Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[C:2]([C:4]1([NH:7][C:8]([C@@H:10]2[CH2:14][C@@H:13]([S:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[C:24]([F:27])([F:26])[F:25])(=[O:17])=[O:16])[CH2:12][NH:11]2)=[O:9])[CH2:6][CH2:5]1)#[N:3].[C:28](OC(=O)C)(=[O:30])[CH3:29]>>[C:2]([C:4]1([NH:7][C:8]([C@@H:10]2[CH2:14][C@@H:13]([S:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[C:24]([F:27])([F:25])[F:26])(=[O:17])=[O:16])[CH2:12][N:11]2[C:28](=[O:30])[CH3:29])=[O:9])[CH2:5][CH2:6]1)#[N:3]
Reactant: N#CC1(NC(=O)[C@@H]2C[C@@H](S(=O)(=O)c3ccccc3C(F)(F)F)CN2)CC1
Reactant: CC(=O)OC(C)=O
Agent: Cl
Product: CC(=O)N1C[C@H](S(=O)(=O)c2ccccc2C(F)(F)F)C[C@H]1C(=O)NC1(C#N)CC1

Procedure:
(2S,4R)-4-(2-trifluoromethyl-benzenesulfonyl)-pyrrolidine-2-carboxylic acid (1-cyano-cyclopropyl)-amide hydrochloride from experiment K5 was acylated with acetic anhydride in analogy to experiment L29 to give (2S,4R)-1-acetyl-4-(2-trifluoromethyl-benzenesulfonyl)-pyrrolidine-2-carboxylic acid (1-cyano-cyclopropyl)-amide as a colorless solid. MS: 430.2 [M+H]+.
Reaction SMILES: [CH3:1][N:2]1[CH2:6][CH2:5][N:4]=[C:3]1[C:7](=[N:10][OH:11])[C:8]#[N:9].[CH3:12][N:13]=[C:14]=[O:15]>C(OCC)(=O)C.C(N(CC)CC)C>[CH3:1][N:2]1[CH2:6][CH2:5][N:4]=[C:3]1[C:7](=[N:10][O:11][C:14]([NH:13][CH3:12])=[O:15])[C:8]#[N:9]
Reactant: CN=C=O
Reactant: CN1CCN=C1C(C#N)=NO
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: CNC(=O)ON=C(C#N)C1=NCCN1C

Procedure:
15.2 g (0.1 mol) of α-[1-methyl-imidazolin-2-yl]-α-oximino-acetonitrile and 6.4 g (0.11 mol) of methyl isocyanate are stirred in 200 ml of ethyl acetate with a few drops of triethylamine for 16 hours. 16 g (76.5% of theory) of end product are filtered off and this is washed with a little ethyl acetate; melting point 186°-190° C. (decomposition).
Reaction SMILES: [C:1]([N:4]1[CH2:11][CH2:10][C:9](=[O:12])[NH:8][CH2:7][C:6]2[CH:13]=[CH:14][CH:15]=[CH:16][C:5]1=2)(=[O:3])[CH3:2].[OH-].[Na+].[N+:19]([O-])([OH:21])=[O:20].OS(O)(=O)=O>>[C:1]([N:4]1[CH2:11][CH2:10][C:9](=[O:12])[NH:8][CH2:7][C:6]2[CH:13]=[C:14]([N+:19]([O-:21])=[O:20])[CH:15]=[CH:16][C:5]1=2)(=[O:3])[CH3:2]
Reactant: CC(=O)N1CCC(=O)NCc2ccccc21
Reactant: O=[N+]([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Product: CC(=O)N1CCC(=O)NCc2cc([N+](=O)[O-])ccc21
Temperature: 0 °C
Reaction time: 3 h

Procedure:
1-Acetyl-2,3,5,6-tetrahydro-1H-benzo[b][1,5]diazocin-4-one (1.05 g, 4.82 mmol) was added to a 1/1 mixture of HNO3/H2SO4 (20 ml) at 0° C. The resulting solution was stirred at 0° C. for 3 h and allowed to warm to rt over 16 h. The reaction mixture was poured onto ice and neutralized with NaOH. The resulting ppt was filtered and washed with H2O to afford title compound as a pale orange solid. (600 mg, 47%). mp 253-256° C.; LCMS: m/z=264.25 (M+H+), HPLC (95% purity); 1H NMR (400 MHz, DMSO-d6) δ 8.31 (s, 1H), 8.24 (d, J=8.8 Hz, 1H), 7.79 (m, 1H), 7.69 (d, J=8.6 Hz, 1H). 4.65 (m, 1H), 4.38 (m, 1H), 4.11 (m, 1H), 2.96 (m, 1H), 2.61 (m, 1H), 2.38 (m, 1H), 1.73 (s, 3H).
Reaction SMILES: [NH:1]=[C:2]1[N:10]([CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[C:9]2[N:8]=[CH:7][NH:6][C:5]=2[C:4](=[O:16])[NH:3]1.[NH2:17]N>O>[NH2:17][N:3]1[C:4](=[O:16])[C:5]2[NH:6][CH:7]=[N:8][C:9]=2[N:10]([CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[C:2]1=[NH:1]
Reactant: NN
Reactant: CCCCCn1c(=N)[nH]c(=O)c2[nH]cnc21
Solvent: O
Product: CCCCCn1c(=N)n(N)c(=O)c2[nH]cnc21

Procedure:
A solution of 2-imino-3-pentyl-1,2,3,7-tetrahydro-6h-purin-6-one (750 mg, 3.39 mmol) and 18 m of hydrazine in water (30 ml) was stirred at 150° C. for 30 min on a microwave reactor. The reaction was diluted with water and extracted with ethyl acetate three times, dried with sodium sulfate, filtered, and concentrated in vacuo to yield the crude product for next step without further purification. LCMS calculated for C10H17N6O (M+H): 237.1. Found: 237.2.
Reaction SMILES: [F:1][C:2]1[C:3]([C:18]2[NH:22][C:21]([CH3:23])=[C:20]([C:24]([O:26]CC)=[O:25])[CH:19]=2)=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH3:12])[C:6]([NH:13][C:14]1([CH3:17])[CH2:16][CH2:15]1)=[N:5]2.Cl>O.O1CCOCC1>[F:1][C:2]1[C:3]([C:18]2[NH:22][C:21]([CH3:23])=[C:20]([C:24]([OH:26])=[O:25])[CH:19]=2)=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH3:12])[C:6]([NH:13][C:14]1([CH3:17])[CH2:15][CH2:16]1)=[N:5]2
Reactant: CCOC(=O)c1cc(-c2c(F)ccc3nc(C)c(NC4(C)CC4)nc23)[nH]c1C
Agent: Cl
Solvent: O
Solvent: C1COCCO1
Product: Cc1nc2ccc(F)c(-c3cc(C(=O)O)c(C)[nH]3)c2nc1NC1(C)CC1
Temperature: 80 °C
Yield: 15.2 %

Procedure:
A mixture of ethyl 5-(6-fluoro-2-methyl-3-((1-methyl-cyclopropyl)amino)quinoxalin-5-yl)-2-methyl-1H-pyrrole-3-carboxylate (417b) (0.555 g, 1.451 mmol), LiOH monohydrate (Sigma Aldrich, 365 mg, 8.71 mmol) in water (9 mL) and dioxane (18.00 mL) was heated to 80° C. overnight. Reaction mixture was then heated to 105° C. for an additional 4 h. Mixture was cooled back to RT and quenched with 4 M HCl in 1,4-dioxane (Sigma Aldrich, 2.177 mL, 8.71 mmol). Volatile solvents were removed by rotovap. The residue was loaded onto a silica gel samplet. Purification by Biotage (0-100% EtOAc/hexanes) produced 5-(6-fluoro-2-methyl-3-((1-methylcyclopropyl)amino)quinoxalin-5-yl)-2-methyl-1H-pyrrole-3-carboxylic acid (417c) (78 mg, 0.220 mmol, 15% yield). m/z (ESI, +ve) 355.0 (M+H).
Reaction SMILES: Cl.[F:2][C:3]1[CH:21]=[C:20]([S:22]([CH3:25])(=[O:24])=[O:23])[CH:19]=[CH:18][C:4]=1[O:5][CH2:6][C:7]1[N:11]=[CH:10][N:9]([CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[N:8]=1.C(=O)([O-])[O-].[K+].[K+].Cl[C:33]1[N:38]=[CH:37][C:36]([CH2:39][CH3:40])=[CH:35][N:34]=1>CN(C)C=O>[CH2:39]([C:36]1[CH:35]=[N:34][C:33]([N:15]2[CH2:16][CH2:17][CH:12]([N:9]3[CH:10]=[N:11][C:7]([CH2:6][O:5][C:4]4[CH:18]=[CH:19][C:20]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:21][C:3]=4[F:2])=[N:8]3)[CH2:13][CH2:14]2)=[N:38][CH:37]=1)[CH3:40]
Reactant: CS(=O)(=O)c1ccc(OCc2ncn(C3CCNCC3)n2)c(F)c1
Reactant: CCc1cnc(Cl)nc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCc1cnc(N2CCC(n3cnc(COc4ccc(S(C)(=O)=O)cc4F)n3)CC2)nc1
Temperature: 90 °C

Procedure:
A mixture of 4-[3-(2-fluoro-4-methanesulfonyl-phenoxymethyl)-[1,2,4]triazol-1-yl]-piperidine hydrochloride salt (Intermediate 6, 0.100 g, 0.256 mmol), potassium carbonate (0.106 g, 0.768 mmol) and 2-chloro-5-ethyl-pyrimidine (0.062 mL, 0.512 mmol) in dimethylformamide (2 mL) was heated at 90° C. for 4 hours or until the starting material was consumed. The reaction was cooled to room temperature, the solution was diluted with water and extracted with ethyl acetate. The organic layer was separated, washed with water and brine, dried over sodium sulfate, filtered and concentration in vacuo. The residue was chromatographed on silica gel (1:1 Hex/EtOAc) to afford the desired product. 1H NMR (CDCl3): δ 8.22 (2H, s), 8.17 (1H, s), 7.68 (2H, m), 7.38 (1H, m), 5.28 (2H, s), 4.92 (2H, d), 4.47 (1H, m), 3.08 (3H, s), 2.94 (2H, m), 2.48 (2H, q), 2.27 (1H, m), 2.18 (1H, m), 1.98 (2H, m), 1.20 (3H, t).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[N:6]=[C:5]([NH:11][C:12]([NH:14][S:15]([C:18]2[CH:23]=[C:22]([NH2:24])[CH:21]=[CH:20][C:19]=2[C:25]([N:27]([CH3:29])[CH3:28])=[O:26])(=[O:17])=[O:16])=[O:13])[N:4]=1.ClCCl.[C:33](OC(=O)C)(=[O:35])C>C(O)=O>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[N:6]=[C:5]([NH:11][C:12]([NH:14][S:15]([C:18]2[CH:23]=[C:22]([NH:24][CH:33]=[O:35])[CH:21]=[CH:20][C:19]=2[C:25]([N:27]([CH3:29])[CH3:28])=[O:26])(=[O:17])=[O:16])=[O:13])[N:4]=1
Reactant: CC(=O)OC(C)=O
Reactant: COc1cc(OC)nc(NC(=O)NS(=O)(=O)c2cc(N)ccc2C(=O)N(C)C)n1
Solvent: ClCCl
Solvent: O=CO
Product: COc1cc(OC)nc(NC(=O)NS(=O)(=O)c2cc(NC=O)ccc2C(=O)N(C)C)n1

Procedure:
A solution of 1.9 g of N-[(4,6-dimethoxypyrimidin-2-yl)aminocarbonyl]-5-amino-2-dimethylaminocarbonylbenzenesulfonamide and 10 ml of dichloromethane is added dropwise to the mixed anhydride, prepared in situ from 0.5 ml of formic acid and 1.0 ml of acetic anhydride in accordance with standard methods. After the end of reaction, the reaction mixture is concentrated and the residue is washed with water and ethyl acetate, to give 1.8 g of desired product; purity>92% (HPLC).
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]([CH3:12])[C:9]2[CH:8]=[C:7]3[O:13][C:14]([CH3:18])([CH3:17])[CH:15]=[CH:16][C:6]3=[CH:5][C:4]=2[N:3]=1.CN1C=CN=C1.Cl[O-].[Na+].S([O-])([O-])(=[O:30])=S.[Na+].[Na+]>C(OCC)(=O)C>[Cl:1][C:2]1[CH:11]=[C:10]([CH3:12])[C:9]2[CH:8]=[C:7]3[O:13][C:14]([CH3:18])([CH3:17])[C@H:15]4[O:30][C@H:16]4[C:6]3=[CH:5][C:4]=2[N:3]=1
Reactant: Cc1cc(Cl)nc2cc3c(cc12)OC(C)(C)C=C3
Reactant: O=S([O-])([O-])=S
Agent: Cn1ccnc1
Agent: [Na+]
Agent: [O-]Cl
Solvent: CCOC(C)=O
Product: Cc1cc(Cl)nc2cc3c(cc12)OC(C)(C)[C@H]1O[C@@H]31
Reaction time: 0.67 h
Yield: 94 %

Procedure:
To a solution of 7-chloro-2,2,9-trimethyl-2H-pyrano[2,3-g]quinoline (200 mg, 0.77 mmol) in ethyl acetate (3.0 mL), N-methyl imidazole (0.012 mL, 0.154 mmol) and ent-Ph,Ph salen manganese complex (8.0 mg, 0.0077 mmol) were added at room temperature and aqueous sodium hypochlorite solution (1.0 g, 1.513 mol/kg, 1.54 mmol) was added dropwise, and the resulting mixture was stirred for 40 minutes. Aqueous sodium hypochlorite solution (1.0 g, 1.513 mol/kg, 1.54 mmol) was added dropwise, and the resulting mixture was further stirred at room temperature for 30 minutes. Upon the completion of the reaction, aqueous sodium thiosulfate solution was added to the reaction solution, the resulting solution was filtered through celite and extracted. The organic phase was washed with aqueous sodium hydrogencarbonate solution and then with aqueous sodium chloride solution, and then dried over anhydrous magnesium sulfate. After distilling off the solvent, the residue was purified by column chromatography (hexane/ethyl acetate=10/1) to obtain (3S*,4S*)-7-chloro-3,4-epoxy-2,2,9-trimethyl-3,4-dihydro-2H-pyrano[2,3-g]quinoline (yield: 94%).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:18])[CH:5]=[CH:6][C:7]1[C:8](Cl)=[N:9][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:11][CH:12]=1)[CH3:2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCN(CC)CC.[CH3:45][Si:46]([C:49]#[CH:50])([CH3:48])[CH3:47]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.CN(C=O)C>[CH2:1]([O:3][C:4](=[O:18])[CH:5]=[CH:6][C:7]1[C:8]([C:50]#[C:49][Si:46]([CH3:48])([CH3:47])[CH3:45])=[N:9][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:11][CH:12]=1)[CH3:2]
Reactant: C#C[Si](C)(C)C
Reactant: CCOC(=O)C=Cc1ccc(C(F)(F)F)nc1Cl
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCOC(=O)C=Cc1ccc(C(F)(F)F)nc1C#C[Si](C)(C)C

Procedure:
Microwave vial was charged with 3-(2-chloro-6-trifluoromethyl-pyridin-3-yl)-acrylic acid ethyl ester (103 mg, 0.368 mmol), Pd(PPh3)2Cl2 (0.06 eq), CuI (0.06 eq), PPh3 (0.2 eq), Et3N (15 eq), (trimethylsilyl)acetylene and DMF (0.25 ml). The vial was irradiated in microwave synthesizer at 120° C. for 25 min. The contents of the vial were filtered through a Celite pad, which was washed out thoroughly with EtOAc. The filtrate was evaporated, and the residue was purified by column chromatography to 3-(6-trifluoromethyl-2-trimethylsilanylethynyl-pyridin-3-yl)-acrylic acid ethyl ester (58 mg, 46%).
Reaction SMILES: [F:1][C:2]([F:21])([F:20])[C:3]([NH:5][CH2:6][C:7]1[C:8]([F:19])=[CH:9][C:10]([Cl:18])=[C:11]([CH:17]=1)[C:12]([N:14]=[C:15]=[O:16])=O)=[O:4].[Cl:22][C:23]1[CH:24]=[C:25]([NH:30][NH:31]C(OC(C)(C)C)=O)[CH:26]=[CH:27][C:28]=1[CH3:29].FC(F)(F)C(O)=O>C(Cl)Cl>[Cl:18][C:10]1[C:11]([C:12]2[NH:14][C:15](=[O:16])[N:30]([C:25]3[CH:26]=[CH:27][C:28]([CH3:29])=[C:23]([Cl:22])[CH:24]=3)[N:31]=2)=[CH:17][C:7]([CH2:6][NH:5][C:3](=[O:4])[C:2]([F:21])([F:20])[F:1])=[C:8]([F:19])[CH:9]=1
Reactant: O=C=NC(=O)c1cc(CNC(=O)C(F)(F)F)c(F)cc1Cl
Reactant: Cc1ccc(NNC(=O)OC(C)(C)C)cc1Cl
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cc1ccc(-n2nc(-c3cc(CNC(=O)C(F)(F)F)c(F)cc3Cl)[nH]c2=O)cc1Cl
Yield: 46.7 %

Procedure:
The title compound was prepared according to the procedure described in Example-83 by using 5-((2,2,2-trifluoroacetamido)methyl)-2-chloro-4-fluorobenzoyl isocyanate (Intermediate-69, 0.300 g), tert-butyl 2-(3-chloro-4-methylphenyl)hydrazinecarboxylate (Intermediate-87, 0.300 g), DCM (20 mL) and trifluoro acetic acid (5.0 mL) to afford 0.200 g of the desired product.
Reaction SMILES: [N:1]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:2]=1[CH3:3].[N+:12]([C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][CH:22]=1)[CH:18]=O)([O-:14])=[O:13]>C(OC(=O)C)(=O)C>[N:1]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:2]=1[CH:3]=[CH:18][C:17]1[CH:16]=[C:15]([N+:12]([O-:14])=[O:13])[CH:22]=[CH:21][CH:20]=1
Reactant: O=Cc1cccc([N+](=O)[O-])c1
Reactant: Cc1ccc2ccccc2n1
Solvent: CC(=O)OC(C)=O
Product: O=[N+]([O-])c1cccc(C=Cc2ccc3ccccc3n2)c1
Temperature: 130 °C
Reaction time: 8 h

Procedure:
A mixture of quinaldine (8 g) and m-nitrobenzaldehyde (8.4 g) in acetic anhydride (24 ml) was stirred at 130° C. overnight. The mixture was cooled to room temperature and poured into aqueous pH 7 buffer (250 ml). The solid was chromatographed on column of flash silica gel using as eluant dichloromethane to afford a solid which was recrystallized from ethyl acetate to afford the title product as a yellow solid: m.p. 145-147° C.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:28]=[CH:29][CH:30]=1)[CH2:5][NH:6][C:7](=[O:27])[NH:8][C:9]1[S:10][CH:11]=[C:12]([CH2:14][N:15]([CH3:26])[C:16]([C:18]2[CH:23]=[C:22]([Cl:24])[N:21]=[N:20][C:19]=2Cl)=[O:17])[N:13]=1.[CH3:31][OH:32].[OH-].[Na+]>O1CCOCC1>[Cl:24][C:22]1[N:21]=[N:20][C:19]([O:32][CH3:31])=[C:18]([C:16]([N:15]([CH2:14][C:12]2[N:13]=[C:9]([NH:8][C:7]([NH:6][CH2:5][C:4]3[CH:28]=[CH:29][CH:30]=[C:2]([F:1])[CH:3]=3)=[O:27])[S:10][CH:11]=2)[CH3:26])=[O:17])[CH:23]=1
Reactant: CO
Reactant: CN(Cc1csc(NC(=O)NCc2cccc(F)c2)n1)C(=O)c1cc(Cl)nnc1Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: COc1nnc(Cl)cc1C(=O)N(C)Cc1csc(NC(=O)NCc2cccc(F)c2)n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 98.9 %

Procedure:
A solution of 3,6-dichloro-pyridazine-4-carboxylic acid {2-[3-(3-fluoro-benzyl)-ureido]-thiazol-4-ylmethyl}-methyl-amide (235 mg, 0.5 mmol) and MeOH (160 mg, 5 mmol) in 1,4-dioxane (10 mL) was added NaOH (20 mg, 0.5 mmol). The mixture was stirred overnight at room temperature and concentrated in vacuo. The residue was dissolved in CH2Cl2+5% MeOH and filtered over a small plug of silica. The volatiles were evaporated and the desired product (230 mg) was obtained as a 5:1 mixture with starting material-3,6-dichloro-pyridazine-4-carboxylic acid {2-[3-(3-fluoro-benzyl)-ureido]-thiazol-4-ylmethyl}-methyl-amide. This mixture was used as such in the subsequent steps.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[OH:15])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC(C)([O-])C.[K+].Cl.Cl[CH2:24][CH2:25][CH:26]1[CH2:30][CH2:29][CH2:28][N:27]1[CH3:31]>CC(N(C)C)=O>[CH3:31][N:27]1[CH2:28][CH2:29][CH2:30][CH:26]1[CH2:25][CH2:24][O:15][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[CH2:8][CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CN1CCCC1CCCl
Reactant: Oc1ccccc1CCc1ccccc1
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: CC(=O)N(C)C
Product: CN1CCCC1CCOc1ccccc1CCc1ccccc1
Yield: 34.2 %

Procedure:
Following a procedure similar to that described in Example 35(a), 900 mg of 2-(2-phenylethyl)phenol (prepared as described in Preparation 19), 1.02 g of potassium t-butoxide and 836 mg of 2-(2-chloroethyl)-1-methylpyrrolidine hydrochloride were reacted in 10 ml of dimethylacetamide. The mixture was then worked up as described in Example 35(a), and the crude product thus obtained was purified by column chromatography through silica gel, using a 10:1 by volume mixture of methylene chloride and methanol as the eluent, to give 480 mg of the title compound as a colorless oil.
Reaction SMILES: B([C:4]1[CH:15]=[C:14]([Cl:16])[CH:13]=[CH:12][C:5]=1[O:6][C@@H:7]([CH3:11])[C:8]([OH:10])=[O:9])(O)O.[Cl:17][C:18]1[CH:19]=[C:20]([S:25]([N:28]([CH3:30])[CH3:29])(=[O:27])=[O:26])[CH:21]=[CH:22][C:23]=1I>CO>[Cl:17][C:18]1[CH:19]=[C:20]([S:25]([N:28]([CH3:30])[CH3:29])(=[O:27])=[O:26])[CH:21]=[CH:22][C:23]=1[C:4]1[CH:15]=[C:14]([Cl:16])[CH:13]=[CH:12][C:5]=1[O:6][C@@H:7]([CH3:11])[C:8]([OH:10])=[O:9]
Reactant: C[C@H](Oc1ccc(Cl)cc1B(O)O)C(=O)O
Reactant: CN(C)S(=O)(=O)c1ccc(I)c(Cl)c1
Solvent: CO
Product: C[C@H](Oc1ccc(Cl)cc1-c1ccc(S(=O)(=O)N(C)C)cc1Cl)C(=O)O

Procedure:
The title compound was prepared by the method of example 144 step (i) using the product from example 151 step (iv), the product from example 148 step (ii) and methanol as solvent. Yield (0.08 g).
Reaction SMILES: [OH-].[K+].[NH:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[N:5]=[CH:4]1.[NH2:12]OS(O)(=O)=O>O.C(O)C>[NH2:12][N:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[N:5]=[CH:4]1
Reactant: c1ccc2[nH]cnc2c1
Reactant: NOS(=O)(=O)O
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: Nn1cnc2ccccc21
Temperature: 30 °C
Reaction time: 18 h

Procedure:
In a mixed slovent of water(50 ml) and ethanol(50 ml) was dissolved 19.64 g(35 mmol) of potassium hydroxide and 5.91 g(5 mmol) of 1H-benzimidazole was added thereto. Water(10 ml) containing 14.41 g (125 mmol) of hydroxylamine-O-sulfonic acid was slowly added while maintaining the temperature at 30° C. and the mixture was stirred at the same temperature for 18 hours.
Reaction SMILES: Cl[C:2]1[C:11]([CH3:12])=[C:10]([Cl:13])[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[CH3:14][C:15]1[CH:20]=[CH:19][N:18]=[C:17]([Sn](CCCC)(CCCC)CCCC)[CH:16]=1>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>[Cl:13][C:10]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]=[C:2]([C:17]2[CH:16]=[C:15]([CH3:14])[CH:20]=[CH:19][N:18]=2)[C:11]=1[CH3:12]
Reactant: CCCC[Sn](CCCC)(CCCC)c1cc(C)ccn1
Reactant: Cc1c(Cl)nc2ncccc2c1Cl
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Product: Cc1ccnc(-c2nc3ncccc3c(Cl)c2C)c1

Procedure:
Prepared according to procedure E and using 2,4-dichloro-3-methyl-1,8-naphthyridine (500 mg, 2.347 mmol), 4-methyl-2-(tributylstannyl)pyridine (897 mg, 2.347 mmol) and Pd(PPh3)4 (271 mg, 0.235 mmol). Purification by column chromatography (hexanes:EtOAc, from 1:0 to 1:2) gave 4-chloro-3-methyl-2-(4-methylpyridin-2-yl)-1,8-naphthyridine. Mass Spectrum (ESI) m/e=270.0 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([Cl:14])=[CH:12][CH:11]=[C:10]([CH2:15][NH:16][CH2:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[CH:9]=2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[Cl:32][C:33]1[C:34]([OH:44])=[C:35]([S:40](Cl)(=[O:42])=[O:41])[CH:36]=[C:37]([Cl:39])[CH:38]=1>C(Cl)Cl>[Cl:32][C:33]1[C:34]([OH:44])=[C:35]([S:40]([N:16]([CH2:15][C:10]2[CH:9]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)[C:13]([Cl:14])=[CH:12][CH:11]=2)[CH2:17][C:18]2[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=2)(=[O:42])=[O:41])[CH:36]=[C:37]([Cl:39])[CH:38]=1
Reactant: O=S(=O)(Cl)c1cc(Cl)cc(Cl)c1O
Reactant: Fc1ccc(CNCc2ccc(Cl)c(-c3ccc(Cl)cc3)c2)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=S(=O)(c1cc(Cl)cc(Cl)c1O)N(Cc1ccc(F)cc1)Cc1ccc(Cl)c(-c2ccc(Cl)cc2)c1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 46 %

Procedure:
1-(4′,6-Dichlorobiphenyl-3-yl)-N-(4-fluorobenzyl)methanamine (200 mg, 0.555 mmol, 1.0 eq) was dissolved in dry DCM and the resulting solution was stirred for 10 minutes and cooled to 0° C. Triethylamine (168 mg, 1.6 mmol, 3 eq) was added to the above solution and the mixture was stirred for 10 minutes. 3,5-Dichloro-2-hydroxybenzene-1-sulfonyl chloride dissolved in DCM was added slowly over a period of 10 minutes and the mixture was stirred for 4 h at ambient temperature. The solvent was evaporated under reduced pressure and the residue was purified by flash column chromatography on silica gel (60-120) eluting with 5-10% ethyl acetate/hexane to give the title compound (0.14 g, 46%). 1H NMR (400 MHz, CD3OD) δ 4.47 (s, 2H), 4.53 (s, 2H), 6.91-6.98 (m, 3H), 7.12-7.15 (m, 1H), 7.22-7.27 (m, 4H), 7.33-7.35 (d, 1H), 7.43-7.45 (d, 2H), 7.54 (d, 1H), 7.67 (d, 1H). MS (ESI): 583.8 (M−H)−.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[N:11]1[CH2:16][CH2:15][CH:14]([CH2:17][CH2:18][N:19]2[C:23](=[O:24])[CH2:22][O:21][C:20]2=[O:25])[CH2:13][CH2:12]1.[NH3:26]>CO>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[N:11]1[CH2:16][CH2:15][CH:14]([CH2:17][CH2:18][NH:19][C:20](=[O:25])[O:21][CH2:22][C:23]([NH2:26])=[O:24])[CH2:13][CH2:12]1
Reactant: N
Reactant: O=C1COC(=O)N1CCC1CCN(c2ccc3ccccc3n2)CC1
Solvent: CO
Product: NC(=O)COC(=O)NCCC1CCN(c2ccc3ccccc3n2)CC1

Procedure:
The process is performed according to the procedure described in Example 3 (step 3.4). Starting with 1.14 g (3.36 mmol) of 3{2-[1-(2-quinolyl)-4-piperidyl]ethyl}-1,3-oxazolidine-2,4-dione, described in Example 8 (step 8.2), and 9.60 ml (67.20 mmol) of a solution (7M) of aqueous ammonia in methanol, and after chromatography on silica gel, eluting with a 95/5 mixture of dichloromethane and methanol, followed by recrystallization from ethyl acetate, 0.360 g of pure product is obtained in the form of a white solid.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1)#[N:2].[OH-:9].[Na+]>>[C:1]([NH2:2])(=[O:9])[C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1
Reactant: N#Cc1ccncc1
Reactant: [OH-]
Agent: [Na+]
Product: NC(=O)c1ccncc1

Procedure:
As to preparative methods for these compounds, cyanopyridines have frequently been hydrolyzed in batch and continuous processes with catalytic to stoichiometric excesses of a base. A majority of the methods reported have been batch processes. For example, 4-cyanopyridine in the presence of sodium hydroxide at a molar ratio of 1:(0.03-0.075) and at 120°-170° C. is reported to give isonicotinamide. See U.S.S.R. SU 1,553,531 (1990); CA:113:78174f (1990). Similarly, 2-cyanopyridine is reported to react with sodium hydroxide at a molar ratio of 1:(0.03-0.20) and at temperatures ranging from 100°-130° C. to give 2-picolinamide. See U.S.S.R. SU 1,553,530 (1990); CA:113:78173e (1990). With a molar ratio of 4-cyanopyridine:sodium hydroxide of 1:(1.5-1.75) and a hydrolysis temperature of 50°-80° C., the reported hydrolysis product was isonicotinic acid. See U.S.S.R. SU 1,288,183; CA:106:176187n (1987). The hydrolysis of 3-cyanopyridine with excess ammonia at 107°-109° C. for 12 hours was reported to give mixtures of nicotinamide and niacin. See J. Am Chem. Soc. 65, at pages 2256-7 (1943). In still another variation, the hydrolysis of 3-cyanopyridine has been reported with a polymeric base, Dowex 1X4 (in the hydroxide form), to yield nicotinamide. See Dutch Patent Application No. 7706612-A; CA:90:186814e. U.S. Pat. No. 4,314,064 describes the continuous hydrolysis of 3-cyanopyridine with 0.3 to 3.0 moles of an alkali metal hydroxide for each 100 moles of cyanopyridine at pressures of between 3 to 20 bars and with heating or cooling to maintain the prescribed reaction temperature. Similarly, 3-cyanopyridine is reported to react in a continuous process with aqueous ammonia at a molar ratio of 1:0.5 and a contact time of 40-50 minutes at 200°-260° C. to give nicotinamide. See Journal of Applied Chemistry of the USSR (English Translation: 45:2716-2718 (1972).