], "amount": {"mass": {"value": 1.91, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "NaOH"}], "amount": {"volume": {"value": 30.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "ethanol"}], "amount": {"volume": {"value": 20.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"stirring": {"type": "CUSTOM", "details": "After stirring for 24 h"}, "conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "ethanol was evaporated", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethanol"}], "reaction_role": "WORKUP"}]}}, {"type": "FILTRATION", "details": "The precipitate was filtered off"}, {"type": "CUSTOM", "details": "dried"}], "outcomes": [{"reaction_time": {"value": 24.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "compound"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 1.36, "units": "GRAM"}}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: 100 mg (274 μmol) of 2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-4-fluorobutanoic acid (racemate), 53.0 mg (274 μmol) of tert-butyl 4-aminobenzoate, 39.0 mg (274 μmol) of Oxima and 43.0 μl (274 μmol) of DIC in 5 ml of dimethylformamide were reacted according to General Method 5B. Filtration gave the title compound. Yield: 117 mg (78% of theory) ### ORD JSON:

{"inputs": {"m1_m2_m3_m4": {"components": [{"identifiers": [{"type": "NAME", "value": "2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-4-fluorobutanoic acid"}], "amount": {"mass": {"value": 100.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "tert-butyl 4-aminobenzoate"}], "amount": {"mass": {"value": 53.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "DIC"}], "amount": {"volume": {"value": 43.0, "units": "MICROLITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "dimethylformamide"}], "amount": {"volume": {"value": 5.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "FILTRATION", "details": "Filtration"}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: 20 g of ethyl 4-nitrophenylacetate are dissolved in 30 ml of DMF and added dropwise to a suspension of 4 g of sodium hydride in 20 ml of DMF with ice-cooling. 8.5 ml of dibromoethane are subsequently added, and the mixture is stirred at 55° C. for 1 h. A further 5 g of sodium hydride and 8.5 ml of dibromoethane are added with ice-cooling, and the mixture is then stirred at 50° C. for 2 h. After cooling, the reaction mixture is stirred into a mixture of 100 ml of 1 N hydrochloric acid and 200 g of ice. The mixture is washed four times with 100 ml of diethyl ether each time, the combined organic phases once with 100 ml of sodium chloride solution, dried over sodium sulfate and, after filtration, evaporated to dryness in vacuo. The residue is purified by column chromatography (reversed phase). Yield: 8.5 g (38%) of ethyl 1-(4-nitrophenyl)cyclopropanecarboxylate; LC-MS retention time: 2.01 min (“nonpolar” gradient); ### ORD JSON:

{"inputs": {"m6_m7": {"components": [{"identifiers": [{"type": "NAME", "value": "hydrochloric acid"}], "amount": {"volume": {"value": 100.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "ice"}], "amount": {"mass": {"value": 200.0, "units": "GRAM"}}, "reaction_role": "REACTANT"}]}, "m1_m8": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl 4-nitrophenylacetate"}], "amount": {"mass": {"value": 20.0, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "DMF"}], "amount": {"volume": {"value": 30.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m2_m9": {"components": [{"identifiers": [{"type": "NAME", "value": "sodium hydride"}], "amount": {"mass": {"value": 4.0, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "DMF"}], "amount": {"volume": {"value": 20.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m4_m5": {"components": [{"identifiers": [{"type": "NAME", "value": "sodium hydride"}], "amount": {"mass": {"value": 5.0, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "dibromoethane"}], "amount": {"volume": {"value": 8.5, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "dibromoethane"}], "amount": {"volume": {"value": 8.5, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"temperature": {"setpoint": {"value": 55.0, "units": "CELSIUS"}}, "stirring": {"type": "CUSTOM", "details": "the mixture is stirred at 55\u00b0 C. for 1 h"}, "conditions_are_dynamic": true}, "workups": [{"type": "TEMPERATURE", "details": "cooling"}, {"type": "TEMPERATURE", "details": "cooling"}, {"type": "STIRRING", "details": "the mixture is then stirred at 50\u00b0 C. for 2 h", "duration": {"value": 2.0, "units": "HOUR"}, "temperature": {"setpoint": {"value": 50.0, "units": "CELSIUS"}}}, {"type": "TEMPERATURE", "details": "After cooling"}, {"type": "WASH", "details": "The mixture is washed four times with 100 ml of diethyl ether each time", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "diethyl ether"}], "amount": {"volume": {"value": 100.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}]}}, {"type": "DRY_WITH_MATERIAL", "details": "the combined organic phases once with 100 ml of sodium chloride solution, dried over sodium sulfate", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "sodium chloride"}], "amount": {"volume": {"value": 100.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "sodium sulfate"}], "reaction_role": "WORKUP"}]}}, {"type": "FILTRATION", "details": "after filtration"}, {"type": "CUSTOM", "details": "evaporated to dryness in vacuo"}, {"type": "CUSTOM", "details": "The residue is purified by column chromatography (reversed phase)"}], "outcomes": [{"reaction_time": {"value": 1.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "Ethyl 1-(4-nitrophenyl)cyclopropanecarboxylate"}]}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: Into a 50-mL 3-necked round-bottom flask, purged and maintained with an inert atmosphere of nitrogen, were placed a solution of 2-hydroxy-6-methyl-4-(tetrahydro-2H-pyran-2-yloxy)benzaldehyde (300 mg, 1.27 mmol, 1.00 equiv) in dichloromethane (20 mL) and triethylamine (510 mg, 5.05 mmol, 3.97 equiv). This was followed by the addition of a solution of Tf2O (720 mg, 2.55 mmol, 2.01 equiv) in dichloromethane (5 mL) dropwise with stirring at −78° C. The resulting solution was stirred for 2 h at −78° C., then quenched by the addition of 5 mL of water. The resulting solution was extracted with 3×30 mL of dichloromethane. The organic layers were combined, washed with 3×10 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether (1:10). This resulted in 110 mg (19%) of 2-formyl-3-methyl-5-(tetrahydro-2H-pyran-2-yloxy)phenyl trifluoromethanesulfonate as a yellow oil. ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "dichloromethane"}], "amount": {"volume": {"value": 20.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m3_m5": {"components": [{"identifiers": [{"type": "NAME", "value": "Tf2O"}], "amount": {"mass": {"value": 720.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "dichloromethane"}], "amount": {"volume": {"value": 5.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m1": {"components": [{"identifiers": [{"type": "NAME", "value": "2-hydroxy-6-methyl-4-(tetrahydro-2H-pyran-2-yloxy)benzaldehyde"}], "amount": {"mass": {"value": 300.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "triethylamine"}], "amount": {"mass": {"value": 510.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"temperature": {"setpoint": {"value": -78.0, "units": "CELSIUS"}}, "stirring": {"type": "CUSTOM", "details": "with stirring at \u221278\u00b0 C"}, "conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "Into a 50-mL 3-necked round-bottom flask, purged"}, {"type": "TEMPERATURE", "details": "maintained with an inert atmosphere of nitrogen"}, {"type": "STIRRING", "details": "The resulting solution was stirred for 2 h at \u221278\u00b0 C.", "duration": {"value": 2.0, "units": "HOUR"}, "temperature": {"setpoint": {"value": -78.0, "units": "CELSIUS"}}}, {"type": "CUSTOM", "details": "quenched by the addition of 5 mL of water", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "water"}], "amount": {"volume": {"value": 5.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}]}}, {"type": "EXTRACTION", "details": "The resulting solution was extracted with 3\u00d730 mL of dichloromethane", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "dichloromethane"}], "amount": {"volume": {"value": 30.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}]}}, {"type": "WASH", "details": "washed with 3\u00d710 mL of brine", "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 sodium sulfate", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "sodium sulfate"}], "reaction_role": "WORKUP"}]}}, {"type": "CONCENTRATION", "details": "concentrated under vacuum"}, {"type": "WASH", "details": "eluted with ethyl acetate/petroleum ether (1:10)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl acetate petroleum ether"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "This resulted in 110 mg (19%) of 2-formyl-3-methyl-5-(tetrahydro-2H-pyran-2-yloxy)phenyl trifluoromethanesulfonate as a yellow oil", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "2-formyl-3-methyl-5-(tetrahydro-2H-pyran-2-yloxy)phenyl trifluoromethanesulfonate"}], "amount": {"mass": {"value": 110.0, "units": "MILLIGRAM"}}, "reaction_role": "WORKUP"}]}}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "2-Formyl-3-methyl-5-(tetrahydro-2H-pyran-2-yloxy)phenyl trifluoromethanesulfonate"}]}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: Formic acid (0.29 g, 6.22 mmol) and purified water (5 ml) were added to ethyl 4-(2-amino-4-ethoxycarbonylphenyl)piperazine-1-carboxylate (2.0 g, 6.22 mmol) prepared in the Step 38-1-2. A 30% hydrogen peroxide solution (0.63 g, 18.67 mmol) was further added thereto, and the mixture was heated and stirred at 50° C. Formic acid (2 ml) and 2 ml of a 30% hydrogen peroxide solution were further added to the mixture. The resulting mixture was stirred for another one hour, then allowed to cool, and stirred. After being cooled to a room temperature, the mixture was neutralized with a saturated sodium bicarbonate solution and subjected to extraction with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated. The concentrate was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1 to 1:2) to give the title compound (0.22 g, 11%) as a white powder. ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "sodium bicarbonate"}], "reaction_role": "REACTANT"}]}, "m5_m3": {"components": [{"identifiers": [{"type": "NAME", "value": "hydrogen peroxide"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "Formic acid"}], "amount": {"volume": {"value": 2.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m1": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl 4-(2-amino-4-ethoxycarbonylphenyl)piperazine-1-carboxylate"}], "amount": {"mass": {"value": 2.0, "units": "GRAM"}}, "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "hydrogen peroxide"}], "amount": {"mass": {"value": 0.63, "units": "GRAM"}}, "reaction_role": "REACTANT"}]}, "m7_m6": {"components": [{"identifiers": [{"type": "NAME", "value": "water"}], "amount": {"volume": {"value": 5.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}, {"identifiers": [{"type": "NAME", "value": "Formic acid"}], "amount": {"mass": {"value": 0.29, "units": "GRAM"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"temperature": {"setpoint": {"value": 50.0, "units": "CELSIUS"}}, "stirring": {"type": "CUSTOM", "details": "stirred at 50\u00b0 C"}, "conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "prepared in the Step 38-1-2"}, {"type": "TEMPERATURE", "details": "the mixture was heated"}, {"type": "STIRRING", "details": "The resulting mixture was stirred for another one hour", "duration": {"value": 1.0, "units": "HOUR"}}, {"type": "TEMPERATURE", "details": "to cool"}, {"type": "STIRRING", "details": "stirred"}, {"type": "TEMPERATURE", "details": "After being cooled to a room temperature", "temperature": {"control": {"type": "AMBIENT"}}}, {"type": "EXTRACTION", "details": "subjected to extraction with ethyl acetate", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl acetate"}], "reaction_role": "WORKUP"}]}}, {"type": "DRY_WITH_MATERIAL", "details": "The extract was dried over anhydrous magnesium sulfate", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "magnesium sulfate"}], "reaction_role": "WORKUP"}]}}, {"type": "CONCENTRATION", "details": "concentrated"}, {"type": "CUSTOM", "details": "The concentrate was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1 to 1:2)", "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": "title compound"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 0.22, "units": "GRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 11.0}}, {"type": "YIELD", "details": "CALCULATEDPERCENTYIELD", "percentage": {"value": 11.1}}], "isolated_color": "white", "texture": {"type": "POWDER", "details": "powder"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: Example 8 was prepared in an analogous manner to Example 1 using a mixture of Intermediate 3 (0.025 g) and (2-isocyanatoethyl)benzene (18.9 μl) to give the title compound (0.0312 g). LC-MS (System A): Rt 2.29 mins, Mass Spectrum m/z 422 [MH+]. ### ORD JSON:

{"inputs": {"m1_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "Intermediate 3"}], "amount": {"mass": {"value": 0.025, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "(2-isocyanatoethyl)benzene"}], "amount": {"volume": {"value": 18.9, "units": "MICROLITER"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "Example 8 was prepared in an analogous manner to Example 1 using"}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 0.0312, "units": "GRAM"}}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: 4-Bromothiophene-2-carbaldehyde (1.9 g, 10 mmol) was dissolved in 40 mL of t-BuOH and 4 mL of 2-methyl-2-butene. The reaction mixture was cooled to 0° C. and NaClO2 (1.1 g, 12 mmol) dissolved in 12 mL of 1M NaH2PO4 was added. The reaction mixture was let warm to room temperature and stirred for 5 hours. The reaction mixture was concentrated to about half the volume, and poured into 20 mL 1N NaOH and 50 mL Et2O. The aqueous layer was made acidic with 6N HCl and extracted with EtOAc. This organic layer was dried over sodium sulfate and concentrated to obtain the product as a white solid, 1.75 g, 8.5 mmol, 85% yield. 1H NMR 500 MHz (DMSO-d6) 8.02 (1H, s), 7.78 (1H, s). ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "2-methyl-2-butene"}], "amount": {"volume": {"value": 4.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m1_m3": {"components": [{"identifiers": [{"type": "NAME", "value": "4-Bromothiophene-2-carbaldehyde"}], "amount": {"mass": {"value": 1.9, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "t-BuOH"}], "amount": {"volume": {"value": 40.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m2_m5": {"components": [{"identifiers": [{"type": "NAME", "value": "NaClO2"}], "amount": {"mass": {"value": 1.1, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "NaH2PO4"}], "amount": {"volume": {"value": 12.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"temperature": {"setpoint": {"value": 0.0, "units": "CELSIUS"}}, "stirring": {"type": "CUSTOM", "details": "stirred for 5 hours"}, "conditions_are_dynamic": true}, "workups": [{"type": "ADDITION", "details": "was added"}, {"type": "TEMPERATURE", "details": "The reaction mixture was let warm to room temperature", "temperature": {"control": {"type": "AMBIENT"}}}, {"type": "CONCENTRATION", "details": "The reaction mixture was concentrated to about half the volume"}, {"type": "ADDITION", "details": "poured into 20 mL 1N NaOH and 50 mL Et2O", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "NaOH"}], "amount": {"volume": {"value": 20.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "Et2O"}], "amount": {"volume": {"value": 50.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}]}}, {"type": "EXTRACTION", "details": "extracted with EtOAc", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "EtOAc"}], "reaction_role": "WORKUP"}]}}, {"type": "DRY_WITH_MATERIAL", "details": "This organic layer was dried over sodium sulfate", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "sodium sulfate"}], "reaction_role": "WORKUP"}]}}, {"type": "CONCENTRATION", "details": "concentrated"}], "outcomes": [{"reaction_time": {"value": 5.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "product"}], "measurements": [{"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 85.0}}], "isolated_color": "white", "texture": {"type": "CUSTOM", "details": "solid"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: A mixture of 1-benzyloxy-2,3-difluoro-4-nitrobenzene (14 g, 52.8 mmol) and Pd/C (10%, 1.4 g) in MeOH (200 mL) was stirred under a hydrogen atmosphere (30 psi) for 2 h. The catalyst was removed by filtration and the filtrate was concentrated in vacuo to afford 4-amino-2,3-difluoro-phenol (7 g, 92% yield). 1H NMR (400 MHz, DMSO-d6) δ 9.05 (s, 1H), 6.45 (t, J=8.8 Hz, 1H), 6.34 (t, J=9.2 Hz, 1H), 4.67 (s, 2H). ### ORD JSON:

{"inputs": {"m1_m3_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "1-benzyloxy-2,3-difluoro-4-nitrobenzene"}], "amount": {"mass": {"value": 14.0, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "MeOH"}], "amount": {"volume": {"value": 200.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}, {"identifiers": [{"type": "NAME", "value": "Pd/C"}], "amount": {"mass": {"value": 1.4, "units": "GRAM"}}, "reaction_role": "CATALYST"}]}}, "conditions": {"stirring": {"type": "CUSTOM", "details": "was stirred under a hydrogen atmosphere (30 psi) for 2 h"}, "conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "The catalyst was removed by filtration"}, {"type": "CONCENTRATION", "details": "the filtrate was concentrated in vacuo"}], "outcomes": [{"reaction_time": {"value": 2.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "4-amino-2,3-difluoro-phenol"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 7.0, "units": "GRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 92.0}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: 2 g of tert-butyl 4-[cis-3-(tert-butyl-diphenylsilanyloxy)cyclohexyl]-2,2-dimethylbutyrate are dissolved in 10 ml of tetrahydrofuran, and 8 ml of a 1 M solution of tetrabutylammonium fluoride and tetrahydrofuran are added. The mixture is stirred at 60° C. for 2 hours. The reaction mixture is concentrated under reduced pressure and purified on silica gel using the mobile phase n-heptane:ethyl acetate=20:1=>1:1. This gives 730 mg of tert-butyl 4-[cis-3-hydroxycyclohexyl)-2,2-dimethylbutyrate as an oil. C16H30O3 (270.42), Rf(n-heptane:ethyl acetate=5:1)=0.22. ### ORD JSON:

{"inputs": {"m2_m3_m5": {"components": [{"identifiers": [{"type": "NAME", "value": "solution"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "tetrabutylammonium fluoride"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "tetrahydrofuran"}], "reaction_role": "SOLVENT"}]}, "m1_m4": {"components": [{"identifiers": [{"type": "NAME", "value": "tert-butyl 4-[cis-3-(tert-butyl-diphenylsilanyloxy)cyclohexyl]-2,2-dimethylbutyrate"}], "amount": {"mass": {"value": 2.0, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "tetrahydrofuran"}], "amount": {"volume": {"value": 10.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"temperature": {"setpoint": {"value": 60.0, "units": "CELSIUS"}}, "stirring": {"type": "CUSTOM", "details": "The mixture is stirred at 60\u00b0 C. for 2 hours"}, "conditions_are_dynamic": true}, "workups": [{"type": "CONCENTRATION", "details": "The reaction mixture is concentrated under reduced pressure"}, {"type": "CUSTOM", "details": "purified on silica gel using the mobile phase n-heptane", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "n-heptane"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"reaction_time": {"value": 2.0, "units": "HOUR"}, "products": [{}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: 3,5-Dibromopyridine (30.5 g, 0.12 mol) was dissolved in dichloromethane (80 mL) and methlytrioxorhenium (150 mg, 0.603 mmol) was added 30% hydrogen peroxide (27 mL) was added slowly over 5 minutes and the mixture was stirred at ambient temperature for 3 hours. An additional 40 mL of hydrogen peroxide was added and the reaction was stirred 16 hours. Manganese dioxide (100 mg) was added and the suspension was stirred 40 minutes. The mixture was extracted with dichloromethane, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Ethyl acetate was added and the suspension was refluxed for 30 minutes until solids dissolved and then the mixture was allowed to cool to ambient temperature and aged 48 hours. 3,5-dibromopyridine 1-oxide (25.09 g, 82% yield) was collected by vacuum filtration as pale yellow needles. 1H NMR (CDCl3) δ 8.27 (s, 2 H), 7.56 (s, 1 H). ### ORD JSON:

{"inputs": {"m5_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "hydrogen peroxide"}], "amount": {"volume": {"value": 27.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "methlytrioxorhenium"}], "amount": {"mass": {"value": 150.0, "units": "MILLIGRAM"}}, "reaction_role": "CATALYST"}]}, "m6": {"components": [{"identifiers": [{"type": "NAME", "value": "Manganese dioxide"}], "amount": {"mass": {"value": 100.0, "units": "MILLIGRAM"}}, "reaction_role": "CATALYST"}]}, "m1_m4": {"components": [{"identifiers": [{"type": "NAME", "value": "3,5-Dibromopyridine"}], "amount": {"mass": {"value": 30.5, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "dichloromethane"}], "amount": {"volume": {"value": 80.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "hydrogen peroxide"}], "amount": {"volume": {"value": 40.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"temperature": {"control": {"type": "AMBIENT"}}, "stirring": {"type": "CUSTOM", "details": "the mixture was stirred at ambient temperature for 3 hours"}, "conditions_are_dynamic": true}, "workups": [{"type": "ADDITION", "details": "was added slowly over 5 minutes", "duration": {"value": 5.0, "units": "MINUTE"}}, {"type": "STIRRING", "details": "the reaction was stirred 16 hours", "duration": {"value": 16.0, "units": "HOUR"}}, {"type": "STIRRING", "details": "the suspension was stirred 40 minutes", "duration": {"value": 40.0, "units": "MINUTE"}}, {"type": "EXTRACTION", "details": "The mixture was extracted with dichloromethane", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "dichloromethane"}], "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 under reduced pressure"}, {"type": "ADDITION", "details": "Ethyl acetate was added", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "Ethyl acetate"}], "reaction_role": "WORKUP"}]}}, {"type": "TEMPERATURE", "details": "the suspension was refluxed for 30 minutes until solids", "duration": {"value": 30.0, "units": "MINUTE"}}, {"type": "DISSOLUTION", "details": "dissolved"}, {"type": "TEMPERATURE", "details": "to cool to ambient temperature and aged 48 hours", "duration": {"value": 48.0, "units": "HOUR"}, "temperature": {"control": {"type": "AMBIENT"}}}], "outcomes": [{"reaction_time": {"value": 3.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "3,5-dibromopyridine 1-oxide"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 25.09, "units": "GRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 82.0}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: 1-Ethyl-3-(4-(4-morpholino-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea (0.0506 g, 0.132 mmol) and 3-chloropyrazine-2-carbonitrile (0.0338 g, 0.242 mmol) were combined then added dry N,N-Dimethylformamide (0.910 mL, 11.8 mmol) followed by N,N-Diisopropylethylamine (0.0456 mL, 0.262 mmol). The reaction was microwaved on 200 watts, 120° C. for 30 minutes on a CEM microwave. The reaction mixture was purified by HPLC. 1H NMR (500 MHz, DMSO) δ 8.80 (s, 1H), 8.50 (d, J=2.2, 1H), 8.21 (d, J=8.7, 2H), 8.15 (d, J=2.2, 1H), 7.50 (d, J=8.7, 2H), 6.30 (t, J=5.5, 1H), 4.86 (s, 2 H), 4.00 (s, 2H), 3.74 (d, J=4.3, 4H), 3.49 (d, J=4.2, 4H), 3.12 (dt, J=13.8, 7.1, 3H), 2.85 (s, 2H), 1.06 (t, J=7.2, 3H). LC/MS-m/z+486.2 (M+H)+. ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "N,N-Diisopropylethylamine"}], "amount": {"volume": {"value": 0.0456, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}, "m1_m2_m3": {"components": [{"identifiers": [{"type": "NAME", "value": "1-Ethyl-3-(4-(4-morpholino-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea"}], "amount": {"mass": {"value": 0.0506, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "3-chloropyrazine-2-carbonitrile"}], "amount": {"mass": {"value": 0.0338, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "N,N-Dimethylformamide"}], "amount": {"volume": {"value": 0.91, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "The reaction was microwaved on 200 watts, 120\u00b0 C. for 30 minutes on a CEM microwave", "duration": {"value": 30.0, "units": "MINUTE"}, "temperature": {"setpoint": {"value": 120.0, "units": "CELSIUS"}}}, {"type": "CUSTOM", "details": "The reaction mixture was purified by HPLC"}], "outcomes": [{"products": [{}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: To CuCN (26.9 g, dried in advance under vacuum) was added under nitrogen atmosphere about 500 ml of dry tetrahydrofuran. The mixture was kept at −78□, and 100 ml of methyl magnesium bromide (3.0M diethylether solution) was slowly added thereto under mechanical stirring. The thick mixture was stirred for about 30 minutes at −78□. Ethyl 2-bromomethylacrylate (28.9 g, 150 mmol, Synthetic method: Villieras, J. and Rambaud, M. Synthesis, 1982, 914) dissolved in about 30 ml of dry tetrahydrofuran was slowly added thereto. The temperature of the reaction mixture was slowly raised to room temperature over two hours. The reaction was completed by slowly adding saturated ammonium chloride solution (˜50 ml). The reaction mixture was filtered through Celite to remove the precipitates, and then washed with diethylether. The organic layer was washed with water and saturated sodium bicarbonate solution (300 ml×2), dried (anhydrous Na2SO4), and concentrated under reduced pressure to give 26.7 g (stoichiometric yield) of a transparent liquid. This liquid was identified by 1H-NMR (500 MHz, CDCl3) and was confirmed to be the title compound having about 75% of w/w purity. ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "ammonium chloride"}], "amount": {"volume": {"value": 50.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}, "m3_m5": {"components": [{"identifiers": [{"type": "NAME", "value": "Ethyl 2-bromomethylacrylate"}], "amount": {"mass": {"value": 28.9, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "tetrahydrofuran"}], "amount": {"volume": {"value": 30.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m1_m6": {"components": [{"identifiers": [{"type": "NAME", "value": "CuCN"}], "amount": {"mass": {"value": 26.9, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "tetrahydrofuran"}], "amount": {"volume": {"value": 500.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "methyl magnesium bromide"}], "amount": {"volume": {"value": 100.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"temperature": {"control": {"type": "AMBIENT"}}, "stirring": {"type": "CUSTOM", "details": "The thick mixture was stirred for about 30 minutes at \u221278\u25a1"}, "conditions_are_dynamic": true}, "workups": [{"type": "ADDITION", "details": "was slowly added"}, {"type": "ADDITION", "details": "was slowly added"}, {"type": "FILTRATION", "details": "The reaction mixture was filtered through Celite"}, {"type": "CUSTOM", "details": "to remove the precipitates"}, {"type": "WASH", "details": "washed with diethylether", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "diethylether"}], "reaction_role": "WORKUP"}]}}, {"type": "WASH", "details": "The organic layer was washed with water and saturated sodium bicarbonate solution (300 ml\u00d72)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "water"}], "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "sodium bicarbonate"}], "amount": {"volume": {"value": 300.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}]}}, {"type": "DRY_WITH_MATERIAL", "details": "dried (anhydrous Na2SO4)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "Na2SO4"}], "reaction_role": "WORKUP"}]}}, {"type": "CONCENTRATION", "details": "concentrated under reduced pressure"}, {"type": "CUSTOM", "details": "to give"}, {"type": "CUSTOM", "details": "26.7 g (stoichiometric yield) of a transparent liquid"}], "outcomes": [{"reaction_time": {"value": 30.0, "units": "MINUTE"}, "products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: A mixture of 0.67 g (2.0 mmol) of methyl 6-benzyloxy-5-nitro-indole-2-carboxylate, 60 ml of tetrahydrofuran and 0.1 g of 10% Pd/C catalyst is hydogenated for 5 h. The catalyst is filtered off and the filtrate containing the title compound is used immediately in the next step. ### ORD JSON:

{"inputs": {"m1_m3_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "methyl 6-benzyloxy-5-nitro-indole-2-carboxylate"}], "amount": {"mass": {"value": 0.67, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "Pd/C"}], "amount": {"mass": {"value": 0.1, "units": "GRAM"}}, "reaction_role": "CATALYST"}, {"identifiers": [{"type": "NAME", "value": "tetrahydrofuran"}], "amount": {"volume": {"value": 60.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "FILTRATION", "details": "The catalyst is filtered off"}, {"type": "ADDITION", "details": "the filtrate containing the title compound", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"reaction_time": {"value": 5.0, "units": "HOUR"}, "products": [{}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: 208 g anthraquinone are nitrated with 2.32 kg of 95 % strength nitric acid (molar ratio 35:1) at 25°C during 1.5 hours. The reaction is stopped by distilling off 1.74 kg of 94 % strength nitric acid (molar fraction 0.73). 1-nitroanthraquinone is obtained after addition of 1.12 kg of 67.5 % strength nitric acid (molar fraction 0.47), filtration at room temperature, washing with 67.5 % strength nitric acid and drying. Thus 199.6 g of 1-nitroanthraquinone are obtained (yield 71 % of theory, purity 90 %) ### ORD JSON:

{"inputs": {"m1_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "anthraquinone"}], "amount": {"mass": {"value": 208.0, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "nitric acid"}], "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "DISTILLATION", "details": "by distilling off 1.74 kg of 94 % strength nitric acid (molar fraction 0.73)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "nitric acid"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "1-nitroanthraquinone"}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: 3-((4-aminophenyl)amino)-5-((4-hydroxybenzyl)amino)-1H-pyrazole-4-carboxamide (100 mg) was dissolved in 3.0 mL of DMF and TEA (125 μL, 3.0 eq.) was then added to the reaction vessel. Reaction was then stirred on an ice bath for 15 min and 3-Chloro-6-fluorobenzo[b]thiophene-2-carbonyl chloride (75 mg, 1.00 eq.) dissolved in DMF (2.0 mL) was slowly added into the reaction. The reaction continued stirring for 18 hrs and allowed to reach room temperature. The reaction was tracked via HPLC, once completed and no traces of starting material is present, the solvent was then removed via vacuo and column chromatography was used to purify the compound. A gradient of 0 to 20% MeOH in dichloromethane was used and the desired fractions were combined, evaporated and triturated with diisoproyl ether then filtered to yield product as an off white powder (0.008 g, 6.0% yield). ### ORD JSON:

{"inputs": {"m3_m5": {"components": [{"identifiers": [{"type": "NAME", "value": "3-Chloro-6-fluorobenzo[b]thiophene-2-carbonyl chloride"}], "amount": {"mass": {"value": 75.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "DMF"}], "amount": {"volume": {"value": 2.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m1_m4": {"components": [{"identifiers": [{"type": "NAME", "value": "3-((4-aminophenyl)amino)-5-((4-hydroxybenzyl)amino)-1H-pyrazole-4-carboxamide"}], "amount": {"mass": {"value": 100.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "DMF"}], "amount": {"volume": {"value": 3.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "TEA"}], "amount": {"volume": {"value": 125.0, "units": "MICROLITER"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"stirring": {"type": "CUSTOM", "details": "was then stirred on an ice bath for 15 min"}, "conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "Reaction"}, {"type": "ADDITION", "details": "was slowly added into the reaction"}, {"type": "STIRRING", "details": "The reaction continued stirring for 18 hrs", "duration": {"value": 18.0, "units": "HOUR"}}, {"type": "CUSTOM", "details": "to reach room temperature", "temperature": {"control": {"type": "AMBIENT"}}}, {"type": "CUSTOM", "details": "the solvent was then removed via vacuo and column chromatography"}, {"type": "CUSTOM", "details": "to purify the compound"}, {"type": "CUSTOM", "details": "evaporated"}, {"type": "CUSTOM", "details": "triturated with diisoproyl ether", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "diisoproyl ether"}], "reaction_role": "WORKUP"}]}}, {"type": "FILTRATION", "details": "then filtered"}], "outcomes": [{"reaction_time": {"value": 15.0, "units": "MINUTE"}, "products": [{"identifiers": [{"type": "NAME", "value": "powder"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 0.008, "units": "GRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 6.0}}, {"type": "YIELD", "details": "CALCULATEDPERCENTYIELD", "percentage": {"value": 4.9}}], "texture": {"type": "POWDER", "details": "powder"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: To a solution of (S)-3-(4-amino-2-benzyloxy-benzenesulfonylamino)-4,4-diethoxy-butyric acid tert-butyl ester from Route J step 7 (0.958 g, 1.88 mmol), in anhydrous methylene chloride (20 mL) at 0° C. was added triethylamine (1.32 mL, 9.42 mmol) followed by 4-chlorobutyryl chloride (0.32 ml, 2.83 mmol) dropwise. The reaction was allowed to stir at 0° C. for 1 h and then allowed to slowly warm to room temperature overnight. The methylene chloride was evaporated and the reaction mixture was dissolved in ethyl acetate and water. The organic layer was collected and washed with 10% sulfuric acid, brine, dried over magnesium sulfate, and concentrated to yield (S)-3-[2-benzyloxy-4-(4-chloro-butanoylamino)-benzenesulfonylamino]-4,4-diethoxy-butyric acid tert-butyl ester (1.32 g) as a crude brown oil. MS (APCI) m/z 611.3 (M−1). ### ORD JSON:

{"inputs": {"m1_m4_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "(S)-3-(4-amino-2-benzyloxy-benzenesulfonylamino)-4,4-diethoxy-butyric acid tert-butyl ester"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "triethylamine"}], "amount": {"volume": {"value": 1.32, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "methylene chloride"}], "amount": {"volume": {"value": 20.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "4-chlorobutyryl chloride"}], "amount": {"volume": {"value": 0.32, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"temperature": {"setpoint": {"value": 0.0, "units": "CELSIUS"}}, "stirring": {"type": "CUSTOM", "details": "to stir at 0\u00b0 C. for 1 h"}, "conditions_are_dynamic": true}, "workups": [{"type": "TEMPERATURE", "details": "to slowly warm to room temperature overnight", "duration": {"value": 8.0, "precision": 8.0, "units": "HOUR"}, "temperature": {"control": {"type": "AMBIENT"}}}, {"type": "CUSTOM", "details": "The methylene chloride was evaporated", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "methylene chloride"}], "reaction_role": "WORKUP"}]}}, {"type": "DISSOLUTION", "details": "the reaction mixture was dissolved in ethyl acetate", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl acetate"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "The organic layer was collected"}, {"type": "WASH", "details": "washed with 10% sulfuric acid, brine", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "sulfuric acid"}], "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"}], "outcomes": [{"reaction_time": {"value": 1.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "(S)-3-[2-benzyloxy-4-(4-chloro-butanoylamino)-benzenesulfonylamino]-4,4-diethoxy-butyric acid tert-butyl ester"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 1.32, "units": "GRAM"}}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: (2S)-3-[4-(3-Bromo-propoxy)-phenyl]-2-methoxy-propionic acid ethyl ester from Example 173, Step A wag treated with (4-Hydroxy-phenyl)-naphthalen-1-yl-methanone from Step A under the Standard Procedure J. The compound thus obtained was allowed to react under Standard hydrolysis procedure C (NaOH) to give the title compound. MS(ES) for C30H28O6 [M+NH4]+: 507, [M+H]+485. ### ORD JSON:

{"inputs": {"m1_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "(2S)-3-[4-(3-Bromo-propoxy)-phenyl]-2-methoxy-propionic acid ethyl ester"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "(4-Hydroxy-phenyl)-naphthalen-1-yl-methanone"}], "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "NaOH"}], "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "The compound thus obtained"}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: Then, 2.6 M n-butylithium hexane solution (1.6 mL) was added to a mixture of 1-bromo-4-ethoxy-2-methylbenzene (0.94 g, 4.37 mmol) and tetrahydrofuran (12 mL) at −78° C. After stirred for one hour, the mixture was added with a tetrahydrofuran (10 mL) solution of 2,3,4,6-tetra-O-benzyl-1-C-(4-chloro-3-formylphenyl)-5-thio-D-glucopyranose (1.52 g, 2.18 mmol), and, further stirred for 20 minutes, and the reaction mixture was warmed to room temperature. After the reaction mixture was added with a saturated ammonium chloride aqueous solution and extracted with ethyl acetate, the organic phase was washed with brine and dried with anhydrous magnesium sulfate. After the desiccant was filtered off, the residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (hexane:ethyl acetate=2:1) to obtain 2,3,4,6-tetra-O-benzyl-1-C-{4-chloro-3-[(4-ethoxy-2-methylphenyl)(hydroxy)methyl]phenyl}-5-thio-D-glucopyranose (1.72 g, 95%) as a yellow amorphous diastereomer mixture. ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "ammonium chloride"}], "reaction_role": "REACTANT"}]}, "m5_m3": {"components": [{"identifiers": [{"type": "NAME", "value": "2,3,4,6-tetra-O-benzyl-1-C-(4-chloro-3-formylphenyl)-5-thio-D-glucopyranose"}], "amount": {"mass": {"value": 1.52, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "tetrahydrofuran"}], "amount": {"volume": {"value": 10.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m1_m2_m6": {"components": [{"identifiers": [{"type": "NAME", "value": "hexane"}], "amount": {"volume": {"value": 1.6, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "1-bromo-4-ethoxy-2-methylbenzene"}], "amount": {"mass": {"value": 0.94, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "tetrahydrofuran"}], "amount": {"volume": {"value": 12.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"temperature": {"control": {"type": "AMBIENT"}}, "stirring": {"type": "CUSTOM", "details": "After stirred for one hour"}, "conditions_are_dynamic": true}, "workups": [{"type": "STIRRING", "details": "further stirred for 20 minutes", "duration": {"value": 20.0, "units": "MINUTE"}}, {"type": "EXTRACTION", "details": "extracted with ethyl acetate", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl acetate"}], "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 with anhydrous magnesium sulfate", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "magnesium sulfate"}], "reaction_role": "WORKUP"}]}}, {"type": "FILTRATION", "details": "After the desiccant was filtered off"}, {"type": "CUSTOM", "details": "the residue obtained"}, {"type": "CUSTOM", "details": "by evaporating the solvent under reduced pressure"}, {"type": "CUSTOM", "details": "was purified by silica gel column chromatography (hexane:ethyl acetate=2:1)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "hexane"}], "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "ethyl acetate"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"reaction_time": {"value": 1.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "2,3,4,6-tetra-O-benzyl-1-C-{4-chloro-3-[(4-ethoxy-2-methylphenyl)(hydroxy)methyl]phenyl}-5-thio-D-glucopyranose"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 1.72, "units": "GRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 95.0}}, {"type": "YIELD", "details": "CALCULATEDPERCENTYIELD", "percentage": {"value": 94.9}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: To a suspension of 5-bromo-pyridine-3-carbaldehyde (10.0 g, 53.7 mmol) in MeOH (100 mL) was added sodium borohydride (2.2 g, 59.1 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 1 hour before it was quenched with water (5.0 mL). Evaporation of solvents afforded light yellowish oil which was re-dissolved in EtOAc and washed with brine. The organic layer was dried over anhy. Na2SO4, filtered and concentrated in vacuo to give the title compound (9.6 g, 95%) as colorless oil. MS: 188.0 & 190.0 (M+H+). ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "EtOAc"}], "reaction_role": "SOLVENT"}]}, "m1_m3": {"components": [{"identifiers": [{"type": "NAME", "value": "5-bromo-pyridine-3-carbaldehyde"}], "amount": {"mass": {"value": 10.0, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "MeOH"}], "amount": {"volume": {"value": 100.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "sodium borohydride"}], "amount": {"mass": {"value": 2.2, "units": "GRAM"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"temperature": {"setpoint": {"value": 0.0, "units": "CELSIUS"}}, "stirring": {"type": "CUSTOM", "details": "The reaction mixture was stirred at 0\u00b0 C. for 1 hour before it"}, "conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "was quenched with water (5.0 mL)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "water"}], "amount": {"volume": {"value": 5.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "Evaporation of solvents"}, {"type": "CUSTOM", "details": "afforded light yellowish oil which"}, {"type": "WASH", "details": "washed with brine", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "brine"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "The organic layer was dried over anhy"}, {"type": "FILTRATION", "details": "Na2SO4, filtered", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "Na2SO4"}], "reaction_role": "WORKUP"}]}}, {"type": "CONCENTRATION", "details": "concentrated in vacuo"}], "outcomes": [{"reaction_time": {"value": 1.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 9.6, "units": "GRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 95.0}}, {"type": "YIELD", "details": "CALCULATEDPERCENTYIELD", "percentage": {"value": 95.1}}], "isolated_color": "colorless", "texture": {"type": "OIL", "details": "oil"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: 6-Chloro-N-(1-ethyl-1H-indol-6-yl)-nicotinamide was prepared from 1-ethyl-1H-indol-5-ylamine (prepared as described in J. Med. Chem. 2007, 5509), and 6-chloronicotincyl chloride in a procedure similar to the one described in the synthesis of 6-chloro-N-(4-Iodo-3-methyl-phenyl)-nicotinamide, above. LCMS calcd for C16H14ClN3O (m/e) 299, obsd 300 (M+H). ### ORD JSON:

{"inputs": {"m0_m1_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "1-ethyl-1H-indol-5-ylamine"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "chloride"}], "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "6-chloro-N-(4-Iodo-3-methyl-phenyl)-nicotinamide"}], "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "6-Chloro-N-(1-ethyl-1H-indol-6-yl)-nicotinamide"}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: (R)-N-Boc-2-Ethynyl-pyrrolidine was prepared according to Method X above by the treatment of (R)-N-Boc-2-formyl-pyrrolidine (700 mg, 3.51 mmol) (Example 89A) with potassium tert-butoxide (510 mg, 4.56 mmol) and diazomethyl-phosphonic-acid-diethylester (820 mg, 4.56 mmol) (also prepared according to Method X). (R)-N-Boc-2-Ethynyl-pyrrolidine was obtained after silica gel cotoumn chromatography with 10% Et2O in hexanes. (Yield 150 mg, 25%). ### ORD JSON:

{"inputs": {"m1": {"components": [{"identifiers": [{"type": "NAME", "value": "(R)-N-Boc-2-formyl-pyrrolidine"}], "amount": {"mass": {"value": 700.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "potassium tert-butoxide"}], "amount": {"mass": {"value": 510.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}]}, "m0_m5_m4": {"components": [{"identifiers": [{"type": "NAME", "value": "hexanes"}], "reaction_role": "SOLVENT"}, {"identifiers": [{"type": "NAME", "value": "Et2O"}], "reaction_role": "SOLVENT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "diazomethyl-phosphonic-acid-diethylester"}], "amount": {"mass": {"value": 820.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "(R)-N-Boc-2-Ethynyl-pyrrolidine was prepared", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "(R)-N-Boc-2-Ethynyl-pyrrolidine"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "also prepared"}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "(R)-N-Boc-2-Ethynyl-pyrrolidine"}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: 2,2,2-Trifluoro-N-(6-fluoro-imidazo[1,2-a]pyridin-2-yl)-acetamide (compound c, 6 g, 0.02 mol), 2-bromo-1,3-benzothiazole (6.8 g, 32 mmol), potassium carbonate (7000 mg, 0.05 mol), and triphenylphosphine (1000 mg, 0.005 mol) were diluted with 60 ml of a 2:1 solution of dioxane/ethanol and treated with palladium acetate (500 mg, 0.002 mol). The reaction was heated at 100° C. overnight. The reaction was cooled and resulting solid was filtered and washed with dichloromethane then dried to give 3-(benzo[d]thiazol-2-yl)-6-fluoroimidazo[1,2-a]pyridin-2-amine as a yellow solid. Rf 0.37, 70% ethyl acetate/hexanes; MS m/z 285 (M+H). ### ORD JSON:

{"inputs": {"m7": {"components": [{"identifiers": [{"type": "NAME", "value": "palladium acetate"}], "amount": {"mass": {"value": 500.0, "units": "MILLIGRAM"}}, "reaction_role": "CATALYST"}]}, "m1_m2_m3_m4_m5_m6": {"components": [{"identifiers": [{"type": "NAME", "value": "2,2,2-Trifluoro-N-(6-fluoro-imidazo[1,2-a]pyridin-2-yl)-acetamide"}], "amount": {"mass": {"value": 6.0, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "compound c"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "2-bromo-1,3-benzothiazole"}], "amount": {"mass": {"value": 6.8, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "potassium carbonate"}], "amount": {"mass": {"value": 7000.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "triphenylphosphine"}], "amount": {"mass": {"value": 1000.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "dioxane ethanol"}], "reaction_role": "SOLVENT"}]}}, "conditions": {"temperature": {"setpoint": {"value": 100.0, "units": "CELSIUS"}}, "conditions_are_dynamic": true}, "workups": [{"type": "TEMPERATURE", "details": "The reaction was cooled"}, {"type": "CUSTOM", "details": "resulting solid"}, {"type": "FILTRATION", "details": "was filtered"}, {"type": "WASH", "details": "washed with dichloromethane", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "dichloromethane"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "then dried"}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "3-(benzo[d]thiazol-2-yl)-6-fluoroimidazo[1,2-a]pyridin-2-amine"}], "isolated_color": "yellow", "texture": {"type": "CUSTOM", "details": "solid"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: To (±)-N-(t-butoxycarbonyl)-1,3,4,10b-tetrahydro-7-chloro-9-methoxy-pyrazino[2,1-a]isoindol-6(2H)-one (20 mg, 0.06 mmol) was added concentrated hydrochloric acid (1 mL). After 15 min, the resulting solution was concentrated, diluted with water, and lyopholized to give (±)-1,3,4,10b-tetrahydro-7-chloro-9-methoxy-pyrazino[2,1-a]isoindol-6(2H)-one hydrochloric acid salt as an off-white solid (15 mg, 91%). MS (ESI) 253.1, 255.1 (M−Cl). ### ORD JSON:

{"inputs": {"m1_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "(\u00b1)-N-(t-butoxycarbonyl)-1,3,4,10b-tetrahydro-7-chloro-9-methoxy-pyrazino[2,1-a]isoindol-6(2H)-one"}], "amount": {"mass": {"value": 20.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "hydrochloric acid"}], "amount": {"volume": {"value": 1.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "CONCENTRATION", "details": "the resulting solution was concentrated"}, {"type": "ADDITION", "details": "diluted with water", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "water"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"reaction_time": {"value": 15.0, "units": "MINUTE"}, "products": [{"identifiers": [{"type": "NAME", "value": "(\u00b1)-1,3,4,10b-tetrahydro-7-chloro-9-methoxy-pyrazino[2,1-a]isoindol-6(2H)-one hydrochloric acid salt"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 15.0, "units": "MILLIGRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 91.0}}], "isolated_color": "off-white", "texture": {"type": "CUSTOM", "details": "solid"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: The title compound, white solid (28 mg, 69.5%), MS (ISP) m/z=493.3 [(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) (30 mg, 0.0818 mmol) and 2,3-dihydrobenzo[1,4]dioxine-6-carboxylic acid. ### ORD JSON:

{"inputs": {"m0_m1_m2_m3_m4": {"components": [{"identifiers": [{"type": "NAME", "value": "solid"}], "amount": {"mass": {"value": 28.0, "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": 30.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "intermediate A"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "2,3-dihydrobenzo[1,4]dioxine-6-carboxylic acid"}], "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: Prepared from the product of step A and (E)-1-hexeneboronic acid according to general procedure 2 providing the title compound (47 mg, 53%) as a brown solid; 1H NMR (500 MHz, CD3OD) δ 8.46-8.44 (m, 2H), 7.61 (d, J=9.1 Hz, 1H), 7.46 (d, J=7.1 Hz, 2H), 7.38 (s, 1H), 6.75 (d, J=9.7 Hz, 1H), 6.56-6.37 (m, 2H), 4.62 (s, 2H), 2.18-2.11 (q, J=6.5 Hz, 2H), 1.39-1.28 (m, 4H), 0.92 (t, J=7.1 Hz, 3H); 13C NMR (125 MHz, CD3OD) δ 154.8, 152.0, 150.0, 138.0, 133.1, 129.4, 128.6, 125.9, 123.9, 116.6, 113.0, 45.5, 34.3, 32.7, 23.3, 14.3; HPLC tR=10.9 min (Luna), 97.4%; ES-MS: (M+H)=308 m/z. ### ORD JSON:

{"inputs": {"m1_m2_m0": {"components": [{"identifiers": [{"type": "NAME", "value": "product"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "(E)-1-hexeneboronic acid"}], "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 47.0, "units": "MILLIGRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 53.0}}], "isolated_color": "brown", "texture": {"type": "CUSTOM", "details": "solid"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: 6.4 g (39 mmol) of N-phenylpiperazine (III) is placed in 2.2 mL of glacial acetic acid, heated to 125° C., then 3.2 g (15 mmol) of 2-ethylsulfanyl-6,7-dihydrothieno[3,2-d]pyrimidin-4-ol (II) is added, and the mixture is heated to 175° C. After 1.5 hours, the resulting solid is stirred with water, suction filtered, washed with ethanol, and dried. 4.3 g product (91%) is obtained as a powder. ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "acetic acid"}], "amount": {"volume": {"value": 2.2, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m1": {"components": [{"identifiers": [{"type": "NAME", "value": "N-phenylpiperazine"}], "amount": {"mass": {"value": 6.4, "units": "GRAM"}}, "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "2-ethylsulfanyl-6,7-dihydrothieno[3,2-d]pyrimidin-4-ol"}], "amount": {"mass": {"value": 3.2, "units": "GRAM"}}, "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "water"}], "reaction_role": "REACTANT"}]}}, "conditions": {"temperature": {"setpoint": {"value": 125.0, "units": "CELSIUS"}}, "conditions_are_dynamic": true}, "workups": [{"type": "TEMPERATURE", "details": "the mixture is heated to 175\u00b0 C", "temperature": {"setpoint": {"value": 175.0, "units": "CELSIUS"}}}, {"type": "FILTRATION", "details": "filtered"}, {"type": "WASH", "details": "washed with ethanol", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethanol"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "dried"}], "outcomes": [{"reaction_time": {"value": 1.5, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "product"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 4.3, "units": "GRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 91.0}}, {"type": "YIELD", "details": "CALCULATEDPERCENTYIELD", "percentage": {"value": 91.2}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: To a stirred solution of [4-({[2-(benzo[1,3]dioxol-5-yloxy)-pyridine-3-carbonyl]-amino}-methyl)-3-fluoro-phenoxy]-acetic acid methyl ester (0.40 g, 0.88 mmol) in tetrahydrofuran (10 mL) and methanol (2 mL) was added aqueous lithium hydroxide (2 mL, 1 M, 2 mmol). The reaction was stirred at room temperature 1 hour. The solvents were stripped in vacuo and the residue partitioned between dilute aqueous hydrochloric acid and ethyl acetate. The aqueous was extracted with 2 aliquots ethyl acetate and the pooled organics were washed with brine, dried over sodium sulfate and concentrated in vacuo to afford a yellow solid. The crude product was recrystallized from ethyl acetate to afford 80 mg of a white crystalline solid (0.18 mmol, 21% yield). mp 180° C. ### ORD JSON:

{"inputs": {"m1_m3_m4_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "[4-({[2-(benzo[1,3]dioxol-5-yloxy)-pyridine-3-carbonyl]-amino}-methyl)-3-fluoro-phenoxy]-acetic acid methyl ester"}], "amount": {"mass": {"value": 0.4, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "lithium hydroxide"}], "amount": {"volume": {"value": 2.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "tetrahydrofuran"}], "amount": {"volume": {"value": 10.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}, {"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 reaction was stirred at room temperature 1 hour"}, "conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "the residue partitioned between dilute aqueous hydrochloric acid and ethyl acetate", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "hydrochloric acid"}], "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "ethyl acetate"}], "reaction_role": "WORKUP"}]}}, {"type": "EXTRACTION", "details": "The aqueous was extracted with 2 aliquots ethyl acetate", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl acetate"}], "reaction_role": "WORKUP"}]}}, {"type": "WASH", "details": "the pooled organics 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 in vacuo"}, {"type": "CUSTOM", "details": "to afford a yellow solid"}, {"type": "CUSTOM", "details": "The crude product was recrystallized from ethyl acetate", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "crude product"}], "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "ethyl acetate"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"reaction_time": {"value": 1.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "white crystalline solid"}], "measurements": [{"type": "AMOUNT", "details": "AMOUNT", "amount": {"moles": {"value": 0.18, "units": "MILLIMOLE"}}}, {"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 80.0, "units": "MILLIGRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 21.0}}], "isolated_color": "white crystalline", "texture": {"type": "CUSTOM", "details": "solid"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: A mixture of 7.6 g (E)/(Z)-2-[(3-fluoro-2-methyl-phenyl)-hydrazono]-propionic acid ethyl ester and 8.2 g p-toluenesulfonic acid (dried by azeotropic distillation with toluene) was heated 1 h at reflux in toluene. The solution was cooled, poured into half-saturated aqueous sodium bicarbonate solution, and the aqueous phase extracted twice with ethyl acetate. The combined organic phases were washed with brine, dried over sodium sulfate and evaporated. The residue was purified by column chromatography on silica gel (8:1 to 6:1 hexane/ethyl acetate eluant) to afford the title compound as a light brown solid, (24% yield, mp 149° C.; EI-MS m/e: 221.1 (M+)) ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "sodium bicarbonate"}], "reaction_role": "REACTANT"}]}, "m1_m2_m3": {"components": [{"identifiers": [{"type": "NAME", "value": "( E )"}], "amount": {"mass": {"value": 7.6, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "(Z)-2-[(3-fluoro-2-methyl-phenyl)-hydrazono]-propionic acid ethyl ester"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "p-toluenesulfonic acid"}], "amount": {"mass": {"value": 8.2, "units": "GRAM"}}, "reaction_role": "REACTANT"}]}, "m5": {"components": [{"identifiers": [{"type": "NAME", "value": "toluene"}], "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "TEMPERATURE", "details": "was heated 1 h", "duration": {"value": 1.0, "units": "HOUR"}}, {"type": "TEMPERATURE", "details": "The solution was cooled"}, {"type": "EXTRACTION", "details": "the aqueous phase extracted twice with ethyl acetate", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl acetate"}], "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 sodium sulfate", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "sodium sulfate"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "evaporated"}, {"type": "CUSTOM", "details": "The residue was purified by column chromatography on silica gel (8:1 to 6:1 hexane/ethyl acetate eluant)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "hexane ethyl acetate"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "measurements": [{"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 24.0}}], "isolated_color": "light brown", "texture": {"type": "CUSTOM", "details": "solid"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: A solution of 4-[3-[4-[bis(4-fluorophenyl)methyl]-1-piperidinyl]-propoxy-3-methoxybenzoic acid methyl ester (18.58 g, 0.0365 mole) in 400 ml of ethanol was heated for 6 hr at reflux with potassium hydroxide (16.8 g) in 50 ml of water. The ethanol was removed by rotary evaporation. Next, 1N sulfuric acid (~200 ml) was added. The aqueous phase was made neutral to litmus paper by the addition of 5% sodium hydroxide. The neutral aqueous layer was extracted several times with chloroform. The chloroform layer was dried over sodium sulfate, filtered, and solvent removed to give a white solid. The white solid was triturated with ethyl ether and cooled to about 0° C. The white solid was then collected by filtration and dried in vacuo overnight at 80° C. to give 11.38 g (61.8% yield) of white, crystalline product, the title compound, mp 123°-126° C. ### ORD JSON:

{"inputs": {"m1_m3": {"components": [{"identifiers": [{"type": "NAME", "value": "3-[4-[bis(4-fluorophenyl)methyl]-1-piperidinyl]-propoxy-3-methoxybenzoic acid methyl ester"}], "amount": {"mass": {"value": 18.58, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "ethanol"}], "amount": {"volume": {"value": 400.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}, "m2_m4": {"components": [{"identifiers": [{"type": "NAME", "value": "potassium hydroxide"}], "amount": {"mass": {"value": 16.8, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "water"}], "amount": {"volume": {"value": 50.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"temperature": {"setpoint": {"value": 0.0, "units": "CELSIUS"}}, "conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "The ethanol was removed by rotary evaporation", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethanol"}], "reaction_role": "WORKUP"}]}}, {"type": "ADDITION", "details": "Next, 1N sulfuric acid (~200 ml) was added", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "sulfuric acid"}], "reaction_role": "WORKUP"}]}}, {"type": "ADDITION", "details": "The aqueous phase was made neutral to litmus paper by the addition of 5% sodium hydroxide", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "sodium hydroxide"}], "reaction_role": "WORKUP"}]}}, {"type": "EXTRACTION", "details": "The neutral aqueous layer was extracted several times with chloroform", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "chloroform"}], "reaction_role": "WORKUP"}]}}, {"type": "DRY_WITH_MATERIAL", "details": "The chloroform layer was dried over sodium sulfate", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "chloroform"}], "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "sodium sulfate"}], "reaction_role": "WORKUP"}]}}, {"type": "FILTRATION", "details": "filtered"}, {"type": "CUSTOM", "details": "solvent removed"}, {"type": "CUSTOM", "details": "to give a white solid"}, {"type": "CUSTOM", "details": "The white solid was triturated with ethyl ether", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl ether"}], "reaction_role": "WORKUP"}]}}, {"type": "FILTRATION", "details": "The white solid was then collected by filtration"}, {"type": "CUSTOM", "details": "dried in vacuo overnight at 80\u00b0 C.", "duration": {"value": 8.0, "precision": 8.0, "units": "HOUR"}, "temperature": {"setpoint": {"value": 80.0, "units": "CELSIUS"}}}, {"type": "CUSTOM", "details": "to give 11.38 g (61.8% yield) of white, crystalline product"}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "measurements": [{"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 61.8}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: N′-(4-iodobenzoyl)-3-methoxybenzohydrazide (7.0 g, 17.67 mmol) was suspended in POCl3 (40.0 ml) and heating was started. The reaction was kept at 100° C. During heating white solid of starting materials dissolved into a clear solution and the reaction was monitor by thin layer chromatography. After 1 h, the reaction mixture was brought to room temperature and was carefully dropped into ice-water (500.0 ml). White solid precipitated out was collected by filtration and washed with water. After dry, the crude product was purified by silica gel column chromatography eluting with dichloromethane and ethyl acetate in 25:1 ratio. After evaporating solvent the white solid was recrystallized from acetone/water and finally dried under vacuum. Pure product was obtained as white solid in 5.8 g (86.8%) yield. 1H NMR (400 MHz, CDCl3, δ): 7.86 (d, J=8.4 Hz, 2H), 7.83 (d, J=8.4 Hz, 2H), 7.67 (dt, J1=8.0 Hz, J2=1.2 Hz, 1H), 7.63 (m, 1H), 7.42 (t, J=8 Hz, 1H), 7.07 (m, 1H), 3.88 (s, 3H, OCH3). 13C NMR (100 MHz, CDCl3, δ): 164.66, 164.00, 159.92, 138.32, 130.23, 128.21, 124.73, 123.26, 119.29, 118.26, 111.56, 98.60, 55.52. ### ORD JSON:

{"inputs": {"m1": {"components": [{"identifiers": [{"type": "NAME", "value": "N\u2032-(4-iodobenzoyl)-3-methoxybenzohydrazide"}], "amount": {"mass": {"value": 7.0, "units": "GRAM"}}, "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "ice water"}], "amount": {"volume": {"value": 500.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "POCl3"}], "amount": {"volume": {"value": 40.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "TEMPERATURE", "details": "heating"}, {"type": "CUSTOM", "details": "was kept at 100\u00b0 C", "temperature": {"setpoint": {"value": 100.0, "units": "CELSIUS"}}}, {"type": "TEMPERATURE", "details": "During heating white solid of starting materials"}, {"type": "DISSOLUTION", "details": "dissolved into a clear solution"}, {"type": "CUSTOM", "details": "was brought to room temperature", "temperature": {"control": {"type": "AMBIENT"}}}, {"type": "CUSTOM", "details": "White solid precipitated out"}, {"type": "FILTRATION", "details": "was collected by filtration"}, {"type": "WASH", "details": "washed with water", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "water"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "After dry"}, {"type": "CUSTOM", "details": "the crude product was purified by silica gel column chromatography", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "crude product"}], "reaction_role": "WORKUP"}]}}, {"type": "WASH", "details": "eluting with dichloromethane and ethyl acetate in 25:1 ratio", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "dichloromethane"}], "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "ethyl acetate"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "After evaporating solvent the white solid"}, {"type": "CUSTOM", "details": "was recrystallized from acetone/water", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "acetone water"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "finally dried under vacuum"}, {"type": "CUSTOM", "details": "Pure product was obtained as white solid in 5.8 g (86.8%)"}, {"type": "CUSTOM", "details": "yield"}], "outcomes": [{"reaction_time": {"value": 1.0, "units": "HOUR"}, "products": [{}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: To a solution of p-toluenesulphonic acid (0.8 g) in IPA (12 mL) at 40° C. was added (5R)-5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione(−)-O,O′-dibenzoyl-L-tartrate (2.0 g, d.e. >99%) to give a suspension which was allowed to cool to ambient temperature. After 30 min, the solid was collected by filtration, washed with 5 ml of IPA at 0° C. and dried under vacuum to give the title compound (1.32 g). (Method 14) 99.41%, Rt 15.49 min.; 0.59%, Rt 17.52 min.; e.e. 98.82%. (Method 2) Rt 2.88 min, m/z 357 [M-C7H8SO3+]. 1H NMR (400 MHz, DMSO-d6): δ 1.23 (3H, t, J 8.2), 2.28 (3H, s), 2.76 (2H, q, J 7.4), 3.05 (1H, dd, J 8.8, 14.0), 3.28 (1H, dd, J 4.1, 14), 3.38 (2H, t, J 5.9), 4.35 (2H, t, J 5.9), 4.86 (1H, dd, J 4.4, 9.1), 6.86 (2H, d, J 8.8), 7.12 (4H, dd, J 8.6, 16.6), 7.47 (2H, d, J 8.8), 7.90 (1H, d, J 8.3), 8.30 (1H, d, J 8), 8.68-8.71 (1H, m). ### ORD JSON:

{"inputs": {"m1_m3_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "p-toluenesulphonic acid"}], "amount": {"mass": {"value": 0.8, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "(5R)-5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione(\u2212)-O,O\u2032-dibenzoyl-L-tartrate"}], "amount": {"mass": {"value": 2.0, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "IPA"}], "amount": {"volume": {"value": 12.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"temperature": {"control": {"type": "AMBIENT"}}, "conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "to give a suspension which"}, {"type": "FILTRATION", "details": "the solid was collected by filtration"}, {"type": "WASH", "details": "washed with 5 ml of IPA at 0\u00b0 C.", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "IPA"}], "amount": {"volume": {"value": 5.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}]}, "temperature": {"setpoint": {"value": 0.0, "units": "CELSIUS"}}}, {"type": "CUSTOM", "details": "dried under vacuum"}], "outcomes": [{"reaction_time": {"value": 30.0, "units": "MINUTE"}, "products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 1.32, "units": "GRAM"}}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: To an ice-cold solution of H2SO4 (150 mL) in water (250 mL), 2-ethyl-6-methylaniline (15.0 g, 111 mmol) is added. The solution is treated with ice (150 g) before a solution of NaNO2 (10.7 g, 155 mmol) in water (150 mL) and ice (50 g) is added dropwise. The mixture is stirred at 0° C. for 1 h. 50% aq. H2SO4 (200 mL) is added and stirring is continued at rt for 18 h. The mixture is extracted with DCM, the org. extracts are dried over MgSO4 and evaporated. The crude product is purified by CC on silica gel eluting with Hept:EA 9:1 to give 2-ethyl-6-methyl-phenol as a crimson oil (8.6 g). LC-MS: tR=0.89 min; 1H NMR (CDCl3): δ 7.03-6.95 (m, 2H), 6.80 (t, J=7.6 Hz, 1H), 4.60 (s, 1H), 2.64 (q, J=7.6 Hz, 2H), 2.25 (s, 3H), 1.24 (t, J=7.6 Hz, 3H). ### ORD JSON:

{"inputs": {"m1_m2_m8_m3": {"components": [{"identifiers": [{"type": "NAME", "value": "ice"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "H2SO4"}], "amount": {"volume": {"value": 150.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "2-ethyl-6-methylaniline"}], "amount": {"mass": {"value": 15.0, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "water"}], "amount": {"volume": {"value": 250.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m7": {"components": [{"identifiers": [{"type": "NAME", "value": "H2SO4"}], "amount": {"volume": {"value": 200.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}, "m4_m5_m9_m6": {"components": [{"identifiers": [{"type": "NAME", "value": "ice"}], "amount": {"mass": {"value": 150.0, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "NaNO2"}], "amount": {"mass": {"value": 10.7, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "ice"}], "amount": {"mass": {"value": 50.0, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "water"}], "amount": {"volume": {"value": 150.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"temperature": {"setpoint": {"value": 0.0, "units": "CELSIUS"}}, "stirring": {"type": "CUSTOM", "details": "The mixture is stirred at 0\u00b0 C. for 1 h"}, "conditions_are_dynamic": true}, "workups": [{"type": "ADDITION", "details": "is added dropwise"}, {"type": "STIRRING", "details": "stirring"}, {"type": "WAIT", "details": "is continued at rt for 18 h", "duration": {"value": 18.0, "units": "HOUR"}, "temperature": {"control": {"type": "AMBIENT"}}}, {"type": "EXTRACTION", "details": "The mixture is extracted with DCM", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "DCM"}], "reaction_role": "WORKUP"}]}}, {"type": "DRY_WITH_MATERIAL", "details": "extracts are dried over MgSO4", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "MgSO4"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "evaporated"}, {"type": "CUSTOM", "details": "The crude product is purified by CC on silica gel eluting with Hept", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "crude product"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"reaction_time": {"value": 1.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "2-ethyl-6-methyl-phenol"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 8.6, "units": "GRAM"}}}], "isolated_color": "crimson", "texture": {"type": "OIL", "details": "oil"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: Triethlamine (3.78 cc) is added to a suspension of 2-phenyl-4-quinolinepropanoic acid (2.5 g) in chloroform (100 cc), followed, under nitrogen and after the mixture has been cooled to 10° C., by ethylchloroformate (1.24 g). The mixture is then stirred for 40 minutes at room temperature (approximately 20° C.), and N-methyl-2-butanamine hydrochloride (1.05 g) is then introduced in small portions. The mixture is stirred for 20 hours at room temperature (approximately 20° C.). After evaporation of the solvent under reduced pressure, the residue is taken up in ethyl acetate, and the organic phase is washed with saturated aqueous sodium carbonate solution and dried over magnesium sulphate. The residue obtained after evaporation of the solvent under reduced pressure is chromatographed under pressure on silica gel, initially with a cyclohexane/toluene/diethylamine (80:15:5 by volume) mixture, a second time with a cyclohexane/toluene/diethylamine (90: 7.5:2.5 by volume) mixture, and a third time with a hexane/ethyl acetate (50:50 by volume) mixture. The residue obtained is taken up in acetone and, after addition of a solution of hydrochloric acid in ethyl ether, the product is isolated in the form of the crude hydrochloride. The latter is recrystallized in an isopropanol/isopropyl ether mixture. After a return to the base using 2 N sodium hydroxide, extraction with ethyl acetate and evaporation under reduced pressure, N-methyl-N-(1-methylpropyl)-2-phenyl-4-quinolinepropanamide (0.45 g) is isolated in the form of an oil, the proton NMR spectrum of which in deuterated chloroform shows the following characteristics: ### ORD JSON:

{"inputs": {"m6": {"components": [{"identifiers": [{"type": "NAME", "value": "acetone"}], "reaction_role": "SOLVENT"}]}, "m8_m1_m5": {"components": [{"identifiers": [{"type": "NAME", "value": "2-phenyl-4-quinolinepropanoic acid"}], "amount": {"mass": {"value": 2.5, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "chloroform"}], "amount": {"volume": {"value": 100.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}, {"identifiers": [{"type": "NAME", "value": "Triethlamine"}], "amount": {"volume": {"value": 3.78, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m4_m7": {"components": [{"identifiers": [{"type": "NAME", "value": "hydrochloric acid"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "ethyl ether"}], "reaction_role": "SOLVENT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "ethylchloroformate"}], "amount": {"mass": {"value": 1.24, "units": "GRAM"}}, "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "N-methyl-2-butanamine hydrochloride"}], "amount": {"mass": {"value": 1.05, "units": "GRAM"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"temperature": {"control": {"type": "AMBIENT"}, "setpoint": {"value": 20.0, "units": "CELSIUS"}}, "stirring": {"type": "CUSTOM", "details": "The mixture is stirred for 20 hours at room temperature (approximately 20\u00b0 C.)"}, "conditions_are_dynamic": true}, "workups": [{"type": "ADDITION", "details": "is then introduced in small portions"}, {"type": "CUSTOM", "details": "After evaporation of the solvent under reduced pressure"}, {"type": "WASH", "details": "the organic phase is washed with saturated aqueous sodium carbonate solution", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "sodium carbonate"}], "reaction_role": "WORKUP"}]}}, {"type": "DRY_WITH_MATERIAL", "details": "dried over magnesium sulphate", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "magnesium sulphate"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "The residue obtained"}, {"type": "CUSTOM", "details": "after evaporation of the solvent under reduced pressure"}, {"type": "CUSTOM", "details": "is chromatographed under pressure on silica gel, initially with a cyclohexane/toluene/diethylamine (80:15:5 by volume) mixture", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "cyclohexane toluene diethylamine"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "The residue obtained"}, {"type": "CUSTOM", "details": "the product is isolated in the form of the crude hydrochloride", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "hydrochloride"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "The latter is recrystallized in an isopropanol/isopropyl ether mixture", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "isopropanol isopropyl ether"}], "reaction_role": "WORKUP"}]}}, {"type": "EXTRACTION", "details": "2 N sodium hydroxide, extraction", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "sodium hydroxide"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "with ethyl acetate and evaporation under reduced pressure", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl acetate"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"reaction_time": {"value": 20.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "N-methyl-N-(1-methylpropyl)-2-phenyl-4-quinolinepropanamide"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 0.45, "units": "GRAM"}}}, {"type": "YIELD", "details": "CALCULATEDPERCENTYIELD", "percentage": {"value": 15.3}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: A charge of 112.7 g (1.00 mol, 40%) dimethylamine is made to a 500 ml three-necked, round-bottomed flask. The amine is heated to 40° C. with stirring while 114.1 g (1.00 mol) allyl glycidyl ether is added over 2.5 hours while keeping the temperature below 50° C. After 3.5 hours at 50° C., GC analysis on a 30 M×0.53 mm SPB-5 polysiloxane column shows a single peak as 98% of the desired product. A viscous oil is obtained in quantitative yield. Analysis by 1H NMR (500 MHz, CDCl3) gives the following results: δ=2.61 (6H, s, —N(CH3)2), 2.62 and 2.71 (2H, m, —CH(OH)CH2N(CH3)2), 3.40 and 3.51 (2H, dd, —OCH2CH(OH)—), 4.04 (1H, bm, —CH2CH(OH)CH2—), 4.36 (2H, m, CH2═CHCH2—), 5.13 (1H, dd, CH2═CH—, cis isomer), 5.22 (1H, dd, CH2═CH—, trans isomer), 5.80 (1H, m, CH2═CH—). This data supports the following structure: ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "polysiloxane"}], "reaction_role": "REACTANT"}]}, "m1": {"components": [{"identifiers": [{"type": "NAME", "value": "dimethylamine"}], "amount": {"mass": {"value": 112.7, "units": "GRAM"}}, "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "amine"}], "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "allyl glycidyl ether"}], "amount": {"mass": {"value": 114.1, "units": "GRAM"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "ADDITION", "details": "is added over 2.5 hours", "duration": {"value": 2.5, "units": "HOUR"}}, {"type": "CUSTOM", "details": "the temperature below 50\u00b0 C"}], "outcomes": [{"reaction_time": {"value": 3.5, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "desired product"}], "measurements": [{"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 98.0}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: A solution of N-bromosuccinimide (0.24 g, 1.3 mmol) in DMF (1 mL) was added dropwise to an ice-cooled solution of tert-butyl {1-[1-(3-fluorophenyl)-1H-indol-2-yl]ethyl}carbamate (0.41 g, 1.2 mmol) in N,N-dimethylformamide (5 mL) The resulting mixture was allowed to warm to room temperature and stirred for an additional 4 hours. The mixture was diluted with water and extracted with EtOAc. The extracts were combined, dried over MgSO4, concentrated, and purified on silica gel (eluting with 0-10% EtOAc/hexane) to give the desired product (0.34 g, 68%). LCMS calculated for C21H22BrFN2O2Na(M+Na)+: m/z=455.1. Found: 455.0. ### ORD JSON:

{"inputs": {"m3_m5": {"components": [{"identifiers": [{"type": "NAME", "value": "tert-butyl {1-[1-(3-fluorophenyl)-1H-indol-2-yl]ethyl}carbamate"}], "amount": {"mass": {"value": 0.41, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "N,N-dimethylformamide"}], "amount": {"volume": {"value": 5.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m6": {"components": [{"identifiers": [{"type": "NAME", "value": "water"}], "reaction_role": "SOLVENT"}]}, "m1_m4_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "N-bromosuccinimide"}], "amount": {"mass": {"value": 0.24, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "ice"}], "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": "stirred for an additional 4 hours"}, "conditions_are_dynamic": true}, "workups": [{"type": "EXTRACTION", "details": "extracted with EtOAc", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "EtOAc"}], "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 (eluting with 0-10% EtOAc/hexane)"}], "outcomes": [{"reaction_time": {"value": 4.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "desired product"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 0.34, "units": "GRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 68.0}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: The process is performed according to the method described in step 13.5 of Example 13, starting with 0.35 g (0.96 mmol) of ethyl 5-trifluoromethyl-1-[(3-fluorophenyl)methyl]-1H-pyrrolo[2,3-b]pyridine-2-carboxylate (Example 13.4) and 0.17 g (1.06 mmol) of 5-amino-2-methylbenzothiazole. 0.34 g of expected compound is isolated. ### ORD JSON:

{"inputs": {"m1": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl 5-trifluoromethyl-1-[(3-fluorophenyl)methyl]-1H-pyrrolo[2,3-b]pyridine-2-carboxylate"}], "amount": {"mass": {"value": 0.35, "units": "GRAM"}}, "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "5-amino-2-methylbenzothiazole"}], "amount": {"mass": {"value": 0.17, "units": "GRAM"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "expected compound"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 0.34, "units": "GRAM"}}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: To a solution of tert-butyl 3-(4-bromophenoxy)azetidine-1-carboxylate (300 mg, 0.90 mmol) in CH2Cl2 (5 mL) was added TFA (5 mL). The mixture was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo to give 3-(4-bromophenoxy)azetidine (207 mg, 100%) as a yellow oil. ### ORD JSON:

{"inputs": {"m1_m3_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "tert-butyl 3-(4-bromophenoxy)azetidine-1-carboxylate"}], "amount": {"mass": {"value": 300.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "TFA"}], "amount": {"volume": {"value": 5.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "CH2Cl2"}], "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 overnight"}, "conditions_are_dynamic": true}, "workups": [{"type": "CONCENTRATION", "details": "The reaction mixture was concentrated in vacuo"}], "outcomes": [{"reaction_time": {"value": 8.0, "precision": 8.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "3-(4-bromophenoxy)azetidine"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 207.0, "units": "MILLIGRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 100.0}}], "isolated_color": "yellow", "texture": {"type": "OIL", "details": "oil"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: 8-(Benzyloxy)-2-chloroquinoline (5.0 g, 18.5 mmol), 7-(2-methoxyethoxy)-imidazo[1,2-a]pyridine (3.56 g, 18.5 mmol), Pd(PPh3)4 (1.07 g, 0.927 mmol), K2CO3 (5.12 g, 37.1 mmol), and Pd(OAc)2 (0.208 g, 0.927 mmol) were added into dioxane (74.1 ml, 18.5 mmol) and water (0.735 ml, 40.8 mmol) and heated to 100° C. overnight under nitrogen. The reaction was diluted with DCM and carbon (5 g) was added, followed by filtration. The filtrate was concentrated and then triturated with 1:1 EtOAc/MTBE (30 mL). The resulting solids were allowed to stir for 5 hours and then filtered to isolate of the desired product as a solid (5.4 g, 69% yield). ### ORD JSON:

{"inputs": {"m6": {"components": [{"identifiers": [{"type": "NAME", "value": "DCM"}], "reaction_role": "SOLVENT"}]}, "m1_m2_m7_m3_m8_m4_m5": {"components": [{"identifiers": [{"type": "NAME", "value": "8-(Benzyloxy)-2-chloroquinoline"}], "amount": {"mass": {"value": 5.0, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "7-(2-methoxyethoxy)-imidazo[1,2-a]pyridine"}], "amount": {"mass": {"value": 3.56, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "K2CO3"}], "amount": {"mass": {"value": 5.12, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "dioxane"}], "amount": {"volume": {"value": 74.1, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "water"}], "amount": {"volume": {"value": 0.735, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "Pd(PPh3)4"}], "amount": {"mass": {"value": 1.07, "units": "GRAM"}}, "reaction_role": "CATALYST"}, {"identifiers": [{"type": "NAME", "value": "Pd(OAc)2"}], "amount": {"mass": {"value": 0.208, "units": "GRAM"}}, "reaction_role": "CATALYST"}]}}, "conditions": {"temperature": {"setpoint": {"value": 100.0, "units": "CELSIUS"}}, "stirring": {"type": "CUSTOM", "details": "to stir for 5 hours"}, "conditions_are_dynamic": true}, "workups": [{"type": "ADDITION", "details": "was added"}, {"type": "FILTRATION", "details": "followed by filtration"}, {"type": "CONCENTRATION", "details": "The filtrate was concentrated"}, {"type": "CUSTOM", "details": "triturated with 1:1 EtOAc/MTBE (30 mL)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "EtOAc MTBE"}], "amount": {"volume": {"value": 30.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}]}}, {"type": "FILTRATION", "details": "filtered"}], "outcomes": [{"reaction_time": {"value": 5.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "desired product"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 5.4, "units": "GRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 69.0}}], "texture": {"type": "CUSTOM", "details": "solid"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: In analogy to the procedure described for the preparation of example 4, (rac)-6-(7-amino-6,7-dihydro-5H-cyclopenta[c]pyridin-4-yl)-1-methyl-3,4-dihydroquinolin-2(1H)-one (intermediate A-4) and ethanesulfonyl chloride gave the title compound as an off-white powder in 39% yield. MS: 386.2 (M+H+). ### ORD JSON:

{"inputs": {"m1_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "(rac)-6-(7-amino-6,7-dihydro-5H-cyclopenta[c]pyridin-4-yl)-1-methyl-3,4-dihydroquinolin-2(1H)-one"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "ethanesulfonyl chloride"}], "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "measurements": [{"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 39.0}}], "isolated_color": "off-white", "texture": {"type": "POWDER", "details": "powder"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: A mixture of cis-4,5-bis-(4-methylphenyl)imidazolidine-2-thione (31) (5.2 g, 0.0184 mol) and methyl iodide (1.72 mL, 0.0276 mol) in abs. EtOH (30 mL) is heated at 90° C. overnight. The reaction mixture is cooled to rt, concentrated in vacuo, and the residue suspended in abs EtOH: Et2O. The insoluble material is filtered to give 7.56 g of the product 48. 1H NMR (DMSO-d6) δ 10.68 (s, 2H), 7.00-6.85 (m, 8H), 5.72 (s, 2H), 2.79 (s, 3H), 2.15 (s, 6H); MS: m/z 297 (M++1). ### ORD JSON:

{"inputs": {"m1_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "cis-4,5-bis-(4-methylphenyl)imidazolidine-2-thione"}], "amount": {"mass": {"value": 5.2, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "methyl iodide"}], "amount": {"volume": {"value": 1.72, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "EtOH"}], "amount": {"volume": {"value": 30.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"temperature": {"control": {"type": "AMBIENT"}}, "conditions_are_dynamic": true}, "workups": [{"type": "CONCENTRATION", "details": "concentrated in vacuo"}, {"type": "FILTRATION", "details": "The insoluble material is filtered"}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "product 48"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 7.56, "units": "GRAM"}}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: Combined 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid (500 mg, 1.561 mmol), EDC (449 mg, 2.342 mmol) and HOBT (316 mg, 2.342 mmol) in DMF (3122 μl) and treated with DIPEA (818 μl, 4.68 mmol). Octahydropyrrolo[1,2-a]pyrazine (296 mg, 2.342 mmol) was then added. The reaction was allowed to stir for 8 hours and filtered and the filtrate was purified by preparative HPLC (15-40% ACN/water under basic conditions) to give a solid which was recrystallized from MeOH, filtered, and dried in vacuum to give the title compound (286 mg, 0.603 mmol, 38.6%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.34 (br. s., 1H) 1.72 (br. s., 3H) 2.12 (br. s., 1H) 2.23 (d, J=7.07 Hz, 2H) 2.42 (s, 3H) 2.51-2.53 (m, 1H) 3.06 (t, J=8.08 Hz, 3H) 3.72 (br. s., 1H) 4.44-4.56 (m, 1H) 7.63 (dd, J=8.08, 1.77 Hz, 1H) 7.69 (d, J=1.26 Hz, 1H) 7.84 (d, J=8.08 Hz, 1H) 8.04 (dd, J=8.59, 2.27 Hz, 1H) 8.09 (s, 1H) 8.40 (d, J=7.58 Hz, 1H) 8.52 (d, J=2.27 Hz, 1H); ESI-MS m/z (M+H)+ calc'd for C24H24N6O2, 429.20. found 429.3. ### ORD JSON:

{"inputs": {"m1_m2_m3_m6_m4": {"components": [{"identifiers": [{"type": "NAME", "value": "6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid"}], "amount": {"mass": {"value": 500.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "EDC"}], "amount": {"mass": {"value": 449.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "HOBT"}], "amount": {"mass": {"value": 316.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "DIPEA"}], "amount": {"volume": {"value": 818.0, "units": "MICROLITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "DMF"}], "amount": {"volume": {"value": 3122.0, "units": "MICROLITER"}}, "reaction_role": "SOLVENT"}]}, "m5": {"components": [{"identifiers": [{"type": "NAME", "value": "Octahydropyrrolo[1,2-a]pyrazine"}], "amount": {"mass": {"value": 296.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"stirring": {"type": "CUSTOM", "details": "to stir for 8 hours"}, "conditions_are_dynamic": true}, "workups": [{"type": "FILTRATION", "details": "filtered"}, {"type": "CUSTOM", "details": "the filtrate was purified by preparative HPLC (15-40% ACN/water under basic conditions)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ACN water"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "to give a solid which"}, {"type": "CUSTOM", "details": "was recrystallized from MeOH", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "MeOH"}], "reaction_role": "WORKUP"}]}}, {"type": "FILTRATION", "details": "filtered"}, {"type": "CUSTOM", "details": "dried in vacuum"}], "outcomes": [{"reaction_time": {"value": 8.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "measurements": [{"type": "AMOUNT", "details": "AMOUNT", "amount": {"moles": {"value": 0.603, "units": "MILLIMOLE"}}}, {"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 286.0, "units": "MILLIGRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 38.6}}, {"type": "YIELD", "details": "CALCULATEDPERCENTYIELD", "percentage": {"value": 38.6}}], "isolated_color": "white", "texture": {"type": "CUSTOM", "details": "solid"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: 3,3'-Dimethyl-1,1'-peroxydicyclohexylamine (10 g.) derived from 3-methylcyclohexanone, hydrogen peroxide and ammonia, and probably a mixture of stereoisomers was added to a solution of sodium methoxide in methanol (2 g. sodium in 40 c.c. methanol) and the mixture heated under reflux for 2 hours; only a small amount of peroxide remained unreacted. The solution was cooled, diluted with water, neutralised with hydrochloric acid and extracted with chloroform. Distillation of the chloroform extract gave 3-methylcyclohexanone (4.7 g.), methylcaprolactam (4.1 g), b.p. 145°-150°/15 mm., and residue (0.5 g.). Examination of the methylcaprolactam fraction by N.M.R. spectroscopy showed it to be a mixture of 3- and 5-methyl-caprolactam; on storage this fraction crystallized and several recrystallisations yielded the 3-methylcaprolactam, m.p. 87°-100°. ### ORD JSON:

{"inputs": {"m6_m9": {"components": [{"identifiers": [{"type": "NAME", "value": "sodium methoxide"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "methanol"}], "amount": {"mass": {"value": 2.0, "units": "GRAM"}}, "reaction_role": "SOLVENT"}]}, "m10": {"components": [{"identifiers": [{"type": "NAME", "value": "water"}], "reaction_role": "SOLVENT"}]}, "m5": {"components": [{"identifiers": [{"type": "NAME", "value": "ammonia"}], "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "3-methylcyclohexanone"}], "reaction_role": "REACTANT"}]}, "m4": {"components": [{"identifiers": [{"type": "NAME", "value": "hydrogen peroxide"}], "reaction_role": "REACTANT"}]}, "m7": {"components": [{"identifiers": [{"type": "NAME", "value": "peroxide"}], "reaction_role": "REACTANT"}]}, "m8": {"components": [{"identifiers": [{"type": "NAME", "value": "hydrochloric acid"}], "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "3,3'-Dimethyl-1,1'-peroxydicyclohexylamine"}], "amount": {"mass": {"value": 10.0, "units": "GRAM"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "ADDITION", "details": "probably a mixture of stereoisomers"}, {"type": "TEMPERATURE", "details": "the mixture heated"}, {"type": "TEMPERATURE", "details": "under reflux for 2 hours", "duration": {"value": 2.0, "units": "HOUR"}}, {"type": "TEMPERATURE", "details": "The solution was cooled"}, {"type": "EXTRACTION", "details": "extracted with chloroform", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "chloroform"}], "reaction_role": "WORKUP"}]}}, {"type": "DISTILLATION", "details": "Distillation of the chloroform", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "chloroform"}], "reaction_role": "WORKUP"}]}}, {"type": "EXTRACTION", "details": "extract"}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "3-methylcyclohexanone"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 4.7, "units": "GRAM"}}}], "reaction_role": "PRODUCT"}, {"identifiers": [{"type": "NAME", "value": "methylcaprolactam"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 4.1, "units": "GRAM"}}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: To a solution of (7R)-N-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-1-azaspiro[4.4]nonane-7-carboxamide (from experiment 9, step C, peak 3, 13 mg, 0.027 mmol) in dichloromethane (0.5 mL) was added triethylamine (7.39 μL, 0.053 mmol) and acetic anhydride (4.06 mg, 0.040 mmol). The resulting mixture was stirred at room temperature for 2 hours. The reaction mixture was subjected to preparative HPLC (Shimadzu VP-ODS 20×100 mm, 8 min. gradient, Solvent A: 10% MeOH, 90% H2O, 0.1% TFA; Solvent B: 90% MeOH, 10% H2O, 0.1% TFA). The peak corresponding to the desired product was collected, concentrated and freeze dried to give (7R)-1-acetyl-N-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-1-azaspiro[4.4]nonane-7-carboxamide (6 mg, 0.011 mmol, 42.5% yield) as a solid. Anal. RP-HPLC: Retention time=3.44 min (YMC S5 ODS 4.6×50 mm; gradient solvent A: 10% MeOH, 90% H2O, 0.2% H3PO4; Solvent B: 90% MeOH, 10% H2O, 0.2% H3PO4). Purity: >95%; MS (ESI) m/z 532 M+ ### ORD JSON:

{"inputs": {"m1_m8_m2_m3": {"components": [{"identifiers": [{"type": "NAME", "value": "(7R)-N-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-1-azaspiro[4.4]nonane-7-carboxamide"}], "amount": {"mass": {"value": 13.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "triethylamine"}], "amount": {"volume": {"value": 7.39, "units": "MICROLITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "acetic anhydride"}], "amount": {"mass": {"value": 4.06, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "dichloromethane"}], "amount": {"volume": {"value": 0.5, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m4_m12_m11_m5_m6_m10_m9_m7": {"components": [{"identifiers": [{"type": "NAME", "value": "Solvent A"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "TFA"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "Solvent B"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "TFA"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "H2O"}], "reaction_role": "SOLVENT"}, {"identifiers": [{"type": "NAME", "value": "MeOH"}], "reaction_role": "SOLVENT"}, {"identifiers": [{"type": "NAME", "value": "H2O"}], "reaction_role": "SOLVENT"}, {"identifiers": [{"type": "NAME", "value": "MeOH"}], "reaction_role": "SOLVENT"}]}}, "conditions": {"temperature": {"control": {"type": "AMBIENT"}}, "stirring": {"type": "CUSTOM", "details": "The resulting mixture was stirred at room temperature for 2 hours"}, "conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "The peak corresponding to the desired product was collected", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "desired product"}], "reaction_role": "WORKUP"}]}}, {"type": "CONCENTRATION", "details": "concentrated"}, {"type": "CUSTOM", "details": "freeze dried"}], "outcomes": [{"reaction_time": {"value": 2.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "(7R)-1-acetyl-N-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-1-azaspiro[4.4]nonane-7-carboxamide"}], "measurements": [{"type": "AMOUNT", "details": "AMOUNT", "amount": {"moles": {"value": 0.011, "units": "MILLIMOLE"}}}, {"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 6.0, "units": "MILLIGRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 42.5}}, {"type": "YIELD", "details": "CALCULATEDPERCENTYIELD", "percentage": {"value": 40.7}}], "texture": {"type": "CUSTOM", "details": "solid"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: N-methyl formanilide, 20.5 ml (166 mmole), was chilled to 13°, where it began to solidify. Phosphorus oxychloride, 14.4 ml (155 mmole), was added with stirring, under nitrogen. After 25 minutes, the temperature was 45°. 3,5-Dimethyl-allyloxy benzene, 16.2 g (100 mmole), prepared as describe above, was added with stirring and heated in a 70° C. oil bath. The reaction exothermed to 93° C. and was stirred under nitrogen for 30 minutes. The bath was removed and when the temperature reached 35°, the product was dissolved in chloroform. Ice was added, the layers were separated and washed once with water, twice with sodium bicarbonate, once with water and once with brine. The product was chromatographed down 500 ml of silica, eluting with chloroform to give 9.67 g (51%) of subtitled product which was used without further purification. ### ORD JSON:

{"inputs": {"m1": {"components": [{"identifiers": [{"type": "NAME", "value": "N-methyl formanilide"}], "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "Phosphorus oxychloride"}], "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "3,5-Dimethyl-allyloxy benzene"}], "reaction_role": "REACTANT"}]}}, "conditions": {"temperature": {"setpoint": {"value": 70.0, "units": "CELSIUS"}}, "stirring": {"type": "CUSTOM", "details": "with stirring, under nitrogen"}, "conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "was 45\u00b0"}, {"type": "ADDITION", "details": "was added"}, {"type": "STIRRING", "details": "with stirring"}, {"type": "CUSTOM", "details": "exothermed to 93\u00b0 C.", "temperature": {"setpoint": {"value": 93.0, "units": "CELSIUS"}}}, {"type": "STIRRING", "details": "was stirred under nitrogen for 30 minutes", "duration": {"value": 30.0, "units": "MINUTE"}}, {"type": "CUSTOM", "details": "The bath was removed"}, {"type": "CUSTOM", "details": "reached 35\u00b0"}, {"type": "DISSOLUTION", "details": "the product was dissolved in chloroform", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "chloroform"}], "reaction_role": "WORKUP"}]}}, {"type": "ADDITION", "details": "Ice was added"}, {"type": "CUSTOM", "details": "the layers were separated"}, {"type": "WASH", "details": "washed once with water, twice with sodium bicarbonate, once with water and once with 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": "CUSTOM", "details": "The product was chromatographed down 500 ml of silica"}, {"type": "WASH", "details": "eluting with chloroform", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "chloroform"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"reaction_time": {"value": 25.0, "units": "MINUTE"}, "products": [{"identifiers": [{"type": "NAME", "value": "subtitled product"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 9.67, "units": "GRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 51.0}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: Boron tribromide (73.1 ml, 1.0 M solution in DCM) was added dropwise to a solution of methyl 4-methoxyindole-carboxylate (5 g) in DCM (200 ml) cooled to −78° C. under argon. The reaction was allowed to warm to room temperature then partitioned between dichloromethane and saturated aqueous sodium hydrogen carbonate solution. Combined organic extracts were dried (MgSO4) and concentrated in vacuo and the residue purified by column chromatography using isohexane-50% ethyl acetate as eluent to give the end product as a yellow solid (2.98 g, 64%); NMR δ (CD3SOCD3) 3.82 (s, 3H), 6.36 (d, 1H), 6.85 (d, 1H), 7.02 (t, 1H), 7.17 (d, 11H), 9.66 (s, 1H), 11.72 (bs, 11H); M/z (+) 192 (MH+). ### ORD JSON:

{"inputs": {"m1_m2_m3": {"components": [{"identifiers": [{"type": "NAME", "value": "Boron tribromide"}], "amount": {"volume": {"value": 73.1, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "methyl 4-methoxyindole-carboxylate"}], "amount": {"mass": {"value": 5.0, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "DCM"}], "amount": {"volume": {"value": 200.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"temperature": {"setpoint": {"value": -78.0, "units": "CELSIUS"}}, "conditions_are_dynamic": true}, "workups": [{"type": "TEMPERATURE", "details": "to warm to room temperature", "temperature": {"control": {"type": "AMBIENT"}}}, {"type": "CUSTOM", "details": "then partitioned between dichloromethane and saturated aqueous sodium hydrogen carbonate solution", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "dichloromethane"}], "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "sodium hydrogen carbonate"}], "reaction_role": "WORKUP"}]}}, {"type": "DRY_WITH_MATERIAL", "details": "Combined organic extracts were dried (MgSO4)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "MgSO4"}], "reaction_role": "WORKUP"}]}}, {"type": "CONCENTRATION", "details": "concentrated in vacuo"}, {"type": "CUSTOM", "details": "the residue purified by column chromatography"}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "product"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 2.98, "units": "GRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 64.0}}, {"type": "YIELD", "details": "CALCULATEDPERCENTYIELD", "percentage": {"value": 64.0}}], "isolated_color": "yellow", "texture": {"type": "CUSTOM", "details": "solid"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: To 1.50 g of 4-nitrophenyl (7-isopropoxycarbonyl-6-methyl-2,3,5,6-tetrahydropyrrolo[2,1-b]thiazol-3-ylidene)acetate, was added 40 ml of a 25% aqueous solution of dimethylamine and the mixture was stirred at room temperature for 3 days. 40 ml of water was added thereto and the precipitate thus formed was collected by filtration, washed with water and dissolved in chloroform. After drying and distilling off the solvent, the crude crystals thus obtained were recrystallized from a solvent mixture of ether and n-hexane. Thus 0.6 g of the title compound was obtained. ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "water"}], "amount": {"volume": {"value": 40.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m1_m2_m3": {"components": [{"identifiers": [{"type": "NAME", "value": "4-nitrophenyl (7-isopropoxycarbonyl-6-methyl-2,3,5,6-tetrahydropyrrolo[2,1-b]thiazol-3-ylidene)acetate"}], "amount": {"mass": {"value": 1.5, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "aqueous solution"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "dimethylamine"}], "reaction_role": "REACTANT"}]}}, "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": "the precipitate thus formed"}, {"type": "FILTRATION", "details": "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 chloroform", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "chloroform"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "After drying"}, {"type": "DISTILLATION", "details": "distilling off the solvent"}, {"type": "CUSTOM", "details": "the crude crystals thus obtained"}, {"type": "CUSTOM", "details": "were recrystallized from a solvent mixture of ether and n-hexane", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ether"}], "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "n-hexane"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"reaction_time": {"value": 3.0, "units": "DAY"}, "products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 0.6, "units": "GRAM"}}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: The title compound was prepared by reacting (S)—N-{3-[4-(4-oxo-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (1.0 mmol), 2-aminoethanethiol (1.0 mmol) and BF3. etherate (2.0 mmol) in tetrahydrofuran (10 ml) at a temperature 65° C. for 12 hours in 68% yield. ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "tetrahydrofuran"}], "amount": {"volume": {"value": 10.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m1": {"components": [{"identifiers": [{"type": "NAME", "value": "(S)\u2014N-{3-[4-(4-oxo-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide"}], "amount": {"moles": {"value": 1.0, "units": "MILLIMOLE"}}, "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "2-aminoethanethiol"}], "amount": {"moles": {"value": 1.0, "units": "MILLIMOLE"}}, "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "BF3"}], "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "measurements": [{"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 68.0}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: A mixture of 8-benzyloxy-3-(2-chloropyrimidin-4-yl)-imidazo[1,2-a]pyridine (0.19 g) and 4-amino-cyclohexanecarboxylic acid ethyl ester (0.29 g) in NMP (1 mL) was stirred at 100° C. for 1 h. The reaction mixture was cooled to RT, diluted with water, and the resulting solid separated, washed with water, and dried. The solid was titurated with hot EtOAc and filtered to provide 4-[4-(8-benzyloxy-imidazo[1,2-a]pyridine-3-yl)-pyrimidin-2-ylamino]-cyclohexanecarboxylic acid ethyl ester (compound 8, 0.25 g), which was used without further purification. ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "water"}], "reaction_role": "SOLVENT"}]}, "m1_m2_m3": {"components": [{"identifiers": [{"type": "NAME", "value": "8-benzyloxy-3-(2-chloropyrimidin-4-yl)-imidazo[1,2-a]pyridine"}], "amount": {"mass": {"value": 0.19, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "4-amino-cyclohexanecarboxylic acid ethyl ester"}], "amount": {"mass": {"value": 0.29, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "NMP"}], "amount": {"volume": {"value": 1.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"temperature": {"setpoint": {"value": 100.0, "units": "CELSIUS"}}, "stirring": {"type": "CUSTOM", "details": "was stirred at 100\u00b0 C. for 1 h"}, "conditions_are_dynamic": true}, "workups": [{"type": "TEMPERATURE", "details": "The reaction mixture was cooled to RT", "temperature": {"control": {"type": "AMBIENT"}}}, {"type": "CUSTOM", "details": "the resulting solid separated"}, {"type": "WASH", "details": "washed with water", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "water"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "dried"}, {"type": "FILTRATION", "details": "filtered"}], "outcomes": [{"reaction_time": {"value": 1.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "4-[4-(8-benzyloxy-imidazo[1,2-a]pyridine-3-yl)-pyrimidin-2-ylamino]-cyclohexanecarboxylic acid ethyl ester"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 0.25, "units": "GRAM"}}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: 1-(5-fluoropyridin-2-yl)cyclopropanecarbonitrile (880 mg) was dissolved in ethanol (10 ml) before slow, dropwise addition of 96% sulfuric acid (10 ml). The reaction mixture was allowed to stir at 60° C. for 24 hr. Upon cooling, NaHCO3 was added until pH 8 and then the solution extracted three times with ethyl acetate, the organics were washed with brine and dried over Na2SO4 before concentration in vacuo. ### ORD JSON:

{"inputs": {"m1_m4": {"components": [{"identifiers": [{"type": "NAME", "value": "1-(5-fluoropyridin-2-yl)cyclopropanecarbonitrile"}], "amount": {"mass": {"value": 880.0, "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": "sulfuric acid"}], "amount": {"volume": {"value": 10.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "NaHCO3"}], "reaction_role": "REACTANT"}]}}, "conditions": {"temperature": {"setpoint": {"value": 60.0, "units": "CELSIUS"}}, "stirring": {"type": "CUSTOM", "details": "to stir at 60\u00b0 C. for 24 hr"}, "conditions_are_dynamic": true}, "workups": [{"type": "TEMPERATURE", "details": "Upon cooling"}, {"type": "EXTRACTION", "details": "the solution extracted three times with ethyl acetate", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl acetate"}], "reaction_role": "WORKUP"}]}}, {"type": "WASH", "details": "the organics were washed with brine", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "brine"}], "reaction_role": "WORKUP"}]}}, {"type": "DRY_WITH_MATERIAL", "details": "dried over Na2SO4 before concentration in vacuo", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "Na2SO4"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"reaction_time": {"value": 24.0, "units": "HOUR"}, "products": [{}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: A glass microwave reaction vessel was charged with 3-bromo-5-chloro-N-(5-fluoro-6-methoxypyridin-3-yl)pyrazin-2-amine (216 mg, 0.648 mmol,), 2-methyl-4-(methylthio)-6-(tributylstannyl)pyrimidine (334 mg, 0.777 mmol), copper (I) iodide (25 mg, 0.130 mmol, Aldrich, St. Louis, Mo.), cesium fluoride (197 mg, 1.295 mmol, Alfa Aesar) and tetrakis(triphenylphosphine)palladium (74.8 mg, 0.065 mmol, Strem) in dioxane (3 mL). The reaction mixture was stirred and heated in a Emrys Optimizer microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 140° C. for 30 min. The reaction mixture was diluted with water (5 mL) and extracted with CH2Cl2 (2×30 mL). The combined organic extracts were washed with saturated NaCl (5 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as a yellow solid. The crude product was purified by silica gel chromatography, eluting with 5% EtOAc/CH2Cl2 to give 5-chloro-N-(5-fluoro-6-methoxypyridin-3-yl)-3-(2-methyl-6-(methylthio)pyrimidin-4-yl)pyrazin-2-amine (176 mg, 0.448 mmol, 69.2% yield). 1H NMR (300 MHz, CDCl3) δ 2.63 (s, 3H) 2.79 (s, 3H) 4.04 (s, 3H) 8.01-8.29 (m, 4H) 12.45 (s, 1H). m/z (ESI, +ve ion) 393.0 (M+H)+. ### ORD JSON:

{"inputs": {"m1_m2_m6_m3_m7_m4": {"components": [{"identifiers": [{"type": "NAME", "value": "3-bromo-5-chloro-N-(5-fluoro-6-methoxypyridin-3-yl)pyrazin-2-amine"}], "amount": {"mass": {"value": 216.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "2-methyl-4-(methylthio)-6-(tributylstannyl)pyrimidine"}], "amount": {"mass": {"value": 334.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "cesium fluoride"}], "amount": {"mass": {"value": 197.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "dioxane"}], "amount": {"volume": {"value": 3.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}, {"identifiers": [{"type": "NAME", "value": "copper (I) iodide"}], "amount": {"mass": {"value": 25.0, "units": "MILLIGRAM"}}, "reaction_role": "CATALYST"}, {"identifiers": [{"type": "NAME", "value": "tetrakis(triphenylphosphine)palladium"}], "amount": {"mass": {"value": 74.8, "units": "MILLIGRAM"}}, "reaction_role": "CATALYST"}]}, "m5": {"components": [{"identifiers": [{"type": "NAME", "value": "water"}], "amount": {"volume": {"value": 5.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"temperature": {"setpoint": {"value": 140.0, "units": "CELSIUS"}}, "stirring": {"type": "CUSTOM", "details": "The reaction mixture was stirred"}, "conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "A glass microwave reaction vessel"}, {"type": "EXTRACTION", "details": "extracted with CH2Cl2 (2\u00d730 mL)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "CH2Cl2"}], "amount": {"volume": {"value": 30.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}]}}, {"type": "WASH", "details": "The combined organic extracts were washed with saturated NaCl (5 mL)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "NaCl"}], "amount": {"volume": {"value": 5.0, "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": "The solution was filtered"}, {"type": "CONCENTRATION", "details": "concentrated in vacuo"}, {"type": "CUSTOM", "details": "to give the crude material as a yellow solid", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "crude material"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "The crude product was purified by silica gel chromatography", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "crude product"}], "reaction_role": "WORKUP"}]}}, {"type": "WASH", "details": "eluting with 5% EtOAc/CH2Cl2", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "EtOAc CH2Cl2"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "5-chloro-N-(5-fluoro-6-methoxypyridin-3-yl)-3-(2-methyl-6-(methylthio)pyrimidin-4-yl)pyrazin-2-amine"}], "measurements": [{"type": "AMOUNT", "details": "AMOUNT", "amount": {"moles": {"value": 0.448, "units": "MILLIMOLE"}}}, {"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 176.0, "units": "MILLIGRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 69.2}}, {"type": "YIELD", "details": "CALCULATEDPERCENTYIELD", "percentage": {"value": 69.1}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: Prepared analogously to Example 4 from 7-chloro-6-hydroxy-4,4-dimethyl-4H-3,1-benzoxazin-2-one and 4-(4-methylphenylmercapto)-butylchloride. ### ORD JSON:

{"inputs": {"m1_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "7-chloro-6-hydroxy-4,4-dimethyl-4H-3,1-benzoxazin-2-one"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "4-(4-methylphenylmercapto)-butylchloride"}], "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "outcomes": [{"products": [{}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: A solution of 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2,5-trimethylhexanoyl fluoride (1.65 g, 4.23 mmol) in anhydrous THF (30 mL) at −78° C. was bubbled NH3 (g) for 10 minutes. The reaction mixture was sealed and stirred at −78° C. for 15 min and at rt for 1 hr. Water (100 mL) was added, the reaction mixture was extracted with ethyl acetate (100 mL), dried (Na2SO4), and concentrated to give 1.62 g (100% yield) of 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2,5-trimethylhexanamide, the NMR spectrum of which was consistent with the desired structure. ### ORD JSON:

{"inputs": {"m1_m4_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2,5-trimethylhexanoyl fluoride"}], "amount": {"mass": {"value": 1.65, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "NH3"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "THF"}], "amount": {"volume": {"value": 30.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "Water"}], "amount": {"volume": {"value": 100.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"temperature": {"control": {"type": "AMBIENT"}, "setpoint": {"value": -78.0, "units": "CELSIUS"}}, "stirring": {"type": "CUSTOM", "details": "stirred at \u221278\u00b0 C. for 15 min and at rt for 1 hr"}, "conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "The reaction mixture was sealed"}, {"type": "EXTRACTION", "details": "the reaction mixture 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": "DRY_WITH_MATERIAL", "details": "dried (Na2SO4)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "Na2SO4"}], "reaction_role": "WORKUP"}]}}, {"type": "CONCENTRATION", "details": "concentrated"}], "outcomes": [{"reaction_time": {"value": 1.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2,5-trimethylhexanamide"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 1.62, "units": "GRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 100.0}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: (S)-2-(Quinazolin-4-ylaminomethyl)-piperidine-1-carboxylic acid tert butyl ester (1.2 g) was dissolved in trifluoroacetic acid (60 ml) and stirred at room temperature for 2 hours. The solution was then evaporated and the residue chromatographed over silica gel, eluting with 0 to 10% (9:1 methanol-concentrated ammonia solution) in dichloromethane. The title compound was obtained as a white foam (0.84 g), MH+ 243. ### ORD JSON:

{"inputs": {"m2_m3": {"components": [{"identifiers": [{"type": "NAME", "value": "(S)-2-(Quinazolin-4-ylaminomethyl)-piperidine-1-carboxylic acid tert butyl ester"}], "amount": {"mass": {"value": 1.2, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "trifluoroacetic acid"}], "amount": {"volume": {"value": 60.0, "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": "The solution was then evaporated"}, {"type": "CUSTOM", "details": "the residue chromatographed over silica gel"}, {"type": "WASH", "details": "eluting with 0 to 10% (9:1 methanol-concentrated ammonia solution) in dichloromethane", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "methanol"}], "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "dichloromethane"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"reaction_time": {"value": 2.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "reaction_role": "PRODUCT"}, {"identifiers": [{"type": "NAME", "value": "foam"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 0.84, "units": "GRAM"}}}], "texture": {"type": "FOAM", "details": "foam"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: 1.03 g (5.5 mmol) of 6-O-acetylglucal are taken up in about 2-5 ml of dimethoxyethane and 10 ml of vinyl chloroacetate and stirred with 1 g of lipase P (Amano) at room temperature for about 2-3 h. Filtering off the enzyme, concentration of the solution and chromatography on silica gel (ether/hexane 1:2) result in 6-O-acetyl-3-O-chloroacetyl-glucal in 80-85% yield. ### ORD JSON:

{"inputs": {"m1": {"components": [{"identifiers": [{"type": "NAME", "value": "6-O-acetylglucal"}], "amount": {"mass": {"value": 1.03, "units": "GRAM"}}, "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "vinyl chloroacetate"}], "amount": {"volume": {"value": 10.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "dimethoxyethane"}], "amount": {"volume": {"value": 3.5, "precision": 1.5, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "FILTRATION", "details": "Filtering off the enzyme, concentration of the solution and chromatography on silica gel (ether/hexane 1:2)"}, {"type": "CUSTOM", "details": "result in 6-O-acetyl-3-O-chloroacetyl-glucal in 80-85% yield", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "6-O-acetyl-3-O-chloroacetyl-glucal"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "6-O-acetyl-3-O-chloroacetyl-glucal"}], "measurements": [{"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 80.0}}]}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: A solution of 2-chloroethyl N-(4-octylphenyl)sulfamoylcarbamate (156 mg, 0.4 mmol) in CH3CN (10 mL) was treated with Et3N (0.14 mL, 1 mmol) and refluxed for 25 min. and cooled. A solution of 2-(3-amino-1-methylpiperidin-3-yl)acetate (62 mg, 0.33 mmol) was added and the resulting mixture was refluxed for 4 h. After removal of the solvent in vacuo, the residue was dissolved in dichloromethane (40 mL) and washed with sat. NaHCO3 (10 mL), H2O (10 mL), brine (10 mL) and dried (Na2SO4). After evaporation, the residue was purified by flash chromatography (EtOAc/hex 1:4 to EtOAc) to give the title compound (41 mg, 27%) as colorless oil. MS ESI 454.3[M+H]+, calcd for [C23H39N3O4S+H]+ 454.27. ### ORD JSON:

{"inputs": {"m1_m4_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "2-chloroethyl N-(4-octylphenyl)sulfamoylcarbamate"}], "amount": {"mass": {"value": 156.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "Et3N"}], "amount": {"volume": {"value": 0.14, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "CH3CN"}], "amount": {"volume": {"value": 10.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "2-(3-amino-1-methylpiperidin-3-yl)acetate"}], "amount": {"mass": {"value": 62.0, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "TEMPERATURE", "details": "refluxed for 25 min.", "duration": {"value": 25.0, "units": "MINUTE"}}, {"type": "TEMPERATURE", "details": "cooled"}, {"type": "TEMPERATURE", "details": "the resulting mixture was refluxed for 4 h", "duration": {"value": 4.0, "units": "HOUR"}}, {"type": "CUSTOM", "details": "After removal of the solvent in vacuo"}, {"type": "DISSOLUTION", "details": "the residue was dissolved in dichloromethane (40 mL)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "dichloromethane"}], "amount": {"volume": {"value": 40.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}]}}, {"type": "WASH", "details": "washed with sat. NaHCO3 (10 mL), H2O (10 mL), brine (10 mL)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "NaHCO3"}], "amount": {"volume": {"value": 10.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "H2O"}], "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 (Na2SO4)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "Na2SO4"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "After evaporation"}, {"type": "CUSTOM", "details": "the residue was purified by flash chromatography (EtOAc/hex 1:4 to EtOAc)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "EtOAc"}], "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "EtOAc"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 41.0, "units": "MILLIGRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 27.0}}, {"type": "YIELD", "details": "CALCULATEDPERCENTYIELD", "percentage": {"value": 27.4}}], "isolated_color": "colorless", "texture": {"type": "OIL", "details": "oil"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: A solution of L-leucyl-L-phenylalanine N-methylamide (1.3 g) in dichloromethane (13 ml) was treated with N-bromomethylphthalimide (1.17 g) and sodium iodide (0.06 g). The resulting yellow solution was stirred at room temperature for 16 h. The solution was treated with saturated sodium bicarbonate solution (ca. 8 ml) and extracted with dichloromethane. The crude, organic extracts were preadsorbed onto silica gel and purified by flash silica chromatography, eluting with ethyl acetate/heptane (5:1), to furnish the title compound as a white solid (0.74 g). ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "sodium bicarbonate"}], "amount": {"volume": {"value": 8.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}, "m1_m5_m2_m3": {"components": [{"identifiers": [{"type": "NAME", "value": "L-leucyl-L-phenylalanine N-methylamide"}], "amount": {"mass": {"value": 1.3, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "N-bromomethylphthalimide"}], "amount": {"mass": {"value": 1.17, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "sodium iodide"}], "amount": {"mass": {"value": 0.06, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "dichloromethane"}], "amount": {"volume": {"value": 13.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}}, "conditions": {"temperature": {"control": {"type": "AMBIENT"}}, "stirring": {"type": "CUSTOM", "details": "The resulting yellow solution was stirred at room temperature for 16 h"}, "conditions_are_dynamic": true}, "workups": [{"type": "EXTRACTION", "details": "extracted with dichloromethane", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "dichloromethane"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "purified by flash silica chromatography"}, {"type": "WASH", "details": "eluting with ethyl acetate/heptane (5:1)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl acetate heptane"}], "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": 0.74, "units": "GRAM"}}}], "isolated_color": "white", "texture": {"type": "CUSTOM", "details": "solid"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: 6,7-Methylenedioxy-4-quinolone (5.0 g, 26.5 mmol) was boiled in POCl3 (75 mL) for 45 min and then cooled. Excess phospohoryl chloride was removed under reduced pressure and ice water (100 mL) was added to hydrolyze any residual phosphoryl chloride. The mixture was basified (pH 9) with ammonium hydroxide, and the solid precipitate was filtered. This material was extracted into ethyl ether (8×100 mL), and the ether solution was dried (MgSO4) and evaporated to provide 4.55 g as a white solid, in 83%; mp 127.5-128° C. (lit. mp 129° C.); 1H NMR (CDCl3) δ 6.15 (s, 2H), 7.35 (d, 1H, J=4.7), 7.39 (s, 1H), 7.49 (s, 1H), 8.56 (d, 1H, J=4.7); 13C NMR (CDCl3) δ 99.8, 102.2, 106.1, 119.9, 123.7, 129.8, 141.2, 147.7, 149.1, 151.4. ### ORD JSON:

{"inputs": {"m1_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "6,7-Methylenedioxy-4-quinolone"}], "amount": {"mass": {"value": 5.0, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "POCl3"}], "amount": {"volume": {"value": 75.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "TEMPERATURE", "details": "cooled"}, {"type": "CUSTOM", "details": "Excess phospohoryl chloride was removed under reduced pressure and ice water (100 mL)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "chloride"}], "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "ice water"}], "amount": {"volume": {"value": 100.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}]}}, {"type": "ADDITION", "details": "was added"}, {"type": "FILTRATION", "details": "the solid precipitate was filtered"}, {"type": "EXTRACTION", "details": "This material was extracted into ethyl ether (8\u00d7100 mL)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl ether"}], "amount": {"volume": {"value": 100.0, "units": "MILLILITER"}}, "reaction_role": "WORKUP"}]}}, {"type": "DRY_WITH_MATERIAL", "details": "the ether solution was dried (MgSO4)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "ether"}], "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "MgSO4"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "evaporated"}, {"type": "CUSTOM", "details": "to provide 4.55 g as a white solid"}], "outcomes": [{"products": [{}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: The title compound was prepared in similar fashion from (S)-(+)-4-(oxiranylmethoxy)-1H-indole and 3,4-dihydro-2-oxospiro[naphthalene-1(2H),4′-piperidine]. The resulting free base was dissolved in ethyl acetate, and precipitated with one equivalent of oxalic acid in ethyl acetate in 68% overall yield. FDMS m/e=404 (M+ of free base). α[D]589=−15.81 (c=0.51, methanol) ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "methanol"}], "reaction_role": "REACTANT"}]}, "m0_m1_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "(S)-(+)-4-(oxiranylmethoxy)-1H-indole"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "3,4-dihydro-2-oxospiro[naphthalene-1(2H),4\u2032-piperidine]"}], "reaction_role": "REACTANT"}]}, "m3_m6": {"components": [{"identifiers": [{"type": "NAME", "value": "oxalic acid"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "ethyl acetate"}], "reaction_role": "SOLVENT"}]}, "m5": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl acetate"}], "reaction_role": "SOLVENT"}]}}, "conditions": {"conditions_are_dynamic": true}, "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: A 4 N-hydrochloric acid-ethyl acetate solution (8.1 mL) was added to a chloroform (10 mL) solution of the compound (1.26 g, 3.24 mmol) synthesized in (3), and the mixture was stirred at room temperature for 13 hours. The reaction mixture was then concentrated under reduced pressure to obtain the title compound (1.15 g, 100%). ### ORD JSON:

{"inputs": {"m1_m4_m2": {"components": [{"identifiers": [{"type": "NAME", "value": "hydrochloric acid ethyl acetate"}], "amount": {"volume": {"value": 8.1, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "compound"}], "amount": {"mass": {"value": 1.26, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "chloroform"}], "amount": {"volume": {"value": 10.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "( 3 )"}], "reaction_role": "REACTANT"}]}}, "conditions": {"temperature": {"control": {"type": "AMBIENT"}}, "stirring": {"type": "CUSTOM", "details": "the mixture was stirred at room temperature for 13 hours"}, "conditions_are_dynamic": true}, "workups": [{"type": "CONCENTRATION", "details": "The reaction mixture was then concentrated under reduced pressure"}], "outcomes": [{"reaction_time": {"value": 13.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 1.15, "units": "GRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 100.0}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: 5-{3-(Cyanomethyl)-3-[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-N-[(1S)-1-cyclopropylethyl]pyrazine-2-carboxamide (0.23 g) was dissolved in a solution of trifluoroacetic acid (2 mL) and methylene chloride (2 mL). The mixture was stirred at room temperature for 2 h, and concentrated to dryness under reduced pressure. The residue was purified by flash chromatography on a silica gel column with methanol in methylene chloride (0-5%) to afford an intermediate which was dissolved in methanol (3.0 mL). To the solution was added ethylenediamine (1.0 mL). The mixture was stirred at room temperature for 2 h. The mixture was concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with methanol in methylene chloride (0-5%) to afford the desired product (0.13 g). LCMS (M+H)+: m/z=468.5. 1H NMR (500 MHz, DMSO-d6): δ 12.13 (s, 1H), 8.96 (s, 1H), 8.65 (d, J=1.3 Hz, 1H), 8.44 (s, 1H), 8.30 (d, J=5.5 Hz, 1H), 8.20 (d, J=8.7 Hz, 1H), 8.00 (d, J=1.3 Hz, 1H), 7.67-7.61 (m, 1H), 7.52 (d, J=5.5 Hz, 1H), 7.09-7.04 (m, 1H), 4.82 (d, J=9.7 Hz, 2H), 4.56 (d, J=9.7 Hz, 2H), 3.77 (s, 2H), 3.50-3.28 (m, 1H), 1.22 (d, J=6.7 Hz, 3H), 1.15-0.98 (m, 1H), 0.49-0.39 (m, 1H), 0.39-0.30 (m, 1H), 0.29-0.22 (m, 1H), 0.22-0.15 (m, 1H). ### ORD JSON:

{"inputs": {"m1_m3_m4": {"components": [{"identifiers": [{"type": "NAME", "value": "5-{3-(Cyanomethyl)-3-[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-N-[(1S)-1-cyclopropylethyl]pyrazine-2-carboxamide"}], "amount": {"mass": {"value": 0.23, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "trifluoroacetic acid"}], "amount": {"volume": {"value": 2.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}, {"identifiers": [{"type": "NAME", "value": "methylene chloride"}], "amount": {"volume": {"value": 2.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "ethylenediamine"}], "amount": {"volume": {"value": 1.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}, "m5": {"components": [{"identifiers": [{"type": "NAME", "value": "methanol"}], "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 2 h"}, "conditions_are_dynamic": true}, "workups": [{"type": "CONCENTRATION", "details": "concentrated to dryness under reduced pressure"}, {"type": "CUSTOM", "details": "The residue was purified by flash chromatography on a silica gel column with methanol in methylene chloride (0-5%)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "methanol"}], "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "methylene chloride"}], "reaction_role": "WORKUP"}]}}, {"type": "CUSTOM", "details": "to afford an intermediate which"}, {"type": "STIRRING", "details": "The mixture was stirred at room temperature for 2 h", "duration": {"value": 2.0, "units": "HOUR"}, "temperature": {"control": {"type": "AMBIENT"}}}, {"type": "CONCENTRATION", "details": "The mixture was concentrated under reduced pressure"}, {"type": "CUSTOM", "details": "The residue was purified by flash chromatography on a silica gel column with methanol in methylene chloride (0-5%)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "methanol"}], "reaction_role": "WORKUP"}, {"identifiers": [{"type": "NAME", "value": "methylene chloride"}], "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": 0.13, "units": "GRAM"}}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: The title compound is prepared as described in Example 1 for [4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-urea but using 1-(4-isothiocyanato-phenyl)-4-methyl-piperazine and stirring the reaction mixture at RT for 17 h. Title compound: ES-MS: 251.0 [M+H]+; major peak at tR=3.56 min (System 1); Rf=0.27 (CH2Cl2/MeOH, 80/20). ### ORD JSON:

{"inputs": {"m1": {"components": [{"identifiers": [{"type": "NAME", "value": "[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-urea"}], "reaction_role": "REACTANT"}]}, "m2": {"components": [{"identifiers": [{"type": "NAME", "value": "1-(4-isothiocyanato-phenyl)-4-methyl-piperazine"}], "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "CH2Cl2 MeOH"}], "reaction_role": "SOLVENT"}]}}, "conditions": {"temperature": {"control": {"type": "AMBIENT"}}, "stirring": {"type": "CUSTOM", "details": "stirring the reaction mixture at RT for 17 h"}, "conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "The title compound is prepared", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"reaction_time": {"value": 17.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "Title compound"}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: To a stirred solution of phosphorus oxychloride (7.0 mL, 75 mmole) in DMF (25 mL) was added dropwise a solution of 1,3-dimethylindole (12.0 g, 83 mmole) in dry DMF (6.0 mL). The reaction was stirred at RT for 2 hr then was poured onto ice. The mixture was basified with a solution of NaOH (13.2 g, 330 mmole) in H2O (44 mL), then was extracted with Et2O (2×50 mL). The combined organic layers were washed with brine, dried (MgSO4), and concentrated under vacuum. Flash chromatography on silica gel (10% ethyl acetate/hexanes) gave the tide compound (13.03 g, 91%) as an off-white solid: LCMS (ES) m/e 174.2 (M+H)+; 1H NMR (400 MHz, CDCl3) δ 10.16 (s, 1 H), 7.68 (d, J=8.1 Hz, 1 H), 7.42 (t, 1 H), 7.32 (d, J=8.5 Hz, 1 H), 7.15 (t, 1 H), 4.04 (s, 3 H), 2.63 (s, 3 H). ### ORD JSON:

{"inputs": {"m6": {"components": [{"identifiers": [{"type": "NAME", "value": "H2O"}], "amount": {"volume": {"value": 44.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m1_m4_m2_m5": {"components": [{"identifiers": [{"type": "NAME", "value": "phosphorus oxychloride"}], "amount": {"volume": {"value": 7.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "1,3-dimethylindole"}], "amount": {"mass": {"value": 12.0, "units": "GRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "DMF"}], "amount": {"volume": {"value": 25.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "DMF"}], "amount": {"volume": {"value": 6.0, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}, "m3": {"components": [{"identifiers": [{"type": "NAME", "value": "NaOH"}], "amount": {"mass": {"value": 13.2, "units": "GRAM"}}, "reaction_role": "REACTANT"}]}}, "conditions": {"temperature": {"control": {"type": "AMBIENT"}}, "stirring": {"type": "CUSTOM", "details": "The reaction was stirred at RT for 2 hr"}, "conditions_are_dynamic": true}, "workups": [{"type": "ADDITION", "details": "then was poured onto ice"}, {"type": "EXTRACTION", "details": "was extracted with Et2O (2\u00d750 mL)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "Et2O"}], "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 (MgSO4)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "MgSO4"}], "reaction_role": "WORKUP"}]}}, {"type": "CONCENTRATION", "details": "concentrated under vacuum"}], "outcomes": [{"reaction_time": {"value": 2.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "compound"}], "measurements": [{"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 13.03, "units": "GRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 91.0}}], "isolated_color": "off-white", "texture": {"type": "CUSTOM", "details": "solid"}, "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: After dissolving 4-(4-amino-3-chlorophenoxy)-6-cyano-7-(((2S)-3-(diethylamino)-2-hydroxypropyl)oxy)quinoline (78.6 mg, 0.18 mmol) in dimethylformamide (1 ml) under a nitrogen atmosphere, pyridine (0.022 ml, 0.27 mmol) and phenyl chloroformate (0.028 ml, 0.22 mmol) were added dropwise at room temperature, and the mixture was stirred for 1 hour. Cyclopropylamine (0.10 ml) was added dropwise, and the mixture was further stirred overnight. The reaction solution was distributed between ethyl acetate and saturated aqueous sodium bicarbonate, and the organic layer was washed with water and saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off, the residue was subjected to silica gel column chromatography (eluent—ethyl acetate), the fraction containing the target substance was concentrated, suspended in ethyl acetate and diluted with hexane, and the crystals were filtered out and blow-dried to obtain the title compound (37.8 mg, 0.072 mmol, 40.5%) as light yellow crystals. ### ORD JSON:

{"inputs": {"m4": {"components": [{"identifiers": [{"type": "NAME", "value": "Cyclopropylamine"}], "amount": {"volume": {"value": 0.1, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}, "m7": {"components": [{"identifiers": [{"type": "NAME", "value": "ethyl acetate"}], "reaction_role": "SOLVENT"}]}, "m2_m3": {"components": [{"identifiers": [{"type": "NAME", "value": "pyridine"}], "amount": {"volume": {"value": 0.022, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "phenyl chloroformate"}], "amount": {"volume": {"value": 0.028, "units": "MILLILITER"}}, "reaction_role": "REACTANT"}]}, "m1_m6": {"components": [{"identifiers": [{"type": "NAME", "value": "4-(4-amino-3-chlorophenoxy)-6-cyano-7-(((2S)-3-(diethylamino)-2-hydroxypropyl)oxy)quinoline"}], "amount": {"mass": {"value": 78.6, "units": "MILLIGRAM"}}, "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "dimethylformamide"}], "amount": {"volume": {"value": 1.0, "units": "MILLILITER"}}, "reaction_role": "SOLVENT"}]}, "m5": {"components": [{"identifiers": [{"type": "NAME", "value": "sodium bicarbonate"}], "reaction_role": "REACTANT"}]}}, "conditions": {"stirring": {"type": "CUSTOM", "details": "the mixture was stirred for 1 hour"}, "conditions_are_dynamic": true}, "workups": [{"type": "WAIT", "details": "the mixture was further stirred overnight", "duration": {"value": 8.0, "precision": 8.0, "units": "HOUR"}}, {"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 anhydrous sodium sulfate", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "sodium sulfate"}], "reaction_role": "WORKUP"}]}}, {"type": "DISTILLATION", "details": "The solvent was distilled off"}, {"type": "ADDITION", "details": "the fraction containing the target substance"}, {"type": "CONCENTRATION", "details": "was concentrated"}, {"type": "ADDITION", "details": "diluted with hexane", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "hexane"}], "reaction_role": "WORKUP"}]}}, {"type": "FILTRATION", "details": "the crystals were filtered out and"}, {"type": "CUSTOM", "details": "blow-dried"}], "outcomes": [{"reaction_time": {"value": 1.0, "units": "HOUR"}, "products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "measurements": [{"type": "AMOUNT", "details": "AMOUNT", "amount": {"moles": {"value": 0.072, "units": "MILLIMOLE"}}}, {"type": "AMOUNT", "details": "MASS", "amount": {"mass": {"value": 37.8, "units": "MILLIGRAM"}}}, {"type": "YIELD", "details": "PERCENTYIELD", "percentage": {"value": 40.5}}, {"type": "YIELD", "details": "CALCULATEDPERCENTYIELD", "percentage": {"value": 40.0}}], "reaction_role": "PRODUCT"}]}]}

Below is a description of an organic reaction. Extract information from it to an ORD JSON record. ### Procedure: The title compound was prepared by reaction of 3,4-difluoro-2-{2-fluoro-4-[4-(tetrahydro-2H-pyran-2-yloxy)-1-butynyl]anilino}benzoic acid with CDI and 2-(aminooxy)ethanol by the general procedure of Example 1, Step E, then purified by column chromatography on silica gel (50% EtOAc/PE as eluant) to give 3,4-difluoro-2-{2-fluoro-4-[4-(tetrahydro-2H-pyran-2-yloxy)-1-butynyl]anilino}-N-(2-hydroxyethoxy)benzamide as a viscous transparent oil which was immediately dissolved in EtOH and treated with 1 M HCl according to the general procedure of Example 10, Step D. Purification of the resulting oil was carried out by filtration through a plug of silica gel (EtOAc as eluant) to give 3,4-difluoro-2-[2-fluoro-4-(4-hydroxy-1-butynyl)anilino]-N-(2-hydroxyethoxy)benzamide as a pale yellow crystalline solid (51%); m.p. (EtOAc/Et2O) 126–129° C. 1H NMR [400 MHz, (CD3)2SO] δ 11.82 (br s, 1 H), 8.85 (br s, 1 H), 7.45–7.39 (m, 1 H), 7.25–7.17 (m, 2H), 7.07 (dd, J=8.3, 1.4 Hz, 1 H), 6.78 (dd, J=8.8, 8.8, 4.7 Hz, 1 H), 4.88 (t, J=5.6 Hz, 1 H), 4.73 (br s, 1 H), 3.85 (t, J=4.8 Hz, 2 H), 3.59–3.53 (m, 4 H), 2.53 (t, J=6.9 Hz, 1 H). Anal. calcd. for C19H17F3N2O4.0.25Et2O: C, 58.2; H, 4.8; N, 6.8. Found C, 58.1; H, 4.8; N, 7.1. ### ORD JSON:

{"inputs": {"m0_m2_m3_m4": {"components": [{"identifiers": [{"type": "NAME", "value": "3,4-difluoro-2-{2-fluoro-4-[4-(tetrahydro-2H-pyran-2-yloxy)-1-butynyl]anilino}benzoic acid"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "CDI"}], "reaction_role": "REACTANT"}, {"identifiers": [{"type": "NAME", "value": "2-(aminooxy)ethanol"}], "reaction_role": "REACTANT"}]}}, "conditions": {"conditions_are_dynamic": true}, "workups": [{"type": "CUSTOM", "details": "purified by column chromatography on silica gel (50% EtOAc/PE as eluant)", "input": {"components": [{"identifiers": [{"type": "NAME", "value": "EtOAc"}], "reaction_role": "WORKUP"}]}}], "outcomes": [{"products": [{"identifiers": [{"type": "NAME", "value": "title compound"}], "reaction_role": "PRODUCT"}, {"identifiers": [{"type": "NAME", "value": "3,4-difluoro-2-{2-fluoro-4-[4-(tetrahydro-2H-pyran-2-yloxy)-1-butynyl]anilino}-N-(2-hydroxyethoxy)benzamide"}], "isolated_color": "viscous transparent", "texture": {"type": "OIL", "details": "oil"}, "reaction_role": "PRODUCT"}]}]}