Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([C:16]2[NH:15][C:14]3[C:7](=[CH:8][CH:9]=[C:10]([CH:13]=3)[O:11][CH3:12])[C:6]=2[CH:5]=[CH:4][N:3]=1)[CH3:2].CN(C=O)C.[H-].[Na+].C([O-])(O)=O.[Na+]>C(OCC)(=O)C.O.C1COCC1>[C:7]1([CH2:6][CH2:5][CH2:4][N:15]2[C:16]3[C:1]([CH3:2])=[N:3][CH:4]=[CH:5][C:6]=3[C:7]3[C:14]2=[CH:13][C:10]([O:11][CH3:12])=[CH:9][CH:8]=3)[CH:14]=[CH:13][CH:10]=[CH:9][CH:8]=1
Reactant: COc1ccc2c(c1)[nH]c1c(C)nccc12
Agent: O=C([O-])O
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: COc1ccc2c3ccnc(C)c3n(CCCc3ccccc3)c2c1
Temperature: 25 °C
Yield: 101.7 %

Procedure:
Harmine 1 (0.53 g, 2.5 mmol), DMF (15 ml) and THF (15 ml) were respectively added in a 100 ml round-bottom flask, and stirred at room temperature until the mixture became clear, then 60% NaH (0.3 g, 7.5 mol) was added and stirred until there were no bubbles formed. 1-Brombenzenepropropane (2 ml) was added dropwise. The mixture was refluxed for 12 h. THF was evaporated in reduced pressure. The residues were poured into 30 ml cold water and extracted with ethyl acetate. The organic phases were combined, and washed with water and brine, dried over anhydrous sodium sulfate, filtered, evaporated in reduced pressure, and the residue dissolved in 50 anhydrous ethanol. The pH was adjusted to 4 with concentrated HCl, the mixture were concentrated in vacuum and then recrystallized with acetone to afford yellow solids. The solids were dissolved into a mixed solution of water and ethyl acetate. The pH was adjusted to 8 with saturated NaHCO3 solution. The organic layer was isolated, and the aqueous phase was extracted with ethyl acetate. The organic phases were combined, washed with water and brine, dried over anhydrous sodium sulfate, decolorized with activated carbon, filtered, concentrated, and recrystallized with ethyl ether to afford gray needle crystals (0.42 g, 51%), mp 117-118° C.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[N:7]([C@@H:10]([CH2:20][O:21][C:22]([C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)([CH3:24])[CH3:23])[CH2:11][O:12][Si](C(C)(C)C)(C)C)=[N+]=[N-]>O1CCCC1>[NH2:7][C@@H:10]([CH2:20][O:21][C:22]([C:25]1[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=1)([CH3:24])[CH3:23])[CH2:11][OH:12]
Reactant: CC(C)(OC[C@@H](CO[Si](C)(C)C(C)(C)C)N=[N+]=[N-])c1ccc(F)cc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CC(C)(OC[C@H](N)CO)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 48 h
Yield: 103.5 %

Procedure:
To a stirred solution of lithiumaluminiumhydride (41 mg) in dry tetrahydrofuran (2 ml) was added dropwise under an argon atmosphere a solution of {(S)-2-azido-3-[1-(4-fluorophenyl)-1-methyl-ethoxy]-propoxy}-tert-butyl-dimethyl-silane (200 mg) in dry tetrahydrofuran (0.5 ml). The reaction mixture was stirred at room temperature for 48 hours and quenched by addition of water (0.04 ml), NaOH 4 N (0.04 ml) and H2O (0.12 ml). The suspension was stirred for 30 min and was filtered through Celite and MgSO4. The filtrate was evaporated to give crude (R)-2-amino-3-[1-(4-fluoro-phenyl)-1-methyl-ethoxy]-propan-1-ol (128 mg) as a light yellow liquid. MS (ISP): 228.3 ([M+H]+)
Reaction SMILES: [CH:1]1([NH:7][C:8]2[C:21]3[C:20](=[O:22])[C:19]4[C:14](=[CH:15][C:16]([N+:23]([O-:25])=[O:24])=[CH:17][CH:18]=4)[C:13](=[O:26])[C:12]=3[C:11](Cl)=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:28]([C:32]1[CH:38]=[CH:37][C:35]([NH2:36])=[CH:34][CH:33]=1)([CH3:31])([CH3:30])[CH3:29].C([O-])(=O)C.[K+].[Cl-]>CO.II>[CH:1]1([NH:7][C:8]2[C:21]3[C:20](=[O:22])[C:19]4[C:14](=[CH:15][C:16]([N+:23]([O-:25])=[O:24])=[CH:17][CH:18]=4)[C:13](=[O:26])[C:12]=3[C:11]([NH:36][C:35]3[CH:37]=[CH:38][C:32]([C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:33][CH:34]=3)=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C1c2cc([N+](=O)[O-])ccc2C(=O)c2c(NC3CCCCC3)ccc(Cl)c21
Reactant: CC(C)(C)c1ccc(N)cc1
Agent: CC(=O)[O-]
Agent: II
Agent: [Cl-]
Solvent: CO
Product: CC(C)(C)c1ccc(Nc2ccc(NC3CCCCC3)c3c2C(=O)c2cc([N+](=O)[O-])ccc2C3=O)cc1

Procedure:
30 g of 1-cyclohexylamino-4-chloro-6-nitroanthraquinone, 90 ml of p-tert.-butylaniline, 9.6 g of potassium acetate, 0.2 g of copperI chloride and 0.05 g of iodine are heated at 120°-130° C until only a little starting material remains detectable (approx. 12 hours being required). The mixture is diluted with 135 ml of methanol and the product is filtered off cold and washed with methanol and hot water. 26 g of 1-cyclohexylamino-4-(p-tert.-butylanilino)-6-nitroanthraquinone are obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:20])[CH2:9][C:10]1[CH:19]=[CH:18][C:13]([C:14]([O:16]C)=[O:15])=[CH:12][CH:11]=1.[OH-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CO.O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:20])[CH2:9][C:10]1[CH:19]=[CH:18][C:13]([C:14]([OH:16])=[O:15])=[CH:12][CH:11]=1
Reactant: COC(=O)c1ccc(CC(=O)c2ccccc2Cl)cc1
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: O=C(O)c1ccc(CC(=O)c2ccccc2Cl)cc1
Yield: 96.7 %

Procedure:
A mixture of 18.78 g of methyl 4-[2-(2-chlorophenyl)-2-oxoethyl]benzoate in 288.8 ml of CH3OH, 72.2 ml of water and 5.2 g of NaOH is refluxed for 3 hours then acidified with 2N citric acid. The reaction mixture is evaporated in vacuo to remove the CH3OH. The aqueous phase is extracted with CH2Cl2 and acidified with 1N HCl. The resulting solid is collected and dried under vacuum to give 17.27 g of the desired product, m.p. 168°-172° C.
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][C:6](=[O:13])[C:5]2=[CH:14]OC.[NH2:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][CH:27]=1)[N:24]=[CH:23][CH:22]=[CH:21]2>CN(C)C=O>[I:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][C:6](=[O:13])/[C:5]/2=[CH:14]\[NH:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][CH:27]=1)[N:24]=[CH:23][CH:22]=[CH:21]2
Reactant: COC=C1C(=O)NC(=O)c2ccc(I)cc21
Reactant: Nc1ccc2ncccc2c1
Solvent: CN(C)C=O
Product: O=C1NC(=O)c2ccc(I)cc2/C1=C/Nc1ccc2ncccc2c1
Temperature: 110 °C
Yield: 85.7 %

Procedure:
A mixture of 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (164.5 mg, 0.5 mmol), 6-aminoquinoline (72.2 mg, 0.5 mmol) in 1 mL of N,N-dimethylformamide is heated at 110° C. for 0.5 h. After cooling in the refrigerator, the precipitate is collected, and washed with N,N-dimethylformamide (DMF) and ether to give 189 mg (85%) of yellow solid. MS (ESI) m/z 442.0 (M+H)+1
Reaction SMILES: C1(=O)CCC1.[CH2:6]([C:8]([CH2:29][CH3:30])=[CH:9][C@H:10]1[CH2:15][CH2:14][C@H:13]([NH:16][C:17](=[O:28])[CH2:18][C:19]2[CH:24]=[CH:23][C:22]([OH:25])=[C:21]([O:26][CH3:27])[CH:20]=2)[CH2:12][CH2:11]1)C>>[C:8]1(=[CH:9][C@H:10]2[CH2:11][CH2:12][C@H:13]([NH:16][C:17](=[O:28])[CH2:18][C:19]3[CH:24]=[CH:23][C:22]([OH:25])=[C:21]([O:26][CH3:27])[CH:20]=3)[CH2:14][CH2:15]2)[CH2:29][CH2:30][CH2:6]1
Reactant: CCC(=C[C@H]1CC[C@H](NC(=O)Cc2ccc(O)c(OC)c2)CC1)CC
Agent: O=C1CCC1
Product: COc1cc(CC(=O)N[C@H]2CC[C@H](C=C3CCC3)CC2)ccc1O

Procedure:
The above desired compound was prepared in a similar manner of Example 90 using cyclobutanone by which 3-pentanone of Example 90 (4) was replaced.
Reaction SMILES: [CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]3[NH:14][CH:15]=[CH:16][C:9]=23)[C:5]([C:17]2[CH:23]=[CH:22][C:20]([NH2:21])=[CH:19][CH:18]=2)=[N:4]1)[CH3:2].[CH2:24]([N:31]=[C:32]=[O:33])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>>[CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]3[NH:14][CH:15]=[CH:16][C:9]=23)[C:5]([C:17]2[CH:23]=[CH:22][C:20]([NH:21][C:32]([NH:31][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:33])=[CH:19][CH:18]=2)=[N:4]1)[CH3:2]
Reactant: O=C=NCc1ccccc1
Reactant: CCn1cc(-c2ccnc3[nH]ccc23)c(-c2ccc(N)cc2)n1
Product: CCn1cc(-c2ccnc3[nH]ccc23)c(-c2ccc(NC(=O)NCc3ccccc3)cc2)n1

Procedure:
Following the procedure described in Example 1 with 4-[1-ethyl-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-3-yl]aniline and benzyl isocyanate provided the title compound. ESMS [M+H]+: 437.2
Reaction SMILES: [CH:1]([C:3]([CH3:5])=[O:4])=[CH2:2].[OH-].[K+].[F:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[CH:16]=O)=[CH:11][CH:10]=1>C(O)C.C(OCC)C>[F:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2([C:18]3[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=3)[CH2:16][CH2:5][C:3](=[O:4])[CH:1]=[CH:2]2)=[CH:13][CH:14]=1
Reactant: C=CC(C)=O
Reactant: O=CC(c1ccc(F)cc1)c1ccc(F)cc1
Agent: [K+]
Agent: [OH-]
Solvent: CCOCC
Solvent: CCO
Product: O=C1C=CC(c2ccc(F)cc2)(c2ccc(F)cc2)CC1
Reaction time: 24 h

Procedure:
1.7 cm3 of methyl vinyl ketone and 0.39 g of potassium hydroxide pellets dissolved in 3 cm3 of ethanol are successively added to a solution, cooled to 0° C., of 4 g of bis(4-fluorophenyl)acetaldehyde in 35 cm3 of ethyl ether. The temperature is left in the region of 20° C. for 24 hours. The mixture is concentrated to dryness under reduced pressure, 75 cm3 of dichloromethane are added and the mixture is washed with twice 75 cm3 of distilled water. After drying over magnesium sulphate and concentrating to dryness under reduced pressure, the residue is purified by flash chromatography on silica gel (30–70 μm), eluting with pure dichloromethane; 3 g of 4,4-bis(4-fluorophenyl)cyclohex-2-enone are thus obtained in the form of a pale yellow oil, the characteristics of which are as follows:
Reaction SMILES: [C:1]([N:4]1[CH2:13][CH2:12][C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2/[C:5]/1=[CH:14]\[C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=1)(=[O:3])[CH3:2]>C(Cl)Cl>[C:1]([N:4]1[CH2:13][CH2:12][C:11]2[C:6]([CH2:7][CH2:8][CH2:9][CH:10]=2)=[C:5]1[CH2:14][C:15]1[CH:16]=[CH:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=1)(=[O:3])[CH3:2]
Reactant: COc1ccc(/C=C2\C3=C(CCCC3)CCN2C(C)=O)cc1
Solvent: ClCCl
Product: COc1ccc(CC2=C3CCCC=C3CCN2C(C)=O)cc1
Yield: 33.3 %

Procedure:
A solution of 2.1 g of (E)-2-acetyl-1,2,S,4,5,6,7,8-octahydro-1-(p-methoxybenzylidene)isoquinoline (prepared according to Example 1) in 120 ml of methylene chloride was heated at reflux for 2 hours under argon. The solvent was then distilled off at 30° C./20 mbar. The residue, 2.3 g of a colorless oil, contained 61% of the desired product according to GC. Column chromatography and crystallization from isopropyl ether gave 700 mg of 2-acetyl-1 -(p-methoxybenzyl)-2,3,4,6,7,8-hexahydroisoquinoline, which was pure according to thin-layer chromatography and gas chromatography, as white crystals. M.p. 48°-50° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[NH:13][C@@H:12]([C@H:14]([OH:16])[CH3:15])[CH2:11][O:10][CH2:9]2)=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N+:36]([C:39]1[CH:47]=[CH:46][C:42]([C:43](O)=[O:44])=[CH:41][CH:40]=1)([O-:38])=[O:37].N(C(OC(C)C)=O)=NC(OC(C)C)=O>O.C(OCC)(=O)C.O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@H:8]2[NH:13][C@@H:12]([C@@H:14]([O:16][C:43](=[O:44])[C:42]3[CH:41]=[CH:40][C:39]([N+:36]([O-:38])=[O:37])=[CH:47][CH:46]=3)[CH3:15])[CH2:11][O:10][CH2:9]2)=[CH:6][CH:7]=1
Reactant: O=C(O)c1ccc([N+](=O)[O-])cc1
Reactant: C[C@@H](O)[C@H]1COC[C@@H](c2ccc(Cl)cc2)N1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: O
Product: C[C@H](OC(=O)c1ccc([N+](=O)[O-])cc1)[C@H]1COC[C@@H](c2ccc(Cl)cc2)N1
Reaction time: 2 h
Yield: 100 %

Procedure:
Under a nitrogen atmosphere, to a tetrahydrofuran (20 mL) solution containing (R)-1-[(3R,5R)-5-(4-chlorophenyl)morpholine-3-yl]ethanol (903 mg), triphenylphosphine (1.81 g) and 4-nitrobenzoic acid (1.16 g) was dropwise added diisopropyl azodicarboxylate (1.36 mL) while cooling with ice. The resultant solution was stirred at the same temperature for 30 minutes, and then at room temperature for 2 hours. The reaction solution was diluted with water and ethyl acetate, and the organic layer was partitioned. The organic layer was washed with brine, and then dried over anhydrous magnesium sulfate. Solvent was removed by distillation under reduced pressure, and the resulting residue was purified by silica gel column chromatography (heptane/ethyl acetate 9/1→8/2→7/3), to thereby obtain the titled compound (1.46 g). The physical properties of the compound were as follows.
Reaction SMILES: [C:1](/[C:3](=[C:5]1/[C:6]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:7]=2[O:8][CH2:9][C:10]2[CH:15]=[C:14]([CH2:16][C:17]3[N:21]4[CH:22]=[CH:23][C:24]([C:26](O)=[O:27])=[CH:25][C:20]4=[N:19][C:18]=3[CH:29]3[CH2:31][CH2:30]3)[CH:13]=[CH:12][C:11]/1=2)/[CH3:4])#[N:2].C(N1C=CN=C1)([N:39]1C=CN=C1)=O.N.Cl>C1COCC1>[C:1](/[C:3](=[C:5]1/[C:6]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:7]=2[O:8][CH2:9][C:10]2[CH:15]=[C:14]([CH2:16][C:17]3[N:21]4[CH:22]=[CH:23][C:24]([C:26]([NH2:39])=[O:27])=[CH:25][C:20]4=[N:19][C:18]=3[CH:29]3[CH2:31][CH2:30]3)[CH:13]=[CH:12][C:11]/1=2)/[CH3:4])#[N:2]
Reactant: C/C(C#N)=C1/c2ccc(Cc3c(C4CC4)nc4cc(C(=O)O)ccn34)cc2COc2cc(F)ccc21
Reactant: O=C(n1ccnc1)n1ccnc1
Agent: Cl
Agent: N
Solvent: C1CCOC1
Product: C/C(C#N)=C1/c2ccc(Cc3c(C4CC4)nc4cc(C(N)=O)ccn34)cc2COc2cc(F)ccc21
Temperature: 60 °C
Yield: 86.1 %

Procedure:
[step 6] (E)-3-{[11(6H)-(1-cyanoethylidene)-3-fluorodibenzo[b,e]oxepin-8-yl]methyl}-2-cyclopropylimidazo[1,2-a]pyridine-7-carboxylic acid (2.4 g, 5.1 mmol) obtained in step 5 was suspended in THF (25 mL), 1,1′-carbonyldiimidazole (4.1 g, 25 mmol) was added, and the mixture was stirred with heating at 60° C. for 1.5 hr. To the reaction mixture was added 25% aqueous ammonia solution (4.4 mL, 51 mmol), and the mixture was stirred at room temperature for 15 min. To the mixture was added 2 mol/L hydrochloric acid, and the mixture was stirred at room temperature for 1.5 hr. The precipitated crystals were collected by suction filtration, and dried at 50° C. under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform/methanol=100/0 v/v-10/90 v/v) to give the title compound (2.1 g, 86%).
Reaction SMILES: [C:1]1([C:7]2[CH2:12][O:11][CH2:10][CH2:9][C:8]=2[CH2:13]O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Br:15]P(Br)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>C(Cl)Cl>[Br:15][CH2:13][C:8]1[CH2:9][CH2:10][O:11][CH2:12][C:7]=1[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: BrP(Br)(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: OCC1=C(c2ccccc2)COCC1
Solvent: ClCCl
Product: BrCC1=C(c2ccccc2)COCC1
Reaction time: 0.5 h
Yield: 79.4 %

Procedure:
To a solution of (5-phenyl-3,6-dihydro-2H-pyran-4-yl)methanol (360 mg, 1.89 mmol) in DCM (6 mL) was added dibromotriphenylphosphorane (880 mg, 2.08 mmol) at room temperature, after stirring for 30 min, it was diluted with DCM, organic layer was washed with Sat. NaHCO3, brine, dried and concentrated to give crude product, which was purified by column(Hexanes/EtOAc=9:1) to give 4-(bromomethyl)-5-phenyl-3,6-dihydro-2H-pyran (380 mg).
Reaction SMILES: C(C1N=C(N2CCC(F)(F)C2)C2C(=NN(CC)N=2)N=1)(C)(C)C.[C:23]([C:27]1[N:28]=[C:29]([N:36]2[CH2:40][CH2:39][C:38]([F:42])([F:41])[CH2:37]2)[C:30]2[N:35]=[N:34][NH:33][C:31]=2[N:32]=1)([CH3:26])([CH3:25])[CH3:24].Br[CH2:44][C:45]([C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)=[O:46]>>[C:23]([C:27]1[N:28]=[C:29]([N:36]2[CH2:40][CH2:39][C:38]([F:41])([F:42])[CH2:37]2)[C:30]2[C:31](=[N:33][N:34]([CH2:44][C:45]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)=[O:46])[N:35]=2)[N:32]=1)([CH3:26])([CH3:24])[CH3:25]
Reactant: O=C(CBr)c1ccccc1
Reactant: CC(C)(C)c1nc(N2CCC(F)(F)C2)c2nn[nH]c2n1
Agent: CCn1nc2nc(C(C)(C)C)nc(N3CCC(F)(F)C3)c2n1
Product: CC(C)(C)c1nc(N2CCC(F)(F)C2)c2nn(CC(=O)c3ccccc3)nc2n1

Procedure:
In analogy to the procedure described for the synthesis of 5-tert-butyl-7-(3,3-difluoro-pyrrolidin-1-yl)-2-ethyl-2H-[1,2,3]triazolo[4,5-d]pyrimidine (example 3, step b), the title compound was prepared from 5-tert-butyl-7-(3,3-difluoropyrrolidin-1-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and 2-bromo-1-phenylethanone and isolated brown gum (0.8 mg, 5%). MS (m/e): 401.4 (MH+).
Reaction SMILES: C1(C)C=CC=CC=1.[F:8][C:9]1[CH:36]=[CH:35][C:12]2[S:13][C:14]([S:17]([NH:20][C:21]3[CH:30]=[CH:29][C:24]([C:25](OC)=[O:26])=[CH:23][C:22]=3[S:31]([CH3:34])(=[O:33])=[O:32])(=[O:19])=[O:18])=[C:15]([CH3:16])[C:11]=2[CH:10]=1.[H-].C([Al+]CC(C)C)C(C)C.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+]>C(OCC)(=O)C.O>[F:8][C:9]1[CH:36]=[CH:35][C:12]2[S:13][C:14]([S:17]([NH:20][C:21]3[CH:30]=[CH:29][C:24]([CH2:25][OH:26])=[CH:23][C:22]=3[S:31]([CH3:34])(=[O:33])=[O:32])(=[O:19])=[O:18])=[C:15]([CH3:16])[C:11]=2[CH:10]=1
Reactant: COC(=O)c1ccc(NS(=O)(=O)c2sc3ccc(F)cc3c2C)c(S(C)(=O)=O)c1
Agent: CC(C)C[Al+]CC(C)C
Agent: O=C([O-])C(O)C(O)C(=O)[O-]
Agent: [H-]
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Solvent: O
Product: Cc1c(S(=O)(=O)Nc2ccc(CO)cc2S(C)(=O)=O)sc2ccc(F)cc12
Temperature: -30 °C
Yield: 70.7 %

Procedure:
Into 120 mL of toluene was dissolved 2.08 g of Compound 17. After cooling to −30° C., 22.5 mL of 1.01 mol/L toluene solution of diisobutylaluminum hydride was added thereto. After 5 hours of stirring at the same temperature, water was added to the reaction solution to terminate the reaction and then the mixture was diluted with ethyl acetate, followed by addition of saturated aqueous potassium sodium tartrate solution and 30 minutes of stirring at room temperature. The mixture was extracted with ethyl acetate and the organic layer was washed with saturated brine and then dried over anhydrous sodium sulfate. The solvent was removed by evaporation under reduced pressure and the resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane=1/1) to obtain 1.38 g of the title compound as colorless powder.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[O:7][C:6]([C:8]2[CH:9]=[C:10]([CH2:16][CH3:17])[C:11](=[O:15])[NH:12][C:13]=2[CH3:14])=[CH:5][CH:4]=1.[C:18]1([CH2:24][C:25](Cl)=[O:26])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[CH2:16]([C:10]1[C:11](=[O:15])[NH:12][C:13]([CH3:14])=[C:8]([C:6]2[O:7][C:3]([CH2:2][NH:1][C:25](=[O:26])[CH2:24][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:4][CH:5]=2)[CH:9]=1)[CH3:17]
Reactant: CCc1cc(-c2ccc(CN)o2)c(C)[nH]c1=O
Reactant: O=C(Cl)Cc1ccccc1
Product: CCc1cc(-c2ccc(CNC(=O)Cc3ccccc3)o2)c(C)[nH]c1=O

Procedure:
Example 269 is substantially repeated except for utilizing 5-(5-aminomethylfuran-2-yl)-3-ethyl-6-methyl-1H-pyridin-2-one and phenylacetyl chloride to afford the title compound. MS: m/e=351 (M+H).
Reaction SMILES: [F:1][C:2]1[C:29]([F:30])=[C:28]([F:31])[C:27]([F:32])=[C:26]([F:33])[C:3]=1[CH:4]([C:6]1[CH:11]=[CH:10][C:9]([S:12][C:13]2[S:17][C:16]([C:18]3([O:24][CH3:25])[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[CH:15][CH:14]=2)=[CH:8][CH:7]=1)[OH:5].[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1>>[F:33][C:26]1[C:27]([F:32])=[C:28]([F:31])[C:29]([F:30])=[C:2]([F:1])[C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][C:9]([S:12][C:13]2[S:17][C:16]([C:18]3([O:24][CH3:25])[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[CH:15][CH:14]=2)=[CH:8][CH:7]=1)=[O:5]
Reactant: COC1(c2ccc(Sc3ccc(C(O)c4c(F)c(F)c(F)c(F)c4F)cc3)s2)CCOCC1
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Product: COC1(c2ccc(Sc3ccc(C(=O)c4c(F)c(F)c(F)c(F)c4F)cc3)s2)CCOCC1
Yield: 75 %

Procedure:
Using the procedure described in Example 18, 4-[5-(4-(2,3,4,5,6-pentafluoro-alpha-hydroxybenzyl)phenylthio)thien-2-yl]-4-methoxytetrahydropyran was reacted with pyridinium chlorochromate to give 4-[5-(4-(2,3,4,5,6-pentafluorobenzoyl)phenylthio)thien-2-yl]-4-methoxytetrahydropyran in 75% yield, m.p. 93°-94° C.
Reaction SMILES: [N:1]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4]1)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>O1CCCC1>[N:3]1([NH2:1])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4]1
Reactant: O=NN1CCc2ccccc21
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: NN1CCc2ccccc21
Temperature: 25 °C
Yield: 88.3 %

Procedure:
A solution of 1-nitroso-2,3-dihydro-1H-indole (5.27 g, 35.6 mmol) in tetrahydrofuran (35 ml) was added dropwise to a refluxing slurry of lithium aluminium hydride (2.98 g, 78.5 mmol) in tetrahydrofuran (100 ml). After 1 hour the mixture was cooled in an ice bath and water (3 ml) carefully added. 2M sodium hydroxide (6 ml) followed by water (6 ml) were added and the mixture heated to reflux for 30 minutes. After cooling to room temperature the precipitate formed was filtered off. The filtrate obtained was evaporated to dryness to yield 2,3-dihydro-indol-1-ylamine as a red/brown oil (4.216 g), which was used for the next step without further purification.
Reaction SMILES: [C:1]([C:3]1[CH:11]=[CH:10][C:6]2[CH:7]=[N:8][NH:9][C:5]=2[CH:4]=1)#[N:2].[OH-].[Na+].[Cl:14][CH2:15][CH2:16][CH2:17]Br>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.ClCCl>[C:1]([C:3]1[CH:11]=[CH:10][C:6]2[CH:7]=[N:8][N:9]([CH2:17][CH2:16][CH2:15][Cl:14])[C:5]=2[CH:4]=1)#[N:2]
Reactant: ClCCCBr
Reactant: N#Cc1ccc2cn[nH]c2c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Agent: [Na+]
Solvent: ClCCl
Product: N#Cc1ccc2cnn(CCCCl)c2c1
Temperature: 60 °C
Yield: 63.3 %

Procedure:
6-cyano-1H-benzopyrazole (14.3 g, 0.10 mol) was dissolved into 200 ml of 20% wt. sodium hydroxide, 3-chlorobromopropane (31.2 g, 0.20 mol) and tetrabutyl ammonium bromide (1.0 g) were added, and mixed for 5 min. The mixture was heated to 60° C., stirred to react for 2 hours. Then the reaction solution was cooled down to ambient temperature, 100 ml of dichloromethane was added for extraction and liquid separation. To the aqueous phase, 100 of dichloromethane was added for extraction. Organic phases were mixed, washed with 100 ml of saturated saline. Liquid was separated, and organic phase was evaporated to dryness to produce oily product. Oily products were separated and purified by chromatography with neutral Al2O3 to produce 13.9 g of 6-cyano-1-(3-chloropropyl)-1H-benzopyrazole, with a yield of 63.8%.
Reaction SMILES: [NH2:1][CH:2]1[C:8](=[O:9])[N:7]([CH3:10])[C:6]2[CH:11]=[CH:12][CH:13]=[CH:14][C:5]=2[C:4]2[CH:15]=[CH:16][CH:17]=[CH:18][C:3]1=2.[F:19][C:20]1[CH:21]=[C:22]([CH:34]=[C:35]([F:37])[CH:36]=1)[CH2:23][NH:24][C:25](=[O:33])[CH:26]([CH:30]([CH3:32])[CH3:31])[C:27](O)=[O:28]>>[F:19][C:20]1[CH:21]=[C:22]([CH:34]=[C:35]([F:37])[CH:36]=1)[CH2:23][NH:24][C:25](=[O:33])[CH:26]([CH:30]([CH3:32])[CH3:31])[C:27]([NH:1][CH:2]1[C:8](=[O:9])[N:7]([CH3:10])[C:6]2[CH:11]=[CH:12][CH:13]=[CH:14][C:5]=2[C:4]2[CH:15]=[CH:16][CH:17]=[CH:18][C:3]1=2)=[O:28]
Reactant: CC(C)C(C(=O)O)C(=O)NCc1cc(F)cc(F)c1
Reactant: CN1C(=O)C(N)c2ccccc2-c2ccccc21
Product: CC(C)C(C(=O)NCc1cc(F)cc(F)c1)C(=O)NC1C(=O)N(C)c2ccccc2-c2ccccc21

Procedure:
The title compound, MS: m/e=491.2 (M+H+), was prepared in analogy to example 16 from 7-amino-5-methyl-5H,7H-dibenzo[b,d]azepin-6-one and N-(3,5-difluoro-benzyl)-2-isopropyl-malonamic acid.
Reaction SMILES: BrCCBr.Cl[Si](C)(C)C.Br[C:11]1[S:12][CH:13]=[CH:14][N:15]=1.[CH3:16][O:17][C:18](=[O:33])[C:19]1[CH:31]=[C:30](I)[CH:29]=[C:21]([C:22]([N:24]([CH3:28])[CH2:25][CH2:26][CH3:27])=[O:23])[CH:20]=1>C1COCC1.[Zn].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]>[CH3:16][O:17][C:18](=[O:33])[C:19]1[CH:31]=[C:30]([C:11]2[S:12][CH:13]=[CH:14][N:15]=2)[CH:29]=[C:21]([C:22]([N:24]([CH3:28])[CH2:25][CH2:26][CH3:27])=[O:23])[CH:20]=1
Reactant: CCCN(C)C(=O)c1cc(I)cc(C(=O)OC)c1
Reactant: Brc1nccs1
Agent: [Pd]
Agent: C[Si](C)(C)Cl
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1CCOC1
Solvent: BrCCBr
Product: CCCN(C)C(=O)c1cc(C(=O)OC)cc(-c2nccs2)c1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 95 %

Procedure:
To a previously nitrogen-flushed vessel, add zinc dust (<10 microns, 0.196 g, 3 mmol) and 1,2-dibromoethane (0.023 mL, 0.27 mmol) to THF (0.5 mL). Heat the solution until bubbles appear. Repeat the heating twice and cool to room temperature. Add chlorotrimethylsilane (15 μL) and 2-bromothiazole (90 μL, 1 mmol) in THF (0.4 mL). Stir at room temperature for 15 min. Add 5-iodo-N-methyl-N-propyl-isophthalamic acid methyl ester (541 mg, 1.5 mmol), tetrakis(triphenylphosphine)palladium (0) (15 mg) and flush the mixture with nitrogen again before heating to reflux for 10 h. Cool to room temperature, concentrate and purify (silica gel chromatography, eluting with 0:100 to 40:60 ethyl acetate:hexanes) to give the title compound (95%).