Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][C:12]#[N:13].[F:14][C:15]1[CH:22]=[CH:21][CH:20]=[CH:19][C:16]=1[CH:17]=O.C([OH:25])C>>[F:14][C:15]1[CH:22]=[CH:21][CH:20]=[CH:19][C:16]=1[CH:17]1[C:1]2[C:2](=[CH:3][CH:4]=[C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:10]3=2)[CH2:11][C:12](=[O:25])[NH:13]1
Reactant: N#CCc1ccc2ccccc2c1
Reactant: O=Cc1ccccc1F
Reactant: CCO
Product: O=C1Cc2ccc3ccccc3c2C(c2ccccc2F)N1

Procedure:
From naphthalene-2-acetonitrile and 2-fluorobenzaldehyde. m.p. 265°-8° (ethanol).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.Cl[C:8]1[NH:9][S:10](=[O:20])(=[O:19])[C:11]2[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:12]=2[N:13]=1>CO>[Cl:18][C:16]1[CH:15]=[CH:14][C:12]2[N:13]=[C:8]([N:1]3[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]3)[NH:9][S:10](=[O:20])(=[O:19])[C:11]=2[CH:17]=1
Reactant: C1CNCCN1
Reactant: O=S1(=O)NC(Cl)=Nc2ccc(Cl)cc21
Solvent: CO
Product: O=S1(=O)NC(N2CCNCC2)=Nc2ccc(Cl)cc21
Temperature: 25 °C
Reaction time: 3 h
Yield: 65.1 %

Procedure:
To a stirred solution of 3.4 g of anhydrous piperazine in 25 ml of methanol is added 5.0 g of 3,7-dichloro-2H-1,2,4-benzothiadiazine 1,1-dioxide, while the mixture is cooled in an ice bath. After the addition, the mixture is stirred at room temperature for 3 hours. The crystalline precipitate is collected by suction filtration and treated with a mixture of 2 ml of concentrated hydrochloric acid and 40 ml of water. After removal of the insoluble materials by suction filtration, the filtrate is adjusted to a pH 8.0 with a dilute aqueous sodium hydroxide solution to give 3.9 g of the desired product, m.p. 292°-295° C. (decomposition).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][CH:9]2[CH2:17][CH:16]3[N:12]([CH2:13][CH2:14][CH2:15]3)[C:11]([CH3:19])([CH3:18])[CH2:10]2)[C:5]([F:20])=[CH:4][N:3]=1.[CH3:21][C:22]1([CH3:37])[O:27][C:26]2[C:28](F)=[CH:29][C:30]([NH2:32])=[CH:31][C:25]=2[N:24]2[N:34]=[N:35][N:36]=[C:23]12.Cl>CC(O)C.O1CCOCC1>[CH3:21][C:22]1([CH3:37])[O:27][C:26]2[CH:28]=[CH:29][C:30]([NH:32][C:2]3[N:7]=[C:6]([NH:8][CH:9]4[CH2:17][CH:16]5[N:12]([CH2:13][CH2:14][CH2:15]5)[C:11]([CH3:19])([CH3:18])[CH2:10]4)[C:5]([F:20])=[CH:4][N:3]=3)=[CH:31][C:25]=2[N:24]2[N:34]=[N:35][N:36]=[C:23]12
Reactant: CC1(C)Oc2c(F)cc(N)cc2-n2nnnc21
Reactant: CC1(C)CC(Nc2nc(Cl)ncc2F)CC2CCCN21
Agent: Cl
Solvent: CC(C)O
Solvent: C1COCCO1
Product: CC1(C)Oc2ccc(Nc3ncc(F)c(NC4CC5CCCN5C(C)(C)C4)n3)cc2-n2nnnc21
Temperature: 100 °C
Yield: 83.4 %

Procedure:
A solution of (R/S,S/R)—N-(2-chloro-5-fluoropyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amine (D1) (0.1 g, 0.3 mmol, single diastereomer) in 3 ml of iPrOH, 4,4-dimethyl-6-fluoro-4H-benzo[b]tetrazolo[1,5-d][1,4]oxazin-8-amine (0.093 g, 0.4 mmol) and 4N HCl in dioxane (0.1 ml) were added. The reaction mixture was heated to 100° C. in a sealed vial for 12 hours. LCMS analysis of the crude reaction mixture indicated the completion of the reaction. The crude product was purified by column chromatography to give 0.12 g (Yield=72%) of the product as a mixture of two enantiomers.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:12])[CH:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)Br.CCN(CC)CC.[N:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1>O1CCCC1>[CH3:1][O:2][C:3](=[O:12])[CH:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[N:29]1[CH2:30][CH2:31][N:26]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][N:20]=2)[CH2:27][CH2:28]1
Reactant: COC(=O)C(Br)c1ccccc1
Reactant: c1ccc(N2CCNCC2)nc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COC(=O)C(c1ccccc1)N1CCN(c2ccccn2)CC1
Temperature: 25 °C

Procedure:
To a solution of racemic α-bromophenylacetic acid methyl ester, 5.0 g (22.0 mmol) in 200 mL of tetrahydrofuran was added 3.4 mL (22.0 mmol) of Et3N and 10 mL (66.0 mmol) of 1-(2-pyridyl)-piperazine. The reaction mixture was refluxed for five hours, cooled to rt. and concentrated to dryness. The residue was partitioned between 20% isopropanol/chloroform and water. The mixture was washed with saturated NaHCO3, washed with brine, dried over Na2SO4, filtered and concentrated to dryness. The residue was purified by column chromatography using MeOH/chloroform as eluant and concentrated to dryness to give a quantitative yield of the desired mixture of isomers as a yellow oil. MS (ion spray) 312.2 (M+).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][C:5](=[O:7])[CH3:6].[CH:8]1[C:18]2[C:17](=[C:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)[C:16]3[CH:25]=[CH:26][CH:27]=[CH:28][C:15]=3[CH2:14][O:13][C:12]=2[CH:11]=[CH:10][CH:9]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)(Cl)Cl>[CH:8]1[C:18]2[C:17](=[C:19]3[CH2:24][CH2:23][N:22]([CH2:2][CH2:3][CH2:4][C:5](=[O:7])[CH3:6])[CH2:21][CH2:20]3)[C:16]3[CH:25]=[CH:26][CH:27]=[CH:28][C:15]=3[CH2:14][O:13][C:12]=2[CH:11]=[CH:10][CH:9]=1
Reactant: CC(=O)CCCBr
Reactant: c1ccc2c(c1)COc1ccccc1C2=C1CCNCC1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: CC(=O)CCCN1CCC(=C2c3ccccc3COc3ccccc32)CC1

Procedure:
A solution of 10 g of 5-bromo-2-pentanone in 40 cc of chloroform is added dropwise within 10 minutes to a mixture of 13.8 g of 4-(6,11-dihydrodibenzo[b,e]oxepin-11-ylidene)piperidine and 12.7 g of sodium carbonate in 200 cc of chloroform, and the mixture is heated at reflux for 18 hours. After cooling, filtration is effected, the filtrate is washed with water, dried over magnesium sulphate, and the solvent is completely removed by distillation. The oily residue is then chromatographed on 250 g of silica gel with a mixture of chloroform/ethanol 95:5, and the so purified title compound is converted into the hydrogen fumarate form. M.P. 228°-230°.
Reaction SMILES: [CH3:1][CH:2](C)[C:3]([O:5][C@@H:6]1[C@@H:14]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:13](=[O:22])[O:12][CH2:11][C@H:10]([NH:23][C:24]([C:26]2[C:31]([O:32][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)=[C:30]([O:40][CH3:41])[CH:29]=[CH:28][N:27]=2)=[O:25])[C:9](=[O:42])[O:8][C@H:7]1[CH3:43])=O.C1C=CC(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CCCCCC.CC(C)=O>[CH2:3]([O:5][C@H:6]1[C@H:7]([CH3:43])[O:8][C:9](=[O:42])[C@@H:10]([NH:23][C:24]([C:26]2[C:31]([O:32][CH2:33][C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)=[C:30]([O:40][CH3:41])[CH:29]=[CH:28][N:27]=2)=[O:25])[CH2:11][O:12][C:13](=[O:22])[C@@H:14]1[CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[CH:2]=[CH2:1]
Reactant: COc1ccnc(C(=O)N[C@H]2COC(=O)[C@H](Cc3ccccc3)[C@@H](OC(=O)C(C)C)[C@H](C)OC2=O)c1OCc1ccccc1
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: c1ccc(P(CCCCP(c2ccccc2)c2ccccc2)c2ccccc2)cc1
Solvent: CCCCCC
Solvent: CC(C)=O
Product: C=CCO[C@H]1[C@H](C)OC(=O)[C@@H](NC(=O)c2nccc(OC)c2OCc2ccccc2)COC(=O)[C@@H]1Cc1ccccc1
Yield: 69 %

Procedure:
Compound 7 was prepared in 69% yield using Compound 2 (65.2 g, 122.1 mmol) with dppb (5.20 g, 12.21 mmol), Pd2dba3 (2.79 g, 3.05 mmol) and ethyl methallylcarbonate (20.63 g, 158.73 mmol). Crude product upon chromatography on silica gel eluting with a mixture of hexane-acetone (1:1) afforded a white foam: m.p.=55-57° C., MS: (M+1)+=585, (M−1)+=583. Spectral data were consistent with the assigned structure.
Reaction SMILES: [C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C@@H:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C@H:17]([O:24][C:25]3[CH:26]=[CH:27][C:28]4[N:29]([C:31]([N:34]5[CH2:39][CH2:38][CH2:37][CH2:36][C@@H:35]5[CH3:40])=[N:32][N:33]=4)[CH:30]=3)[CH2:16][CH2:15]2)=[O:12])[N:7]([C:41]2[CH:42]=[C:43]([CH2:47][CH2:48][O:49]S(C)(=O)=O)[CH:44]=[CH:45][CH:46]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH:54]1[CH2:59][CH2:58][O:57][CH2:56][CH2:55]1>C1COCC1>[CH:48]([OH:49])=[O:57].[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C@@H:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C@H:17]([O:24][C:25]3[CH:26]=[CH:27][C:28]4[N:29]([C:31]([N:34]5[CH2:39][CH2:38][CH2:37][CH2:36][C@@H:35]5[CH3:40])=[N:32][N:33]=4)[CH:30]=3)[CH2:16][CH2:15]2)=[O:12])[N:7]([C:41]2[CH:46]=[CH:45][CH:44]=[C:43]([CH2:47][CH2:48][N:54]3[CH2:59][CH2:58][O:57][CH2:56][CH2:55]3)[CH:42]=2)[N:6]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: C[C@H]1CCCCN1c1nnc2ccc(O[C@@H]3CC[C@H](NC(=O)Nc4cc(C(C)(C)C)nn4-c4cccc(CCOS(C)(=O)=O)c4)c4ccccc43)cn12
Reactant: C1COCCN1
Solvent: C1CCOC1
Product: C[C@H]1CCCCN1c1nnc2ccc(O[C@@H]3CC[C@H](NC(=O)Nc4cc(C(C)(C)C)nn4-c4cccc(CCN5CCOCC5)c4)c4ccccc43)cn12
Product: O=CO

Procedure:
A solution of Intermediate 131d (44.5 mg, 0.06 mmol) and morpholine (25.9 μL, 0.30 mmol) in THF (1 mL) was stirred at 60° C. for 20 h in a sealed tube. The mixture was concentrated in vacuo and the residue purified by MDAP (Method 7). The title product was isolated as an off-white solid (12 mg, 27%). LCMS (Method 5): Rt 3.64 min, m/z 732.6 [MH+]. 1H NMR (400 MHz, d6-DMSO): 0.91 (3H, d, J=6.2 Hz), 1.28 (9H, s), 1.50 (2H, m), 1.66 (2H, m), 1.76-2.18 (6H, overlapped m), 2.40 (4H, m), 2.53 (m, obscured by solvent), 2.80 (2H, m), 2.90 (1H, m), 3.15 (1H, m, obscured by solvent), 3.31 (m, obscured by solvent), 3.54 (4H, m), 4.82 (1H, m), 5.51 (1H, t, J=4.0 Hz), 6.32 (1H, s), 7.09 (1H, d, J=8.7 Hz), 7.19 (1H, dd, J=9.8, 2.4 Hz), 7.24-7.44 (8H, m), 7.63 (1H, m), 7.69 (1H, m), 8.10 (1H, s), 8.20 (1H, s).
Reaction SMILES: C(C1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=[CH:6][C:5]=1[OH:14])(=O)C.C1C2CC(=[O:22])C(C2)C1.N1CCOCC1>C1(C)C=CC=CC=1>[O:22]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][CH2:6][CH:5]1[OH:14]
Reactant: CC(=O)c1c(O)ccc2ccccc12
Reactant: O=C1CC2CCC1C2
Solvent: Cc1ccccc1
Solvent: C1COCCN1
Product: OC1CCc2ccccc2O1
Reaction time: 5 h

Procedure:
A solution was prepared by dissolving 10 g (0.054 mole) of 1-acetyl-2-naphthol, 6.6 g (0.06 mole) of norcamphor and 8.7 g (0.10 mole) of morpholine in 300 cc of toluene, and the solution was boiled for 5 hours and water was separated. After termination of the reaction toluene was removed under reduced pressure, and the remaining chromanone compound was recrystallized from acetone, and the chromanon compound was dissolved in 200 cc of methanol and lithium aluminum hydride was added to the solution to form a chromanol compound. Then, 6.49 g of this chromanol compound was heated at 170° to 180° C. together with anhydrous copper sulfate in a carbon dioxide current for 10 minutes and the obtained brown viscous liquid was purified by the chromatography on silica gel to obtain 5.1 g of a chromene compound represented by the following formula: ##STR68##
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3[C:19]4[C:20](=[O:23])[O:21][CH2:22][C:18]=4[C:17]([OH:24])=[C:16]4[C:11]=3[CH:12]=[C:13]([O:27][CH3:28])[C:14]([O:25][CH3:26])=[CH:15]4)=[CH:9][C:4]=2[O:3][CH2:2]1.CI.[CH3:31]C(C)=O>>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3[C:19]4[C:20](=[O:23])[O:21][CH2:22][C:18]=4[C:17]([O:24][CH3:31])=[C:16]4[C:11]=3[CH:12]=[C:13]([O:27][CH3:28])[C:14]([O:25][CH3:26])=[CH:15]4)=[CH:9][C:4]=2[O:3][CH2:2]1
Reactant: CC(C)=O
Reactant: COc1cc2c(O)c3c(c(-c4ccc5c(c4)OCO5)c2cc1OC)C(=O)OC3
Solvent: CI
Product: COc1cc2c(OC)c3c(c(-c4ccc5c(c4)OCO5)c2cc1OC)C(=O)OC3

Procedure:
The product of step F, diphyllin, (10; 75 mg; 0.197 mmol), and 1 ml methyl iodide were dissolved in 5 ml acetone containing 82 mg potassium carbonate (0.6 mmol), and the resulting solution heated at about 60° for one hour. After removing acetone, a residue remained which was treated with methylene chloride and 10% aqueous hydrogen chloride. After separation of aqueous and organic layers, the organic layer was washed with saturated sodium chloride and dried over magnesium sulfate. Evaporation of solvent and purification on a preparative thin-layer chromatography plate provided ca. 67 mg of 9-(1,3-benzodioxol-5-yl)-4,6,7-trimethoxynaphtho[2,3-c]furan-1-(3H)-one, 11, mp 248°-250°. IR(CHCl3): 1770, 1620 cm-1 ; PMR (CDCl3): δ7.39 (s, 1H), 6.91 (s, 1H), 6.83-6.64 (m, 3H), 5.94 (2s, 2H), 5.42 (s, 2H), 4.05 (s, 3H), 3.98 (s, 3H), and 3.73 (s, 3H); MS: m/z 394.1006 (M+), calcd. for C22H18O7, 394.1049. A separate sample of product 11, prepared by substantially the foregoing procedure, was recrystallized from chloroform-ether, mp 256°-258°. This crystalline product was again recrystallized from chloroform-ether, mp 258°-260°.
Reaction SMILES: [BH4-].[Na+].C[O:4][C:5]([C@@H:7]1[CH2:11][C@@H:10]([O:12][Si:13]([C:26]([CH3:29])([CH3:28])[CH3:27])([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:9][N:8]1[C:30](=[O:43])[NH:31][C:32]1[CH:37]=[CH:36][C:35]([O:38][C:39]([F:42])([F:41])[F:40])=[CH:34][CH:33]=1)=O.O>CO>[F:42][C:39]([F:40])([F:41])[O:38][C:35]1[CH:36]=[CH:37][C:32]([NH:31][C:30]([N:8]2[CH2:9][C@H:10]([O:12][Si:13]([C:26]([CH3:27])([CH3:28])[CH3:29])([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:11][C@H:7]2[CH2:5][OH:4])=[O:43])=[CH:33][CH:34]=1
Reactant: COC(=O)[C@@H]1C[C@@H](O[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)CN1C(=O)Nc1ccc(OC(F)(F)F)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CC(C)(C)[Si](O[C@@H]1C[C@@H](CO)N(C(=O)Nc2ccc(OC(F)(F)F)cc2)C1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 87.6 %

Procedure:
NaBH4 (200 mg, 5.3 mmol) was added to a solution of (2S,4R)-4-(tert-Butyl-diphenyl-silanyloxy)-1-(4-trifluoromethoxy-phenylcarbamoyl)-pyrrolidine-2-carboxylic acid methyl ester (2.8 g, 4.8 mmol) in methanol (50 mL) portion-wise. The mixture was stirred at room temperature for 4 hours. Then the mixture was poured into water (50 mL), extracted with ethyl acetate (3×50 mL). The organic layers was combined, washed with brine (50 mL), dried over anhydrous sodium sulphate, filtered and concentrated. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate=5:1) to give 2.35 g (88%) of the title compound.
Reaction SMILES: [CH2:1]([O:3][CH2:4][C:5](Cl)=O)[CH3:2].[NH2:8][C:9]1[CH:10]=[N:11][C:12]2[C:17]([C:18]=1[NH:19][CH2:20][C:21]1([OH:31])[CH2:30][CH2:29][C:24]3([O:28][CH2:27][CH2:26][O:25]3)[CH2:23][CH2:22]1)=[CH:16][CH:15]=[CH:14][CH:13]=2.C(N(CC)CC)C>ClCCl.C(O)C>[CH2:1]([O:3][CH2:4][C:5]1[N:19]([CH2:20][C:21]2([OH:31])[CH2:30][CH2:29][C:24]3([O:28][CH2:27][CH2:26][O:25]3)[CH2:23][CH2:22]2)[C:18]2[C:17]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[N:11]=[CH:10][C:9]=2[N:8]=1)[CH3:2]
Reactant: CCOCC(=O)Cl
Reactant: Nc1cnc2ccccc2c1NCC1(O)CCC2(CC1)OCCO2
Solvent: CCN(CC)CC
Solvent: CCO
Solvent: ClCCl
Product: CCOCc1nc2cnc3ccccc3c2n1CC1(O)CCC2(CC1)OCCO2
Temperature: 25 °C
Reaction time: 1 h
Yield: 19.4 %

Procedure:
A solution of ethoxyacetyl chloride (4.38 g, 35.7 mmol) in dichloromethane (50 mL) was added to a 0° C. solution of 8-{[(3-aminoquinolin-4-yl)amino]methyl}-1,4-dioxaspiro[4.5]decan-8-ol (10.7 g, 32.5 mmol) and triethylamine (4.98 mL, 35.7 mmol) in dichloromethane (250 mL). After one hour, the solution was allowed to warm to rt and stir for 2 d. More ethoxyacetyl chloride (0.15 equivalent) was added. After two hours, the solution was transferred to a separatory funnel and washed with water (200 mL). The organic layer was dried with Na2SO4, filtered, and concentrated under reduced pressure to yield an orange solid. The solid was dissolved in ethanol (150 mL) and triethylamine (13.6 mL, 97.4 mmol) was added. The solution was heated at reflux for 16 h. The volatiles were removed under reduced pressure to yield a brown oil that was crystallized from isopropanol to yield 8-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}-1,4-dioxaspiro[4.5]decan-8-ol as off-white crystals (2.50 g) and a second crop (1.50 g) of crystals. A third crop (4.91 g) was isolated after recrystallization of the mother liquor from ethyl acetate. A total of 8.91 g (69%) of 8-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}-1,4-dioxaspiro[4.5]decan-8-ol was isolated.
Reaction SMILES: [NH2:1][C:2]1[CH:13]=[CH:12][C:11]([C:14]#[C:15][Si:16]([CH3:19])([CH3:18])[CH3:17])=[CH:10][C:3]=1[C:4](N(OC)C)=[O:5].Br[C:21]1[CH:26]=[CH:25][C:24]([C:27]2([C:38]([F:41])([F:40])[F:39])[N:29]([Si](C)(C)C)[N:28]2[Si](C)(C)C)=[CH:23][CH:22]=1.C([Li])CCC>>[F:41][C:38]([F:39])([F:40])[C:27]1([C:24]2[CH:25]=[CH:26][C:21]([C:4]([C:3]3[CH:10]=[C:11]([C:14]#[C:15][Si:16]([CH3:17])([CH3:18])[CH3:19])[CH:12]=[CH:13][C:2]=3[NH2:1])=[O:5])=[CH:22][CH:23]=2)[NH:28][NH:29]1
Reactant: C[Si](C)(C)N1N([Si](C)(C)C)C1(c1ccc(Br)cc1)C(F)(F)F
Reactant: CON(C)C(=O)c1cc(C#C[Si](C)(C)C)ccc1N
Agent: [Li]CCCC
Product: C[Si](C)(C)C#Cc1ccc(N)c(C(=O)c2ccc(C3(C(F)(F)F)NN3)cc2)c1
Temperature: 25 °C
Yield: 58 %

Procedure:
2-amino-N-methoxy-N-methyl-5-[2-(trimethylsilyl)ethynyl]benzamide (403 mg, 1.5 mmol, 1 eq.) and 3-(4-bromophenyl)-3-(trifluoromethyl)-1,2-bis(trimethylsilyl)diaziridine (synthesized by a 5-step process: Bender et al., 2007, 599 mg, 1.5 mmol, 1 eq.) were added together in a round-bottom flask and purged with nitrogen. THF was added, and the reaction was stirred at room temperature until all solids dissolved. The reaction was then cooled to −80° C. in a diethyl ether/dry ice bath, and 2.5 M n-butyllithium in hexanes (1.0 mL, 2.6 mmol, 1.8 eq.) was added, causing the reaction to turn a dark red color. The reaction was stirred at −80° C. for 2 hours and then quenched with saturated ammonium chloride solution (20 mL). The quenched reaction was extracted three times with ethyl acetate (50 mL each). The organic layer was then dried over sodium sulfate, and the solvent was evaporated. Purification on silica column (hexanes/ethyl acetate, 3:1→1:1) resulted in 342 mg (58%) of the title compound as a yellow solid. 1H NMR (500 MHz, CDCl3) δ 7.69 (dd, J=8.2, 37.0, 4H, Ar—H), 7.50 (d, J=1.8, 1H, Ar—H), 7.37 (dd, J=1.9, 8.6, 1H, Ar—H), 6.65 (d, J=8.6, 1H, Ar—H), 6.32 (s, 2H, NH2), 2.88 (d, J=8.6, 1H, CNH), 2.32 (d, J=8.8, 1H, CNH), 0.18 (s, 9H, Si(CH3)3). 13C NMR (126 MHz, CDCl3) δ 197.58 (CO), 151.25 (C—Ar), 141.43 (C—Ar), 138.23 (C—Ar), 138.06 (C—Ar), 134.66 (C—Ar), 129.57 (C—Ar), 128.37 (q, C—Ar, J=0.57), 123.55 (q, J=278.40, CF3), 117.35 (C—Ar), 117.19 (C—Ar), 110.28 (C—Ar), 104.90 (CSi(CH3)3), 92.18 (CCSi(CH3)3), 58.05 (q, J=36.3, C(NH)2), 0.25 (Si(CH3)3). Exact Mass, 403.13. 402.1046 [M−H]−, 404.1982 [M+H]+.
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][C:5]2[S:6][CH:7]=[CH:8][C:4]=2[CH:3]=1.[Li]CCCC.[C:16]1([C:22]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[N:23]2[CH:27]=[C:26]([CH2:28][CH2:29][CH:30]=[O:31])[N:25]=[CH:24]2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C1COCC1.[Cl-].[NH4+]>[F:1][C:2]1[CH:10]=[CH:9][C:5]2[S:6][C:7]([CH:30]([OH:31])[CH2:29][CH2:28][C:26]3[N:25]=[CH:24][N:23]([C:22]([C:38]4[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=4)([C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=4)[C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH:27]=3)=[CH:8][C:4]=2[CH:3]=1
Reactant: Fc1ccc2sccc2c1
Reactant: O=CCCc1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: C1CCOC1
Product: OC(CCc1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1)c1cc2cc(F)ccc2s1
Temperature: -40 °C
Reaction time: 1 h
Yield: 62.2 %

Procedure:
To a solution of 5-fluorobenzo[b]thiophene (1.22 g) in THF (22 ml) was added n-BuLi (1.6 M solution in hexane, 5.0 ml) at −78° C., and the mixture was stirred for 1 hour. To this mixture was added a solution of 3-(1-triphenylmethyl-1H-imidazole-4-yl)propanal (2.93 g) in THF (10 ml), and the mixture was allowed to warm to −40° C. over 1 hour. The mixture was diluted with 10% aqueous ammonium chloride, warmed to room temperature, and extracted with ethyl acetate. The extract was washed with brine, dried over MgSO4, and concentrated. The residue was chromatographed on silica gel using hexane-ethyl acetate (1:1) as an eluent to give the titled compound as colorless crystals (2.58 g).
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C:3]([C:8]([F:11])([F:10])[F:9])([OH:7])[CH2:4][CH:5]=C.[CH2:14]1[CH:18]2[CH:19]3[CH:23]=[CH:22][CH:21]([CH:17]2[CH:16]=[CH:15]1)[CH2:20]3>>[F:1][C:2]([F:12])([F:13])[C:3]([CH:4]1[CH2:5][CH:14]2[CH2:15][CH:16]1[CH:17]1[CH:18]2[CH:19]2[CH2:20][CH:21]1[CH:22]=[CH:23]2)([C:8]([F:10])([F:9])[F:11])[OH:7]
Reactant: C=CCC(O)(C(F)(F)F)C(F)(F)F
Reactant: C1=CC2C3C=CC(C3)C2C1
Product: OC(C1CC2CC1C1C3C=CC(C3)C21)(C(F)(F)F)C(F)(F)F
Temperature: 190 °C
Yield: 22.2 %

Procedure:
A 500 ml autoclave was charged with 230 g of 1,1-bis(trifluoromethyl)-3-butenol, 73 g of dicyclopentadiene, and 0.15 g of 2,6-di-t-butylparacresol, and the mixture was heated at 190° C. for 12 hours. The reaction solution was cooled to room temperature and purified by distillation to obtain 40 g of 8-(2,2,2-trifluoro-1-trifluoromethyl-1-hydroxyethyl)tetracyclo[4.4.0.12,5.17,10]dodec-3-ene of the following formula (13).
Reaction SMILES: [CH:1]1([N:13]2[CH2:18][CH2:17][CH:16]([N:19]3[C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=4[N:21]([CH2:28][C:29](O)=[O:30])[C:20]3=[O:32])[CH2:15][CH2:14]2)[C:11]2=[C:12]3[C:7](=[CH:8][CH:9]=[CH:10]2)[CH:6]=[CH:5][CH:4]=[C:3]3[CH2:2]1.[CH3:33][N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1.CCN=C=NCCCN(C)C.[ClH:51].C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C>CN(C=O)C.O>[ClH:51].[ClH:51].[CH:1]1([N:13]2[CH2:14][CH2:15][CH:16]([N:19]3[C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=4[N:21]([CH2:28][C:29]([N:37]4[CH2:38][CH2:39][N:34]([CH3:33])[CH2:35][CH2:36]4)=[O:30])[C:20]3=[O:32])[CH2:17][CH2:18]2)[C:11]2=[C:12]3[C:7](=[CH:8][CH:9]=[CH:10]2)[CH:6]=[CH:5][CH:4]=[C:3]3[CH2:2]1
Reactant: O=C(O)Cn1c(=O)n(C2CCN(C3Cc4cccc5cccc3c45)CC2)c2ccccc21
Reactant: CN1CCNCC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: O
Solvent: CN(C)C=O
Product: CN1CCN(C(=O)Cn2c(=O)n(C3CCN(C4Cc5cccc6cccc4c56)CC3)c3ccccc32)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 104.4 %

Procedure:
(RS)-2-{3-[1-(Acenaphthen-1-yl)piperidin-4-yl]-2,3-dihydro-2-oxo-benzoimidazol-1-yl}acetic acid (0.85 g, 2 mmol) was dissolved in DMF (10 ml). 1-Methylpiperazine (0.2 g, 2 mmol), WSC•HCl (0.46 g, 2.4 mmol), HOBt (0.37 g, 2.4 mmol) and triethylamine (0.53 ml, 3.8 mmol) were added and the mixture was stirred at room temperature for 8 hr. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated aqueous ammonium chloride solution, dried over magnesium sulfate, and concentrated. The obtained residue was purified by silica gel column chromatography (chloroform/methanol) and hydrochloric acid/ethanol was added to give the title compound (0.73 g) as a yellow solid.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](C=O)=[CH:2]1.[OH-].[K+].[C:14]1([S:20](Cl)(=[O:22])=[O:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[CH2:24]([OH:26])C>>[C:14]1([S:20]([N:1]2[C:9]3[C:4](=[CH:5][C:6]([CH:24]=[O:26])=[CH:7][CH:8]=3)[CH:3]=[CH:2]2)(=[O:22])=[O:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: O=S(=O)(Cl)c1ccccc1
Reactant: O=Cc1c[nH]c2ccccc12
Reactant: CCO
Agent: [K+]
Agent: [OH-]
Product: O=Cc1ccc2c(ccn2S(=O)(=O)c2ccccc2)c1
Yield: 32.6 %

Procedure:
To a solution of indole-3-carboxaldehyde (100 mmol) in ethanol (500 mL) at room temperature was added potassium hydroxide (110 equiv), the mixture was stirred until total solubilization. The ethanol was completely removed in vacuum and acetone (250 mL) added followed by benzenesulfonyl chloride (110 equiv). The precipitate was filtered off and the filtrate was concentrated and recrystallized from methanol to give a white solid. Yield: 32.6% 1H NMR (500 MHz, CDCl3) δ 10.17 (s, 1H), 8.25-8.39 (m, 2H), 7.97-8.09 (m, 3H), 7.69 (t, J=7.33 Hz, 1H), 7.59 (t, J=7.5 Hz, 2H), 7.39-7.54 (m, 2H). MS (ESI) calcd for C15H11NO3S 285.1. found 286.0 [M+H]+.