Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:10]=[CH:9][C:8](Br)=[C:7]2[C:3]=1[CH:4]=[C:5]([CH3:12])[CH2:6]2.[C:13]1(B(O)O)[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][CH:14]=1.C(=O)([O-])[O-].[K+].[K+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[C:13]1([C:2]2[CH:10]=[CH:9][C:8]([C:21]3[C:22]4[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=4)[CH:18]=[CH:19][CH:20]=3)=[C:7]3[C:3]=2[CH:4]=[C:5]([CH3:12])[CH2:6]3)[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][CH:14]=1
Reactant: OB(O)c1cccc2ccccc12
Reactant: CC1=Cc2c(Br)ccc(Br)c2C1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: O
Product: CC1=Cc2c(-c3cccc4ccccc34)ccc(-c3cccc4ccccc34)c2C1
Temperature: 25 °C
Yield: 65.5 %

Procedure:
In a 500 ml roundbottom flask were placed 17.6 g (61.1 mmol) 4,7-Dibromo-2-methyl-1H-indene, 26.3 g (2.5 eq.) 1-napthyl boronic acid, 274 mg (2 mol %) palladium acetate, 42.23 g (2.5 eq.) potassium carbonate, 39.4 g (2 eq.) tetrabutylammonium bromide, 169 ml degassed water and 169 ml degassed toluene. The mixture was stirred under reflux for 20 h. After cooling to room temperature, 100 ml toluene and 100 ml water were added. The aqueous phase was extracted 3 times with 100 ml toluene. The combined organic layers were washed once with 100 ml of 2M sodium hydroxide solution and 3 times with 50 ml water each, and dried over magnesium sulfate. Removal of the solvent in vacuo and purification via flash chromatography on silica using heptane/dichloromethane (10:1) yielded 15.3 g (40 mmol, 65%) of the desired indene as a white solid. 1H-NMR (500 MHz, CDCl3): δ=8.11, 7.89-7.77, 7.57-7.26 (3×m, 16H, aromatic), 6.61, 6.18 (2×s, 1H, indenyl-C═CH), 3.49 (“d”, 2H, benzylic), 2.09 (2×s, 3H, CH3) ppm.
Reaction SMILES: [CH3:1][O:2][C:3]([CH:5]1[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6]1)=[O:4].N1C=CC=CC=1.[Cl:20][C:21]1[CH:22]=[C:23]([S:28](Cl)(=[O:30])=[O:29])[CH:24]=[CH:25][C:26]=1[Cl:27]>C(Cl)Cl>[Cl:20][C:21]1[CH:22]=[C:23]([S:28]([N:6]2[C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH2:13][CH:5]2[C:3]([O:2][CH3:1])=[O:4])(=[O:29])=[O:30])[CH:24]=[CH:25][C:26]=1[Cl:27]
Reactant: O=S(=O)(Cl)c1ccc(Cl)c(Cl)c1
Reactant: COC(=O)C1Cc2ccccc2N1
Solvent: c1ccncc1
Solvent: ClCCl
Product: COC(=O)C1Cc2ccccc2N1S(=O)(=O)c1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Indoline-2-carboxylic acid methyl ester (33.0 g, 149.7 mmol) was dissolved in DCM (400 ml), and pyridine (37.8 ml, 463.2 mmol) was added thereto. A solution of 3,4-dichlorobenzenesulfonyl chloride (24.1 ml, 154.4 mmol) dissolved in DCM (100 ml) was then added, and the mixture was stirred overnight under reflux and then cooled to room temperature. The mixture was diluted with DCM and washed in succession with 0.5 M KHSO4, saturated NaHCO3 solution and saturated NaCl solution. The organic phase was dried (sodium sulfate) and concentrated in vacuo.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)[C:2]1=[O:15].[H-].[Na+].[F:18][C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH2:22]Br>CN(C)C=O>[F:18][C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH2:22][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)[C:2]1=[O:15]
Reactant: Fc1cccc(CBr)c1
Reactant: O=C1Nc2ccccc2C12CCCCC2
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=C1N(Cc2cccc(F)c2)c2ccccc2C12CCCCC2
Reaction time: 0.5 h
Yield: 51.7 %

Procedure:
Spiro[cyclohexane-1,3′-indol]-2′(1′H)-one (1.0 g, 5 mmol) was dissolved in dimethylformamide (10 mL) and NaH (0.21 g, 5.5 mmol) was added and the mixture was stirred 30 minutes then 3-fluorobenzyl bromide (1.04 g, 5.5 mmol) was added. The mixture was stirred 2 hours then quenched with saturated aqueous ammonium chloride, diluted with ether, washed with water, and saturated brine. The organic layer was separated, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The crude product was purified via Isco chromatography (Redisep, silica, gradient 0-20% ethyl acetate in hexane) to afford 0.8 g of 1′-(3-fluorobenzyl)spiro[cyclohexane-1,3′-indol]-2′(1′H)-one.
Reaction SMILES: [CH:1]1[CH:2]=[CH:3][N:4]2[CH2:10][C:9]3[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=3[N:7]([C:15]([C:17]3[CH:22]=[CH:21][C:20](B4OC(C)(C)C(C)(C)O4)=[CH:19][CH:18]=3)=[O:16])[CH2:6][C:5]=12.FC(F)(F)S(O[C:38]1[CH:43]([CH3:44])[CH2:42][CH2:41][CH2:40][C:39]=1[CH3:45])(=O)=O>>[CH:1]1[CH:2]=[CH:3][N:4]2[CH2:10][C:9]3[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=3[N:7]([C:15]([C:17]3[CH:18]=[CH:19][C:20]([C:38]4[CH:43]([CH3:44])[CH2:42][CH2:41][CH2:40][C:39]=4[CH3:45])=[CH:21][CH:22]=3)=[O:16])[CH2:6][C:5]=12
Reactant: CC1(C)OB(c2ccc(C(=O)N3Cc4cccn4Cc4ccccc43)cc2)OC1(C)C
Reactant: CC1=C(OS(=O)(=O)C(F)(F)F)C(C)CCC1
Product: CC1=C(c2ccc(C(=O)N3Cc4cccn4Cc4ccccc43)cc2)C(C)CCC1

Procedure:
(10,11-Dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-methanone of Step B (0.300 g, 0.746 mmol) and 2,6-dimethyl-cyclohex-1-en-1-yl trifluoromethanesulfonate (0.255 g, 0.821 mmol) were reacted by the procedure described in Example 1, Step F. Purification by flash column chromatography on silica gel, eluting with a solvent gradient of from 30 to 60% ethyl acetate in hexane, followed by recrystallization from petroleum ether (−20° C.) afforded the title compound as white crystals, m.p. 153–154° C.
Reaction SMILES: [OH-].[Na+].[O:3]=[C:4]1[C:13]([NH:19][C:20](=[O:23])[CH2:21][CH3:22])([C:14]([O:16]CC)=[O:15])[CH2:12][C:11]2=[CH:24][CH:25]=[CH:26][C:9]3=[C:10]2[N:5]1[CH2:6][CH2:7][CH2:8]3.Cl>CO>[O:3]=[C:4]1[C:13]([NH:19][C:20](=[O:23])[CH2:21][CH3:22])([C:14]([OH:16])=[O:15])[CH2:12][C:11]2=[CH:24][CH:25]=[CH:26][C:9]3=[C:10]2[N:5]1[CH2:6][CH2:7][CH2:8]3
Reactant: CCOC(=O)C1(NC(=O)CC)Cc2cccc3c2N(CCC3)C1=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CCC(=O)NC1(C(=O)O)Cc2cccc3c2N(CCC3)C1=O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 94.6 %

Procedure:
Sodium hydroxide solution (10 mL of 4.0 N, 0.04 mol) was slowly added to ethyl 2,3,6,7-tetrahydro-3-oxo-2-((1-oxopropyl)amino)-1H,5H-benzo(ij)quinolizine-2-carboxylate (3.33 g, 0.010 mol) in methanol (50 mL). After stirring at room temperature for 30 minutes, the solvent was removed under reduced pressure. The resulting solid was dissolved in water (20 mL) and methanol (trace), neutralized with 4N HCl (10 mL, 0.04 mol), cooled to -10° C., and the precipitate was filtered off and air dried to give 2.86 g of 2,3,6,7-tetrahydro-3-oxo-2-((1-oxopropyl)amino)-1H,5H-benzo(ij)quinolizine-2-carboxylic acid. This was refluxed in ethanol for 20 minutes to effect decarboxylation. The ethanol was removed under reduced pressure and the solid was crystallized from ethyl acetate:hexane to give 1.85 g of N-(2,3,6,7-tetrahydro-3-oxo-1H,5H-benzo(ij)quinolizin-2-yl)propanamide, mp 149°-152° C. A sample was recrystallized for analysis; mp 152°- 154° C. Anal. Calcd. for C15H18N2O2 : C, 69.74; H, 7.02; N, 10.85. Found: C, 69.33; H, 7.33; N, 10.68.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].Br.Br[CH:12]([C:14]1[CH:15]=[C:16]([C:31]([N:33]([CH3:35])[CH3:34])=[O:32])[CH:17]=[C:18]2[C:23]=1[O:22][C:21]([N:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1)=[CH:20][C:19]2=[O:30])[CH3:13]>>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][CH:12]([C:14]2[CH:15]=[C:16]([C:31]([N:33]([CH3:35])[CH3:34])=[O:32])[CH:17]=[C:18]3[C:23]=2[O:22][C:21]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)=[CH:20][C:19]3=[O:30])[CH3:13])[CH:6]=[CH:7][C:8]=1[F:9]
Reactant: CC(Br)c1cc(C(=O)N(C)C)cc2c(=O)cc(N3CCOCC3)oc12
Reactant: Nc1ccc(F)c(Cl)c1
Agent: Br
Product: CC(Nc1ccc(F)c(Cl)c1)c1cc(C(=O)N(C)C)cc2c(=O)cc(N3CCOCC3)oc12
Yield: 62.8 %

Procedure:
3-chloro-4-fluoroaniline (238 mg, 1.63 mmol) was reacted with 8-(1-bromoethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide hydrobromide (200 mg, 0.41 mmol, as described in Example 3.03) to give 8-(1-(3-chloro-4-fluorophenylamino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (122 mg, 63.1%) as a white solid. Mass Spectrum: M+H+ 474. NMR Spectrum: (DMSOd6) 1.51 (d, 3H), 2.70 (s, 3H), 2.94 (s, 3H), 3.50-3.64 (m, 4H), 3.69-3.81 (m, 4H), 4.94-5.05 (m, 1H), 5.60 (m, 1H), 6.47 (ddd, 1H), 6.52 (d, 1H), 6.67 (dd, 1H), 7.05 (dd, 1H), 7.55 (d, 1H), 7.79 (d, 1H).
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:15]1([NH2:21])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1>C1(C)C=CC=CC=1>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=[N:21][CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C1CCN(Cc2ccccc2)CC1
Reactant: NC1CCCCC1
Solvent: Cc1ccccc1
Product: c1ccc(CN2CCC(=NC3CCCCC3)CC2)cc1
Temperature: 25 °C

Procedure:
A solution of 3.347 g (17.69 mmol) of 1-benzyl-4-piperidinone and 1.75 g (17.7 mmol) of cyclohexylamine in 150 ml of toluene was refluxed under dehydrating conditions for 2.5 hours in a Dean-Stark trap. After the reaction mixture was cooled to room temperature, the solvent was distilled off under reduced pressure to yield N-(1-benzyl-4-piperidylidene)cyclohexylamine. This product was used for the next reaction without purification.
Reaction SMILES: [F:1][C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)[CH:5]=[CH:4][C:3]=1B(O)O.Cl[C:18]1[N:23]=[C:22]([CH3:24])[N:21]=[C:20]([N:25]([CH2:35][C:36]2[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=2)[CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)[N:19]=1.CC(N)CC1C=CC=CC=1.OP(O)(O)=O.C([O-])(=O)C.[K+]>O1CCOCC1.O>[F:1][C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)[CH:5]=[CH:4][C:3]=1[C:18]1[N:23]=[C:22]([CH3:24])[N:21]=[C:20]([N:25]([CH2:26][C:27]2[CH:28]=[CH:29][C:30]([O:33][CH3:34])=[CH:31][CH:32]=2)[CH2:35][C:36]2[CH:37]=[CH:38][C:39]([O:42][CH3:43])=[CH:40][CH:41]=2)[N:19]=1
Reactant: COc1ccc(CN(Cc2ccc(OC)cc2)c2nc(C)nc(Cl)n2)cc1
Reactant: OB(O)c1ccc(-c2cccnc2)nc1F
Agent: CC(=O)[O-]
Agent: CC(N)Cc1ccccc1
Agent: O=P(O)(O)O
Solvent: O
Solvent: C1COCCO1
Product: COc1ccc(CN(Cc2ccc(OC)cc2)c2nc(C)nc(-c3ccc(-c4cccnc4)nc3F)n2)cc1
Temperature: 120 °C
Yield: 51.6 %

Procedure:
A mixture of 6-fluoro-2,3′-bipyridin-5-ylboronic acid (555 mg, 2.55 mmol), 4-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (700 mg, 1.819 mmol), Amphos 2 (64.4 mg, 0.091 mmol) (Aldrich) and potassium acetate (548 mg, 5.58 mmol) (Aldrich) in dioxane (12 mL) and water (3.0 mL) was purged with argon and heated in a microwave reactor at 120° C. for 30 min. The reaction mixture was treated with 1 N NaOH (15 mL) and extracted with EtOAc (50 mL), washed with brine and dried over MgSO4, filtered and concentrated. The crude product was purified on the ISCO (40 g column, 40-100% EtOAc in hexanes) to give 4-(6-fluoro-2,3′-bipyridin-5-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (490.3 mg, 0.938 mmol, 51.6% yield) as a bright yellow crystalline solid. m/z (ESI, +ve ion) 523.0 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 9.26 (1H, d, J=1.8 Hz); 8.67-8.72 (2H, m); 8.40 (1H, dt, J=8.0, 2.0 Hz); 7.77 (1H, dd, J=7.8, 1.6 Hz); 7.43 (1H, dd, J=8.0, 5.3 Hz); 7.20-7.25 (4H, m); 6.83-6.90 (4H, m); 4.83 (4H, s); 3.82 (3H, s); 3.80 (3H, s); 2.56 (3H, s).
Reaction SMILES: [CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:15]3[N:19]([CH3:20])[NH:18][C:17](=[O:21])[CH2:16]3)[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Br[CH2:25][CH2:26][CH2:27][C:28]1[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=1>CN(C)C=O>[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:15]3[N:19]([CH3:20])[N:18]([CH2:25][CH2:26][CH2:27][C:28]4[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=4)[C:17](=[O:21])[CH2:16]3)[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: COc1ccc(C2CC(=O)NN2C)cc1OC1CCCC1
Reactant: BrCCCc1cccnc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccc(C2CC(=O)N(CCCc3cccnc3)N2C)cc1OC1CCCC1
Yield: 52 %

Procedure:
To a solution of 5-[3-(cyclopentyloxy)-4-methoxy-phenyl]-1-methyl-3-pyrazolidinone (1.10 gms, 3.79 mmol), NaH (0.15 gms, 60%, 3.75 mmol), and dimethylformamide (15 mls) is added a solution of 1-bromo-3-(3-pyridinyl)propane [see Mioque, M., and Gautier, J. A. (1961). C. R. Hebd. Seances Acad. Sci. 252, 2416.] (1.66 gms, 8.30 mmol) in dimethylformamide (5 mls). The reaction is immersed in an oil bath (65° C.). After 20 hours dimethylformamide is removed in vacuo , the residue is diluted in methylene chloride, washed with saturated aqueous NaHCO3 and dried over Na2SO4 - The product was concentrated and chromatographed (SiO2 : 1) 1:1 ethyl acetate:hexane; 2) 2:1 ethyl acetate:hexane; 3) ethyl acetate; 4) 3% methanol:ethyl acetate) to yield 0.85 gms (52%) of an oil. 1H NMR (DMSO-d6, 400 MHz) δ 8.40 (m,2H), 7.55 (m,1H), 7.25 (m,1H), 6.95 (s,1H), 6.85 (m,1H), 5.75 (s,0.5H) 4.70 (m,1H), 4.00 (m,1H), 3.70 (s,3H), 3.60 (m,1H), 3.10 (m,1H), 2.55 (s,3H), 2.45 (m,4H) 1.75 (m,4H), 1.65 (m,4H), 1.50 (m,2H). IR(KBR, cm-) 1685 (C=O).
Reaction SMILES: [CH3:1][C:2]12[O:10][B:9]([C@@H:11]([NH:28][C:29]([C:31]3[CH:32]=[C:33]4[C:37](=[CH:38][CH:39]=3)[CH2:36][NH:35][CH2:34]4)=[O:30])[CH2:12][C:13]3[C:14]([O:26][CH3:27])=[C:15]([CH:23]=[CH:24][CH:25]=3)[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[O:8][CH:7]1[CH2:6][CH:5]1[CH2:40][CH:3]2[C:4]1([CH3:42])[CH3:41].[CH:43](=O)[C:44]1[CH:49]=[CH:48][CH:47]=[N:46][CH:45]=1.O>ClCCCl>[CH3:27][O:26][C:14]1[C:13]([CH2:12][C@H:11]([NH:28][C:29]([C:31]2[CH:32]=[C:33]3[C:37](=[CH:38][CH:39]=2)[CH2:36][N:35]([CH2:43][C:44]2[CH:45]=[N:46][CH:47]=[CH:48][CH:49]=2)[CH2:34]3)=[O:30])[B:9]2[O:8][CH:7]3[C:2]([CH3:1])([CH:3]4[CH2:40][CH:5]([CH2:6]3)[C:4]4([CH3:42])[CH3:41])[O:10]2)=[CH:25][CH:24]=[CH:23][C:15]=1[C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17]
Reactant: COc1c(C[C@H](NC(=O)c2ccc3c(c2)CNC3)B2OC3CC4CC(C4(C)C)C3(C)O2)cccc1C(=O)OC(C)(C)C
Reactant: O=Cc1cccnc1
Solvent: ClCCCl
Solvent: O
Product: COc1c(C[C@H](NC(=O)c2ccc3c(c2)CN(Cc2cccnc2)C3)B2OC3CC4CC(C4(C)C)C3(C)O2)cccc1C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 6 h

Procedure:
To tert-butyl 3-((2R)-2-(2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]dec-4-yl)-2-(isoindoline-5-carboxamido)ethyl)-2-methoxybenzoate from Example 9 step 2 (240 mg, 0.42 mmol) in 1,2-dichloroethane (5 mL) was added nicotinaldehyde (90 mg, 0.84 mmol) and Na(OAc)3BH4 (211 mg, 1 mmol). The reaction mixture was stirred at room temperature for 6 hr. Water (10 mL) was added at 0° C. and the aqueous phase was extracted with EtOAc. The organic phase was washed brine, dried over Na2SO4 and concentrated in vacuo. The crude product was carried to the next step without further purification. ESI-MS m/z 666.1 (MH)+.
Reaction SMILES: [Si:1]([O:8][CH2:9][C:10]1[CH:15]=[C:14]([Cl:16])[CH:13]=[CH:12][C:11]=1[CH:17]([C:19]1[CH:20]=[CH:21][C:22]2[N:26]=[N:25][N:24]([CH3:27])[C:23]=2[CH:28]=1)O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].N1C=CC=CC=1.S(Cl)([Cl:37])=O>C(Cl)Cl>[C:4]([Si:1]([CH3:3])([CH3:2])[O:8][CH2:9][C:10]1[CH:15]=[C:14]([Cl:16])[CH:13]=[CH:12][C:11]=1[CH:17]([C:19]1[CH:20]=[CH:21][C:22]2[N:26]=[N:25][N:24]([CH3:27])[C:23]=2[CH:28]=1)[Cl:37])([CH3:7])([CH3:6])[CH3:5]
Reactant: O=S(Cl)Cl
Reactant: Cn1nnc2ccc(C(O)c3ccc(Cl)cc3CO[Si](C)(C)C(C)(C)C)cc21
Solvent: ClCCl
Solvent: c1ccncc1
Product: Cn1nnc2ccc(C(Cl)c3ccc(Cl)cc3CO[Si](C)(C)C(C)(C)C)cc21
Reaction time: 0.5 h

Procedure:
To the solution of α-[2-(t-butyldimethylsilyloxy)methyl-4-chlorophenyl]-1-methyl-1H-benzotriazole-6-methanol (0.5 g) from Example 75 and pyridine (0.11 ml) in methylene chloride (5 ml) was added thionyl chloride (0.1 ml) at 0° C. the mixture was stirred for 30 minutes. The reaction solution was diluted with methylene chloride (5 ml),and sequentially washed with water and saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure, to give the crude 6-[2-(t-butyldimethyl-silyloxy)methyl-α,4-dichlorobenzyl]-1-methyl-1H-benzotriazole.
Reaction SMILES: [OH:1][CH:2]([C:9]1[CH:20]=[CH:19][C:12]([CH:13]=[CH:14][C:15]([O:17][CH3:18])=[O:16])=[CH:11][CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[H-].[Na+].[CH3:23][N:24]([CH3:28])[CH2:25][CH2:26]Cl.O>CN(C)C=O>[CH3:23][N:24]([CH3:28])[CH2:25][CH2:26][O:1][CH:2]([C:9]1[CH:10]=[CH:11][C:12]([CH:13]=[CH:14][C:15]([O:17][CH3:18])=[O:16])=[CH:19][CH:20]=1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: COC(=O)C=Cc1ccc(C(O)c2ccccc2)cc1
Reactant: CN(C)CCCl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)C=Cc1ccc(C(OCCN(C)C)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 4.9 %

Procedure:
3.04 g (11.33 mmol) of methyl 4-(α-hydroxybenzyl)cinnamate was dissolved in 35 ml of N,N-dimethylformamide, thereafter 0.45 g (11.33 mmol) of 60% sodium hydride was added thereto, and the mixture was stirred overnight at room temperature. 2.44 g (22.66 mmol) of 2-dimethylaminoethyl chloride was then added thereto. The resulting mixture was heated at 80° C. and stirred for 5 hours. After cooling, the reaction mixture was poured into water, the obtained mixture was extracted twice with ethyl acetate, and the extract was washed with brine. The organic phase was dried (MgSO4) and the solvent was distilled off. The resulting residue was purified by silica gel column chromatography (chloroform:methanol =50:1 (v/v)) followed by alumina column chromatography (n-hexane:ethyl acetate=5:1 (v/v)) to obtain 0.19 g (0.560 mmol) of methyl 4-[α-(2-dimethylaminoethoxy)benzyl]cinnamate as a pale yellow oily substance. Its spectroscopic data are as follows:
Reaction SMILES: C(O)(C)C.[NH3:5].[CH3:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:22]3[C:17](=[CH:18][C:19]([C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([N+:29]([O-:31])=[O:30])[CH:24]=4)=[CH:20][CH:21]=3)[N:16]([C:32]3[CH:37]=[CH:36][N:35]=[C:34](S(C)=O)[N:33]=3)[CH:15]=2)=[CH:10][CH:9]=1>>[CH3:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:22]3[C:17](=[CH:18][C:19]([C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([N+:29]([O-:31])=[O:30])[CH:24]=4)=[CH:20][CH:21]=3)[N:16]([C:32]3[CH:37]=[CH:36][N:35]=[C:34]([NH2:5])[N:33]=3)[CH:15]=2)=[CH:10][CH:9]=1
Reactant: COc1ccc(-c2cn(-c3ccnc(S(C)=O)n3)c3cc(-c4cccc([N+](=O)[O-])c4)ccc23)cc1
Reactant: N
Solvent: CC(C)O
Product: COc1ccc(-c2cn(-c3ccnc(N)n3)c3cc(-c4cccc([N+](=O)[O-])c4)ccc23)cc1
Temperature: 100 °C
Reaction time: 3 h

Procedure:
2.0 M ammonia isopropanol solution (2 mL) was added to 3-(4-methoxyphenyl)-1-(2-(methylsulfinyl)pyrimidin-4-yl)-6-(3-nitrophenyl)-1H-indole (90 mg) and then stirred at 100° C. for 3 hours in a sealed state. After cooling to room temperature, thus produced solid was filtered. After washing with isopropanol and then drying, the target compound (50 mg) was obtained as white solid.
Reaction SMILES: O[CH:2]1[CH2:6][N:5]([CH3:7])[C:4](=[O:8])[C:3]1([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.S(Cl)(Cl)=O.N1C=CC=CC=1.[CH:31](Cl)(Cl)[Cl:32]>>[Cl:32][CH2:31][CH:2]1[CH2:6][N:5]([CH3:7])[C:4](=[O:8])[C:3]1([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: ClC(Cl)Cl
Reactant: CN1CC(O)C(c2ccccc2)(c2ccccc2)C1=O
Solvent: O=S(Cl)Cl
Solvent: c1ccncc1
Product: CN1CC(CCl)C(c2ccccc2)(c2ccccc2)C1=O
Yield: 59 %

Procedure:
To 25.0 g. (0.09 mole) of 4-hydroxy-1-methyl-3,3-diphenyl-2-pyrrolidinone, in 200 ml. of chloroform was added 21.4 g. (0.18 mole) of thionyl chloride. With stirring and ice bath cooling, 18.0 g. (0.23 mole) of pyridine was added dropwise. The solution was refluxed for 2 hours. After concentrating in vacuo, the residue was dissolved in chloroform and washed successively with dilute hydrochloric acid solution and dilute sodium hydroxide. The chloroform solution was dried, filtered, and concentrated in vacuo. The solid residue was recrystallized from a 50:50 ethyl acetate-isopropyl ether mixture. It weighed 16.0 g. (59% yield) and melted at 120°-122° C.
Reaction SMILES: [O:1]([C:8]1[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=1[CH2:10]O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.[I-:28].[Na+]>C(Cl)Cl.CCCCCC>[O:1]([C:8]1[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=1[CH2:10][I:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OCc1ccccc1Oc1ccccc1
Reactant: [I-]
Agent: CS(=O)(=O)Cl
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CCCCCC
Product: ICc1ccccc1Oc1ccccc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 67.3 %

Procedure:
To a solution of o-phenoxybenzyl alcohol (5.0 g, 25 mmol) and triethylamine (10.4 mL, 75 mmol) in CH2Cl2 (50 mL) at 0° C. was added methanesulfonyl chloride (3.9 mL, 50 mmol). The reaction mixture was stirred at 0° C. for 1 h and then at room temperature for 3.5 h. The mixture was washed H2O and brine. It was filtered through phase separator paper and concentrated to a yellow oil. The oil was then dissolved in 50 mL of acetone, and sodium iodide (7.5 g, 50 mmol) was then added. The mixture was stirred at more temperature overnight. Hexane was added to the mixture. The solid was filtered off. The filtrate was concentrated and chromatographed on silica gel with hexane to give 5.22 g of yellow oil. MS m/e 183.1, [M+H-HI]+ ; 1H NMR (300 MHz, CDCl3): δ 4.52 (s, 2H, CH2Ar), 6.82-7.48 (m, 9H, ArH). ##STR65##
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[CH:6]=[O:7].[CH:13]([Mg]Br)=[CH2:14].[Cl-].[NH4+]>O1CCCC1>[F:1][C:2]([F:11])([F:12])[C:3]1[CH:4]=[C:5]([CH:6]([OH:7])[CH:13]=[CH2:14])[CH:8]=[CH:9][CH:10]=1
Reactant: C=C[Mg]Br
Reactant: O=Cc1cccc(C(F)(F)F)c1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: C=CC(O)c1cccc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 3-trifluoromethylbenzaldehyde (6.7 mL) in tetrahydrofuran (40 mL) was stirred on an ice bath and treated dropwise over 25 min with a solution of vinylmagnesium bromide in tetrahydrofuran (1.0 M, 60 mL). The mixture was stirred for 2 h while allowing to warm slowly to room temperature, then was treated with saturated aqueous ammonium chloride. The mixture was extracted with ether, and the organic extracts were washed with water and brine, then dried over sodium sulfate and concentrated under vacuum. Purification by flash column chromatography, eluting with 10% ethyl acetate in hexane, provided 1-(3-trifluoromethylphenyl)prop-2-en-1-ol (2.33 g) as a colorless oil. MS found: (M+H−H2O)+=185.19.
Reaction SMILES: C([O:3][C:4]([C:6]1[N:7]=[CH:8][N:9]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:10]=1[F:11])=O)C.[H-].C([Al+]CC(C)C)C(C)C>C1(C)C=CC=CC=1>[F:11][C:10]1[N:9]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:17])([CH3:19])[CH3:18])[CH:8]=[N:7][C:6]=1[CH2:4][OH:3]
Reactant: CCOC(=O)c1ncn(COCC[Si](C)(C)C)c1F
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: Cc1ccccc1
Product: C[Si](C)(C)CCOCn1cnc(CO)c1F
Temperature: -78 °C
Reaction time: 2 h

Procedure:
To a stirred solution of 5-fluoro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-4-carboxylic acid ethyl ester (400 mg) in toluene (10 ml) at −78° C. under an argon atmosphere was added dropwise diisobutylaluminium hydride (DIBAL) (1.72 ml; 20 wt % solution in toluene) for 10 minutes (temperature below −75° C.). After 2 hours of stirring at −78° C., conversion of the ester was found to be incomplete. More DIBAL solution (1.17 ml.) was added over a period of 5 minutes and stirring at −78° C. was continued for 1 hour and 30 minutes. The mixture was quenched by the addition of 10 ml potassium-sodium tartrate concentrated aqueous solution. The aqueous phase was back extracted with ethyl acetate. The combined organics were washed with H2O and brine, dried over MgSO4, filtered and concentrated to leave [5-fluoro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-4-yl]-methanol as (346 mg) as off-white solid. The crude product was used in the next reaction step without further purification. MS (ISP): 247.3 ([M+H]+).