Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3]([C:5]1[N:10]2[N:11]=[C:12]([NH:14][C:15]([NH:17][CH2:18][CH3:19])=[O:16])[N:13]=[C:9]2[CH:8]=[C:7]([C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)[CH:6]=1)=O.[CH3:26][NH2:27]>CCO>[CH3:26][NH:27][C:3]([C:5]1[N:10]2[N:11]=[C:12]([NH:14][C:15]([NH:17][CH2:18][CH3:19])=[O:16])[N:13]=[C:9]2[CH:8]=[C:7]([C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)[CH:6]=1)=[O:2]
Reactant: CN
Reactant: CCNC(=O)Nc1nc2cc(-c3cccnc3)cc(C(=O)OC)n2n1
Solvent: CCO
Product: CCNC(=O)Nc1nc2cc(-c3cccnc3)cc(C(=O)NC)n2n1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
2-(3-Ethyl-ureido)-7-pyridin-3-yl-[1,2,4]triazolo[1,5-a]pyridine-5-carboxylic acid methyl ester, prepared as in Example 6, (46 mg, 0.14 mmol) was suspended/dissolved in 33% methylamine in EtOH (15 mL), then stirred overnight at room temperature. After this time the reaction mixture was concentrated to a volume of ca 5 mL, then diluted with Et2O (5 mL). The resulting precipitate was isolated by filtration and washed well with Et2O to give the final product mp. >300° C. LCMS (APCI+) 340.
Reaction SMILES: [OH-].[Na+].CN(C)/[CH:5]=[CH:6]/[C:7]([C:9]1[S:13][C:12]([N:14]=CN(C)C)=[N:11][C:10]=1[CH3:19])=O.Cl.[F:22][C:23]([F:31])([F:30])[C:24]([CH3:29])([CH3:28])[C:25]([NH2:27])=[NH:26].O>COCCO>[CH3:19][C:10]1[N:11]=[C:12]([NH2:14])[S:13][C:9]=1[C:7]1[CH:6]=[CH:5][N:27]=[C:25]([C:24]([CH3:29])([CH3:28])[C:23]([F:31])([F:30])[F:22])[N:26]=1
Reactant: Cc1nc(N=CN(C)C)sc1C(=O)/C=C/N(C)C
Reactant: CC(C)(C(=N)N)C(F)(F)F
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: COCCO
Product: Cc1nc(N)sc1-c1ccnc(C(C)(C)C(F)(F)F)n1
Temperature: 125 °C

Procedure:
Powdered sodium hydroxide (0.42 g) is added to a solution of N′-[5-((E)-3-dimethylamino-acryloyl)-4-methyl-thiazol-2-yl]-N,N-dimethyl-formamidine (0.93 g, prepared as described by S. Wang et al J. Med. Chem. 2004, 47, 1662-1675.) and 3,3,3-trifluoro-2,2-dimethyl-propionamidine hydrochloride (0.54 g) in 2-methoxyethanol (7 ml) and the mixture is heated at 125° C. for 1 hour with stirring. The reaction mixture is cooled, water is added, and the aqueous layer is extracted 4-times with 10% methanol in dichloromethane. The combined organic layers are purified by reversed phase chromatography and sodium bicarbonate is added to the fractions containing the title compound to give a white precipitate, which is collected by filtration. HPLC/MS: retention time 1.47 minutes, M+H 303.1.
Reaction SMILES: C([O:4][C:5]1[CH:10]=[C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:19]#[N:20])[CH:8]=[C:7]([C:21]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([N+:30]([O-:32])=[O:31])=[CH:26][N:25]=2)=[O:22])[CH:6]=1)(=O)C.C[O-].[Na+].Cl>C1COCC1.CO>[N+:30]([C:27]1[CH:28]=[CH:29][C:24]([NH:23][C:21](=[O:22])[C:7]2[CH:6]=[C:5]([OH:4])[CH:10]=[C:9]([O:11][CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[C:19]#[N:20])[CH:8]=2)=[N:25][CH:26]=1)([O-:32])=[O:31]
Reactant: CC(=O)Oc1cc(OCc2ccccc2C#N)cc(C(=O)Nc2ccc([N+](=O)[O-])cn2)c1
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Product: N#Cc1ccccc1COc1cc(O)cc(C(=O)Nc2ccc([N+](=O)[O-])cn2)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 84.5 %

Procedure:
A suspension of 3-{[(5-nitropyridin-2-yl)amino]carbonyl}-5-[(2-cyanobenzyl)oxy]phenyl acetate (5710 mg) in THF (35 ml) was treated with 25% NaOMe in methanol (6 ml). Stirred at ambient temperature for 30 minutes. Acidified with 2 m hydrochloric acid (25 ml), then extracted with ethyl acetate (100 ml). The extract was washed with water (50 ml), brine (50 ml), dried over MgSO4. Volatile material was removed by evaporation to give a solid. This was washed with hot methanol to give the title compound (4358 mg) as a solid, LCMS rt=2.38 min (90.5%). ES+391.45 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:8](=O)[CH3:9])[CH:5]=[CH:6][CH:7]=1.BrBr.[NH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1.C(=O)([O-])O.[Na+]>O.C(O)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]3[CH:9]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: Nc1ccccn1
Reactant: CC(=O)c1cccc(Br)c1
Agent: BrBr
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: Brc1cccc(-c2cn3ccccc3n2)c1
Yield: 25.6 %

Procedure:
Dissolving 10 g (50 mmol) of 3′-bromoacetophenone into 20 milliliter of acetic acid and adding 7.0 g (44 mmol) of bromine at the temperature of about 5 to 10° C., stirred at the temperature of about 5 to 10° C. for 4 hours until the color of bromine disappeared. After completion of the reaction, adding water and an extraction was carried out using dichloro-methane. Further, washing with water, dried with the use of sodium sulfate. The solvent was removed by distillation and the resultant crude 2,3′-dibromo acetophenone was dissolved into 30 milliliter of ethanol, adding 5.0 g (53 mmol) of 2-aminopyridine and 7.0 g of sodium hydrogen carbonate, the resultant suspension was refluxed under heating for 8 hours. After completion of the reaction, separation with filtration was carried out and resultant crystals were washed with water and methanol, thereby obtaining 3.5 g of 2-(3-bromo-phenyl)-imidazo [1,2-a] pyridine (yield: 26%).
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C:3]1[CH:11]=[CH:10][C:6]([C:7](Cl)=[O:8])=[CH:5][N:4]=1.[NH2:14][CH:15]1[C:20](=[O:21])[N:19]2[CH:22]([CH2:30][C:31]3[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=3)[C:23](=[O:29])[N:24]([CH:26]([CH3:28])[CH3:27])[CH2:25][CH:18]2[N:17]([S:38]([C:41]2[CH:46]=[CH:45][C:44]([Cl:47])=[CH:43][C:42]=2[Cl:48])(=[O:40])=[O:39])[CH2:16]1>>[Cl:37][C:34]1[CH:35]=[CH:36][C:31]([CH2:30][CH:22]2[N:19]3[C:20](=[O:21])[CH:15]([NH:14][C:7](=[O:8])[C:6]4[CH:10]=[CH:11][C:3]([C:2]([F:13])([F:12])[F:1])=[N:4][CH:5]=4)[CH2:16][N:17]([S:38]([C:41]4[CH:46]=[CH:45][C:44]([Cl:47])=[CH:43][C:42]=4[Cl:48])(=[O:40])=[O:39])[CH:18]3[CH2:25][N:24]([CH:26]([CH3:28])[CH3:27])[C:23]2=[O:29])=[CH:32][CH:33]=1
Reactant: CC(C)N1CC2N(C(=O)C(N)CN2S(=O)(=O)c2ccc(Cl)cc2Cl)C(Cc2ccc(Cl)cc2)C1=O
Reactant: O=C(Cl)c1ccc(C(F)(F)F)nc1
Product: CC(C)N1CC2N(C(=O)C(NC(=O)c3ccc(C(F)(F)F)nc3)CN2S(=O)(=O)c2ccc(Cl)cc2Cl)C(Cc2ccc(Cl)cc2)C1=O

Procedure:
Synthesis took place in analogy to Example 22 using 6-(trifluoromethyl)nicotinoyl chloride and 3-amino-6-(4-chlorobenzyl)-1-(2,4-dichlorobenzenesulfonyl)-8-isopropyl-hexahydropyrazino[1,2-a]pyrimidine-4,7-dione. The desired product is obtained with MW=731.08 (calculated, monoisotopic); measured value (M+H)+: 732.01
Reaction SMILES: [OH-].[NH4+:2].[F:3][C:4]1[CH:12]=[C:11]([F:13])[CH:10]=[C:9]2[C:5]=1[CH2:6][CH2:7]/[C:8]/2=[CH:14]\[C:15](Cl)=[O:16]>ClCCl>[F:3][C:4]1[CH:12]=[C:11]([F:13])[CH:10]=[C:9]2[C:5]=1[CH2:6][CH2:7]/[C:8]/2=[CH:14]\[C:15]([NH2:2])=[O:16]
Reactant: O=C(Cl)/C=C1\CCc2c(F)cc(F)cc21
Reactant: [NH4+]
Agent: [OH-]
Solvent: ClCCl
Product: NC(=O)/C=C1\CCc2c(F)cc(F)cc21
Yield: 59.9 %

Procedure:
A 30% aqueous ammonium hydroxide solution (1.7 mL, 0.026 mol) was added dropwise to a stirred, chilled (ice bath) solution of (E)-2-(4,6-difluoro-1-indanylidene)acetyl chloride (2.97 g, 0.013 mol) in dichloromethane (50 mL). After 4.5 h the mixture was concentrated in vacuo and the residue was partitioned between 5% aqueous sodium bicarbonate solution and ethyl acetate. The ethyl acetate solution was washed with saturated aqueous sodium chloride, dried over sodium sulfate, filtered and concentrated in vacuo Chromatography on silica gel with ethyl acetate: hexanes (7:3)as eluent and trituration of the resulting solid with pentane gave 1.63 g (60%) of (E)-2-(4,6difluoro-1-indanylidene)acetamide as a white solid: mp 178°-180° C.; NMR (DMSO-d6): d 6.94-7.45 (m, 4H), 6.46 (s, 1H), 2.94-3.00, 3.21-3.27 (2 m's, 4H); steady-state nOe: irradiation at 6.46 d, observed 19% nOe at 7.26 d.
Reaction SMILES: [CH:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:13][CH:14]=3)[N:9]([CH2:20][CH:21]([O:24][CH3:25])[O:22][CH3:23])[C:8]=2[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[CH:32]=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:34][N:35]([CH3:39])[CH2:36][CH2:37][NH2:38].C(O)(=O)C.[BH4-].[Na+]>C1COCC1>[CH:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:13][CH:14]=3)[N:9]([CH2:20][CH:21]([O:24][CH3:25])[O:22][CH3:23])[C:8]=2[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[CH2:32][NH:38][CH2:37][CH2:36][N:35]([CH3:39])[CH3:34])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: COC(=O)c1ccc2c(C3CCCCC3)c(-c3ccccc3C=O)n(CC(OC)OC)c2c1
Reactant: CN(C)CCN
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: COC(=O)c1ccc2c(C3CCCCC3)c(-c3ccccc3CNCCN(C)C)n(CC(OC)OC)c2c1

Procedure:
To a stirred solution of methyl 3-cyclohexyl-1-(2,2-dimethoxyethyl)-2-(2-formylphenyl)-1H-indole-6-carboxylate (0.16 M, 1 eq, from Step 2) and 2-dimethylaminoethylamine (2 eq) in THF was added glacial acetic acid to adjust the pH of the reaction to ca. pH 4. The reaction was stirred for 1 h after which the THF was removed under reduced pressure and the residue redissolved in MeOH. NaBH4 (8 eq) was added portionwise until complete conversion was observed by LC-MS analysis. The reaction was quenched by addition of sat. aq. NaHCO3 and extracted into EtOAc (×3). The combined organics were washed with H2O and brine before being dried (Na2SO4), filtered and concentrated in vacuo. The title compound was obtained as a pale yellow oil and taken on without further purification (quantitative); MS (ES+) m/z 522 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]([CH:5]1[CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:4].Cl[CH2:11][C:12]#[N:13]>>[CH3:1][O:2][C:3]([C:5]1([CH2:11][C:12]#[N:13])[CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:4]
Reactant: COC(=O)C1CCCC1
Reactant: N#CCCl
Product: COC(=O)C1(CC#N)CCCC1
Yield: 38 %

Procedure:
1-(Cyanomethyl)cyclopentane carboxylic acid methyl ester was prepared from cyclopentane carboxylic acid methyl ester and chloroacetonitrile using the procedure described in example 7 to give a 38% yield. HR MS (C9H13NO2): Obs mass, Calcd mass, 167.0146 (M+).
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:6]=[C:7]([CH:12]=[C:13]([N:15]2[CH2:19][CH2:18][CH2:17][C:16]2=[O:20])[CH:14]=1)[C:8]([O:10]C)=[O:9])(=[O:4])=[O:3].O.[OH-].[Li+]>O1CCOCC1.O>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([CH:12]=[C:13]([N:15]2[CH2:19][CH2:18][CH2:17][C:16]2=[O:20])[CH:14]=1)[C:8]([OH:10])=[O:9])(=[O:4])=[O:3]
Reactant: COC(=O)c1cc(N2CCCC2=O)cc(S(C)(=O)=O)c1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: CS(=O)(=O)c1cc(C(=O)O)cc(N2CCCC2=O)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Methyl 3-methylsulfonyl-5-(2-oxopyrrolidin-1-yl)-benzoate (D18) (0.717 g) was suspended in dioxan (3.6 ml) and treated with a solution of lithium hydroxide monohydrate (0.153 g) in water (3.6 ml). The mixture was stirred for 2 h at room temperature and a clear solution was formed. The pH was adjusted to ˜4 by addition of Amberlyst-15 H+ resin. The resin was removed by filtration and washed well with dioxan. The combined filtrates were evaporated and the residue dried. Trituration with ether gave D19 (0.51 g) as a pale cream solid.
Reaction SMILES: [Li+].CC([N-]C(C)C)C.[CH2:9]([O:11][C:12]1[CH2:17][CH2:16][CH2:15][C:14](=[O:18])[CH:13]=1)[CH3:10].C([C:21]([O:23][CH2:24][CH3:25])=[O:22])#N>C1COCC1>[CH2:24]([O:23][C:21]([CH:15]1[CH2:16][CH2:17][C:12]([O:11][CH2:9][CH3:10])=[CH:13][C:14]1=[O:18])=[O:22])[CH3:25]
Reactant: CCOC1=CC(=O)CCC1
Reactant: CCOC(=O)C#N
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: CCOC(=O)C1CCC(OCC)=CC1=O
Temperature: -78 °C
Reaction time: 1 h

Procedure:
To a −78° C. solution of LDA (192 mmol) in THF (200 mL) was added 3-ethoxy-cyclohex-2-enone (23 mL) dropwise. After stirring for 1 h at −78° C., ethyl cyanoformate (16 mL) was added. The mixture was stirred at −78° C. for 4 h and then was warmed to rt and stirred for 1 h. The mixture was concentrated, diluted with aq. NH4Cl (300 mL), and poured into water. The resulting solids were collected by suction filtration and washed with hexanes followed by water, then was dried and concentrated to provide 17.1 g of a brown solid. TLC (SiO2, 33% EtOAc/hexanes): Rf=0.43.
Reaction SMILES: Cl.Cl.[F:3][C:4]1[CH:5]=[C:6]([CH:8]=[C:9]([CH2:17][NH:18][CH3:19])[C:10]=1[O:11][C@@H:12]([CH3:16])[CH2:13][O:14][CH3:15])[NH2:7].C(N(CC)C(C)C)(C)C.[CH2:29]([O:36][C:37]([O:39]N1C(=O)CCC1=O)=O)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>CN(C=O)C>[NH2:7][C:6]1[CH:5]=[C:4]([F:3])[C:10]([O:11][C@@H:12]([CH3:16])[CH2:13][O:14][CH3:15])=[C:9]([CH:8]=1)[CH2:17][N:18]([CH3:19])[C:37](=[O:39])[O:36][CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1
Reactant: CNCc1cc(N)cc(F)c1O[C@@H](C)COC
Reactant: O=C(OCc1ccccc1)ON1C(=O)CCC1=O
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: COC[C@H](C)Oc1c(F)cc(N)cc1CN(C)C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 92.3 %

Procedure:
To a solution of 37A (472 mg, 1.497 mmol) and N,N-diisopropylethylamine (1.043 ml, 5.99 mmol) in DMF (10 ml), was added N-(benzyloxycarbonyloxy) succinimide (411 mg, 1.647 mmol). The mixture was stirred rt for 1 h, then quenched with water, extracted with EtOAc (3×30 ml). The organic layer was washed with brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0-60% EtOAc in hexanes) to give 37B (520 mg, 1.381 mmol, 92% yield). MS (ESI) m/z: 377.3 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[C:7]([O:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH3:23])=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][CH:11]=2)[CH:6]=[CH:5][C:3]=1[NH2:4].[C:24]1([CH3:33])[C:25]([N:30]=[C:31]=[O:32])=[CH:26][CH:27]=[CH:28][CH:29]=1.CO>C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:8]=[C:7]([O:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH3:23])=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][CH:11]=2)[CH:6]=[CH:5][C:3]=1[NH:4][C:31]([NH:30][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[CH3:33])=[O:32]
Reactant: COc1cc2nccc(Oc3ccc(N)c(Cl)c3)c2cc1OC
Reactant: Cc1ccccc1N=C=O
Solvent: CO
Solvent: ClC(Cl)Cl
Product: COc1cc2nccc(Oc3ccc(NC(=O)Nc4ccccc4C)c(Cl)c3)c2cc1OC
Temperature: 25 °C
Reaction time: 8 h
Yield: 34.5 %

Procedure:
2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (122 mg) was dissolved in chloroform (10 ml), and o-toluyl isocyanate (59 mg) was added to the solution. The mixture was stirred at room temperature overnight. Methanol was added to the reaction solution, and the solvent was removed by distillation under the reduced pressure. The residue was dissolved in a minor amount of chloroform, and a large amount of ether was added to the solution to precipitate a crystal. The crystal was collected by filtration to give 59 mg (yield 34%) of the title compound.
Reaction SMILES: [C:1]([C:3]1[C:4]([CH:20]([CH3:22])[CH3:21])=[N:5][C:6]2[C:11]([C:12]=1[C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2)#[CH:2].CC(N=NC(C#N)(C)C)(C#N)C.[I:35]I>C([SnH](CCCC)CCCC)CCC.CCOCC>[F:19][C:16]1[CH:15]=[CH:14][C:13]([C:12]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=[C:4]([CH:20]([CH3:22])[CH3:21])[C:3]=2/[CH:1]=[CH:2]/[I:35])=[CH:18][CH:17]=1
Reactant: II
Reactant: C#Cc1c(C(C)C)nc2ccccc2c1-c1ccc(F)cc1
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Agent: CCCC[SnH](CCCC)CCCC
Solvent: CCOCC
Product: CC(C)c1nc2ccccc2c(-c2ccc(F)cc2)c1/C=C/I
Temperature: 120 °C
Reaction time: 2.5 h

Procedure:
A mixture of 3-Ethynyl-4-(4-fluorophenyl)-2-(1-methylethyl)quinoline (1.500 gm, 5.18 mmol) (the preparation of which is described in Example 8) and AIBN (15 mg) in tri-n-butylstannyl hydride (2.1 ml) was rapidly heated to 120° C. After 3 minutes of heating, the mixture was treated with additional Bu3SnH (0.6 ml) and the temperature of the reaction was raised to 130° C. Approximately 15 mg of AIBN was added to the reaction mixture of 0.5, 1, and 2 hours after heating was initiated. After 2.5 hours, the mixture was cooled to room temperature, diluted with Et2O (30 ml) and treated with solid I2 (3.86 gm, 15.2 mmol). The dark reaction mixture was stirred for 1 hour, then quenched with 10% Na2SO3 in saturated NaHCO3. The layers were shaken and separated. The ethereal layer was washed with brine, dried (Na2 SO4), filtered and stripped to yield a liquid/solid residue. The residue was chromatographed (flash, Merck SiO2, 4% EtOAc in hexane) to give slightly impure (E)-4-(4-Fluorophenyl)-3-(2-iodoethenyl)-2-(1-methylethyl)quinoline as a solid. Recrystallization of the solid from hot hexane gave (E)-4-(4-Fluorophenyl)-3-(2-iodoethenyl)-2-(1-methylethyl)quinoline (1.725 gm, 80%) as light yellow crystals.
Reaction SMILES: [CH2:1]([CH:4]([CH2:15][CH:16]=[CH2:17])[CH2:5][O:6][SiH2:7][C:8]1[CH:13]=[CH:12][C:11](I)=[CH:10][CH:9]=1)[CH:2]=[CH2:3].C(=O)([O-])[O-].[K+].[K+].[C:24]1(B(O)O)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C1(C)C=CC=CC=1>CCOCC>[CH2:1]([CH:4]([CH2:15][CH:16]=[CH2:17])[CH2:5][O:6][SiH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[CH:10][CH:9]=1)[CH:2]=[CH2:3]
Reactant: OB(O)c1ccccc1
Reactant: C=CCC(CC=C)CO[SiH2]c1ccc(I)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOCC
Solvent: Cc1ccccc1
Product: C=CCC(CC=C)CO[SiH2]c1ccc(-c2ccccc2)cc1
Yield: 78 %

Procedure:
At first, a mixture of the 4-(diallylethoxysilyl)iodobenzene (148 mg, 0.41 mmol) obtained in Example 2, tetrakistriphenylphosphine palladium (Pd(PPh3)4: 14.3 mg, 0.012 mmol), potassium carbonate (K2CO3: 85.1 mg, 0.62 mmol), and phenyl boronic acid (60 mg, 0.49 mmol) was added with distilled toluene (dist.toluene: 5 mL). Subsequently, the resultant mixture was stirred under a nitrogen atmosphere at 80° C. for 13 hours to obtain a reaction mixture. Thereafter, the reaction mixture was diluted with ether, and a salt thus formed was removed by filtering with celite. The solvent was distilled from the organic layer with an evaporator to obtain a crude product. After that, the crude product thus obtained was separated and purified by silica gel column chromatography (hexane/EtOAc=10/1), and thereby 4-(diallylethoxysilyl)biphenyl (a second organosilane compound of the present invention) was obtained (99.6 mg, 78% yield).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][CH2:7][NH:8][CH:9]=O.[BH4-].[Na+].II.CO>O1CCCC1>[CH3:9][NH:8][CH2:7][CH2:6][C:2]1[S:1][CH:5]=[CH:4][CH:3]=1
Reactant: O=CNCCc1cccs1
Agent: II
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Product: CNCCc1cccs1
Temperature: 7 °C
Reaction time: 0.17 h
Yield: 31.3 %

Procedure:
At 7° C., a solution of N-(2-(2-thienyl)ethyl)formamide (9,98 g, 63.8 mmol) in tetrahydrofuran (200 ml) was added to a suspension of sodium borohydride (2.89 g, 76.5 mmol) in tetrahydrofuran (200 ml). The mixture was stirred for 10 min. A solution of iodine (8.09 g, 31.9 mmol) in tetrahydrofuran (200 ml) was added dropwise. The reaction mixture was stirred for 30 min at 7° C. and 30 min at room temperature. It was heated to reflux for 16 h. The reaction mixture was cooled to 7° C. Methanol (500 ml) was added dropwise. The solvent was removed in vacuo. The residue was dissolved in 20% aqueous sodium hydroxide solution (500 ml) and tert-butyl methyl ether (200 ml). The phases were separated. The aqueous phase was extracted with tert-butyl methyl ether (2×200 ml). The combined organic layers were dried over magensium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (220 g), using dichloromethane/methanol/25% aqueous ammonia (100:10:1) as eluent to give 2.82 g of N-methyl-N-(2-(2-thienyl)ethyl)amine.
Reaction SMILES: [NH2:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=2)[NH:4][N:3]=1.C(O)(=O)C.[NH:23]1[CH:27]=[CH:26][N:25]=[C:24]1[CH:28]=O>CO>[Cl:18][C:14]1[CH:13]=[C:12]([NH:11][C:9]2[N:8]=[CH:7][N:6]=[C:5]3[NH:4][N:3]=[C:2]([N:1]=[CH:28][C:24]4[NH:23][CH:27]=[CH:26][N:25]=4)[C:10]=23)[CH:17]=[CH:16][CH:15]=1
Reactant: Nc1n[nH]c2ncnc(Nc3cccc(Cl)c3)c12
Reactant: O=Cc1ncc[nH]1
Solvent: CO
Solvent: CC(=O)O
Product: Clc1cccc(Nc2ncnc3[nH]nc(N=Cc4ncc[nH]4)c23)c1

Procedure:
Analogously to Example 32, 261 mg (1.00 mmol) of 3-amino-4-(3-chlorophenylamino)-1H-pyrazolo[3,4-d]pyrimidine (see Step 1.6) and 180 mg of acetic acid are dissolved in 26 ml of methanol and reacted with 144 mg (1.5 mmol) of imidazole-2-carbaldehyde to form 4-(3-chloro-phenylamino)-3-[(1H-imidazol-2-yl)-methyleneamino]-1H-pyrazolo[3,4-d]pyrimidine. Reduction of the above intermediate in 15 ml of DMEU with 8 ml (8 mmol) of DIBAL-H, analogous working-up and digestion in ethanol yield 4-(3-chlorophenylamino)-3-(1H-imidazol-2-yl)-methylamino]-1H-pyrazolo[3,4-d]pyrimidine; HPLC: tRet(grad20-100/20) 5.8; FABMS: (M+H)+=341.
Reaction SMILES: [CH2:1]=[C:2]1[CH2:5][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:3]1.[Cl:13][C:14]([Cl:19])(Cl)[C:15](Cl)=[O:16].COCCOC>C(OCC)C.[Zn]>[Cl:13][C:14]1([Cl:19])[C:15](=[O:16])[CH2:1][C:2]21[CH2:3][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:5]2
Reactant: C=C1CN(C(=O)OC(C)(C)C)C1
Reactant: O=C(Cl)C(Cl)(Cl)Cl
Agent: [Zn]
Solvent: COCCOC
Solvent: CCOCC
Product: CC(C)(C)OC(=O)N1CC2(CC(=O)C2(Cl)Cl)C1
Temperature: 10 °C
Reaction time: 14 h

Procedure:
Under an inert atmosphere, 7.728 g (118.19 mmoles) of zinc in nanopowder form are suspended in 100 ml of diethyl ether. 5.00 g (29.55 mmoles) of tert-butyl 3-methylene-azetidine-1-carboxylate (WO 2008124085) are added, then the medium is cooled to 10° C. A solution of 6.60 ml (59.09 mmoles) of trichloroacetyl chloride in ml of 1,2-dimethoxyethane is added drop by drop while maintaining the temperature of the reaction medium between 26 and 30° C. After stirring for 14 hrs at ambient temperature, the medium is filtered over celite, the celite is copiously rinsed with diethyl ether and the filtrate is partially concentrated under reduced pressure. The crude reaction product thus obtained is used as such in the following stage.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([Cl:11])[CH:3]=1.O[N:13]1[C:17](=[O:18])[CH2:16][CH2:15][C:14]1=[O:19].CCN=C=NCCCN(C)C>O1CCCC1.CN(C)C=O>[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([O:8][N:13]2[C:17](=[O:18])[CH2:16][CH2:15][C:14]2=[O:19])=[O:7])=[C:4]([Cl:11])[CH:3]=1
Reactant: O=C(O)c1ccc(Br)cc1Cl
Reactant: O=C1CCC(=O)N1O
Agent: CCN=C=NCCCN(C)C
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: O=C(ON1C(=O)CCC1=O)c1ccc(Br)cc1Cl
Yield: 91.6 %

Procedure:
A solution of 4-bromo-2-chlorobenzoic acid (2.00 g, 8.5 mmol), N-hydroxysuccinimide (1.07 g, 9.3 mmol) and EDCI (1.79 g, 9.3 mmol) in tetrahydrofuran/N,N-dimethylformamide (3:1; 40 Ml) was stirred at room temperature for 18 h. The reaction was concentrated and water (50 Ml) was added. The mixture was extracted with ethyl acetate (3×50 Ml) and the combined organic layers were washed with brine, dried (Na2SO4), concentrated, and dried in vacuo to give 1-[(4-bromo-2-chlorobenzoyl)oxy]-2,5-pyrrolidinedione (2.59 g, 92%) as an off-white solid which was used directly in the next step without further purification.
Reaction SMILES: [CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:13][CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:21][C:22]1[N:23]=[C:24]([NH2:37])[S:25][C:26]=1[S:27]([N:30]1[CH2:35][CH2:34][N:33]([CH3:36])[CH2:32][CH2:31]1)(=[O:29])=[O:28]>>[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:13][CH:12]=2)[C:8]([NH:37][C:24]2[S:25][C:26]([S:27]([N:30]3[CH2:35][CH2:34][N:33]([CH3:36])[CH2:32][CH2:31]3)(=[O:29])=[O:28])=[C:22]([CH3:21])[N:23]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: Cc1nc(N)sc1S(=O)(=O)N1CCN(C)CC1
Reactant: CS(=O)(=O)c1ccc(C(CC2CCCC2)C(=O)O)cc1
Product: Cc1nc(NC(=O)C(CC2CCCC2)c2ccc(S(C)(=O)=O)cc2)sc1S(=O)(=O)N1CCN(C)CC1

Procedure:
3-Cyclopentyl-2-(4-methanesulfonyl-phenyl)-N-[4-methyl-5-(4-methylpiperazine-1-sulfonyl)-thiazol-2-yl]-propionamide was prepared from 3-cyclopentyl-2-(4-methanesulfonylphenyl)propionic acid and 4-methyl-5-(4-methyl-piperazine-1-sulfonyl)-thiazol-2-ylamine as described in Example 1. 1H-NMR (CDCl3): δ 13.03 (broad s, 1H), 7.91 (d, 2H), 7.64 (d, 2H), 4.05 (t, 1H), 3.20 (s, 3H), 2.99 (m, 4H), 2.47 (s, 3H), 2.39 (m, 4H), 2.16 (m, 4H), 1.84-1.77 (m, 1H), 1.75-1.39 (m, 7H), 1.19-1.07 (m, 2H); HPLC-MS: m/z=555 (M+1); Rt=3.08 min.