Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C1(S([NH2:10])(=O)=O)C=CC=CC=1.C([O-])([O-])=O.[K+].[K+].[CH:17]1([N:23]=[C:24]=[O:25])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1>CC(C)=O.O1CCOCC1.O>[CH:17]1([NH:23][C:24](=[O:25])[NH2:10])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1
Reactant: NS(=O)(=O)c1ccccc1
Reactant: O=C=NC1CCCCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC(C)=O
Solvent: C1COCCO1
Product: NC(=O)NC1CCCCC1
Reaction time: 6 h

Procedure:
7.6 g of 4-(β-<1-butyl-1,2-dihydro-2-oxo-nicotinamido>-ethyl)-benzenesulfonamide (melting point 162 - 163° C, prepared from 4-(β-aminoethyl)-benzenesulfonamide and 1-butyl-1,2-dihydro-2-oxo-nicotinic acid chloride in chloroform/soda solution) in 100 ml acetone and 50 ml dioxane were refluxed for 3 hours while stirring together with 5.5 g of pulverized potash. 2.5 g cyclohexyl isocyanate were then added and stirring was continued for 6 hours with reflux. After cooling, the reaction mixture was diluted with water, filtered and the filtrate acidified with 2N hydrochloric acid. The formed precipitate was filtered off with suction, dissolved in dilute ammonia and reprecipitated with dilute hydrochloric acid and finally recrystallized from methanol. The N-[4-(β-<1-butyl-1,2-dihydro-2-oxo-nicotinamido>-ethyl benzenesulfonyl]-N'-cyclohexyl urea obtained melted at 178 - 179° C.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[C:10]([NH:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][C:22]([S:25]([N:28]([CH3:37])[C@@H:29]([C:33]([O:35]C)=[O:34])[CH:30]([CH3:32])[CH3:31])(=[O:27])=[O:26])=[CH:21][CH:20]=2)=[CH:15][CH:14]=1)=[O:11].[I-].[Li+]>C(OCC)(=O)C.Cl>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[C:10]([NH:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][C:22]([S:25]([N:28]([CH3:37])[C@@H:29]([C:33]([OH:35])=[O:34])[CH:30]([CH3:32])[CH3:31])(=[O:26])=[O:27])=[CH:21][CH:20]=2)=[CH:15][CH:14]=1)=[O:11]
Reactant: COC(=O)[C@@H](C(C)C)N(C)S(=O)(=O)c1ccc(-c2ccc(NC(=O)c3cc4ccccc4o3)cc2)cc1
Agent: Cl
Agent: [I-]
Agent: [Li+]
Solvent: CCOC(C)=O
Product: CC(C)[C@H](C(=O)O)N(C)S(=O)(=O)c1ccc(-c2ccc(NC(=O)c3cc4ccccc4o3)cc2)cc1
Yield: 78.3 %

Procedure:
To 0.13 g of methyl N-({4′-[(1-benzofuran-2-ylcarbonyl)amino]-1,1′-biphenyl-4-yl}sulfonyl)-N-methyl-D-valinate in 12 mL ethyl acetate was added 0.67 g of lithium iodide and the mixture was refluxed overnight. The reaction was diluted with ethyl acetate and 1N HCl. The organic layer was washed with water, sodium thiosulfate solution, water and brine, dried over Na2SO4, filtered, and concentrated to provide 0.099 g of N-({4′-[(1-benzofuran-2-ylcarbonyl)amino]-1,1′-biphenyl-4-yl}sulfonyl)-N-methyl-D-valine. Yield 77.9%. m.p. 239-241° C.; MS 505.1(M−H)−.
Reaction SMILES: [F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[C:7]2[CH:12]=O.[CH3:14][NH2:15]>>[F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[C:7]2[CH2:12][NH:15][CH3:14]
Reactant: CN
Reactant: O=Cc1cccc2c(F)cccc12
Product: CNCc1cccc2c(F)cccc12

Procedure:
The compound is obtained from 5-fluoro-1-naphthaldehyde and methylamine analogously to Example 2 as a colourless oil.
Reaction SMILES: [C:1]([NH:8][C@H:9]([C@H:17]1[O:21][C:20](=[O:22])[CH2:19][CH2:18]1)[CH2:10][CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN1C(=O)N(C)CCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:42][O:43][C:44]1[C:51]([O:52][CH3:53])=[C:50]([O:54][CH3:55])[CH:49]=[CH:48][C:45]=1[CH2:46]I.C(O)(=O)CC.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.C(OCC)(=O)C.O>[C:1]([NH:8][C@H:9]([C@H:17]1[O:21][C:20](=[O:22])[C@H:19]([CH2:46][C:45]2[CH:48]=[CH:49][C:50]([O:54][CH3:55])=[C:51]([O:52][CH3:53])[C:44]=2[O:43][CH3:42])[CH2:18]1)[CH2:10][CH:11]1[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]1)([O:3][C:4]([CH3:6])([CH3:7])[CH3:5])=[O:2]
Reactant: CC(C)(C)OC(=O)N[C@@H](CC1CCCCC1)[C@@H]1CCC(=O)O1
Reactant: COc1ccc(CI)c(OC)c1OC
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: CN1CCCN(C)C1=O
Product: COc1ccc(C[C@@H]2C[C@@H]([C@H](CC3CCCCC3)NC(=O)OC(C)(C)C)OC2=O)c(OC)c1OC
Reaction time: 0.33 h

Procedure:
A solution of 1.47 g (4.72 mmol) of 5(S)-[1(S)-(Boc-amino)-2-cyclohexylethyl]dihydrofuran-2-(3H)-one in 6 ml of abs. THF and 1 ml (1.65 equivalents) of DMPU is cooled down to -75° C., under argon, and treated dropwise, at an internal temperature of below -70° C. and over the space of approximately 20 min, with 9.44 ml of a 1M solution of lithium bis(trimethylsilyl)amide in THF (Aldrich). After a further 20 min at -75° C., a solution of 1.45 g (4.72 mmol) of 2,3,4-trimethoxybenzyl iodide [Example 47b)] in 3 ml of abs. THF is added dropwise to this mixture, within the space of approximately 10 min, and this mixture is allowed to react at -75° C. for a further 2.5 h. For the working up, the reaction mixture is treated with 1.76 ml of propionic acid, followed by 1.76 ml of water, and the temperature is allowed to rise to 0° C. The reaction mixture is diluted with approximately 70 ml of ethyl acetate and stirred up with 30 ml of (cold) 10% citric acid. The aqueous phase is separated off and the organic phase is washed, in succession, with saline, sat. sodium bicarbonate solution and with saline once again. The combined aqueous phases are reextracted twice with ethyl acetate. The combined organic phases are dried over sodium sulfate and concentrated. The residue which remains after removing the solvent is chromatographed on silica gel (toluene:ethyl acetate, 5:1). HPLC tRet =19.13 min (gradient II). FAB-MS (M+H)+ =491. IR(CH2Cl2)=inter alia 3429, 1766, 1711, 1602, 1495, 1165 und 1100 cm-1. 1H-NMR(CD3OD)=inter alia 6.86 (d, 1H); 6.70 (d, 1H); 4.37 (m, 1H); 3.87, 3.82 and 3.81 (each s, each 3H); 3.37 (m, 1H); 3.13 (dxd, 1H); 2.94 (m, 1H); 2.59 (dxd, 1H) and 1.40 (s, 9H).
Reaction SMILES: [CH:1]([CH2:3][CH2:4][CH2:5][CH2:6][C:7]([O:9]C)=[O:8])=[O:2].O>CO>[CH:1]([CH2:3][CH2:4][CH2:5][CH2:6][C:7]([OH:9])=[O:8])=[O:2]
Reactant: COC(=O)CCCCC=O
Solvent: CO
Solvent: O
Product: O=CCCCCC(=O)O
Yield: 73.9 %

Procedure:
36 g of methyl 5-formylvalerate, 90 g of water and 2 g of cation exchanger made of crosslinked polystyrene having sulfo groups were heated under reflux for 8.5 hours, the methanol formed being distilled off continuously. Fractional vacuum distillation gave 24 g of 5-formylvaleric acid (yield 74% of theory).
Reaction SMILES: Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][N:5]=[C:4]2[CH:11]=[CH:12][S:13][C:3]=12.[NH2:14][CH:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1.C(N(CC)C(C)C)(C)C>C(O)(C)C>[N+:8]([C:7]1[C:2]([NH:14][CH:15]2[CH2:16][CH2:17][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:19][CH2:20]2)=[C:3]2[S:13][CH:12]=[CH:11][C:4]2=[N:5][CH:6]=1)([O-:10])=[O:9]
Reactant: O=[N+]([O-])c1cnc2ccsc2c1Cl
Reactant: CC(C)(C)OC(=O)N1CCC(N)CC1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(C)O
Product: CC(C)(C)OC(=O)N1CCC(Nc2c([N+](=O)[O-])cnc3ccsc23)CC1
Temperature: 90 °C
Yield: 83 %

Procedure:
A mixture of 7-chloro-6-nitrothieno[3,2-b]pyridine (0.48 g, 2.2 mmol) (Example 1, Step 2), tert-butyl 4-aminopiperidine-1-carboxylate (from Aldrich, 0.67 g, 3.4 mmol) and N,N-diisopropylethylamine (1.2 mL, 6.7 mmol) in isopropyl alcohol (7.6 mL) was heated at 90° C. for 2 h. The precipitate was washed with isopropyl alcohol to give the desired product (0.70 83%). LCMS calculated for C17H23N4O4S (M+H)+: m/z=379.1. Found: 379.2.
Reaction SMILES: [C:1]1([C:7]([CH:9]=O)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:11][C@H:12]([C:14]([NH2:16])=[O:15])[CH3:13].[OH-].[Na+]>CO>[CH3:13][C:12]1[C:14](=[O:15])[NH:16][CH:9]=[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[N:11]=1
Reactant: O=CC(=O)c1ccccc1
Reactant: C[C@H](N)C(N)=O
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: Cc1nc(-c2ccccc2)c[nH]c1=O
Temperature: 41 °C
Reaction time: 2 h
Yield: 18 %

Procedure:
This compound was prepared following the procedure of Jones (J. Amer. Chem. Soc. 1949, 71, 78-81). Briefly, commercially available phenylglyoxal 22 (1.02 g, 7.62 mmol) was dissolved in methanol and cooled to 41° C. Commercially available alanine amide 23 (672 mg, 7.62 mmol) was dissolved in 25 ml methanol and added to the reaction mixture. A 12.5 N NaOH (0.760 mL, 9.53 mmol) solution was added dropwise while stirring, maintaining the temperature of the reaction below 40° C. When the addition was complete, the reaction was placed at =5° C. for 2 h. The reaction was then warmed to room temperature and quenched with 12 N HCl solution (0.76 mL), followed by sodium bicarbonate to neutralize the solution. The methanol was removed under reduced pressure, and the residue was extracted with chloroform and precipitated with ethyl acetate. The compound was isolated as a white powder to give 24 in 18% yield. HPLC (tr/purity): 1531 min, >97%. ESI m/z (MeOH): 187.35 (MH+).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([CH2:8]O)[C:5]([I:10])=[CH:4][CH:3]=1.S(Cl)([Cl:13])=O>C(Cl)Cl>[Cl:1][C:2]1[N:7]=[C:6]([CH2:8][Cl:13])[C:5]([I:10])=[CH:4][CH:3]=1
Reactant: O=S(Cl)Cl
Reactant: OCc1nc(Cl)ccc1I
Solvent: ClCCl
Product: ClCc1nc(Cl)ccc1I
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a stirred solution of (6-chloro-3-iodo-pyridin-2-yl)-methanol (2.5 g, 9.3 mmol, 1 eq) in DCM (25 mL) was added thionyl chloride (0.68 mL, 9.3 mmol, 1 eq) in drop wise manner at 0° C. under nitrogen atmosphere. Resulting reaction mixture was stirred at room temperature for 16 hours. After complete consumption of starting material, reaction mixture was cooled to 0° C. and quenched by aqueous sodium bicarbonate (25 mL), extracted with DCM (3×70 mL). Combined organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure to get brown semisolid (2.5 g, crude). Crude title compound was used as such for the next reaction. 1H NMR not clean. LC-MS: No ionization.
Reaction SMILES: Cl[C:2]1[N:7]2[N:8]=[C:9]([NH:11][C:12](=[O:19])[C:13]3[CH:18]=[CH:17][CH:16]=[N:15][CH:14]=3)[N:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1.[CH:20]1([SH:26])[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1>C1COCC1>[CH:20]1([S:26][C:2]2[N:7]3[N:8]=[C:9]([NH:11][C:12](=[O:19])[C:13]4[CH:18]=[CH:17][CH:16]=[N:15][CH:14]=4)[N:10]=[C:6]3[CH:5]=[CH:4][CH:3]=2)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1
Reactant: SC1CCCCC1
Reactant: O=C(Nc1nc2cccc(Cl)n2n1)c1cccnc1
Solvent: C1CCOC1
Product: O=C(Nc1nc2cccc(SC3CCCCC3)n2n1)c1cccnc1
Temperature: 25 °C
Reaction time: 14 h
Yield: 44.1 %

Procedure:
To a solution of N-(5-chloro[1,2,4]triazolo[1,5-a]pyridin-2-yl)nicotinamide ((B4), 136 mg; 0.5 mmol; 1.0 eq.) in dry THF (10 mL) was added in one pot cyclohexyl mercaptan (58 mg; 0.5 mmol; 1.0 eq.). The reaction mixture was stirred at rt for 14 h. The product precipitated upon addition of water after which filtration and washing with MeOH and Et2O gave the title compound as a white solid (78 mg, 44%). HPLC, Rt: 2.94 min. (purity 94.6%). LC/MS, M+(ESI): 354.1, M−(ESI): 352.0.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[CH3:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([SH:24])=[CH:20][CH:19]=1>>[CH3:13][O:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[O:14][CH3:15])[N:5]=[CH:4][CH:3]=[C:2]2[S:24][C:21]1[CH:22]=[CH:23][C:18]([O:17][CH3:16])=[CH:19][CH:20]=1
Reactant: COc1ccc(S)cc1
Reactant: COc1cc2nccc(Cl)c2cc1OC
Product: COc1ccc(Sc2ccnc3cc(OC)c(OC)cc23)cc1
Temperature: 150 °C
Reaction time: 0.08 h
Yield: 109.3 %

Procedure:
4-Chloro-6,7-dimethoxyquinoline (50 mg) and commercially available 4-methoxybenzenethiol (63 mg) were mixed and stirred at 150° C. for 5 minutes. Purification was carried out in the same manner as described in Example 18, and further crystallization with chloroform gave 80 mg of the title compound (yield: 100%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13]3[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]4[CH:25]=[CH:24][C:23]([CH2:26][N:27]5[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]5)=[CH:22][CH:21]=4)[N:14]=3)=[CH:11][NH:10][N:9]=2)=[CH:4][CH:3]=1.[CH3:34]O>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13]3[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]4[CH:21]=[CH:22][C:23]([CH2:26][N:27]5[CH2:28][CH2:29][N:30]([CH3:33])[CH2:31][CH2:32]5)=[CH:24][CH:25]=4)[N:14]=3)=[CH:11][N:10]([CH3:34])[N:9]=2)=[CH:4][CH:3]=1
Reactant: CO
Reactant: CN1CCN(Cc2ccc(Nc3nccc(-c4c[nH]nc4-c4ccc(Cl)cc4)n3)cc2)CC1
Product: CN1CCN(Cc2ccc(Nc3nccc(-c4cn(C)nc4-c4ccc(Cl)cc4)n3)cc2)CC1

Procedure:
The title compound is prepared as described in Example 55 starting from {4-[3-(4chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-yl}-[4-(4-methyl-piperazin-1-yl-methyl-phenyl]-amine (Example 32) and methanol.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10](Cl)[N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[CH3:13][S-:14].[Na+]>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([S:14][CH3:13])[N:11]=1)[C:5]([O:7][CH3:8])=[O:6]
Reactant: C[S-]
Reactant: COC(=O)c1cc(Cl)nc(Cl)c1
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COC(=O)c1cc(Cl)nc(SC)c1
Temperature: 25 °C
Reaction time: 4 h
Yield: 93.1 %

Procedure:
Methyl 2,6-dichloroisonicotinate (300 mg, 1.45 mmol) was dissolved in anhydrous DMF. Sodium thiomethoxide (102 mg, 1.45 mmol) was added and the mixture was stirred at room temperature for 4 h. The mixture was diluted with EtOAc and washed with water (×3), brine (×1) and dried over sodium sulfate and concentrated in vacuo to afford title compound (294 mg).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13])[CH2:6][CH2:5]2.[CH3:22][S:23](Cl)(=[O:25])=[O:24]>N1C=CC=CC=1>[CH3:22][S:23]([NH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13])[CH2:6][CH2:5]2)(=[O:25])=[O:24]
Reactant: CS(=O)(=O)Cl
Reactant: Nc1ccc2c(c1)CCN2CC(=O)OCc1ccccc1
Solvent: c1ccncc1
Product: CS(=O)(=O)Nc1ccc2c(c1)CCN2CC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 72.6 %

Procedure:
To a solution of benzyl 2-(5-aminoindolin-1-yl)acetate (0.610 g, 2.161 mmol) in pyridine (15 ml), methanesulfonyl chloride (0.251 ml, 3.24 mmol) was added at 0° C. The mixture was allowed to warm to room temperature and stirred for 1 hour. The solvent was removed under vacuum and the residue was partitioned between DCM and water; the organic phase was washed with brine, dried over sodium sulfate and evaporated to dryness. The crude was purified by flash chromatography on silica gel column (petroleum ether:ethyl acetate=70:30 to 60:40) affording benzyl 2-(5-(methylsulfonamido)indolin-1-yl)acetate (0.565 g, 1.568 mmol, 73% yield). MS/ESI+ 361.0 [MH]+.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[OH:11][CH:12]([C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[N:26]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[CH:25]=[CH:24]2)[C:13]1[CH:20]=[CH:19][CH:18]=[CH:17][C:14]=1[C:15]#[N:16].C(N(CC)CC)C>ClCCl>[CH3:35][Si:34]([CH3:37])([CH3:36])[CH2:33][CH2:32][O:31][CH2:30][N:26]1[C:27]2[C:23](=[CH:22][C:21]([C:12]([C:13]3[CH:20]=[CH:19][CH:18]=[CH:17][C:14]=3[C:15]#[N:16])=[O:11])=[CH:29][CH:28]=2)[CH:24]=[CH:25]1
Reactant: C[Si](C)(C)CCOCn1ccc2cc(C(O)c3ccccc3C#N)ccc21
Agent: O=C(Cl)C(=O)Cl
Solvent: CS(C)=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: C[Si](C)(C)CCOCn1ccc2cc(C(=O)c3ccccc3C#N)ccc21
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 57.9 %

Procedure:
To a solution of oxalyl chloride (0.097 mL, 1.1 mmol) in dichloromethane cooled to −60° C. was added dimethyl sulfoxide (0.16 mL, 2.2 mmol), followed by 2-{hydroxy[1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-indol-5-yl]methyl}benzonitrile (0.21 g, 0.55 mmol in 2 mL dichloromethane). Triethylamine (0.46 mL, 3.3 mmol) was added and the solution was allowed to warm to room temperature and stirred for 30 min. The reaction mixture was quenched with an excess of water, and diluted with dichloromethane and brine. The layers were separated, and the aqueous layer was extracted (2×100 mL dichloromethane), dried (sodium sulfate), filtered and concentrated in vacuo. Column chromatography (silica gel, 4:1 hexanes/ethyl acetate) gave 0.12 g (58%) of 2-{[1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-indol-5-yl]carbonyl}benzonitrile. 1H NMR (400 MHz, CDCl3): 8.07 (d, 1H), 7.88 (dd, 2H), 7.70 (m, 3H), 7.60 (d, 1H), 7.30 (d, 1H), 6.65 (m, 1H), 5.56 (s, 2H), 3.53 (m, 2H), 0.95 (m, 2H), 0.00 (s, 9H); 13C NMR (400 MHz, CDCl3): 194.90 (C═O), 144.16, 140.45, 135.12, 133.07, 131.72, 131.03, 130.81, 129.82, 129.66, 127.08, 125.30, 118.39, 112.98, 111.50, 105.56, 77.05, 67.48, 19.09, 0.00.
Reaction SMILES: Br[C:2]1[C:7]([Br:8])=[CH:6][C:5]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=2)=[CH:4][N:3]=1.[CH3:16][Si:17]([C:20]#[CH:21])([CH3:19])[CH3:18].BrCl>>[Br:8][C:7]1[C:2]([C:21]#[C:20][Si:17]([CH3:19])([CH3:18])[CH3:16])=[N:3][CH:4]=[C:5]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=2)[CH:6]=1
Reactant: C#C[Si](C)(C)C
Reactant: Clc1ccc(-c2cnc(Br)c(Br)c2)cc1
Agent: ClBr
Product: C[Si](C)(C)C#Cc1ncc(-c2ccc(Cl)cc2)cc1Br

Procedure:
The product was prepared analogously to Example 7.1b starting from 2,3-dibromo-5-(4-chlorophenyl)pyridine and trimethylsilylacetylene. Yield: 1.00 g (95% of theoretical); C16H15BrClNSi (M=364.739); calc.: molpeak (M+H)+: 364/366/368 (BrCl); found: molpeak (M+H)+: 364/366/368 (BrCl).
Reaction SMILES: [OH:1][C:2]([CH3:35])([CH3:34])[CH2:3][C@@:4]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16](B3OC(C)(C)C(C)(C)O3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1.Br[C:37]1[CH:38]=[CH:39][C:40]([C:43]2([C:47]([NH2:49])=[O:48])[CH2:46][CH2:45][CH2:44]2)=[N:41][CH:42]=1>>[OH:1][C:2]([CH3:34])([CH3:35])[CH2:3][C@@:4]1([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:14]=[CH:15][C:16]([C:37]3[CH:38]=[CH:39][C:40]([C:43]4([C:47]([NH2:49])=[O:48])[CH2:44][CH2:45][CH2:46]4)=[N:41][CH:42]=3)=[CH:17][CH:18]=2)[CH3:12])[CH2:6][CH2:5]1
Reactant: NC(=O)C1(c2ccc(Br)cn2)CCC1
Reactant: C[C@@H](c1ccc(B2OC(C)(C)C(C)(C)O2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
Product: C[C@@H](c1ccc(-c2ccc(C3(C(N)=O)CCC3)nc2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
Yield: 41 %

Procedure:
The title compound was prepared from (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-{(S)-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-ethyl}-1,3-oxazinan-2-one and 1-(5-bromo-pyridin-2-yl)-cyclobutanecarboxylic acid amide following a procedure analogous to that described in Example 1. Yield: 41% of theory; LC (method 1): tR=1.94 min; Mass spectrum (ESI+): m/z=528 [M+H]+.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:11]3[CH:19]=[CH:20][CH:21]=[CH:22][C:10]=3[N:9]=2)=[CH:4][CH:3]=1.C([Li])CCC.[C:28]1([C:34]2[CH:47]=[C:46]([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[C:45]3[C:36](=[C:37]4[C:42](=[CH:43][CH:44]=3)[C:41]([C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)=[CH:40][CH:39]=[N:38]4)[N:35]=2)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.O>C1COCC1>[C:28]1([C:34]2[CH:47]=[C:46]([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[C:45]3[C:36](=[C:37]4[C:42](=[CH:43][CH:44]=3)[C:41]([C:54]3[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=3)=[CH:40][C:39]([C:2]3[CH:7]=[CH:6][C:5]([C:8]5[N:12]([C:13]6[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=6)[C:11]6[CH:19]=[CH:20][CH:21]=[CH:22][C:10]=6[N:9]=5)=[CH:4][CH:3]=3)=[N:38]4)[N:35]=2)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: c1ccc(-c2cc(-c3ccccc3)c3ccc4c(-c5ccccc5)ccnc4c3n2)cc1
Reactant: Brc1ccc(-c2nc3ccccc3n2-c2ccccc2)cc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: O
Product: c1ccc(-c2cc(-c3ccccc3)c3ccc4c(-c5ccccc5)cc(-c5ccc(-c6nc7ccccc7n6-c6ccccc6)cc5)nc4c3n2)cc1
Temperature: -78 °C
Yield: 47 %

Procedure:
To a three-necked flask of 250 ml, 3.84 g (11 mmol) of 2-(4-bromophenyl)-1-phenyl-1H-benzo[d]imidazole and 70 ml of THF were charged, then 6.9 ml (11 mmol) n-butyllithium (1.6M in Hexane solution) was dropped under stirring at −78° C. in a nitrogen atmosphere. The mixture was stirred for one hour at −78° C., and a solution of 2.29 g (5.6 mmol) 2,4,7-triphenyl-1,10-phenanthroline in 30 ml THF was dropped. Then the mixture was stirred at room temperature for overnight and was added with water. The organic layer was extracted with Dichloromethane and dried with anhydrous magnesium sulfate, the solvent was removed by rotary evaporation. The product was purified by column chromatography on alumina using Dichloromethane/Hexane as eluent and dried in vacuo, obtaining white powder compound 1.78 g (yield of 47.12%). MS (m/z, FAB+) 676.8(100%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:12]2[CH2:17][CH2:16][N:15]([C:18](=[O:20])[CH3:19])[CH2:14][CH2:13]2)[CH:6]=[CH:7][C:8]=1[N+:9]([O-])=O.[H][H]>CCO.[Pd]>[NH2:9][C:8]1[CH:7]=[CH:6][C:5]([N:12]2[CH2:17][CH2:16][N:15]([C:18](=[O:20])[CH3:19])[CH2:14][CH2:13]2)=[CH:4][C:3]=1[O:2][CH3:1]
Reactant: [H][H]
Reactant: COc1cc(N2CCN(C(C)=O)CC2)ccc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CCO
Product: COc1cc(N2CCN(C(C)=O)CC2)ccc1N
Yield: 99 %

Procedure:
A solution of 1-(4-(3-methoxy-4-nitrophenyl)piperazin-1-yl)ethanone (20a) in 10 mL of EtOH was hydrogenated with a balloon filled with hydrogen in the presence of palladium (10 wt. % on activated carbon, 0.61 g, 0.57 mmol) for 18 h at RT. It was filtered through a pad of Celite and rinsed with EtOAc (2×20 mL). The filtrate was concentrated. The brown residue was triturated with 10 mL of hexanes. The liquid was decanted. The solid was dried in a vacuum oven at 40° C. for 1 h to give 1-(4-(4-amino-3-methoxyphenyl)piperazin-1-yl)ethanone (20b; 1.42 g, 5.70 mmol, 99% yield) as a brown solid. Crude material used in the next step. 1H NMR (400 MHz, DMSO-d6) δ ppm 6.54 (2H, m), 6.32 (1H, dd, J=8.3, 2.4 Hz), 4.63 (2H, br.), 3.76 (3H, s), 3.54 (4H, m), 2.95 (2H, m), 2.89 (2H, m), 2.02 (3H, s). m/z (ESI, +ve ion) 250.1 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[S:10](Cl)(=[O:12])=[O:11].[CH2:14]1[C:19]2[NH:20][C:21]3[C:26]([C:18]=2[CH2:17][CH:16]([C:27]([NH2:29])=[O:28])[NH:15]1)=[CH:25][CH:24]=[CH:23][CH:22]=3.C(N(CC)CC)C.O>CC(C)=O.CN(C=O)C>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[S:10]([N:15]1[CH:16]([C:27]([NH2:29])=[O:28])[CH2:17][C:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[NH:20][C:19]=2[CH2:14]1)(=[O:12])=[O:11]
Reactant: NC(=O)C1Cc2c([nH]c3ccccc23)CN1
Reactant: Cc1cc(C)c(S(=O)(=O)Cl)c(C)c1
Solvent: CCN(CC)CC
Solvent: CC(C)=O
Solvent: CN(C)C=O
Product: Cc1cc(C)c(S(=O)(=O)N2Cc3[nH]c4ccccc4c3CC2C(N)=O)c(C)c1
Reaction time: 8 h

Procedure:
2,4,6trimethyl benzene sulphonyl chloride (0.524 gm, 2.4 mmol) in dry acetone was added to a stirred solution of dl 1,2,3,4-tetrahydro-9H-pyrido(3,4-b)indole-3-amide (0.430 gm, 2.0 mmol) and dry triethylamine (0.56 ml, 4.0 mmol) in dry DMF (8 ml) during 15 and was allowed to stirr for 8 hrs. at room temperature. Water (20 ml) was added to the reaction mixture and extracted with chloroform (3×15 ml). The tract was dried over Na2SO4 and concentrated over reduced pressure to give 2-[2,4,6trimethylbenzenesulfonyl]-1,2,3,4,-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylic acid amide which was purified by column chromatography over silica gel using 2% methanol chloroform as eluent Yield=0.35 gm (44.08%) m.p.=212° C.: Mass (FAB) m/z=398 (M+). IR (KBr cm−1): 3394, 3299, 1668, 1596, 1455, 1324, 1155, 752. H1NMR (200 MHz, DMSO d6) δ 2.30 (s, 3H), δ2.56-2.74 (m, 7H), δ3.55-3.62 (d, 1H), δ4.49-4.70 (m, 3H), δ5.17 (s, 1H), δ5.49 (s, 1H), δ6.96-7.77 (m, 6H). Molecular Formula=C21H23N3O3S.