Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]([OH:29])[CH2:9][NH:10][CH:11]([CH3:28])[CH2:12][C:13]2[CH:27]=[CH:26][C:16]3[O:17][C:18]([C:23]([OH:25])=[O:24])([C:20]([OH:22])=[O:21])[O:19][C:15]=3[CH:14]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:30][CH:31]([CH3:36])[CH2:32][CH2:33][CH2:34]O.Cl.[K+].[Br-]>C(Cl)(Cl)Cl>[CH3:30][CH:31]([CH3:36])[CH2:32][CH2:33][CH2:34][O:24][C:23]([C:18]1([C:20]([O:22][CH2:7][CH2:2][CH2:3][CH:4]([CH3:8])[CH3:5])=[O:21])[O:17][C:16]2[CH:26]=[CH:27][C:13]([CH2:12][CH:11]([NH:10][CH2:9][CH:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=3)[OH:29])[CH3:28])=[CH:14][C:15]=2[O:19]1)=[O:25]
Reactant: CC(Cc1ccc2c(c1)OC(C(=O)O)(C(=O)O)O2)NCC(O)c1cccc(Cl)c1
Reactant: CC(C)CCCO
Agent: Cl
Agent: [Br-]
Agent: [K+]
Solvent: ClC(Cl)Cl
Product: CC(C)CCCOC(=O)C1(C(=O)OCCCC(C)C)Oc2ccc(CC(C)NCC(O)c3cccc(Cl)c3)cc2O1

Procedure:
The title compound was prepared from 5-{2-[2-(3-chloro-phenyl)-2-hydroxy-ethylamino]-propyl}-benzo[1,3]dioxole-2,2-dicarboxylic acid and 4-methylpentanol according to the procedure of Example 30 as a colorless gum (HCl salt); 1H NMR (CDCl3) δ 0.87 (d, J=6.5 Hz, 12H), 1.33 (bs, 3H), 1.10-2.0 (m, 10H), 2.80 (bs, 1H), 3.18 (bs, 2H), 3.48 (bs, 2H), 4.28(m, 4H), 5.60 (bs, 2H), 6.80 (m, 3H), 7.25 (m, 2H), 7.43 (s, 1H), 8.70 (bs, 1H), 10.10 (bs, 1H); IR (KBr): 1765 cm-1 (C=O); MS (CI) m/z 590 (MH+); [α]D25 -24° (c, 1.0, CHCl3). Anal. Calcd. for C32H44ClNO7HCl: C, 61.34; H, 7.08; N, 2.24; Cl, 11.32. Found: C, 60.50; H, 7.36; N, 2.13; Cl, 11.66.
Reaction SMILES: [SH:1][C:2]([CH3:14])([CH3:13])[CH2:3][NH:4][CH2:5][CH2:6][NH:7][CH2:8][C:9]([CH3:12])([SH:11])[CH3:10].N.[CH3:16][O:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22]Cl)=[CH:20][CH:19]=1.Cl>CO>[CH3:16][O:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22][S:1][C:2]([CH3:14])([CH3:13])[CH2:3][NH:4][CH2:5][CH2:6][NH:7][CH2:8][C:9]([CH3:12])([S:11][CH2:22][C:21]2[CH:24]=[CH:25][C:18]([O:17][CH3:16])=[CH:19][CH:20]=2)[CH3:10])=[CH:20][CH:19]=1
Reactant: CC(C)(S)CNCCNCC(C)(C)S
Reactant: COc1ccc(CCl)cc1
Agent: Cl
Agent: N
Solvent: CO
Product: COc1ccc(CSC(C)(C)CNCCNCC(C)(C)SCc2ccc(OC)cc2)cc1
Temperature: 25 °C
Yield: 81.8 %

Procedure:
A solution of N,N'-bis(2-mercapto-2-methylpropyl)ethylene diamine (11.23 g, 47.5 mmol; see, DiZio et al., 1991, Bioconjugate Chem 2: 353 and Corbin et al., 1976, J. Org. Chem. 41: 489) in methanol (500 mL) was cooled in ice/water bath and then saturated with gaseous ammonia over 45 min. To this was added 4-methoxybenzyl chloride (17.0 mL, 125 mmol, 264 mol %). The reaction was allowed to warm to room temperature overnight with stirring under argon. The solution was concentrated to a paste and then partitioned between diethyl ether (150 mL)and 0.5M KOH (200 mL). The aqueous layer was further extracted with diethyl ether (2×50 mL). The combined organic layers were washed with NaCl solution and concentrated to a clear colorless oil. The oil dissolved in diethyl ether (200 mL)and then acidified with 4.0M HCl in dioxane until no further precipitation was seen. The white precipitate was collected by filtration and washed with diethyl ether. The white solid was recrystallized from hot water at a pH of ~2. The product was collected by filtration to afford 29.94 g as a mix of mono- and di- HCl salts. The HCl salts were partitioned between 1M KOH (100 mL)and ethyl acetate (100 mL). The aqueous was extracted with ethyl acetate (2×30 mL)and the combined organic layers were washed with NaCl solution, dried with Na2SO4 and concentrated to give pure product as the free base as a light yellow oil (18.53 g, 82% yield). Nuclear magnetic resonance characterization experiments yielded the following molecular signature: 1H NMR (300 MHz, CDCL3): δ7.25 (d, 4H, J=9), 6.83 (d, 4H, J=9), 3.78 (s, 6H), 3.67 (s, 4H), 2.63 (s, 4H), 2.56 (s, 4H), 1.34 (s, 12H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([C:16]1[C:21]([N+:22]([O-])=O)=[CH:20][CH:19]=[C:18]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[N:17]=1)[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H][H]>[Pd].CO>[C:1]([O:5][C:6]([N:8]([C:16]1[C:21]([NH2:22])=[CH:20][CH:19]=[C:18]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[N:17]=1)[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: [H][H]
Reactant: CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)c1nc(-c2ccccc2)ccc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)c1nc(-c2ccccc2)ccc1N

Procedure:
A solution of di-tert-butyl(3-nitro-6-phenylpyridin-2-yl)imidodicarbonate (378 mg, 0.910 mmol) and MeOH (18.1 mL) was treated with 10% palladium on carbon (˜20 mg) and fitted with a hydrogen balloon. After 30 min the reaction was filtered through celite and concentrated to afford a residue which was used in the next reaction without purification. MS cal'd 386 (M+H)+, exp 386 (M+H)+.
Reaction SMILES: Cl.[Cl:2][CH2:3][CH2:4][C:5]1[C:10](=[O:11])[N:9]2[CH:12]=[CH:13][CH:14]=[C:15]([OH:16])[C:8]2=[N:7][C:6]=1[CH3:17].[H][H]>[C].[Pd].C(O)(=O)C>[Cl:2][CH2:3][CH2:4][C:5]1[C:10](=[O:11])[N:9]2[CH2:12][CH2:13][CH2:14][CH:15]([OH:16])[C:8]2=[N:7][C:6]=1[CH3:17]
Reactant: Cc1nc2c(O)cccn2c(=O)c1CCCl
Reactant: [H][H]
Agent: [Pd]
Agent: Cl
Solvent: CC(=O)O
Product: Cc1nc2n(c(=O)c1CCCl)CCCC2O
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A mixture of 3-(2-chloroethyl)-9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one hydrochloride (formula-5) (40 grams), acetic acid (200 ml) and palladium carbon (40 grams) was taken in an autoclave. Hydrogen gas with a pressure of 3.0-3.5 Kg/cm2 was applied to the above mixture at 35° C. for 6 hrs. The reaction was quenched with water and filtered the resultant mixture through a hyflow bed. The pH of the filtrate was adjusted to 6 using aqueous sodium hydroxide solution The reaction mixture was cooled to 0° C. and stirred for 1 hr. The solid formed was filtered, washed with water and dried to yield the title compound.
Reaction SMILES: [BH4-].[Na+].[Cl:3][CH2:4][CH2:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([C:14](=[O:16])[CH3:15])=[CH:10][C:9]=1[OH:17]>C(O)C.O1CCCC1>[Cl:3][CH2:4][CH2:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([CH:14]([CH3:15])[OH:16])=[CH:10][C:9]=1[OH:17]
Reactant: CC(=O)c1ccc(OCCCCl)c(O)c1
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCO
Product: CC(O)c1ccc(OCCCCl)c(O)c1
Temperature: 10 °C
Reaction time: 3 h
Yield: 54.6 %

Procedure:
To a flask charged with sodium borohydride (1.5 g, 39.4 mmol) under nitrogen and chilled to 10° C. was added, slowly, a solution of 1-[4-(3-chloropropoxy)-3-hydroxyphenyl]ethanone (6.0 g, 26.2 mmol) dissolved in ethanol-tetrahydrofuran (120 ml, 2:1). After total addition, the ice bath was removed and the reaction was stirred at ambient temperature for 3 hours. An additional amount of sodium borohydride (0.2 g, 5.3 mmol) was carefully added. After stirring at ambient temperature for one hour, the solvent was removed in vacuo. The resultant solid residue was diluted with water (100 ml) and left overnight. The product was isolated by vacuum filtration yielding 3.8 g. Two consecutive recrystallizations from toluene provided 3.3 g (55%) of 4-(3-chloropropoxy)-3-hydroxy-α-methylbenzene methanol as a light brown solid, m.p.=107°-109° C.
Reaction SMILES: [H-].[Na+].[F:3][C:4]1[CH:22]=[CH:21][C:7]([CH2:8][N:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12](=[O:19])[N:11]=[C:10]2[NH2:20])=[CH:6][CH:5]=1.[CH3:23]I>CC(N(C)C)=O>[F:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:8][N:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12](=[O:19])[N:11]([CH3:23])[C:10]2=[NH:20])=[CH:21][CH:22]=1
Reactant: Nc1nc(=O)c2ccccc2n1Cc1ccc(F)cc1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CC(=O)N(C)C
Product: Cn1c(=O)c2ccccc2n(Cc2ccc(F)cc2)c1=N
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a mixture of 570 mg. of sodium hydride in 50.0 ml. of dimethylacetamide is added 2.7 g. of 1-(4'-fluorobenzyl)-2-amino-quinazolin-4(1H)-one followed by stirring for one hour at room temperature. There is then added 3.0 g. of methyl iodide and the resulting solution is stirred for 18 hours at room temperature. The resulting mixture is then evaporated in vacuo to remove the solvent and the residue stripped twice with benzene. The resulting residue is poured over ice-water and the precipitate which forms (about 0.5 hour) is washed with water, dried by suction, dissolved in methylene chloride, treated with sodium sulfate, alumina and charcoal and then filtered through Celite. The solvent is exchanged for ether and concentration results in a precipitate which is recovered by filtering, washed with pentane and dried under reduced pressure to obtain 1-(4'-fluorobenzyl)-2-imino-3-methyl-2,3-dihydro-quinazolin-4(1H)-one, m.p. 135°-137°C.
Reaction SMILES: C([Li])CCC.[Cl:6][C:7]1[CH:8]=[CH:9][C:10]2[O:14][CH:13]=[C:12]([CH3:15])[C:11]=2[CH:16]=1.CN([CH:20]=[O:21])C>C1COCC1>[Cl:6][C:7]1[CH:8]=[CH:9][C:10]2[O:14][C:13]([CH:20]=[O:21])=[C:12]([CH3:15])[C:11]=2[CH:16]=1
Reactant: Cc1coc2ccc(Cl)cc12
Reactant: CN(C)C=O
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: Cc1c(C=O)oc2ccc(Cl)cc12
Temperature: -78 °C
Reaction time: 1 h
Yield: 95.9 %

Procedure:
n-Butyl lithium (2.5 M in hexane, 6.6 mmol, 2.6 mL) was added dropwise over 15 minutes to a solution of 5-chloro-3-methyl benzofuran (6.0 mmol, 1 g) in THF (8 mL) cooled to −78° C. To this was added DMF (12 mmol, 0.6 mL) and stirred for one hour. The reaction mixture was allowed to come to room temperature overnight and then quenched with EtOAc (20 mL) and H2O (10 mL). The organic portion, was collected, dried, filtered and the filtrate was evaporated to dryness to obtain 5-chloro-3-methyl benzofuran-2-carboxaldehyde (96%, 1.12 g), which was carried on without further purification.
Reaction SMILES: [C@@H:1]1([N:10]2[CH:15]=[C:14]3[CH:16]=[CH:17][C:18](=[O:20])[N:19]=[C:13]3[NH:12][C:11]2=[O:21])[O:7][C@H:6]([CH2:8][OH:9])[C@@H:4]([OH:5])[C@H:2]1[OH:3].P(Cl)(Cl)(Cl)=O.[CH2:27](OP(OCC)(OCC)=O)C>>[C@@H:1]1([N:10]2[CH:15]=[C:14]3[CH:16]=[CH:17][C:18](=[O:20])[N:19]([CH3:27])[C:13]3=[N:12][C:11]2=[O:21])[O:7][C@H:6]([CH2:8][OH:9])[C@@H:4]([OH:5])[C@H:2]1[OH:3]
Reactant: O=c1ccc2cn([C@@H]3O[C@H](CO)[C@@H](O)[C@H]3O)c(=O)[nH]c-2n1
Reactant: CCOP(=O)(OCC)OCC
Solvent: O=P(Cl)(Cl)Cl
Product: Cn1c(=O)ccc2cn([C@@H]3O[C@H](CO)[C@@H](O)[C@H]3O)c(=O)nc21
Temperature: 0 °C

Procedure:
A solution of 560 mg of 3-β-D deoxyribofuranosyl-2,7-dioxopyrido[2,3-d]pyrimidine (a) in 5 ml of triethylphosphate was cooled to 0° C. and 613 mg of phosphorus oxychloride was added thereto. After the mixture was made to undergo a reaction for 6 hours, 1 g of ice was added to effect a hydrolysis. The reaction mixture was concentrated at reduced pressure and the resulting residue was dissolved in 1 ml of distilled water. The purification of the product was carried out by column chromatography on DEAE-Sephadex A-25 (HCO3 -form) by use of a linear gradient of triethylammonium bicarbonate to obtain 575 mg of 3-(5'-O-phosphoryl-β-D-2'-deoxyribofuranosyl)-2,7-dioxopyrido[2,3-d]pyrimidine (b).
Reaction SMILES: [Cl:1][C:2]1[CH:21]=[CH:20][C:5]2[C:6](=[O:19])[NH:7][C:8]3[CH:18]=[CH:17][CH:16]=[N:15][C:9]=3[N:10]([C:11](=[O:14])[CH2:12]Cl)[C:4]=2[CH:3]=1.[CH3:22][CH2:23][N:24]([CH2:27][CH:28]1[NH:33][CH2:32][CH2:31][CH2:30][CH2:29]1)[CH2:25][CH3:26].C(N(CC)CC)C.[I-].[Na+]>CN(C)C=O>[Cl:1][C:2]1[CH:21]=[CH:20][C:5]2[C:6](=[O:19])[NH:7][C:8]3[CH:18]=[CH:17][CH:16]=[N:15][C:9]=3[N:10]([C:11](=[O:14])[CH2:12][N:33]3[CH2:32][CH2:31][CH2:30][CH2:29][CH:28]3[CH2:27][N:24]([CH2:25][CH3:26])[CH2:23][CH3:22])[C:4]=2[CH:3]=1
Reactant: O=C1Nc2cccnc2N(C(=O)CCl)c2cc(Cl)ccc21
Reactant: CCN(CC)CC1CCCCN1
Agent: [I-]
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCN(CC)CC1CCCCN1CC(=O)N1c2cc(Cl)ccc2C(=O)Nc2cccnc21
Temperature: 50 °C
Reaction time: 32 h

Procedure:
A mixture of 125 g (0.388 mole) of 9-chloro-11-(chloroacetyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]-benzodiazepin-6-one, 2480 ml of dry dimethyl formamide, 73.0 g (0.429 mole) of D,L-2-[(diethylamino)methyl]piperidine, 60 ml (0.429 mole) of anhydrous triethylamine and 3.0 g of sodium iodide was stirred at an internal temperature of 50° C. for 32 hours and then at room temperature for 15 hours. Insolubles were removed by filtration, and the filtrate was evaporated at the oil pump and at a bath temperature of 45° C. The remaining product was dissolved in 5% hydrochloric acid, and the solution was extracted by shaking twice with 50 ml of dichloromethane each time. The aqueous layer was made alkaline by addition of concentrated potassium carbonate solution, and the liberated base was taken up in dichloromethane, and the solution was treated with 2 g of active charcoal and dried over sodium sulphate. The dark oil remaining after the solvent had been removed by evaporation was purified by column chromatography on 800 g of silica gel (35-70 mesh) using dichloro- methane/methanol/ethyl acetate/cyclohexane/concentrated ammonia 59/7.5/25/7.5/1 (v/v) for elution. The fractions containing the compound which was sought (132 g) were dissolved in dilute aqueous maleic acid solution. The filtered solution was washed four times with 50 ml of ethyl acetate each time, and was then saturated with solid potassium carbonate and exhaustively extracted with dichloromethane. The combined dichloromethane phases were dried over sodium sulphate and evaporated, and 109 g of a partially crystallised oil remained. After recrystallisation twice from 450 ml of acetonitrile each time, using 2 g of active charcoal each time, 63.0 g (36% of theory) of colourless crystals of m.p. 167.5-169° C. were obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]2[CH2:13][CH2:12][S:11][NH:10][C@@H:9]2[C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)[CH:5]=[CH:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].I[CH:28]([CH3:30])[CH3:29]>CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]2[CH2:13][CH2:12][S:11][N:10]([CH:28]([CH3:30])[CH3:29])[C@@H:9]2[C:14]2[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: Clc1ccc([C@H]2NSCC[C@@H]2c2cccc(Cl)c2)cc1
Reactant: CC(C)I
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)N1SCC[C@H](c2cccc(Cl)c2)[C@H]1c1ccc(Cl)cc1
Temperature: 85 °C

Procedure:
To a solution of 1.21 g (3.40 mmol) of (3S,4R)-4-(3-chlorophenyl)-3-(4-chlorophenyl)-1,2-thiazinan (Example 117, Step C) in DMF (8.5 mL) was added cesium carbonate (4.31 g, 13.23 mmol), followed by 2-iodopropane (2.9 mL, 29.0 mmol). The resulting mixture was heated at 85° C. for 23 hours. After cooling to room temperature, the reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with sat. NaCl solution, dried over Na2SO4, filtered and the filtrate was concentrated. Purification by flash chromatography on silica gel (0 to 2% MeOH in DCM gradient) provided the title compound as a white solid.
Reaction SMILES: OS(O)(=O)=O.[NH2:6][C:7]1[CH:8]=[C:9]([OH:16])[C:10](=[CH:14][CH:15]=1)[C:11]([OH:13])=[O:12].[CH3:17]O>>[NH2:6][C:7]1[CH:8]=[C:9]([OH:16])[C:10](=[CH:14][CH:15]=1)[C:11]([O:13][CH3:17])=[O:12]
Reactant: CO
Reactant: Nc1ccc(C(=O)O)c(O)c1
Agent: O=S(=O)(O)O
Product: COC(=O)c1ccc(N)cc1O
Yield: 88 %

Procedure:
Absolute methanol (100 mL) and fresh concentrated H2SO4 are carefully combined in a 250 mL round botton flask with continuous stirring (exothermic). 4-Aminosalicylic acid (10.0 grams, 65.4 mmol) is added to produce a dark solution, which is heated under reflux for 6 hours. The product is allowed to cool and then concentrated on a rotary evaporator to approximately half the original volume. At this point a solid precipitate appears. The concentrate is poured into 400 mL of water, and the resulting suspension titrated to approximately pH 3, by stepwise addition of 5N NaOH (to pH 6.5), followed by solid Na2CO3, with evolution of CO2 gas. The concentrate was chilled on ice, and the resulting precipitate collected by filtration. The filtrate is washed with cold water, and then dried in vacuo over NaOH pellets, to afford 9.6 grams (88% yield) of methyl 4-aminosalicylate, a pale lavendar powder (m.p. 115°-117° C.). The structure was confirmed by 1H NMR spectrometry in d6 -acetone.
Reaction SMILES: [NH:1]1[C:5]([CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8])=[N:4][N:3]=[N:2]1.C(N(CC)CC)C.Br[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31]>C(#N)C>[CH2:31]([N:3]1[N:2]=[N:1][C:5]([CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8])=[N:4]1)[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH3:20]
Reactant: CCCCCCCCCCCCBr
Reactant: CCOC(=O)Cc1nnn[nH]1
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CCCCCCCCCCCCn1nnc(CC(=O)OCC)n1
Temperature: 24 °C
Yield: 49.5 %

Procedure:
The tetrazoleacetic acid, ethyl ester (50 g, 0.26 tool) obtained in (a) was suspended in acetonitrile (600 mL) and triethylamine (52.4 g, 0.52 tool)was added in one portion. The solution was heated at reflux for 5 minutes, cooled to 24° C., and then treated dropwise with 1-bromododecane (64.5 g, 0.26 mol). The solution was refluxed overnight, cooled, and the solvent concentrated in vacuo. The residue was triturated with ethyl acetate (300 mL), filtered, and the filtrate was washed with aqueous HCl (1M), brine, dried (MgSO4), and filtered. The filtrate was concentrated in vacuo leaving a viscous liquid. The 2-isomer was separated from the crude mixture using silica gel chromatography (elution with 25% EtOAc/75% hexane), isolating 2-dodecyltetrazoleacetic acid, ethyl ester (41.8 g, 49%) as a pale yellow liquid.
Reaction SMILES: [Cl:1][C:2]1[C:10]([Cl:11])=[C:9]2[C:5]([CH2:6][C:7]([CH2:16][CH:17]=[C:18](Cl)[CH3:19])([CH2:13][CH2:14][CH3:15])[C:8]2=[O:12])=[CH:4][C:3]=1[CH2:21][C:22]([OH:24])=[O:23].[OH:25]S(O)(=O)=O>C(Cl)Cl>[Cl:1][C:2]1[C:10]([Cl:11])=[C:9]2[C:5]([CH2:6][C:7]([CH2:16][CH2:17][C:18](=[O:25])[CH3:19])([CH2:13][CH2:14][CH3:15])[C:8]2=[O:12])=[CH:4][C:3]=1[CH2:21][C:22]([OH:24])=[O:23]
Reactant: O=S(=O)(O)O
Reactant: CCCC1(CC=C(C)Cl)Cc2cc(CC(=O)O)c(Cl)c(Cl)c2C1=O
Solvent: ClCCl
Product: CCCC1(CCC(C)=O)Cc2cc(CC(=O)O)c(Cl)c(Cl)c2C1=O
Reaction time: 1 h

Procedure:
[6,7-Dichloro-2-(3-chloro-2-butenyl)-2,3-dihydro-1-oxo-2-propyl-1H-inden-5-yl]acetic acid (6 g, 0.0154 mole) dissolved in methylene chloride (65 ml) was added with rapid stirring to a mixture of H2SO4 (75 ml) and methylene chloride (35 ml) chilled in an ice bath. After stirring 1 hour at ice bath temperature the mixture was poured over ice and extracted with diethyl ether. The ether extracts were washed with water, dried over MgSO4 and concentrated under vacuum. The residue was recrystallized from butyl chloride to obtain the product mp 137°-9°.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([N:12]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH2:34][CH2:35][N:36]3[CH2:40][CH2:39][CH2:38][CH2:37]3)=[CH:29][CH:28]=2)[CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20]C3CCCCO3)=[CH:16][CH:15]=2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.[ClH:41].O1CCOCC1>C(O)C>[ClH:41].[OH:20][C:17]1[CH:16]=[CH:15][C:14]([CH2:13][N:12]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH2:34][CH2:35][N:36]3[CH2:37][CH2:38][CH2:39][CH2:40]3)=[CH:29][CH:28]=2)[S:9]([C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)(=[O:10])=[O:11])=[CH:19][CH:18]=1
Reactant: COc1ccc(S(=O)(=O)N(Cc2ccc(OC3CCCCO3)cc2)c2ccc(OCCN3CCCC3)cc2)cc1
Agent: Cl
Solvent: C1COCCO1
Solvent: CCO
Product: COc1ccc(S(=O)(=O)N(Cc2ccc(O)cc2)c2ccc(OCCN3CCCC3)cc2)cc1
Temperature: 25 °C

Procedure:
4-Methoxy-N-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-N-[4-(tetrahydro-pyran-2-yloxy)-benzyl]-benzenesulfonamide (1.58 g, 2.79 mmol) was suspended in 3:1 ethanol:1N HCl (30 mL) and the solution was stirred at room temperature for 24 hr. The reaction mixture was quenched with sodium bicarbonate solution and the aqueous solution was washed with methylene chloride. The organic layer was dried (sodium sulfate), filtered, and concentrated to a white solid. The crude material was purified via Biotage® (A Dynax Corp., Charlottesville, Va.) chromatography using 10% methanol/methylene chloride as the eluant. The purified material was suspended in methanol (15 mL) and 4.0M HCl in dioxane (1.5 equiv.) was added. The mixture was stirred at room temperature and was concentrated to dryness to yield the title compound as the HCl salt. MS 483.1 (M+1)+
Reaction SMILES: [H-].[Na+].[Si:3]([O:10][CH2:11][CH2:12][N:13]([CH2:28][CH2:29][O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[C:14]1[CH:27]=[CH:26][C:17]([NH:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[CH:16][CH:15]=1)([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4].[CH2:38](Br)[CH:39]=[CH2:40].O>CN(C=O)C>[CH2:40]([N:18]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C:17]1[CH:16]=[CH:15][C:14]([N:13]([CH2:28][CH2:29][O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:32])[CH3:33])[CH2:12][CH2:11][O:10][Si:3]([C:6]([CH3:9])([CH3:7])[CH3:8])([CH3:5])[CH3:4])=[CH:27][CH:26]=1)[CH:39]=[CH2:38]
Reactant: CC(C)(C)OC(=O)Nc1ccc(N(CCO[Si](C)(C)C(C)(C)C)CCO[Si](C)(C)C(C)(C)C)cc1
Reactant: C=CCBr
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: C=CCN(C(=O)OC(C)(C)C)c1ccc(N(CCO[Si](C)(C)C(C)(C)C)CCO[Si](C)(C)C(C)(C)C)cc1
Temperature: 0 °C
Reaction time: 12 h

Procedure:
Sodium hydride (60% dispersion in mineral oil; 0.265 g) was added to a stirred solution of 4-[bis(2-tert-butyldimethylsilyloxyethyl)amino]-N-(tert-butoxycarbonyl)aniline (3.15 g) in DMF (20 ml) which had been cooled to 0° C. The resultant mixture was stirred at ambient temperature for 1 hour. Allyl bromide (0.625 ml) was added and the mixture was stirred at ambient temperature for 12 hours. Water (5 ml) was added and the mixture was partitioned between diethyl ether and water. The organic phase was dried (MgSO4) and evaporated to give N-allyl-4-[bis(2-tert-butyldimethylsilyloxyethyl)amino]-N-(tert-butoxycarbonyl)aniline (3.5g); NMR Spectrum: (CDCl3) 0.0 (s, 12H), 0.81 (s, 9H), 0.82 (s, 9H), 1.4 (s, 9H), 3.43 (t, 4H), 3.71 (t, 4H), 4.11 (d, 2H), 5.07 (m, 2H), 5.87 (m, 1H), 6.58 (d, 2H), 6.93 (d, 2H).
Reaction SMILES: C([O:4][C:5](=[O:21])[CH2:6][CH2:7][CH2:8][CH2:9][CH:10]([S:17][C:18](=[O:20])[CH3:19])[CH2:11][CH2:12][S:13][C:14](=[O:16])[CH3:15])(=O)C.O>CC(O)C>[C:18]([S:17][CH:10]([CH2:11][CH2:12][S:13][C:14](=[O:16])[CH3:15])[CH2:9][CH2:8][CH2:7][CH2:6][C:5]([OH:21])=[O:4])(=[O:20])[CH3:19]
Reactant: CC(=O)OC(=O)CCCCC(CCSC(C)=O)SC(C)=O
Solvent: CC(C)O
Solvent: O
Product: CC(=O)SCCC(CCCCC(=O)O)SC(C)=O
Reaction time: 4.25 h

Procedure:
The anhydride from step 2 (8.0 g) was mixed with 30 mL of water and 30 mL of 2-propanol and stirred at 40 for 4.25 hr. After about 2 hr there was a clear solution. The solvent was evaporated under vacuum (2 mm) at 25. The oil remaining was evaporated with 10 mL of water to remove any residual 2-propanol and acetic acid. An almost colorless oil weighing 6.8 g was isolated.
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[CH3:12][S:13][CH2:14][C:15]1[C:24]([C:25]([O:27][CH3:28])=[O:26])=[N+:23]([O-:29])[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N+:16]=1[O-:30].C(OCC)C>C(Cl)(Cl)Cl>[CH3:12][S:13]([CH2:14][C:15]1[C:24]([C:25]([O:27][CH3:28])=[O:26])=[N+:23]([O-:29])[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N+:16]=1[O-:30])=[O:9]
Reactant: COC(=O)c1c(CSC)[n+]([O-])c2ccccc2[n+]1[O-]
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClC(Cl)Cl
Solvent: CCOCC
Product: COC(=O)c1c(CS(C)=O)[n+]([O-])c2ccccc2[n+]1[O-]
Reaction time: 1 h

Procedure:
A solution of m-chloroperbenzoic acid (9.4 g., 0.0465 m of 85 percent material) in chloroform (75 ml.) was added dropwise to a solution of 2-methylthiomethyl-3-carbomethoxyquinoxaline 1,4-dioxide (13.0 g. 0.0465 m) in chloroform (100 ml.). The mixture was stirred for one hour and then added dropwise, with stirring, to diethyl ether (1.1 liters). The yellow solid which precipitated was filtered off, washed with diethyl ether (50 ml.) and then with hexane (100 ml.) and dried. Yield = 13.4 g., 97 percent of product: m.p. 141°-142°C.