Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[C:15]([SH:20])=[CH:16][CH:17]=[CH:18][CH:19]=3)=[CH:10][C:9]=2[F:21])=[CH:4][N:3]=1.[Cl:22][C:23]1[CH:28]=[N:27][CH:26]=[CH:25][N:24]=1>>[ClH:22].[F:21][C:9]1[CH:10]=[C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[S:20][C:23]2[CH:28]=[N:27][CH:26]=[CH:25][N:24]=2)[CH:12]=[CH:13][C:8]=1[C:5]1[CH:6]=[N:7][C:2]([NH2:1])=[N:3][CH:4]=1
Reactant: Nc1ncc(-c2ccc(-c3ccccc3S)cc2F)cn1
Reactant: Clc1cnccn1
Product: Cl
Product: Nc1ncc(-c2ccc(-c3ccccc3Sc3cnccn3)cc2F)cn1

Procedure:
The title compound was prepared using analogous conditions to those described in Example 213 utilizing 4′-(2-aminopyrimidin-5-yl)-3′-fluoro-[1,1′-biphenyl]-2-thiol and 2-chloropyrazine. MS (ESI): mass calcd. for C20H14FN5S, 375.10; m/z found, 375.9 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 8.70-8.57 (m, 2H), 8.41 (dd, J=2.5, 1.6, 1H), 8.35 (d, J=2.6, 1H), 8.27 (d, J=1.5, 1H), 7.72 (dd, J=8.0, 1.2, 1H), 7.64-7.57 (m, 2H), 7.56-7.50 (m, 2H), 7.34 (d, J=11.8, 1H), 7.27 (d, J=8.0, 1H), 6.01 (s, 2H).
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[CH:9][NH:10]2)=[C:6]([N+:13]([O-:15])=[O:14])[CH:5]=1.Cl[CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22].O>CN(C)C=O>[Cl:3][C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[CH:9][N:10]2[CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])=[C:6]([N+:13]([O-:15])=[O:14])[CH:5]=1
Reactant: C[Si](C)(C)CCOCCl
Reactant: O=[N+]([O-])c1cc(Cl)cc2[nH]ccc12
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: C[Si](C)(C)CCOCn1ccc2c([N+](=O)[O-])cc(Cl)cc21
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 109.4 %

Procedure:
Sodium hydride (60% dispersion in mineral oil, 0.17 g, 6.61 mmol) was suspended in 30 mL dimethylformamide. The mixture was stirred for 15 min and was cooled at 0° C. with an ice bath. 6-Chloro-4-nitro-1H-indole (1 g, 5.09 mmol) dissolved in 5 mL dimethylformamide was added dropwise and the mixture was stirred 30 min. At the same temperature [2-(chloromethoxy)ethyl](trimethyl)silane (1.1 g, 6.61 mmol) dissolved in 5 mL dimethylformamide was added dropwise and stirred for 30 min at 0° C. The mixture was poured into water and extracted twice with ethyl acetate. The organic were dried over sodium sulphate and concentrated under reduced pressure to give 1.82 g (100% yield) of the title compound as a yellow oil. Purity 96%.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][NH:10][C:11]([C:13]2[N:14]=[N:15][C:16](Cl)=[CH:17][CH:18]=2)=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N:20]1([C:26]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[C:34]([F:37])([F:36])[F:35])=[O:27])[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1>>[C:1]1([CH2:7][CH2:8][CH2:9][NH:10][C:11]([C:13]2[N:14]=[N:15][C:16]([N:23]3[CH2:24][CH2:25][N:20]([C:26](=[O:27])[C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=4[C:34]([F:37])([F:35])[F:36])[CH2:21][CH2:22]3)=[CH:17][CH:18]=2)=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(NCCCc1ccccc1)c1ccc(Cl)nn1
Reactant: O=C(c1ccccc1C(F)(F)F)N1CCNCC1
Product: O=C(NCCCc1ccccc1)c1ccc(N2CCN(C(=O)c3ccccc3C(F)(F)F)CC2)nn1

Procedure:
Following the procedure of Example 15, making variations only as required to use 6-chloropyridazine-3-carboxylic acid (3-phenylpropyl)amide in place of 6-chloropyridazine-3-carboxylic acid (2-cyclopropyl-2-hydroxyethyl)amide to react with piperazin-1-yl-(2-trifluoromethylphenyl)methanone, the title compound was obtained as a white solid (15% yield). 1H NMR (500 MHz, CDCl3) δ 8.05, 7.93, 7.74, 7.63, 7.56, 7.39, 7.29-7.13, 6.92, 4.12-3.29, 2.68, 2.02-1.83.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([N:14]([S:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)(=[O:24])=[O:23])[CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:9]=1)(C)(C)C.FC(F)(F)C(O)=O>ClCCl.O>[NH2:7][C:8]1[CH:9]=[C:10]([N:14]([CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[S:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)(=[O:24])=[O:23])[CH:11]=[CH:12][CH:13]=1
Reactant: CC(C)(C)OC(=O)Nc1cccc(N(Cc2ccccc2)S(=O)(=O)c2ccccc2)c1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Solvent: O
Product: Nc1cccc(N(Cc2ccccc2)S(=O)(=O)c2ccccc2)c1
Yield: 98.5 %

Procedure:
A solution of [3-(benzenesulfonyl-benzyl-amino)-phenyl]-carbamic acid tert-butyl ester (1.09 g, 2.49 mmol) and trifluoroacetic acid (2.5 ml) in dichloromethane (22.5 ml) were stirred at room temperature for 90 minutes. The reaction mixture was diluted with water (100 ml) and extracted with dichloromethane (3×75 ml). The combined organics were dried (magnesium sulphate) and concentrated in vacuo to afford the title compound as a brown oil (0.83 g, 99%). HPLC retention time 5.9 min.
Reaction SMILES: [Cl:1][C:2]1[C:3]([N:27]([CH:29]([CH3:31])[CH3:30])[CH3:28])=[CH:4][C:5]2[N:11]=[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([N:18]4[C:22]([CH2:23]O)=[CH:21][N:20]=[N:19]4)[CH:13]=3)[CH2:9][C:8](=[O:25])[NH:7][C:6]=2[CH:26]=1.S(Cl)(Cl)=O.[Cl-].[CH2:37]([NH2:41])[CH:38]([CH3:40])[CH3:39]>ClCCl.CN(C=O)C>[Cl:1][C:2]1[C:3]([N:27]([CH:29]([CH3:30])[CH3:31])[CH3:28])=[CH:4][C:5]2[N:11]=[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([N:18]4[C:22]([CH2:23][NH:41][CH2:37][CH:38]([CH3:40])[CH3:39])=[CH:21][N:20]=[N:19]4)[CH:13]=3)[CH2:9][C:8](=[O:25])[NH:7][C:6]=2[CH:26]=1
Reactant: CC(C)CN
Reactant: CC(C)N(C)c1cc2c(cc1Cl)NC(=O)CC(c1cccc(-n3nncc3CO)c1)=N2
Agent: [Cl-]
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: O=S(Cl)Cl
Product: CC(C)CNCc1cnnn1-c1cccc(C2=Nc3cc(N(C)C(C)C)c(Cl)cc3NC(=O)C2)c1

Procedure:
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-[1,2,3]triazol-1-yl)-phenyl]-7-(isopropyl-methyl-amino)-1,3-dihydro-benzo[b][1,4]-diazepin-2-one (Example 96) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with isobutylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (160 mg, 65%).
Reaction SMILES: [CH3:1][C:2]1[N:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)[C:6](=[O:18])[C:5]([C:19]([OH:21])=O)=[CH:4][C:3]=1[C:22]1[N:26]([CH3:27])[N:25]=[CH:24][CH:23]=1.Cl.[CH3:29][S:30]([C:33]1[CH:34]=[CH:35][C:36]([CH2:39][NH2:40])=[N:37][CH:38]=1)(=[O:32])=[O:31].O>C(#N)C>[CH3:1][C:2]1[N:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:16])([F:15])[F:17])[CH:9]=2)[C:6](=[O:18])[C:5]([C:19]([NH:40][CH2:39][C:36]2[CH:35]=[CH:34][C:33]([S:30]([CH3:29])(=[O:32])=[O:31])=[CH:38][N:37]=2)=[O:21])=[CH:4][C:3]=1[C:22]1[N:26]([CH3:27])[N:25]=[CH:24][CH:23]=1
Reactant: Cc1c(-c2ccnn2C)cc(C(=O)O)c(=O)n1-c1cccc(C(F)(F)F)c1
Reactant: CS(=O)(=O)c1ccc(CN)nc1
Agent: Cl
Solvent: CC#N
Solvent: O
Product: Cc1c(-c2ccnn2C)cc(C(=O)NCc2ccc(S(C)(=O)=O)cn2)c(=O)n1-c1cccc(C(F)(F)F)c1
Temperature: 50 °C
Yield: 96 %

Procedure:
6-Methyl-5-(1-methyl-1H-pyrazol-5-yl)-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxylic acid (52.0 kg, 1 mol eq, limiting reagent) and acetonitrile (208 L, 4 rel vol,) were charged. The reaction mixture was heated to 50° C. 1,1′-s carbonyldiimidazole as a solution in acetonitrile (208 L, 4 rel vol) is charged to the reaction until the reaction is complete as judged by HPLC. C-(5-(Methanesulfonyl)pyridine-2-yl)methylamine monohydrochloride (33.8 kg, 1.1 mol eq) was charged and the reaction maintained at 50° C. until the reaction was deemed complete as judged by HPLC. Water (780 L, 15 rel vol) was charged. The reaction mixture was stirred, cooled and further stirred. The solid was collected by filtration and washed twice with water (2×104 L, 2×2 rel vol) and dried to constant weight to yield the title compound (96.0 kg, 176.0 mol, 96%); 1H NMR (d6-DMSO): δ 1.83 (s, 3H); 3.29 (s, 3H); 3.72 (s, 3H); 4.73 (d, 2H, J 5.8 Hz); 6.33 (d, 1H, J=1.9 Hz); 7.53 (d, 1H, J=1.9 Hz); 7.57 (d, 1H, J 8.3 Hz); 7.81-7.88 (m, 2H); 7.92-7.94 (m, 1H); 8.03 (s, 1H); 8.21 (s, 1H); 8.27 (dd, 1H, J 2.3, 7.9 Hz); 8.99 (d, 1H, J=2.3 Hz); 10.06 (t, 1H, J 6.0 Hz); LCMS: m/z 546.3 (MH+).
Reaction SMILES: S(Cl)([Cl:3])=O.[ClH:5].Cl.[N:7]1[C:15]2[CH2:14][C@@H:13]([C:16]([OH:18])=[O:17])[NH:12][CH2:11][C:10]=2[NH:9][CH:8]=1.[CH3:19]O>>[ClH:3].[ClH:5].[N:7]1[C:15]2[CH2:14][C@@H:13]([C:16]([O:18][CH3:19])=[O:17])[NH:12][CH2:11][C:10]=2[NH:9][CH:8]=1
Reactant: CO
Reactant: O=C(O)[C@@H]1Cc2nc[nH]c2CN1
Reactant: O=S(Cl)Cl
Agent: Cl
Product: COC(=O)[C@@H]1Cc2nc[nH]c2CN1
Temperature: 25 °C
Yield: 100 %

Procedure:
Thionylchloride (200 mL, 2.74 mol, 3.0 mol eqv.) was added dropwise to methanol (3.5 L), which was cooled to 0-5° C. (6S)-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-6-carboxylic acid dihydrochloride (210.0 g, 0.87 mol) was added The suspension was allowed to warm up to room temperature, and refluxed for 3.5 h. After cooling to room temperature, the solvent was removed under reduced pressure. The white residue was suspended in ether (3 L). The solid was filtered and washed with ether. After drying in a vacuum oven (40° C.), the title compound was obtained (225.0 g, 100% yield, 95% pure). 1H NMR (DMSO-d6): δ ppm 12.65 (br s, 2H), 9.04 (s, 1H), 4.71 (m, 1H), 4.33 (t, J=16.2 Hz, 2H), 3.81 (s, 3H), 3.10-3.33 (m, 2H), LCMS: Rt=0.61 min and M+1=182.1 u/e (M+1 of free base).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][CH:17]=1.C(N(C(C)C)CC)(C)C.ClC(Cl)(O[C:36](=[O:42])OC(Cl)(Cl)Cl)Cl.[NH2:44][C:45]1[S:46][C:47]([C:50]([F:53])([F:52])[F:51])=[N:48][N:49]=1>C(Cl)(Cl)Cl.O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH:20][C:36]([NH:44][C:45]2[S:46][C:47]([C:50]([F:53])([F:52])[F:51])=[N:48][N:49]=2)=[O:42])=[CH:18][CH:17]=1
Reactant: COc1cc2nccc(Oc3ccc(N)cc3)c2cc1OC
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: Nc1nnc(C(F)(F)F)s1
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClC(Cl)Cl
Product: COc1cc2nccc(Oc3ccc(NC(=O)Nc4nnc(C(F)(F)F)s4)cc3)c2cc1OC
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 26 %

Procedure:
4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (100 mg) was dissolved in chloroform (5 ml) and diisopropylethylamine (0.5 ml) to prepare a solution. A solution of triphosgene (100 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 15 min. Next, 2-amino-5-trifluoromethyl-1,3,4-thiadiazole (70 mg) was added thereto, and the mixture was further stirred at room temperature overnight. Distilled water was added to the reaction solution, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine and was dried over sodium sulfate. The organic layer was concentrated under the reduced pressure, and the residue was purified by HPLC using chloroform/acetone for development to give 43 mg of the title compound.
Reaction SMILES: [Se](=O)=O.[O:4]1CCOCC1.[CH2:10]([S:13]([NH:16][C:17]1[S:18][CH:19]=[C:20]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[N:21]=1)(=[O:15])=[O:14])[CH2:11][CH3:12]>O>[CH2:10]([S:13]([NH:16][C:17]1[S:18][CH:19]=[C:20]([C:22](=[O:4])[C:23]([O:25][CH2:26][CH3:27])=[O:24])[N:21]=1)(=[O:15])=[O:14])[CH2:11][CH3:12]
Reactant: C1COCCO1
Reactant: CCCS(=O)(=O)Nc1nc(CC(=O)OCC)cs1
Agent: CCCS(=O)(=O)N=c1[nH]c(CC(=O)OCC)cs1
Agent: O=[Se]=O
Solvent: O
Product: CCCS(=O)(=O)Nc1nc(C(=O)C(=O)OCC)cs1

Procedure:
To a solution prepared by stirring a mixture of selenium dioxide (6.2 g.), dioxane (320 ml.) and water (6.4 ml.) at 50° to 60° C. was added ethyl 2-(2-propanesulfonylamino-1,3-thiazol-4-yl)acetate, which can be represented as ethyl 2-(2-propanesulfonylimino-2,3-dihydro-1,3-thiazol-4-yl)acetate, (16.3 g.), and the mixture was refluxed for 1 hour. To the mixture was added selenium dioxide (0.6 g.), and the mixture was further refluxed for 30 minutes and selenium dioxide (0.3 g.) was added thereto, and then the mixture was further refluxed for 30 minutes. After the reaction, the reaction mixture was filtered, and then dioxane was distilled off. The residue was dissolved in ethyl acetate under heating and then treated with activated charcoal. The solvent was distilled off, and the residue was washed with a small amount of ethyl acetate and diethyl ether in turn and dried to give ethyl 2-(2-propane-sulfonylamino-1,3-thiazol-4-yl)glyoxylate, which can be represented as ethyl 2(2-propanesulfonylimino-2,3-dihydro-1,3-thiazol-4-yl)glyoxylate, (12.5 g.), mp 132° to 134° C.
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH:12]=[C:11]([CH2:14][CH3:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=C[CH:3]=1.ClC(OC(Cl)=O)C.[NH:23]1[CH:28]=CCC[CH2:24]1.C[N:30](CC1C2C(=NC=CC=2)NC=1)C>ClCCl.C1(C)C=CC=CC=1>[CH2:14]([C:11]1[CH2:10][CH2:9][N:8]([C:1]2[C:2]3[C:3](=[N:30][CH:5]=[CH:6][CH:7]=3)[N:23]([CH3:28])[CH:24]=2)[CH2:13][CH:12]=1)[CH3:15]
Reactant: CCC1=CCN(Cc2ccccc2)CC1
Reactant: C1=CNCCC1
Reactant: CN(C)Cc1c[nH]c2ncccc12
Agent: CC(Cl)OC(=O)Cl
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: CCC1=CCN(c2cn(C)c3ncccc23)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 42.9 %

Procedure:
A solution of 1-benzyl-4-ethyl-1,2,3,6-tetrahydropyridine (1.92 g, 9.6 mmol) in anhydrous dichloromethane (50 ml) was cooled to 0° C. and treated with a solution of 1-chloroethylchloroformate (1.34 ml, 12.4 mmol) in anhydrous dichloromethane (10 ml). After stirring at room temperature for one hour, the solvent was evaporated and the residue redissolved in methanol (50 ml). This solution was heated at reflux for one hour. The solvent was evaporated and the residue partitioned between dichloromethane and saturated aqueous potassium carbonate solution. The organic phase was separated, dried (MgSO4) and evaporated in vacuo to afford the crude product (320 mg, 30%) as a colourless oil. A solution of the crude tetrahydropyridine (320 mg, 2.9 mmol) and 3-dimethylaminomethyl-1H-pyrrolo[2,3-b]pyridine (504 mg, 2.9 mmol) in toluene (10 ml) was stirred at reflux for 16 hours. The solvent was evaporated and the residue chromatographed with 3% methanol in dichloromethane as eluant to afford the title compound (300 mg, 43%) as a colourless solid, m.p. 88°-90° C.; (Found: C, 74.03; H, 7.94; N, 16.97. C15H19N3.0.125H2O requires C, 73.96; H, 7.97; N, 17.25%); δH (DMSO-d6) 0.99 (3H, t, J 7.5 Hz, CH2CH3), 1.97 (2H, q, J 7.5 Hz, CH2CH3), 2.06-2.12 (2H, m, tetrahydropyridinyl CH2), 2.61 (2H, t, J 5.8 Hz, tetrahydropyridinyl CH2), 3.02-3.08 (2H, m, tetrahydropyridinyl CH2), 3.78 (2H, s, NCH2Ar), 5.34-5.40 (1H, m, tetrahydropyridinyl 5-H), 7.08 (1H, dd, J 7.9, 4.8 Hz, 5-H), 7.29 (1H, m, 2-H), 8.06-8.04 (1H, m, 4-H), 8.28-8.32 (1H, m, 6-H), 9.28 (1H, br s, NH). m/z (CI+, NH3) 242 (M+1)+.
Reaction SMILES: [H-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]2[C:11](=[C:12]([O:14][CH3:15])[CH:13]=1)[NH:10][CH:9]=[C:8]2[C:16]1[N:24]([S:25]([C:28]2[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=2)(=[O:27])=[O:26])[C:19]2=[N:20][CH:21]=[CH:22][CH:23]=[C:18]2[CH:17]=1.I[CH3:36].O>CN(C)C=O>[CH3:3][O:4][C:5]1[CH:6]=[C:7]2[C:11](=[C:12]([O:14][CH3:15])[CH:13]=1)[N:10]([CH3:36])[CH:9]=[C:8]2[C:16]1[N:24]([S:25]([C:28]2[CH:29]=[CH:30][C:31]([CH3:34])=[CH:32][CH:33]=2)(=[O:27])=[O:26])[C:19]2=[N:20][CH:21]=[CH:22][CH:23]=[C:18]2[CH:17]=1
Reactant: COc1cc(OC)c2[nH]cc(-c3cc4cccnc4n3S(=O)(=O)c3ccc(C)cc3)c2c1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1cc(OC)c2c(c1)c(-c1cc3cccnc3n1S(=O)(=O)c1ccc(C)cc1)cn2C
Temperature: 20 °C
Reaction time: 1 h

Procedure:
0.028 g of sodium hydride at 60% in oil is added, in small portions, to solution of 0.26 g of 2-(5,7-dimethoxy-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine in 11.5 ml of dimethylformamide. The suspension is agitated for approximately 1 hour at around 20° C. and then 0.04 ml of iodomethane is added. After agitation for approximately 18 hours at around 20° C., the mixture is run into 100 ml of a mixture of ice plus water, and extracted with three times 75 ml of ethyl acetate. The combined organic phases are dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure. 0.3 g of 2-(5,7-dimethoxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine is obtained in the form of a foam, the characteristics of which are as follows:
Reaction SMILES: I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([NH:11][S:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[S:21]([CH3:24])(=[O:23])=[O:22])(=[O:14])=[O:13])[CH:9]=2)[N:4](C(OC(C)(C)C)=O)[N:3]=1.B(O)(O)[C:33]1[S:41][C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH:34]=1.C(=O)([O-])O.[Na+]>CN(C)C=O>[S:41]1[C:33]([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([NH:11][S:12]([C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=4[S:21]([CH3:24])(=[O:23])=[O:22])(=[O:13])=[O:14])[CH:9]=3)[NH:4][N:3]=2)=[CH:34][C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][C:40]1=2
Reactant: OB(O)c1cc2ccccc2s1
Reactant: CC(C)(C)OC(=O)n1nc(I)c2cc(NS(=O)(=O)c3ccccc3S(C)(=O)=O)ccc21
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Product: CS(=O)(=O)c1ccccc1S(=O)(=O)Nc1ccc2[nH]nc(-c3cc4ccccc4s3)c2c1
Yield: 35.8 %

Procedure:
N-(3-Benzo[b]thiophen-2-yl-1H-indazol-5-yl)-2-methylsulfonylbenzenesulfonamide can be obtained as described in Example 59 from 0.5 g of tert-butyl 3-iodo-5-(2-methylsulfonylbenzenesulfonylamino)indazole-1-carboxylate, 300 mg of thianaphthene-2-boronic acid, 20 ml of dimethylformamide, 1.9 ml of a saturated aqueous solution of sodium hydrogencarbonate and 25 mg of tetrakis(triphenylphosphine)palladium[0]. 150 mg of N-(3-benzo[b]thiophen-2-yl-1H-indazol-5-yl)-2-methylsulfonylbenzenesulfonamide are thus obtained in the form of a white solid melting at 270° C. (analysis C22H17N3O4S3% calculated C, 54.64; H, 3.54; N, 8.69; O, 13.23; S, 19.89. % found C, 54.59H, 3.47; N, 8.79; S, 19.98).
Reaction SMILES: C(N(CC)C(C)C)(C)C.ClCO[CH2:13][O:14][CH2:15][O:16][CH2:17]Cl.[CH3:19][O:20][C:21]1[CH:26]=[C:25]([N+:27]([O-:29])=[O:28])[CH:24]=[CH:23]C=1O.O>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.ClCCl>[CH3:19][O:20][C:21]1[CH:26]=[C:25]([N+:27]([O-:29])=[O:28])[CH:24]=[CH:23][C:17]=1[O:16][CH2:15][O:14][CH3:13]
Reactant: ClCOCOCOCCl
Reactant: COc1cc([N+](=O)[O-])ccc1O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: COCOc1ccc([N+](=O)[O-])cc1OC
Temperature: 25 °C
Reaction time: 1 h
Yield: 100 %

Procedure:
N,N-diisopropylethylamine (1.24 ml, 7.09 mmol), chloromethoxymethyl ether (0.494 ml, 6.50 mmol) and tetrabutylammonium bromide (218 mg, 0.591 mmol) were added to a solution of 2-methoxy-4-nitrophenol (1.0 g, 5.91 mmol) in dichloromethane (20 ml) at 0° C. After 1 hour, the mixture thus obtained was warmed up to room temperature. After 15 hours, the mixture was poured into water (50 ml) and extracted with chloroform (50 ml×2), and the organic layer was dried over anhydrous magnesium sulfate. The organic layer dried was concentrated under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate) to obtain 2-methoxy-1-(methoxymethoxy)-4-nitrobenzene (1.26 g, 100%).
Reaction SMILES: [CH2:1]([NH:11][C:12](=[O:29])[CH:13]=[CH:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][C:22](=[O:28])/[CH:23]=[CH:24]\[C:25]([OH:27])=[O:26])[CH:16]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].C(N1C=CN=C1)(N1C=CN=C1)=O.[CH2:42]([N:44]([CH2:47][CH2:48]O)[CH2:45][CH3:46])[CH3:43]>O1CCCC1>[CH2:1]([NH:11][C:12](=[O:29])[CH:13]=[CH:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][C:22](=[O:28])/[CH:23]=[CH:24]\[C:25]([O:27][CH2:43][CH2:42][N:44]([CH2:47][CH3:48])[CH2:45][CH3:46])=[O:26])[CH:16]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: CCN(CC)CCO
Reactant: CCCCCCCCCCNC(=O)C=Cc1cccc(NC(=O)/C=C\C(=O)O)c1
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: CCCCCCCCCCNC(=O)C=Cc1cccc(NC(=O)/C=C\C(=O)OCCN(CC)CC)c1
Temperature: 25 °C

Procedure:
To a stirred solution of 800 mg. of N-decyl-3-(3-[cis-3-carboxypropenamido]phenyl)propenamide in 25 ml. of tetrahydrofuran is added 357 mg. of carbonyldiimidazole. The mixture is heated under reflux for 10 minutes, and then 258 mg. of 2-(N,N-diethylamino)ethanol is added. The mixture is again heated under reflux for 10 minutes, and then an additional 258 mg. of 2-(N,N-diethylamino)ethanol is added. The mixture is heated under reflux for 15 minutes and then it is cooled to room temperature. The solvent is removed by evaporation in vacuo, and the residue is dissolved in 75 ml. of ethyl acetate. The ethyl acetate solution is washed successively with water, 1 N sodium hydroxide, water and saturated sodium chloride solution. The ethyl acetate solution is then dried and evaporated in vacuo to give the title compound.
Reaction SMILES: [CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][NH:2]1.[CH3:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]=[C:19]=[O:20])=[C:14]([CH3:21])[CH:13]=1>O1CCOCC1>[CH3:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([NH:18][C:19]([N:2]2[CH2:3][C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[CH2:1]2)=[O:20])=[C:14]([CH3:21])[CH:13]=1
Reactant: COc1ccc(N=C=O)c(C)c1
Reactant: c1ccc2c(c1)CNC2
Solvent: C1COCCO1
Product: COc1ccc(NC(=O)N2Cc3ccccc3C2)c(C)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 104.5 %

Procedure:
To a solution of isoindoline (576 mg, 4.0 mmol) in dry 1,4-dioxane (20 mL) was added 4-methoxy-2-methylphenyl isocyanate (815 mg, 5.0 mmol) under argon at room temperature. The reaction mixture was then stirred at RT overnight. The solvent was evaporated under reduced pressure, and the residue was purified by chromatography on silica gel (EtOAc/hexanes: 1:1) to give the title compound (1.18 g, 84%) as a white solid. 1H NMR (500 MHz, DMSO-d6): δ 2.19 (s, 3H), 3.72 (s, 3H), 4.73 (s, 4H), 6.72 (dd, J=2.5 Hz, 8.5 Hz, 1H), 6.78 (d, J=2.5 Hz, 1H), 7.17 (d, J=8.5 Hz, 1H), 7.30-7.32 (m, 2H), 7.34-7.36 (m, 2H), 7.74 (s, 1H), 13C NMR (DMSO-d6): δ 18.2, 51.9, 55.1, 110.9, 115.1, 122.8, 127.2, 127.8, 130.6, 135.1, 137.0, 154.9, 156.5; MS (MH+, 283); EA calc'd for C17H18N2O2: C, 72.32; H, 6.43; N, 9.92. Found C, 72.16; H, 6.82; N, 9.98.
Reaction SMILES: [C:1]([C:3]1[C:7](I)=[CH:6][N:5]([C:9]2[C:14]([Cl:15])=[CH:13][C:12]([C:16]([F:19])([F:18])[F:17])=[CH:11][C:10]=2[Cl:20])[N:4]=1)#[N:2].[CH:21]([Sn](CCCC)(CCCC)CCCC)=[CH2:22].O.CCOCC>CN(C)C=O.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>[C:1]([C:3]1[C:7]([CH:21]=[CH2:22])=[CH:6][N:5]([C:9]2[C:14]([Cl:15])=[CH:13][C:12]([C:16]([F:19])([F:18])[F:17])=[CH:11][C:10]=2[Cl:20])[N:4]=1)#[N:2]
Reactant: N#Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)cc1I
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: O
Solvent: CCOCC
Product: C=Cc1cn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)nc1C#N
Temperature: 75 °C
Reaction time: 3 h

Procedure:
A solution of 3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-iodopyrazole (58 g) in dimethylformamide (350 ml) containing vinyltri-n-butyltin (116 ml) and tetrakis(triphenylphosphine)palladium(0) (3.5 g,) was stirred at 75° C. for 3 hours. The reaction mixture was poured into water (600 ml) and ether (600 ml). The organic layer was separated, washed with water (×5), brine (700 ml), dried (Na2SO4) and evaporated. The residue was recrystallised from propan-2-ol to give the title compound as a pale brown solid, m.p.75-6° C.