Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][NH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:9]1(=[O:16])[CH2:14][CH2:13][C:12](=O)[CH2:11][CH2:10]1.C(N(CC)CC)C>C(O)C>[OH:16][C:9]1[CH:10]=[CH:11][C:12]([N:2]([CH3:1])[C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)=[CH:13][CH:14]=1
Reactant: O=C1CCC(=O)CC1
Reactant: CNc1ccccc1
Solvent: CCN(CC)CC
Solvent: CCO
Product: CN(c1ccccc1)c1ccc(O)cc1
Yield: 32.2 %

Procedure:
1.07 g of N-methylaniline, 2.24 g of 1,4-cyclohexanedione and 1.4 ml of triethylamine were heated with stirring in 15 ml of ethanol at 50° C. to 60° C. and reacted in air for 8 hours. During the reaction, ethanol was added as needed. After the completion of the reaction, the reaction mixture was concentrated under reduced pressure and the resultant was separated by silica gel column chromatography (n-hexane:ethyl acetate=3:1) and 0.64 g of N-(4-hydroxyphenyl)-N-methylaniline was obtained (yield 32.1%).
Reaction SMILES: [NH3:1].[C:2]([Si:6]([CH3:29])([CH3:28])[O:7][C:8]1[C:9]([O:26][CH3:27])=[C:10]([C:16]([C:18]2[C:19](Cl)=[N:20][C:21]([Cl:24])=[N:22][CH:23]=2)=[O:17])[C:11]([F:15])=[C:12]([F:14])[CH:13]=1)([CH3:5])([CH3:4])[CH3:3]>C1(C)C=CC=CC=1>[NH2:1][C:19]1[C:18]([C:16]([C:10]2[C:11]([F:15])=[C:12]([F:14])[CH:13]=[C:8]([O:7][Si:6]([C:2]([CH3:3])([CH3:5])[CH3:4])([CH3:28])[CH3:29])[C:9]=2[O:26][CH3:27])=[O:17])=[CH:23][N:22]=[C:21]([Cl:24])[N:20]=1
Reactant: COc1c(O[Si](C)(C)C(C)(C)C)cc(F)c(F)c1C(=O)c1cnc(Cl)nc1Cl
Reactant: N
Solvent: Cc1ccccc1
Product: COc1c(O[Si](C)(C)C(C)(C)C)cc(F)c(F)c1C(=O)c1cnc(Cl)nc1N

Procedure:
Ammonia gas was bubbled through a solution of [3-(tert-butyl-dimethyl-silanyloxy)-5,6-difluoro-2-methoxy-phenyl]-(2,4-dichloro-pyrimidin-5-yl)-methanone (900 mg, 2.003 mmol, Example 268) in toluene (10 mL) for about 30 minutes. The reaction mixture was concentrated to dryness to give (4-amino-2-chloro-pyrimidin-5-yl)-[3-(tert-butyl-dimethyl-silanyloxy)-5,6-difluoro-2-methoxy-phenyl]-methanone (1.02 g, yellow gum). The crude product was used without further purification.
Reaction SMILES: [C:1]([NH:4][CH2:5][C:6]([N:8]1[C:14]2[CH:15]=[CH:16][C:17]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][O:28][CH2:29][CH2:30][CH2:31][CH3:32])=[CH:21][CH:20]=3)=[CH:18][C:13]=2[CH:12]=[C:11]([C:33]([O:35]C)=[O:34])[CH2:10][CH2:9]1)=[O:7])(=[O:3])[CH3:2].[OH-].[Na+]>CO>[C:1]([NH:4][CH2:5][C:6]([N:8]1[C:14]2[CH:15]=[CH:16][C:17]([C:19]3[CH:20]=[CH:21][C:22]([O:25][CH2:26][CH2:27][O:28][CH2:29][CH2:30][CH2:31][CH3:32])=[CH:23][CH:24]=3)=[CH:18][C:13]=2[CH:12]=[C:11]([C:33]([OH:35])=[O:34])[CH2:10][CH2:9]1)=[O:7])(=[O:3])[CH3:2]
Reactant: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)OC)CCN3C(=O)CNC(C)=O)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)O)CCN3C(=O)CNC(C)=O)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 102.9 %

Procedure:
In methanol (50 ml) was dissolved methyl 1-(N-acetylglycyl)-7-[4-(2-butoxyethoxy)phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxylate (1.2 g). To the solution was added 1N sodium hydroxide solution (13 ml), and the mixture was stirred at room temperature overnight, concentrated, neutralized with 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried with anhydrous magnesium sulfate. The solvent was evaporated to give 1-(N-acetylglycyl)-7-[4-(2-butoxyethoxy)phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid (1.2 g) as colorless crystals.
Reaction SMILES: [F:1][C:2]1[CH:29]=[CH:28][C:5]([C:6]([C:8]2[CH:27]=[CH:26][C:11]([CH2:12][N:13]3[C:17]4[N:18]=[C:19]([S:23][CH3:24])[NH:20][C:21](=[O:22])[C:16]=4[C:15]([CH3:25])=[CH:14]3)=[CH:10][CH:9]=2)=[O:7])=[CH:4][CH:3]=1.[H-].[Na+].[CH3:32]I>COCCOC.C(OCC)(=O)C>[CH3:32][N:20]1[C:21](=[O:22])[C:16]2[C:15]([CH3:25])=[CH:14][N:13]([CH2:12][C:11]3[CH:26]=[CH:27][C:8]([C:6](=[O:7])[C:5]4[CH:28]=[CH:29][C:2]([F:1])=[CH:3][CH:4]=4)=[CH:9][CH:10]=3)[C:17]=2[N:18]=[C:19]1[S:23][CH3:24]
Reactant: CI
Reactant: CSc1nc2c(c(C)cn2Cc2ccc(C(=O)c3ccc(F)cc3)cc2)c(=O)[nH]1
Agent: [H-]
Agent: [Na+]
Solvent: COCCOC
Solvent: CCOC(C)=O
Product: CSc1nc2c(c(C)cn2Cc2ccc(C(=O)c3ccc(F)cc3)cc2)c(=O)n1C
Reaction time: 0.5 h
Yield: 68.5 %

Procedure:
Under argon gas, 7-[4-(4-fluorobenzoyl)benzyl]-5-methyl-2-methylthio-7H-pyrrolo[2,3-d]pyrimidin-4(3H)-one (1.85 g) was dissolved in anhydrous DME (50 ml)anhydrous DMF (50 ml) and, under ice-cooling, 60% sodium hydride-oil (176 mg) was added in two installments. After 30 minutes of stirring, methyl iodide (681 mg) was added. Then, at room temperature, the mixture was stirred overnight. This reaction mixture was diluted with ethyl acetate, washed with saturated aqueous NaCl solution, and dried over anhydrous sodium sulfate. The solvent was then distilled off under reduced pressure and the residue was purified by flash column chromatography (silica gel; ethyl acetate: hexane=1:5.6-1:2.3) to provide the title compound (1.31 g).
Reaction SMILES: [C:1]1([CH2:7][C:8]([CH2:18][C:19]([OH:21])=[O:20])([C:14]([CH3:17])([CH3:16])[CH3:15])[C:9]([O:11]CC)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[K+]>C(O)C.O>[C:1]1([CH2:7][C:8]([CH2:18][C:19]([OH:21])=[O:20])([C:14]([CH3:15])([CH3:16])[CH3:17])[C:9]([OH:11])=[O:10])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCOC(=O)C(CC(=O)O)(Cc1ccccc1)C(C)(C)C
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CC(C)(C)C(CC(=O)O)(Cc1ccccc1)C(=O)O
Temperature: 25 °C
Reaction time: 3 h
Yield: 80.9 %

Procedure:
Dissolve 3-phenyl-2-t-butylcarboxymethylpropionic acid, ethyl ester (2.68 g, 9.17 mmol) in ethanol (95%, 60 mL) and water (30 mL). Treat with potassium hydroxide (2.94 g, 52 mmol). Stir at room temperature for 3 hours. Add water (75 mL) and extract with ethyl ether (2×50 mL). Extract the combined ethereal phases with water (75 mL) and acidify the combined aqueous phases with aqueous 1 M tartaric acid (pH 2-3). Extract with ethyl acetate (2×125 mL), dry (Na2SO4) and evaporate the solvent in vacuo. Take the residue up in methylene chloride and filter to give 3-phenyl-2-t-butylcarboxymethylpropionic acid as a pale yellow solid (1.96 g, 81%).
Reaction SMILES: [CH3:1][CH2:2][O:3][C:4]([C:6]1[CH:11]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=2[Cl:18])[C:10]([C:19]([O:21][CH3:22])=[O:20])=[C:9]([CH3:23])[NH:8][C:7]=1[CH2:24][O:25][CH2:26][CH2:27][NH2:28])=[O:5].COC(C1C(C2C=CC=CC=2Cl)C(C(OC)=O)=C(C)NC=1COCCN[C:56](=[O:73])[CH2:57][O:58][C:59]1[CH:64]=[CH:63][C:62]([C:65]2[CH2:70][CH2:69][C:68](=[O:71])[NH:67][N:66]=2)=[CH:61][C:60]=1[Cl:72])=O>C(OCC)(=O)C>[CH3:22][O:21][C:19]([C:10]1[CH:11]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=2[Cl:18])[C:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])=[C:7]([CH2:24][O:25][CH2:26][CH2:27][NH:28][C:56](=[O:73])[CH2:57][O:58][C:59]2[CH:64]=[CH:63][C:62]([C:65]3[CH2:70][CH2:69][C:68](=[O:71])[NH:67][N:66]=3)=[CH:61][C:60]=2[Cl:72])[NH:8][C:9]=1[CH3:23])=[O:20]
Reactant: COC(=O)C1=C(C)NC(COCCNC(=O)COc2ccc(C3=NNC(=O)CC3)cc2Cl)=C(C(=O)OC)C1c1ccccc1Cl
Reactant: CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1c1ccccc1Cl
Solvent: CCOC(C)=O
Product: CCOC(=O)C1=C(COCCNC(=O)COc2ccc(C3=NNC(=O)CC3)cc2Cl)NC(C)=C(C(=O)OC)C1c1ccccc1Cl

Procedure:
2-(2-{2-[2-Chloro-4-(6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl)-phenoxy]-acetylamino}-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester (Compound 9) (12b) was synthesized from commercial amlodipine (5b, 1.73 g, 4.23 mmol) and 6-{4-[3-carboxymethoxy]-3-chlorophenyl}-4,5-dihydro-3(2H)-pyridazinone (11) using the same procedure as for Compound 8. Pure Compound 9 was obtained by re-crystallization from ethyl acetate (1.45 g, 51% yield, 99% pure by 10 min. LCMS (UV @ 215 nm: retention time=6.86 min., peak area=99%, TOF-ES+ with 25 eV cone voltage: m/z=673.30 (100%) & 675.30 (30%)). 1H NMR: (CDCl3, TMS internal standard, δ in ppm): 8.50 (1H, s), 7.85 (1H, d, J=2.20 Hz), 7.59 (1H, dd, J1=8.60 Hz, J2=2.20 Hz), 7.38 (1H, dd, J1=7.78 Hz, J2=1.65 Hz), 7.23 (1H, dd, J1=7.87 Hz, J2=1.28 Hz), 7.17 (1H, broad s), 7.13 (2H, td, J1=7.43 Hz, J2=1.28 Hz), 7.04 (1H, J=7.57 Hz, J2=1.71 Hz), 6.94 (1H, d, J=8.78 Hz), 5.40 (1H, s), 4.76 (1H, d, J=15.83 Hz), 4.68 (1H, d, J=15.83 Hz), 4.62 (2H, s), 4.04 (2H, m, J1=7.12 Hz), 3.77–3.63 (4H, m), 3.62 (3H, s), 2.94 (2H, t, J=8.32 Hz), 2.61 (2H, t, J=8.23 Hz), 2.35 (3H, s), 1.18 (3H, t, J=7.14)
Reaction SMILES: [NH2:1][C@H:2]([C:5]([OH:7])=[O:6])[CH2:3][OH:4].FC(F)(F)C(O)=O.[C:15](Cl)(=[O:18])[CH2:16][CH3:17]>C(OCC)C>[C:15]([O:4][CH2:3][C@@H:2]([C:5]([OH:7])=[O:6])[NH2:1])(=[O:18])[CH2:16][CH3:17]
Reactant: CCC(=O)Cl
Reactant: N[C@@H](CO)C(=O)O
Solvent: O=C(O)C(F)(F)F
Solvent: CCOCC
Product: CCC(=O)OC[C@H](N)C(=O)O
Temperature: 25 °C
Reaction time: 1 h
Yield: 65 %

Procedure:
L-Serine (5.25 g, 50 mmol) was added with stirring to trifluoroacetic acid (35 ml) and the resultant was decanted from the insoluble material. Propionyl chloride (5.66 ml, 64.0 mmol) was then added to the solution and the mixture was stirred for 1 h at room temperature. Upon the addition of diethyl ether (6 ml), a white solid precipitated which redissolved upon stirring. The reaction vessel was sealed and left to stand overnight in a refrigerator. Further diethyl ether (30 ml) was added to the cold solution with stirring. The resultant fine white precipitate was collected by filtration, washed with diethyl ether, and dried under vacuum to afford 6.43 g (32.5 mmol, 65%) of 2020370, m.p. 148-150° C. (dec.). 1H NMR (300 MHz, d6-DMSO) δ 0.96 (t, J 7 Hz, 3H), 2.29 (m, 2H), 4.21 (br s, 1H), 4.39 (m, 2H), 8.75 (br s, 3H). 13C NMR (75.5 MHz, d6-DMSO) δ 8.7, 27.2, 52.0, 61.3, 168.9, 174.0. m/z 162.1 [M+H]+.
Reaction SMILES: [C:1]([O:5][C:6](=[O:23])[CH2:7][C@H:8]([CH2:12][C@H:13]([CH3:22])[CH2:14][CH2:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)C(O)=O)(C)(C)C.C([N:26](CC)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1>C1(C)C=CC=CC=1>[CH3:1][O:5][C:6](=[O:23])[CH2:7][C@@H:8]([NH2:26])[CH2:12][C@H:13]([CH3:22])[CH2:14][CH2:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1
Reactant: CCN(CC)CC
Reactant: C[C@H](CCC1CCCCC1)C[C@@H](CC(=O)OC(C)(C)C)C(=O)O
Agent: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Solvent: Cc1ccccc1
Product: COC(=O)C[C@@H](N)C[C@H](C)CCC1CCCCC1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
A flask was charged with 2.19 g (6.71 mmol) of (S)-2-((R)-4-cyclohexyl-2-methyl-butyl)-succinic acid 4-tert-butyl ester, 40 mL of toluene, 0.935 mL (6.71 mmol) of triethylamine, and 1.45 mL (6.71 mmol) of diphenylphosphorylazide. The mixture was stirred for 15 minutes at room temperature and then heated to 110° C. and stirred for 6 hours. The toluene was removed under reduced pressure, and the residue was taken up in diethyl ether. The ether layer was washed with 3M HCl aq., water, and brine. The ether was removed under reduced pressure, and the crude isocyanate was taken up in 3 M HCl aq. and heated at reflux for 8 hours. The water was removed under reduced pressure, and the residue was triturated with ether. This provided 1.45 g of an impure white solid. A portion of the white solid was dissolved in methanol, and HCl gas was bubbled through for 15 minutes. The acidic solution was stirred 2 hours. The methanol was removed under reduced pressure, and the crude ester was purified by column chromatography (4:1 dichloromethane:methanol). This gave 0.356 g of the pure ester: 1H NMR (400 MHz, CDCl3) δ ppm 0.85 (m, 2H) 0.88 (d, J=8.00 Hz, 3H) 1.15 (m, 6H) 1.26 (m, 1H) 1.36 (ddd, J=13.73, 9.21, 4.64 Hz, 1H) 1.51 (m, 1H) 1.65 (m, 7H) 2.28 (dd, J=15.86, 8.78 Hz, 1H) 2.43 (dd, J=16.0, 4.00 Hz, 1H) 3.28 (m, J=8.97, 8.97, 4.39, 4.27 Hz, 1H) 3.69 (s, 3H). MS (APCI) m+1/z=256.
Reaction SMILES: [CH3:1][CH:2]([CH3:11])[CH2:3][CH:4]1[CH2:9][CH2:8][CH2:7][C:6](=[O:10])[CH2:5]1.[CH3:12][Mg]I>CCOCC>[CH3:12][C:6]1([OH:10])[CH2:7][CH2:8][CH2:9][CH:4]([CH2:3][CH:2]([CH3:11])[CH3:1])[CH2:5]1
Reactant: CC(C)CC1CCCC(=O)C1
Reactant: C[Mg]I
Solvent: CCOCC
Product: CC(C)CC1CCCC(C)(O)C1
Yield: 62 %

Procedure:
A solution of 62.7 g (0.407 mol) of the distilled ketone in 200 ml ether was added dropwise to a stirred solution of 0.6 mol methyl magnesium iodide in 200 ml ether at such a rate that the reaction mixture was allowed gradually to reach and then maintain a steady reflux. When the addition was complete heat was applied to maintain reflux for a further 30 minutes. Thereafter the reaction mixture was quenched with 1.01 of water and the resulting precipitate in the aqueous phase dissolved by the addition of saturated aqueous ammonium chloride (1.01). The organic phase was separated, washed, dried and the solvent was removed in vacuo. The crude consisted of a mixture of trans and cis 1-methyl-3-(2-methylpropyl)cyclohexan-1-ol in a ratio of 2:1. It could be purified by distillation under reduced pressure to obtain a mixture of about the same isomer distribution. Alternatively it could be separated into the cis and trans isomers by column chromatography over silica (200 g for 4 g of crude) using a mixture of diethyl ether and pentane (1.5 v/v ratio) as the eluent. It could also be separated into the isomers by fractional distillation under reduced pressure over a 1 m Sulzer column using a reflux: take off ratio of 10:1. Thus, 217 g of crude yields 102 g (>94% pure on gc) of the trans isomer (head temperature 69° C. at 0.04 kPa) and 50 g (>97% pure on gc) of the cis isomer (62° C. at 0.01 kPa) and 43 g of an intermediate fraction consisting of a mixture of the two isomers.
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].[C:5]([NH:9][S:10]([C:13]1[CH:18]=[C:17]([CH2:19][NH2:20])[CH:16]=[CH:15][C:14]=1[C:21]([O:23][CH3:24])=[O:22])(=[O:12])=[O:11])([CH3:8])([CH3:7])[CH3:6].C(N(CC)CC)C>ClCCl>[C:5]([NH:9][S:10]([C:13]1[CH:18]=[C:17]([CH2:19][NH:20][C:1](=[O:3])[CH3:2])[CH:16]=[CH:15][C:14]=1[C:21]([O:23][CH3:24])=[O:22])(=[O:12])=[O:11])([CH3:8])([CH3:7])[CH3:6]
Reactant: CC(=O)Cl
Reactant: COC(=O)c1ccc(CN)cc1S(=O)(=O)NC(C)(C)C
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)c1ccc(CNC(C)=O)cc1S(=O)(=O)NC(C)(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 91.5 %

Procedure:
0.63 g (8 mmol) of acetyl chloride dissolved in 10 ml of dichloromethane is added dropwise to a solution, cooled to 0° C., of 2.01 g (6.7 mmol) of N-tert-butyl-5-aminomethyl-2-methoxycarbonylbenzenesulfonamide and 0.93 ml (6.7 mmol) of triethylamine in 30 ml of dichloromethane, and the mixture is then stirred at room temperature for 2 h. The reaction solution is washed with water, dried and evaporated to dryness i.v. 2.1 g (91%) of N-tertbutyl-5-acetamidomethyl-2-methoxycarbonylbenzenesulfonamide are obtained as a viscous oil.
Reaction SMILES: Cl.[CH2:2]([O:4][C:5](=[O:8])[CH2:6][NH2:7])[CH3:3].C(N(CC)CC)C.[CH2:16]([O:23][C:24]([NH:26][CH2:27][CH2:28][CH2:29][CH2:30][C@@H:31]([C:40](O)=[O:41])[NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[O:25])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)(Cl)Cl>[CH2:2]([O:4][C:5](=[O:8])[CH2:6][NH:7][C:40](=[O:41])[C@H:31]([CH2:30][CH2:29][CH2:28][CH2:27][NH:26][C:24]([O:23][CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)=[O:25])[NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:37])[CH3:38])=[O:34])[CH3:3]
Reactant: CC(C)(C)OC(=O)N[C@@H](CCCCNC(=O)OCc1ccccc1)C(=O)O
Reactant: CCOC(=O)CN
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: CCOC(=O)CNC(=O)[C@H](CCCCNC(=O)OCc1ccccc1)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 47 %

Procedure:
To a solution of 0.73 g (5.26 mmol) of glycine ethyl ester hydrochloride and 0.74 mL (5.26 mmol) of triethylamine in 42 mL of chloroform were added successively, at 0° C., 2.0 g (5.26 mmol) of Nε -benzyloxycarbonyl-Nα -(tert-butoxycarbonyl)-L-lysine and 1.09 g (5.26 mmol) of dicyclohexylcarbodiimide. The reaction mixture was stirred overnight at room temperature. The resulting precipitate was removed by filtration and the filtrate was washed successively with 0.5N hydrochloric acid, water, 3% aqueous sodium bicarbonate solution and water, then dried over anhydrous sodium sulfate. Evaporation of the solvent afforded a residue which was triturated with ethyl acetate. Insoluble materials were removed by filtration and the filtrate was evaporated in vacuo. The residue was recrystallized from a mixture of ethyl acetate and isopropyl ether to give 1.15 g (48%) of the title compound as colorless crystals. The mother liquor was concentrated under reduced pressure and the residue was crystallized as before to give a second crop of crystals (0.77 g, 32.1%). Total yield 80.1%, melting point 69°-70° C. NMR and IR spectral analyses confirmed the identity of the product, which has the formula: ##STR102##
Reaction SMILES: [C:1]1([NH:7][S:8]([CH3:11])(=[O:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:12][CH2:13][C:14](Cl)=[O:15].[Cl-].[Al+3].[Cl-].[Cl-].Cl>C(Cl)Cl>[Cl:12][CH2:13][C:14]([C:4]1[CH:3]=[CH:2][C:1]([NH:7][S:8]([CH3:11])(=[O:10])=[O:9])=[CH:6][CH:5]=1)=[O:15]
Reactant: CS(=O)(=O)Nc1ccccc1
Reactant: O=C(Cl)CCl
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: CS(=O)(=O)Nc1ccc(C(=O)CCl)cc1
Temperature: -10 °C
Reaction time: 2 h

Procedure:
In a flask containing 128.4 g (0.75 mole) of N-phenylmethanesulfonamide, 169.5 g (1.50 mole) of chloroacetyl chloride in 1 L of methylene chloride under an atmosphere of nitrogen and cooled to about -10° C. add 300 g (2.25 mole) of aluminum chloride. Stir the resulting mixture for about 2 hours at -10° C. then warm to room temperature for about 16 hours. Pour the reaction mixture onto 2 Kg of ice containing 600 mL of concentrated hydrochloric acid. Collect the precipitate and wash with methanol (3×300 mL) and dry in vacuo to give the title compound.
Reaction SMILES: [NH2:1][C:2]1[N:6]=[CH:5][NH:4][N:3]=1.[OH:7][C:8]([CH3:19])([CH3:18])[CH2:9][O:10][CH:11]1[CH2:16][CH2:15][C:14](=O)[CH2:13][CH2:12]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C>[CH3:19][C:8]([OH:7])([CH3:18])[CH2:9][O:10][CH:11]1[CH2:16][CH2:15][CH:14]([NH:1][C:2]2[N:6]=[CH:5][NH:4][N:3]=2)[CH2:13][CH2:12]1
Reactant: CC(C)(O)COC1CCC(=O)CC1
Reactant: Nc1nc[nH]n1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Product: CC(C)(O)COC1CCC(Nc2nc[nH]n2)CC1
Temperature: 25 °C
Reaction time: 15 h
Yield: 64.3 %

Procedure:
To a solution of 3-amino-1H-1,2,4-triazole (1.46 g) and 4-(2-hydroxy-2-methylpropoxy)cyclohexanone (3.25 g) in acetic acid (30 mL) was added sodium triacetoxyborohydride (5.53 g), and the mixture was stirred at room temperature for 15 hr. The solvent was evaporated under reduced pressure, and the residue was diluted with saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate-isopropyl alcohol (3:1). The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography [eluent: methanol/ethyl acetate=0/10→06/94 (volume ratio)] to give colorless amorphous 2-methyl-1-{[4-(1H-1,2,4-triazol-3-ylamino)cyclohexyl]oxy}propan-2-ol (2.84 g, 64%) as a diastereomixture.
Reaction SMILES: [CH2:1]([NH2:4])[CH2:2][NH2:3].F[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][N:7]=1>>[N:7]1[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=1[NH:3][CH2:2][CH2:1][NH2:4]
Reactant: Fc1ccccn1
Reactant: NCCN
Product: NCCNc1ccccn1

Procedure:
Ethylenediamine (6 g, 0.1 mol) and 2-fluoropyridine (10 g, 0.1 mol) were heated neat at 120° C. overnight. The reaction was cooled and the residue was used in next step without further purification.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][C:5]([C:7]1[CH:16]=[CH:15][C:10]2[NH:11][C:12](=[O:14])[O:13][C:9]=2[CH:8]=1)=O.[F:17][C:18]([F:23])([F:22])[C:19]([OH:21])=[O:20].C([SiH](CC)CC)C>O>[F:17][C:18]([F:23])([F:22])[C:19]([O:21][CH2:2][CH2:3][CH2:4][CH2:5][C:7]1[CH:16]=[CH:15][C:10]2[NH:11][C:12](=[O:14])[O:13][C:9]=2[CH:8]=1)=[O:20]
Reactant: O=C(O)C(F)(F)F
Reactant: O=C(CCCBr)c1ccc2[nH]c(=O)oc2c1
Agent: CC[SiH](CC)CC
Solvent: O
Product: O=C(OCCCCc1ccc2[nH]c(=O)oc2c1)C(F)(F)F
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a 100 ml three-necked round-bottomed flask equipped with dropping funnel, thermometer, and N2 inlet were added 10 g (0.035 mol) 6-(4-bromobutyryl)-benzoxazolone and 26.08 ml (0.35 mol) trifluoroacetic acid. To the stirring suspension was added dropwise 12.93 ml (0.080 mol) triethylsilane, and the reaction stirred at room temperature for 16 hours. The reaction was then poured into water, and the resulting white solid filtered and washed with water. It was then suspended in isopropyl ether, stirred, and filtered to afford white solid 6-(4-trifluoroacetoxybutyl)-benzoxazolone, m.p. 100°-103° C., 10.47 g (98.7%).
Reaction SMILES: [Cl:1][CH:2]=[CH:3]Cl.N1CCCCC1.[C:11]([C:13]1[CH:20]=[CH:19][C:16]([CH:17]=[O:18])=[CH:15][CH:14]=1)#[CH:12]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I.C1COCC1>[Cl:1]/[CH:2]=[CH:3]/[C:12]#[C:11][C:13]1[CH:20]=[CH:19][C:16]([CH:17]=[O:18])=[CH:15][CH:14]=1
Reactant: C#Cc1ccc(C=O)cc1
Reactant: ClC=CCl
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCNCC1
Solvent: C1CCOC1
Product: O=Cc1ccc(C#C/C=C/Cl)cc1
Temperature: 25 °C
Reaction time: 22.5 h
Yield: 59 %

Procedure:
1,2-Dichloroethylene (3.0 mL), tetrakis(triphenylphosphine)palladium (0.44 g), CuI (73 mg) and piperidine (1.1 mL) were added to a THF (20 mL) solution of 4-ethynylbenzaldehyde (1.0 g), and the mixture was stirred for 22.5 hours at room temperature in a nitrogen atmosphere. IPE was added, the insolubles were filtered out, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by OH type silica gel column chromatography (hexane/ethyl acetate/chloroform=9/1/1) to obtain 4-((E)-4-chlorobut-3-en-1-yn-1-yl)benzaldehyde (light brown solid) (0.87 g, 59%).
Reaction SMILES: [CH2:1]([N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:11]=[C:10]([C:18](O)=[O:19])[C:9]1=[O:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.C(Cl)(=O)OCC.[CH2:35]([NH:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH3:47])[CH2:36][CH2:37][CH2:38][CH2:39][CH3:40]>O1CCCC1>[CH2:42]([N:41]([CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[C:18]([C:10]1[C:9](=[O:21])[N:8]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:17]2[C:12]([N:11]=1)=[CH:13][CH:14]=[CH:15][CH:16]=2)=[O:19])[CH2:43][CH2:44][CH2:45][CH2:46][CH3:47]
Reactant: CCCCCCNCCCCCC
Reactant: O=C(O)c1nc2ccccc2n(Cc2ccccc2)c1=O
Agent: CCOC(=O)Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CCCCCCN(CCCCCC)C(=O)c1nc2ccccc2n(Cc2ccccc2)c1=O
Temperature: -40 °C
Reaction time: 0.17 h

Procedure:
In 30 ml of tetrahydrofuran were dissolved 0.50 g of 1-benzyl-1,2-dihydro-2-oxoquinoxaline-3-carboxylic acid and 0.87 ml of triethylamine, and after cooling to —40° C., 0.19 ml of ethyl chlorocarbonate was added dropwise over 5 minutes. After stirring at −40° C. for 10 minutes, 0.46 ml of dihexylamine was added dropwise over 5 minutes. After stirring at −40° C. for an hour, the temperature was raised to room temperature over an hour, followed by stirring at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and the residue, after addition of ethyl acetate, was washed with water, 1N hydrochloric acid, a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution, and dried over anhydrous sodium sulfate. After removal of the drying agent by filtration, the filtrate was concentrated under reduced pressure. The residue was purified by chromatography (silica gel; Wakogel C200 (manufactured by Wako Pure Chemicals), developing solvent; chloroform) and recrystallized from hexane to give 0.53 g of N,N-dihexyl-1-benzyl-1,2-dihydro-2-oxoquinoxaline-3-carboxamide.