Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [BH4-].[Na+].[Cl:3][C:4]1[CH:16]=[CH:15][C:7]([C:8]([CH:10]2[CH2:12][CH:11]2[C:13]#[N:14])=[O:9])=[C:6]([O:17][CH3:18])[CH:5]=1.[Cl-].[NH4+]>C(O)C.C(OCC)(=O)C>[Cl:3][C:4]1[CH:16]=[CH:15][C:7]([CH:8]([OH:9])[CH:10]2[CH2:12][CH:11]2[C:13]#[N:14])=[C:6]([O:17][CH3:18])[CH:5]=1
Reactant: COc1cc(Cl)ccc1C(=O)C1CC1C#N
Agent: [BH4-]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOC(C)=O
Solvent: CCO
Product: COc1cc(Cl)ccc1C(O)C1CC1C#N
Temperature: 40 °C
Reaction time: 1 h

Procedure:
49.1 mg (1.30 mmol) of sodium borohydride were added to 278 mg (1.18 mmol) of the compound from Example 128A in 23 ml of ethanol and 10 ml of ethyl acetate under argon, and the mixture was stirred at 40° C. for 1 h. The reaction mixture was added to saturated aqueous ammonium chloride solution and ethyl acetate, the phases were separated, the aqueous phase was extracted twice with ethyl acetate, and the combined organic phases were dried over magnesium sulfate, filtered and concentrated. 190 mg (68% of theory) of a mixture of the diastereomerse of the title compound were obtained.
Reaction SMILES: [Br:1][C:2]1[C:3]2[N:12]([CH:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)[N:11]=[C:10]([C:18]3[CH:19]=[C:20]([C:23]([O:25]C)=[O:24])[S:21][CH:22]=3)[C:4]=2[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[OH-].[Na+]>CO>[Br:1][C:2]1[C:3]2[N:12]([CH:13]3[CH2:14][CH2:15][CH2:16][CH2:17]3)[N:11]=[C:10]([C:18]3[CH:19]=[C:20]([C:23]([OH:25])=[O:24])[S:21][CH:22]=3)[C:4]=2[C:5]([O:8][CH3:9])=[N:6][CH:7]=1
Reactant: COC(=O)c1cc(-c2nn(C3CCCC3)c3c(Br)cnc(OC)c23)cs1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: COc1ncc(Br)c2c1c(-c1csc(C(=O)O)c1)nn2C1CCCC1
Temperature: 50 °C
Reaction time: 4 h
Yield: 99.6 %

Procedure:
To a solution of methyl 4-(7-bromo-1-cyclopentyl-4-methoxy-1H-pyrazolo[4,3-c]pyridin-3-yl)thiophene-2-carboxylate (111 mg) in methanol (10 mL) was added 1N aqueous sodium hydroxide solution (2 mL) under ice-cooling, and the mixture was stirred at 50° C. for 4 hr. The reaction mixture was concentrated under reduced pressure to evaporate the methanol, and the mixture was partitioned between ethyl acetate and 1N hydrochloric acid (5 mL). The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound (107 mg).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4](I)[C:3]=1[F:9].[CH3:10][S:11]([O-])(=[O:13])=[O:12].[Na+]>CN(C)C(=O)C.[Cu](I)I>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([S:11]([CH3:10])(=[O:13])=[O:12])[C:3]=1[F:9]
Reactant: Fc1cccc(I)c1F
Reactant: CS(=O)(=O)[O-]
Agent: I[Cu]I
Agent: [Na+]
Solvent: CC(=O)N(C)C
Product: CS(=O)(=O)c1cccc(F)c1F
Yield: 72.5 %

Procedure:
1,2-Difluoro-3-iodobenzene (1.70 g; 7.08 mmol), 2.17 g (21.2 mmol) of sodium methanesulfonate and 4.03 g (21.2 mmol) of copper iodide were heated with stirring at 111° C. for 20 hours in 50 ml of N,N-dimethylacetamide. The reaction solution was filtered, chloroform was added to the filtrate and the mixture was washed with a saturated aqueous solution of sodium hydrogen carbonate. The organic layer was dried and concentrated and the resulting residue was purified by a silica gel column chromatography (hexane:ethyl acetate=2:1) to give 987 mg (yield: 72%) of 1,2-difluoro-3-methanesulfonylbenzene as a colorless transparent solution.
Reaction SMILES: [OH-].[Na+].[CH2:3]([SH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH:11](Cl)([F:13])[F:12]>O>[F:12][CH:11]([S:10][CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[F:13]
Reactant: FC(F)Cl
Reactant: SCc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: FC(F)SCc1ccccc1
Yield: 75 %

Procedure:
One equivalent of 40% by weight of sodium hydroxide in water was mixed with one equivalent of benzyl mercaptan with R-22 (1.1 molar equivalents) at 60° C. for 1 h. The tests are carried out in a 500 ml Hastelloy reactor at an autogenous pressure at 60° C. The pressure is 3.5 bar. A chemical yield of 75%, by quantitative determination by 19F NMR, is obtained over two tests carried out under the same conditions.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:23])[CH2:4][C:5]1([CH2:21][CH3:22])[C:10]2[NH:11][C:12]3[C:17]([C:9]=2[CH:8]([OH:20])[CH2:7][O:6]1)=[CH:16][CH:15]=[CH:14][C:13]=3[CH2:18][CH3:19]>CCOCC.[O-2].[O-2].[Mn+4]>[CH3:1][O:2][C:3](=[O:23])[CH2:4][C:5]1([CH2:21][CH3:22])[C:10]2[NH:11][C:12]3[C:17]([C:9]=2[C:8](=[O:20])[CH2:7][O:6]1)=[CH:16][CH:15]=[CH:14][C:13]=3[CH2:18][CH3:19]
Reactant: CCc1cccc2c3c([nH]c12)C(CC)(CC(=O)OC)OCC3O
Agent: [Mn+4]
Agent: [O-2]
Solvent: CCOCC
Product: CCc1cccc2c3c([nH]c12)C(CC)(CC(=O)OC)OCC3=O
Temperature: 25 °C
Reaction time: 16 h
Yield: 57.5 %

Procedure:
1,8-Diethyl-4-hydroxy-1,3,4,9-tetrahydro[3,4-b]indole-1-acetic acid methyl ester 15 (2.5 g, 8.0 mmol) was added in one portion to a suspension of manganese dioxide (15 g) in 150 mL of ether. The solution was allowed to stir at room temperature for 16 hours, after which time an extra 2 g of manganese dioxide was added and the mixture allowed to stir an additional 2 hours to complete the reaction. The manganese dioxide was removed by filtration through celite, and the pad was washed with 500 mL of CH2Cl2. The solvent was concentrated in vacuo to provide 2.2 g of crude solid, which was recrystallized from hot EtOAc-hexane to yield 1.45 g of colorless crystals, m.p. 192°-193° C. Concentration of the mother liquor provided a second crop (210 mg) of crystals for a total yield of 64%. 1H NMR (400 MHz, DMSO-d6): δ 7.77 (d, J=7, 1H), 7.14 (t, J=7, 1H), 7.07 (d, J=7, 1H), 4.27 (d, J=17, 1H), 4.21 (d, J=17, 1H), 3.52 (s, 3H), 3.31 (s, 2H), 2.90 (m, 2H), 2.23 (m, 1H), 1.88 (m, 1H), 1.25 (t, J=7.5, 3H), 0.81 (t, J=7, 3H);
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([C:14]([OH:16])=O)[CH:11]=[CH:10][C:9]=2[CH:17]2[CH2:21][CH2:20][O:19][CH2:18]2)[CH:5]=[CH:6][CH:7]=1.[CH3:22][C:23]([CH3:31])([C:25]1[N:29]=[C:28]([CH3:30])[O:27][N:26]=1)[NH2:24]>>[CH3:22][C:23]([NH:24][C:14]([C:12]1[CH:11]=[CH:10][C:9]([CH:17]2[CH2:21][CH2:20][O:19][CH2:18]2)=[C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[N:13]=1)=[O:16])([C:25]1[N:29]=[C:28]([CH3:30])[O:27][N:26]=1)[CH3:31]
Reactant: Cc1nc(C(C)(C)N)no1
Reactant: O=C(O)c1ccc(C2CCOC2)c(-c2cccc(Cl)c2)n1
Product: Cc1nc(C(C)(C)NC(=O)c2ccc(C3CCOC3)c(-c3cccc(Cl)c3)n2)no1

Procedure:
The title compound was synthesized in analogy to Example 1, using 6-(3-chloro-phenyl)-5-(tetrahydro-furan-3-yl)-pyridine-2-carboxylic acid (Example 101.0 and α,α,5-trimethyl-1,2,4-oxadiazole-3-methanamine (CAN 1153831-97-0) as starting materials, MS (EI): m/e=427.1 [M+H]+.
Reaction SMILES: [CH2:1]([O:8][C@:9]1([CH:33]=C)[C@@H:13]([CH2:14][O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:12][C@@H:11]([N:23]2[CH:31]=[C:29]([CH3:30])[C:27](=[O:28])[NH:26][C:24]2=[O:25])[C@H:10]1[OH:32])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.I([O-])(=O)(=O)=[O:36].[Na+].[BH4-].[Na+]>C1COCC1.O.[Os](=O)(=O)(=O)=O.C(O)(C)(C)C>[CH2:1]([O:8][C@:9]1([CH2:33][OH:36])[C@@H:13]([CH2:14][O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:12][C@@H:11]([N:23]2[CH:31]=[C:29]([CH3:30])[C:27](=[O:28])[NH:26][C:24]2=[O:25])[C@H:10]1[OH:32])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: [O-][I+3]([O-])([O-])[O-]
Reactant: C=C[C@]1(OCc2ccccc2)[C@H](O)[C@H](n2cc(C)c(=O)[nH]c2=O)O[C@@H]1COCc1ccccc1
Agent: O=[Os](=O)(=O)=O
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CC(C)(C)O
Solvent: C1CCOC1
Product: Cc1cn([C@@H]2O[C@H](COCc3ccccc3)[C@@](CO)(OCc3ccccc3)[C@@H]2O)c(=O)[nH]c1=O
Temperature: 25 °C
Reaction time: 18 h
Yield: 36.3 %

Procedure:
To a solution of nucleoside 26 (2.00 g, 4.31 mmol) in a mixture of THF (15 cm3) and water (15 cm3) was added sodium periodate (2.76 g, 12.9 mmol) and a 2.5% solution of osmium tetraoxide in t-butanol (w/w, 0.54 cm3, 43 μmol). The reaction was stirred at room temperature for 18 h, quenched with water (50 cm3), and the mixture was extracted with dichloromethane (2×100 cm3). The combined extract was washed with saturated aqueous sodium hydrogen carbonate (3×75 cm3), dried (Na2SO4) and evaporated under reduced pressure. The residue was redissolved in a mixture of THF (15 cm3) and water (15 cm3), and sodium borohydride (488 mg, 12.9 mmol) was added. The reaction mixture was stirred at room temperature for 1 h, water (50 cm3) was added, and the mixture was extracted with dichloromethane (2×100 cm3). The combined organic phase was washed with saturated aqueous sodium hydrogencarbonate (3×75 cm3) and dried (Na2SO4). The solvent was removed and the residue was purified by silica gel column chromatography using dichloromethane/methanol (98:2, v/v) as eluent to give nucleoside 27 as a white foam (732 mg, 36%). δH (CDCl3) 11.09 (1H, br s, NH), 7.41 (1H, d, J 1.0, 6-H), 7.38-7.26 (Bn), 6.16 (1H, d, J 2.6, 1′-H), 5.12 (1H, d, J 5.4, 2′-OH), 4.66-4.29 (6H, m, 2′-H, 4′-H, Bn), 4.02-3.96 (2H, m, 1″-Ha, 1″-Hb), 3.90 (1H, dd, J 7.2, 9.7, 5′-Ha), 3.79 (1H, dd, J 5.6, 9.7, 5′-Hb), 2.49 (1H, t, J 6.4, 1″-OH), 1.68 (3H, d, J 0.6, CH3); δC (CDCl3) 166.1 (C-4), 150.6 (C-2), 139.0, 137.9, 137.0 (C-6, Bn), 128.7, 128.6, 128.4, 128.3, 128.0 (Bn), 107.5 (C-5), 88.2 (C-1′), 88.1 (C-3′), 84.2 (C-4′), 73.7 (C-5′), 72.1 (C-2′), 69.3, 65.4 (Bn), 58.6 (C-1″), 12.3 (CH3).
Reaction SMILES: [CH2:1]1[C:9]2[C:4](=[CH:5][C:6]([CH:10]([OH:31])[CH2:11][CH2:12][N:13]3[CH2:18][CH2:17][CH:16]([C:19]4[CH:20]=[C:21]([NH:25][C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])[CH:22]=[CH:23][CH:24]=4)[CH2:15][CH2:14]3)=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[F:32][C:33]([F:42])([F:41])[C:34]1[CH:39]=[CH:38][C:37](O)=[CH:36][CH:35]=1>>[CH2:1]1[C:9]2[C:4](=[CH:5][C:6]([CH:10]([O:31][C:37]3[CH:38]=[CH:39][C:34]([C:33]([F:42])([F:41])[F:32])=[CH:35][CH:36]=3)[CH2:11][CH2:12][N:13]3[CH2:14][CH2:15][CH:16]([C:19]4[CH:20]=[C:21]([NH:25][C:26](=[O:30])[CH:27]([CH3:28])[CH3:29])[CH:22]=[CH:23][CH:24]=4)[CH2:17][CH2:18]3)=[CH:7][CH:8]=2)[CH2:3][CH2:2]1
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(CCC(O)c3ccc4c(c3)CCC4)CC2)c1
Reactant: Oc1ccc(C(F)(F)F)cc1
Product: CC(C)C(=O)Nc1cccc(C2CCN(CCC(Oc3ccc(C(F)(F)F)cc3)c3ccc4c(c3)CCC4)CC2)c1

Procedure:
Prepared by Procedure A and Scheme AN using N-(3-{1-[3-(2,3-dihydro-1H-inden-5-yl)-3-hydroxypropyl]-4-piperidinyl}phenyl)-2-methylpropanamide and 4-trifluoromethylphenol: ESMS m/e: 565.0 (M+H)+.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:23])[CH2:5][C:6]1[CH:7]=[C:8]([C:14]2[CH:19]=[CH:18][C:17](Br)=[CH:16][C:15]=2[CH:21]=[O:22])[C:9]([O:12][CH3:13])=[CH:10][CH:11]=1)[CH3:2].[CH3:24][N:25]1[CH:29]=[C:28](B2OC(C)(C)C(C)(C)O2)[CH:27]=[N:26]1>>[CH2:1]([O:3][C:4](=[O:23])[CH2:5][C:6]1[CH:7]=[C:8]([C:14]2[CH:19]=[CH:18][C:17]([C:28]3[CH:27]=[N:26][N:25]([CH3:24])[CH:29]=3)=[CH:16][C:15]=2[CH:21]=[O:22])[C:9]([O:12][CH3:13])=[CH:10][CH:11]=1)[CH3:2]
Reactant: CCOC(=O)Cc1ccc(OC)c(-c2ccc(Br)cc2C=O)c1
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Product: CCOC(=O)Cc1ccc(OC)c(-c2ccc(-c3cnn(C)c3)cc2C=O)c1

Procedure:
Prepared according to the procedure described in Example 1, Step 4, using the following starting materials: (4′-bromo-2′-formyl-6-methoxy-biphenyl-3-yl)-acetic acid ethyl ester and 1-methylpyrazole-4-boronic acid pinacol ester.
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[CH3:6][O:7][C:8]1[CH:9]=[C:10]2[CH:13]([CH2:14][OH:15])[CH2:12][C:11]2=[CH:16][CH:17]=1.C(N(CC)CC)C>C(Cl)Cl>[S:2]([OH:4])(=[O:7])(=[O:3])[CH3:1].[CH3:6][O:7][C:8]1[CH:9]=[C:10]2[CH:13]([CH2:14][OH:15])[CH2:12][C:11]2=[CH:16][CH:17]=1
Reactant: CS(=O)(=O)Cl
Agent: COc1ccc2c(c1)C(CO)C2
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)O
Temperature: 0 °C
Reaction time: 2 h

Procedure:
Methane sulphonyl chloride (13.4 ml) is added dropwise to a stirred solution of 5-methoxy-1-hydroxymethyl benzocyclobutene (26 g) and triethylamine (26.5 ml) in methylene chloride (670 ml) cooled to 0° C. under nitrogen. The reaction mixture is allowed to warm to RT, stirred for 2 hours at RT, washed with water and saturated salt, dried over Na2SO4, and filtered. The filtrate is concentrated in vacuo yielding the desired product as a liquid.
Reaction SMILES: C[O:2][C:3]1[N:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH:15][CH3:16])[CH:10]=2)=[CH:5][C:4]=1[NH:17][CH:18]1[CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19]1.CO.[BrH:31]>>[BrH:31].[BrH:31].[NH:20]1[CH2:21][CH:18]([NH:17][C:4]2[C:3](=[O:2])[NH:8][CH:7]=[C:6]([C:9]3[CH:14]=[CH:13][N:12]=[C:11]([NH:15][CH3:16])[CH:10]=3)[CH:5]=2)[CH2:19]1
Reactant: CNc1cc(-c2cnc(OC)c(NC3CN(C(=O)OC(C)(C)C)C3)c2)ccn1
Agent: Br
Solvent: CO
Product: CNc1cc(-c2c[nH]c(=O)c(NC3CNC3)c2)ccn1
Temperature: 25 °C
Yield: 89 %

Procedure:
A solution of tert-butyl 3-((6-methoxy-2′-(methylamino)-[3,4′-bipyridin]-5-yl)amino)azetidine-1-carboxylate (890 mg, 2.31 mmol) in 40% HBr (9 mL) was stirred at 50° C. for 14 h. After the mixture was cooled to RT, 9 mL of methanol was added, the residue filtered, washed with ethyl acetate (5 mL), and dried in vacuo to afford 5-(azetidin-3-ylamino)-2′-(methylamino)-[3,4′-bipyridin]-6(1H)-one di-hydrobromide (947 mg, 89%) as yellow solid: 1H NMR (400 MHz, DMSO-d6) δ 12.97 (s, 1H), 12.18 (d, J=5.9 Hz, 1H), 8.87 (s, 1H), 8.68 (s, 1H), 8.50 (s, 1H), 7.89 (d, J=6.8 Hz, 1H), 7.52 (dd, J=5.8, 2.6 Hz, 1H), 7.23 (s, 1H), 7.20 (dd, J=7.0, 1.8 Hz, 1H), 6.60 (s, 1H), 6.50 (d, J=2.5 Hz, 1H), 4.48 (d, J=8.9 Hz, 1H), 4.34 (m, 2H), 4.09-3.97 (m, 2H), 2.99 (d, J=4.8 Hz, 3H); MS (ES) m/z 272 (M+H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.C(Cl)(C(Cl)=O)=O.[F:18][C:19]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:20]=1[NH2:21]>C1COCC1.C(Cl)Cl.O>[Br:1][C:2]1[CH:3]=[N:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([NH:21][C:20]1[CH:22]=[CH:23][C:24]([F:26])=[CH:25][C:19]=1[F:18])=[O:9]
Reactant: Nc1ccc(F)cc1F
Reactant: O=C(O)c1cc(Br)cnc1F
Agent: O=C(Cl)C(=O)Cl
Solvent: O
Solvent: C1CCOC1
Solvent: ClCCl
Product: O=C(Nc1ccc(F)cc1F)c1cc(Br)cnc1F
Temperature: 40 °C
Reaction time: 8 h
Yield: 72.5 %

Procedure:
To a solution of 5-bromo-2-fluoronicotinic acid (55 mg, 0.25 mmol) in a mixture of 2.0 mL of THF and 5.0 mL of DCM was added (COCl)2 (0.13 mL, 1.5 mmol). The mixture was stirred at room temperature for 1 h and at 40° C. overnight. After cooling, the solvent was removed under reduced pressure. The residue was dissolved in 2.0 mL of DCM and to it were added 2,4-difluoroaniline (0.05 mL, 0.5 mmol) and 0.1 mL of TEA. The mixture was stirred at room temperature for 2 h and diluted with H2O. The organic layer was separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine and dried over MgSO4. After filtration and concentration in vacuo, the residue was purified on preparative (RP) HPLC to give the desired product (60 mg, 73% yield). MS(ESI+) m/z 331.18, 333.18 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][NH:6][C:5]2=[O:12].[CH3:13][O:14][C:15]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][C:16]=1[CH:17]=O>CO>[CH3:13][O:14][C:15]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][C:16]=1[CH2:17][NH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][NH:6][C:5]2=[O:12]
Reactant: COc1ccc(OC)c(C=O)c1
Reactant: Nc1ccc2nc[nH]c(=O)c2c1
Solvent: CO
Product: COc1ccc(OC)c(CNc2ccc3nc[nH]c(=O)c3c2)c1
Temperature: 25 °C

Procedure:
A mixture of 200 mg of 6-amino-3H-quinazolin-4-one and 206 mg of 2,5-dimethoxybenzaldehyde in 12 ml of dry methanol is heated to 60° for 16 hours. cooling the yellow precipitate is filtered and resuspended in 10 ml of dry methanol. This mixture is treated with 85 mg of sodium cyanoborohydride and heated for some minutes until all the materials are dissolved. After stirring for 2 at room temperature, the mixture is poured into water and extracted with acetate. The combined organic extracts are dried over magnesium sulfate and evaporated in vacuo. The pure title compound is obtained by crystallisation from ethanol as colourless crystals. mp: 203-205°.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:20]#[N:21])=[C:7]([C:12]3[CH:13]=[N:14][CH:15]=[C:16]([CH:18]=O)[CH:17]=3)[N:8]2[CH3:11])=[CH:4][CH:3]=1.[C:22]1([CH2:28][S:29]([NH2:32])(=[O:31])=[O:30])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:20]#[N:21])=[C:7]([C:12]3[CH:17]=[C:16]([CH2:18][NH:32][S:29]([CH2:28][C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)(=[O:30])=[O:31])[CH:15]=[N:14][CH:13]=3)[N:8]2[CH3:11])=[CH:4][CH:3]=1
Reactant: Cn1c(-c2cncc(C=O)c2)c(C#N)c2ccc(Cl)cc21
Reactant: NS(=O)(=O)Cc1ccccc1
Product: Cn1c(-c2cncc(CNS(=O)(=O)Cc3ccccc3)c2)c(C#N)c2ccc(Cl)cc21

Procedure:
6-Chloro-2-(5-formyl-pyridin-3-yl)-1-methyl-1H-indole-3-carbonitrile (Example 126) and phenyl-methanesulfonamide are processed according to the method described in Example 170 to give N-[5-(6-chloro-3-cyano-1-methyl-1H-indol-2-yl)-pyridin-3-ylmethyl]-C-phenyl-methanesulfonamide. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.77 (s, 3H), 4.31 (s, 2H), 4.44 (s, 2H), 7.30-7.41 (m, 6H), 7.73 (d, J=8.3 Hz, 1H), 7.83 (br. s., 1H), 7.97 (d, J=1.5 Hz, 1H), 8.03 (t, J=2.1 Hz, 1H), 8.73 (d, J=2.0 Hz, 1H), 8.79 (d, J=2.0 Hz, 1H). HRMS (ESI) m/z 451.1006 [(M+H)+ Calcd for C23H20ClN4O2S: 451.0996].
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4](/[CH:8]=[C:9](\[C:13]2[CH:18]=[CH:17][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:15][CH:14]=2)/[C:10]([OH:12])=O)[CH:5]=[CH:6][CH:7]=1.S(Cl)(Cl)=O.C(N(CC)CC)C.[CH:34]([NH2:37])([CH3:36])[CH3:35].[NH4+].[Cl-]>C1(C)C=CC=CC=1>[CH:34]([NH:37][C:10](=[O:12])/[C:9](/[C:13]1[CH:18]=[CH:17][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:15][CH:14]=1)=[CH:8]/[C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Br:1])[CH:3]=1)([CH3:36])[CH3:35]
Reactant: CS(=O)(=O)c1ccc(/C(=C\c2cccc(Br)c2)C(=O)O)cc1
Reactant: CC(C)N
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Solvent: O=S(Cl)Cl
Product: CC(C)NC(=O)/C(=C/c1cccc(Br)c1)c1ccc(S(C)(=O)=O)cc1
Temperature: 21 °C
Reaction time: 0.5 h

Procedure:
To a solution of (E)-3-(3-bromophenyl)-2-[4-(methylsulfonyl)phenyl]-2-propenoic acid from Step 1 (24.9 g, 65 mmol) in toluene (250 mL) was added thionyl chloride (14.3 mL, 196 mmol) and triethylamine (34 mL, 245 mmol). After stirring at 21° C. for 0.5 h., isopropyl amine (28 mL, 327 mmol) was added. After a further 2 h at r.t., the mixture was cooled to 0° C. and was neutralised with saturated NH4Cl solution, then extracted with EtOAc. The organic extracts were washed (H2O, brine), dried (MgSO4), filtered and concentrated. Purification by flash chromatography (Hex:EtOAc, 1:1 to pure EtOAc) yielded the (E)-N-isopropyl-3-(3-bromophenyl)-2-[4-(methylsulfonyl)phenyl]-2-propenamide compound.
Reaction SMILES: CS(C)=O.I[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[NH2:12].O=[C:14]([CH3:21])[CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17].C(=O)([O-])[O-].[Cs+].[Cs+]>[Cu-]=O.O>[CH3:21][C:14]1[NH:12][C:7]2[C:6]([C:15]=1[C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:11][CH:10]=[CH:9][CH:8]=2
Reactant: Nc1ccccc1I
Reactant: CCOC(=O)CC(C)=O
Agent: O=[Cu-]
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CS(C)=O
Solvent: O
Product: CCOC(=O)c1c(C)[nH]c2ccccc12
Temperature: 100 °C
Reaction time: 16 h
Yield: 57.4 %

Procedure:
To a mixed solution of dimethyl sulfoxide (100 mL) and water (34 mL), 2-iodobenzenamine (50 g, 228 mmol), ethyl 3-oxobutanoate (35.6 g, 274 mmol), copper(I) oxide (3.3 g, 22.8 mmol) and cesium carbonate (75 g, 228 mmol) was added. The mixture was stirred at 100° C. for 16 hours under nitrogen gas atmosphere. The reaction mixture was filtered through a pad of celite. The filtrate was diluted with water and extracted with ethyl acetate. The organic phase was concentrated in vacuo, and then the residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=5:1) to afford the title compound as a light yellow solid (26.6 g, 57.5%). LCMS 204 (M+H)+.
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][C:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:12].C(O)C.[C:22](OC)(=[O:25])[C:23]#[CH:24]>>[C:11]([C:10]1[CH:24]=[CH:23][C:22](=[O:25])[N:1]2[C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[NH:3][C:2]=12)(=[O:12])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: O=C(Cc1nc2ccccc2[nH]1)c1ccccc1
Reactant: C#CC(=O)OC
Solvent: CCO
Product: O=C(c1ccccc1)c1ccc(=O)n2c1[nH]c1ccccc12
Temperature: 25 °C
Reaction time: 24 h
Yield: 36.6 %

Procedure:
200 mg (0.733 mmol) of the compound of Example II are dissolved in 5 mL ethanol 70 mg (0.833 mmol) sodium bicarbonate and 70 mg (0.833 mmol) methyl propiolate are added at room temperature and the mixture is stirred for 24 h at room temperature. The solvent is evaporated under vacuum and the crude is stirred with ethyl acetate, filtered and dried to yield 77.3 mg (37% of th.) 4-benzoylpyrido[1,2-a]-benzimidazol-1(5H)-one.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]#[C:10][CH2:11][OH:12])=[CH:5][CH:4]=1)#[N:2]>C1(C)C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl-].[Rh]>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][CH2:11][OH:12])=[CH:5][CH:4]=1)#[N:2]
Reactant: N#Cc1ccc(C#CCO)cc1
Agent: [Rh]
Agent: [Cl-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: N#Cc1ccc(CCCO)cc1
Temperature: 65 °C
Reaction time: 15 h
Yield: 70.7 %

Procedure:
A suspension of Compound 72-1 (5.79 g) and chlorotris(triphenylphosphine)rhodium(I) (5.00 g) in toluene (150 ml) was stirred under a hydrogen atmosphere at 65° C. for 15 hr. The reaction mixture was concentrated, diisopropyl ether was added and the mixture was filtered through celite. The filtrate was concentrated and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=99:1-50:50) to give the object product (4.20 g) as a brown oil.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[NH:9][S:10]([C:13]1[N:21]=[C:20]2[N:15]([C:16](Cl)=[N:17][C:18]([O:22][CH3:23])=[CH:19]2)[N:14]=1)(=[O:12])=[O:11].[CH3:25][OH:26].C[O-].[Na+]>C(O)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[NH:9][S:10]([C:13]1[N:21]=[C:20]2[N:15]([C:16]([O:26][CH3:25])=[N:17][C:18]([O:22][CH3:23])=[CH:19]2)[N:14]=1)(=[O:12])=[O:11]
Reactant: CO
Reactant: COc1cc2nc(S(=O)(=O)Nc3c(Cl)cccc3Cl)nn2c(Cl)n1
Agent: C[O-]
Agent: [Na+]
Solvent: CC(=O)O
Product: COc1cc2nc(S(=O)(=O)Nc3c(Cl)cccc3Cl)nn2c(OC)n1

Procedure:
N-(2,6-Dichlorophenyl)-5-chloro-7-methoxy-1,2,4-triazolo[1,5-c]pyrimidine-2-sulfonamide (0.8 g, 0.002 mol) was mixed with 25 ml of methanol and 1.34 ml of 25 percent sodium methoxide in methanol (0.006 mol) added with stirring. After 10 min 2 ml of acetic acid was added and the mixture was concentrated under reduced pressure. The residue was dissolved in methylene chloride and the solution extracted with water, dried over sodium sulfate, and concentrated under reduced pressure. The residue was mixed with carbon tetrachloride, collected by filtration, and dried to obtain 0.5 g of the title compound as an off-white powder melting at 211°-212° C.