Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:9][CH3:10])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:11]1(O)[CH:16]=[CH:15]C=[CH:13][CH:12]=1>CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4].CO>[C:1]([O:9][C:10]1[CH:15]=[CH:16][CH:11]=[CH:12][CH:13]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Oc1ccccc1
Reactant: COC(=O)c1ccccc1
Agent: [Ti+4]
Agent: CC(C)[O-]
Solvent: CO
Product: O=C(Oc1ccccc1)c1ccccc1
Temperature: 190 °C
Reaction time: 4 h
Yield: 74 %

Procedure:
A Claisen head was attached to a flask having an internal volume of 1000 ml, and a receiver having a gage was attached to the Claisen head via a condenser to make a distillation apparatus. Into this apparatus were charged methyl benzoate 100 g (735 mmole), phenol 553 g (5876 mmole) and titanium tetraisopropoxide 2.1 g (7.4 mmole). The contents were reacted with stirring at 190° C. in a bath. The reaction was conducted at atmospheric pressure, and the methanol thus produced was removed together with phenol. After reacting for 4 hours, excess phenol was distilled at atmospheric pressure. The remaining phenol and methyl benzoate were distilled under vacuum to obtain phenyl benzoate. The boiling point was 140° C./4mmHg. The yield was 108 g (74% yield in terms of methyl benzoate).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:25]=[CH:26][N:27]=1)[C:5]([NH:7][C:8]1[S:9][C:10]2[C:16]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[CH:15][CH:14]=[C:13]([O:23][CH3:24])[C:11]=2[N:12]=1)=[O:6].[H-].[Na+].[CH3:30][CH:31]([CH3:34])[CH2:32][OH:33]>O1CCOCC1.CN(C=O)C>[CH2:32]([O:33][C:2]1[CH:3]=[C:4]([CH:25]=[CH:26][N:27]=1)[C:5]([NH:7][C:8]1[S:9][C:10]2[C:16]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[CH:15][CH:14]=[C:13]([O:23][CH3:24])[C:11]=2[N:12]=1)=[O:6])[CH:31]([CH3:34])[CH3:30]
Reactant: CC(C)CO
Reactant: COc1ccc(N2CCOCC2)c2sc(NC(=O)c3ccnc(Br)c3)nc12
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: C1COCCO1
Product: COc1ccc(N2CCOCC2)c2sc(NC(=O)c3ccnc(OCC(C)C)c3)nc12

Procedure:
From 2-bromo-N-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-isonicotinamide with sodium hydride and 2-methyl-propanol in dioxane and DMF. ES-MS m/e (%): 443 (M+H+, 100).
Reaction SMILES: [C:1]([CH2:3][CH2:4][NH:5][C:6](=O)[CH2:7][Br:8])#[N:2].[N-:10]=[N+:11]=[N-:12].[Na+].FC(F)(F)C(OC(=O)C(F)(F)F)=O.C(=O)([O-])O.[Na+]>C(Cl)Cl>[Br:8][CH2:7][C:6]1[N:5]([CH2:4][CH2:3][C:1]#[N:2])[N:12]=[N:11][N:10]=1
Reactant: [N-]=[N+]=[N-]
Reactant: N#CCCNC(=O)CBr
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Solvent: ClCCl
Product: N#CCCn1nnnc1CBr

Procedure:
1.50 g (7.85 mmol) of bromoacetic acid-(2-cyanoethyl)-amide are dissolved in 50 ml of methylene chloride and mixed with 508 mg (7.85 mmol) of sodium azide. At 0° C. a solution of 2.20 g (7.85 mmol) of trifluoroacetic acid anhydride in 5 ml of methylene chloride is added dropwise. After 22 hours at ambient temperature saturated sodium hydrogen carbonate solution is added and the resulting mixture is extracted 3 x with methylene chloride. The combined organic phases are dried over sodium sulphate and concentrated by evaporation. The crude product is chromatographed on silica gel, eluting first with methylene chloride, later with methylene chloride/ethanol (50:1). The desired fractions are combined and concentrated by evaporation.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:12]2[O:13][CH:14]=[CH:15][CH:16]=2)=[N:4][C:5]([NH2:11])=[N:6][C:7]=1S(C)=O.[CH2:17]([OH:25])[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C1CCN2C(=NCCC2)CC1>O1CCOCC1>[Cl:1][C:2]1[C:3]([C:12]2[O:13][CH:14]=[CH:15][CH:16]=2)=[N:4][C:5]([NH2:11])=[N:6][C:7]=1[O:25][CH2:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: OCCc1ccccc1
Reactant: CS(=O)c1nc(N)nc(-c2ccco2)c1Cl
Solvent: C1COCCO1
Solvent: C1CCC2=NCCCN2CC1
Product: Nc1nc(OCCc2ccccc2)c(Cl)c(-c2ccco2)n1

Procedure:
From 5-chloro-4-furan-2-yl-6-methanesulfinyl-pyrimidin-2-yl-amine, phenethyl alcohol and DBU in dioxane. ES-MS m/e (%): 318 (M{37Cl}+H+, 33), 316 (M{35Cl}+H+, 100).
Reaction SMILES: C(O)(=O)C.I[CH:6]([CH2:14][C:15]([F:27])([F:26])[C:16]([F:25])([F:24])[C:17]([F:23])([F:22])[C:18]([F:21])([F:20])[F:19])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][OH:13]>C(O)C.[Zn]>[F:22][C:17]([F:23])([C:18]([F:19])([F:20])[F:21])[C:16]([F:24])([F:25])[C:15]([F:27])([F:26])[CH2:14][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][OH:13]
Reactant: OCCCCCCC(I)CC(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Agent: [Zn]
Solvent: CCO
Solvent: CC(=O)O
Product: OCCCCCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Temperature: 50 °C
Reaction time: 0.25 h

Procedure:
To a slurry of 98.0 g of zinc powder in 600 mL of ethanol was added 3.0 g of acetic acid. A solution of the crude 7-iodo-8-(nonafluorobutyl)-1-octanol prepared above in 100 mL of ethanol was added dropwise with stirring over 15 min, and the reaction mixture was heated at 50° C. for 3 hr. The mixture was filtered, and the filtrate was concentrated to 100.0 g of a viscous, light yellow fluid. A 79.6 g portion of this material was stirred with 300 mL of hexanes, and the supernatant was filtered through diatomaceous earth (marketed under the trade designation “CELITE” by Johns-Manville Corporation, Denver, Colo.) and concentrated to give 44.24 g of 8-(nonafluorobutyl)-1-octanol as a clear, colorless oil, which was used without further purification.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:23]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[CH:22][C:21]([N+:30]([O-])=O)=[C:20](Cl)[N:19]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)(C)(C)C.Cl.[CH3:36][NH:37][CH2:38][C:39](OC)=[O:40].C(N(CC)CC)C>CO>[NH2:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:23]([C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=4)=[CH:22][C:21]4[NH:30][C:39](=[O:40])[CH2:38][N:37]([CH3:36])[C:20]=4[N:19]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1
Reactant: CC(C)(C)OC(=O)NC1(c2ccc(-c3nc(Cl)c([N+](=O)[O-])cc3-c3ccccc3)cc2)CCC1
Reactant: CNCC(=O)OC
Agent: Cl
Solvent: CO
Solvent: CCN(CC)CC
Product: CN1CC(=O)Nc2cc(-c3ccccc3)c(-c3ccc(C4(N)CCC4)cc3)nc21
Temperature: 80 °C
Yield: 64.2 %

Procedure:
In a microwave vial were added tert-butyl(1-(4-(6-chloro-5-nitro-3-phenylpyridin-2-yl)phenyl)cyclobutyl)carbamate (200 mg, 0.417 mmol), methyl 2-(methylamino)acetate hydrochloride (58 mg, 0.417 mmol) and triethylamine (58 μl, 0.417 mmol) in methanol (2 ml). The solution was heated to 80° C. under microwave irradiation for 1 hour. The reaction mixture was concentrated to dryness under reduced pressure and purified by Biotage chromatography (cyclohexane:ethyl acetate, gradient elution from 100:0 to 0:100) to afford the title compound (103 mg, 65%). 1H NMR (500 MHz, CDCl3): 8.29 (1H, s), 7.25-7.38 (7H, m), 7.15-7.23 (2H, m), 5.05 (1H, br s), 4.39 (2H, s), 3.83 (3H, s), 3.11 (3H, s), 2.25-2.65 (4H, m), 2.05-2.20 (1H, m), 1.80-1.95 (1H, m), 1.10-1.50 (9H, br).
Reaction SMILES: I[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[C:9]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:14]=[CH:13][C:12]([CH2:15][N:16]2[C:20]3[CH:21]=[C:22]([F:27])[C:23]([I:26])=[C:24]([F:25])[C:19]=3[NH:18][C:17]2=[S:28])=[CH:11][CH:10]=1>C1COCC1>[C:9]1([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH:14]=[CH:13][C:12]([CH2:15][N:16]2[C:20]3[CH:21]=[C:22]([F:27])[C:23]([I:26])=[C:24]([F:25])[C:19]=3[N:18]=[C:17]2[S:28][CH3:2])=[CH:11][CH:10]=1
Reactant: Fc1cc2c([nH]c(=S)n2Cc2ccc(-c3ccccc3)cc2)c(F)c1I
Reactant: CI
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: C1CCOC1
Product: CSc1nc2c(F)c(I)c(F)cc2n1Cc1ccc(-c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Iodomethane (2 M in methyl-tert-butyl ether, 22.87 mL, 453 mmol) was added to a solution of cesium carbonate (14.9 g, 45.7 mmol) and 1-(biphenyl-4-ylmethyl)-4,6-difluoro-5-iodo-1,3-dihydro-2H-benzimidazole-2-thione (10.94 g, 22.87 mmol) in THF (100 mL). After stirring at rt overnight, volatiles were removed. Chromatography over silica eluting with 15-60% EtOAc/hexanes afforded the desired product as a beige solid.
Reaction SMILES: [C:1]([C:3]1[CH:21]=[CH:20][C:6]([C:7]([NH:9][C:10]2[CH:11]=[C:12]([CH:17]=[CH:18][CH:19]=2)[C:13](OC)=[O:14])=[O:8])=[CH:5][CH:4]=1)#[N:2].O.[NH2:23][NH2:24]>CCO>[C:1]([C:3]1[CH:21]=[CH:20][C:6]([C:7]([NH:9][C:10]2[CH:19]=[CH:18][CH:17]=[C:12]([C:13]([NH:23][NH2:24])=[O:14])[CH:11]=2)=[O:8])=[CH:5][CH:4]=1)#[N:2]
Reactant: NN
Reactant: COC(=O)c1cccc(NC(=O)c2ccc(C#N)cc2)c1
Solvent: O
Solvent: CCO
Product: N#Cc1ccc(C(=O)Nc2cccc(C(=O)NN)c2)cc1
Temperature: 25 °C
Reaction time: 15 h
Yield: 68 %

Procedure:
To a suspension of methyl 3-[(4-cyanobenzoyl)amino]benzoate (762 mg, 2.72 mmol) in EtOH (8 mL) was added hydrazine hydrate (1.79 mL). After stirring for 15 h at reflux, the reaction mixture was cooled to rt and a white solid precipitated out. Filtration, washing with EtOH (3 mL) and water (3×3 mL) and drying under vacuo at 60° C. for 2 hrs gave 518 mg of the title compound (68%) as a white solid in 98.8% purity by HPLC (MaxPlot detection between 230 and 400 nm).
Reaction SMILES: [OH-].[Na+].CO.C[O:6][C:7](=[O:23])[CH2:8][C:9]1[C:17]2[C:12](=[CH:13][C:14]([C:18]([F:21])([F:20])[F:19])=[CH:15][CH:16]=2)[NH:11][C:10]=1[CH3:22]>O>[CH3:22][C:10]1[NH:11][C:12]2[C:17]([C:9]=1[CH2:8][C:7]([OH:23])=[O:6])=[CH:16][CH:15]=[C:14]([C:18]([F:20])([F:19])[F:21])[CH:13]=2
Reactant: COC(=O)Cc1c(C)[nH]c2cc(C(F)(F)F)ccc12
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: Cc1[nH]c2cc(C(F)(F)F)ccc2c1CC(=O)O
Yield: 6 %

Procedure:
A 2 N sodium hydroxide aqueous solution (1 ml) and methanol (1 ml) were added to the obtained 2-(2-methyl-6-trifluoromethyl-1H-indol-3-yl)acetic acid methyl ester, and the mixture was heated to reflux for one hour. Water was added to the reaction mixture, which was then rendered acidic with concentrated aqueous hydrochloric acid, extracted with ethyl acetate, dried over sodium sulfate and concentrated under reduced pressure, to obtain 79 mg of the title compound as a colorless powder (6% yield).
Reaction SMILES: [NH2:1][C:2]1[C:7]([NH:8][C:9](=O)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[S:16][CH2:17][CH3:18])=[CH:6][C:5]([C:20]([F:23])([F:22])[F:21])=[CH:4][N:3]=1.C(O)(C)(C)C.[H-].[Na+]>C1COCC1>[CH2:17]([S:16][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=1[C:9]1[NH:1][C:2]2=[N:3][CH:4]=[C:5]([C:20]([F:23])([F:22])[F:21])[CH:6]=[C:7]2[N:8]=1)[CH3:18]
Reactant: CCSc1ccccc1C(=O)Nc1cc(C(F)(F)F)cnc1N
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC(C)(C)O
Product: CCSc1ccccc1-c1nc2cc(C(F)(F)F)cnc2[nH]1
Temperature: 80 °C
Yield: 69.7 %

Procedure:
A mixture of N-(2-amino-5-trifluoromethylpyridine-3-yl)-2-ethylsulfanyl-benzamide (200 mg), tert-butylalcohol (1 ml), and THF (9 ml) was stirred with heating at 80° C., then 60% of sodium hydride (in oil, 56 mg) was added thereto. The mixture was stirred with heating at 80° C. for 2 hours, and then 60% of sodium hydride (in oil, 56 mg) was added. The mixture was further stirred with heating at the same temperature for 2 hours, and then to the mixture, 60% of sodium hydride (in oil, 56 mg) was added, and stirred with heating at the same temperature for 2 hours. The reaction mixture was cooled to room temperature, and evaporated to remove the solvent, and then to the mixture, saturated ammonium chloride solution was added, and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to give 132 mg of 2-(2-ethylsulfanylphenyl)-6-trifluoromethyl-3H-imidazo[4,5-b]pyridine (hereinafter, Present Compound 351).
Reaction SMILES: C(O[C:9]([N:11]1[CH2:15][C@H:14]([C:16]2([NH:19]C(OC(C)(C)C)=O)[CH2:18][CH2:17]2)[C@H:13]([F:27])[CH2:12]1)=O)C1C=CC=CC=1.[NH2:28][C:29]1[C:38]([F:39])=C(F)[C:36]([O:41][CH3:42])=[C:35]2[C:30]=1[C:31](=[O:50])[C:32]([C:47]([OH:49])=[O:48])=[CH:33][N:34]2[C@@H:43]1[CH2:45][C@@H:44]1[F:46].C(N(CC)CC)C>C(O)C.[C].[Pd]>[NH2:28][C:29]1[C:38]([F:39])=[C:9]([N:11]2[CH2:15][C@H:14]([C:16]3([NH2:19])[CH2:17][CH2:18]3)[C@H:13]([F:27])[CH2:12]2)[C:36]([O:41][CH3:42])=[C:35]2[C:30]=1[C:31](=[O:50])[C:32]([C:47]([OH:49])=[O:48])=[CH:33][N:34]2[C@@H:43]1[CH2:45][C@@H:44]1[F:46]
Reactant: COc1c(F)c(F)c(N)c2c(=O)c(C(=O)O)cn([C@@H]3C[C@@H]3F)c12
Reactant: CC(C)(C)OC(=O)NC1([C@H]2CN(C(=O)OCc3ccccc3)C[C@H]2F)CC1
Agent: [Pd]
Solvent: CCO
Solvent: CCN(CC)CC
Product: COc1c(N2C[C@@H](F)[C@@H](C3(N)CC3)C2)c(F)c(N)c2c(=O)c(C(=O)O)cn([C@@H]3C[C@@H]3F)c12
Reaction time: 18 h
Yield: 42.7 %

Procedure:
1-Benzyloxycarbonyl-4-(R)-(1-tert-butoxycarbonylaminocyclopropyl)-3-(S)-fluoropyrrolidine (400 mg, 1.06 mmol) was dissolved in ethanol (20 ml), and the solution was mixed with a 5% palladium-carbon catalyst (water content, 55.6%; 500 mg) and stirred for 18 hours under a hydrogen atmosphere. The catalyst was removed by celite filtration (methanol washing), and the filtrate was concentrated under reduced pressure. The thus obtained residue was dissolved in dimethyl sulfoxide (8 ml), and the solution was mixed with 5-amino-6,7-difluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid (289 mg, 0.88 mmol) and triethylamine (2 ml) and stirred for 26 hours at 100° C. in a nitrogen atmosphere. After cooling, dimethyl sulfoxide was evaporated under reduced pressure, the thus obtained residue was dissolved in chloroform (80 ml) and washed-with a 10% citric acid aqueous solution (80 ml) and then the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The thus obtained residue was subjected to flash silica gel chromatography and eluted with a mixture of chloroform:methanol=9:1, and the eluate was concentrated under reduced pressure. To the thus obtained residue, which was cooled in an ice bath, was added dropwise concentrated hydrochloric acid (5 ml), followed by 20 minutes of stirring at room temperature. After adding 1 N hydrochloric acid (30 ml) to the reaction solution, the aqueous solution was washed with chloroform (50 ml×2) and adjusted to pH 12.0 with a sodium hydroxide aqueous solution. The aqueous solution was washed with chloroform (100 ml×2), adjusted to pH 7.4 with 1 N hydrochloric acid and then extracted with chloroform (200 ml×3). The organic layers were combined, dried over anhydrous sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. Thereafter, the resulting residue was purified by recrystallization from ethanol and then dried under reduced pressure to obtain 170 mg (42.6%) of the title compound as a yellow powder.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:31])[NH:4][C@H:5]1[CH2:9][CH2:8][C@H:7]([N:10]2[C:21]3[C:13](=[CH:14][N:15]=[C:16]4[C:20]=3[CH:19]=[CH:18][N:17]4S(C3C=CC=CC=3)(=O)=O)[N:12]=[N:11]2)[CH2:6]1.[OH-].[Na+].Cl>CO.C1COCC1>[CH3:1][O:2][C:3](=[O:31])[NH:4][C@H:5]1[CH2:9][CH2:8][C@H:7]([N:10]2[C:21]3[C:13](=[CH:14][N:15]=[C:16]4[C:20]=3[CH:19]=[CH:18][NH:17]4)[N:12]=[N:11]2)[CH2:6]1
Reactant: COC(=O)N[C@H]1CC[C@H](n2nnc3cnc4c(ccn4S(=O)(=O)c4ccccc4)c32)C1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: COC(=O)N[C@H]1CC[C@H](n2nnc3cnc4[nH]ccc4c32)C1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 42.1 %

Procedure:
A solution of racemic trans [3-(6-benzenesulfonyl-6H-1,2,3,5,6-pentaaza-as-indacen-1-yl)-cyclopentyl]-carbamic acid methyl ester (171 mg, 380 μmol) in methanol (2 mL) and THF (1 mL) was treated with a 1M sodium hydroxide solution (2 mL) and stirred at ambient temperature for 1.5 hours. Dilute HCl was added and the mixture purified by Isolute® SCX-2 column (gradient: methanol to 2M NH3 in methanol solution). The residue obtained was purified further by column chromatography on silica gel (gradient: 50% ethyl acetate in cyclohexane then 0-10% methanol in ethyl acetate). The product was further purified by a diethyl ether/cyclohexane trituration to afford 48 mg (41%) of racemic trans [3-(6H-1,2,3,5,6-pentaaza-as-indacen-1-yl)-cyclopentyl]-carbamic acid methyl ester as a white solid. LCMS (Method A, ESI): RT=2.92 min, m+H=301.3; 1H NMR (400 MHz, DMSO) δ: 12.35 (s, 1H), 8.99 (s, 1H), 7.60 (d, 1H), 7.47 (d, 1H), 7.03 (d, 1H), 5.66 (m, 1H), 4.28 (m, 1H), 3.55 (s, 3H), 2.50 (m, 2H), 2.23 (m, 3H), 1.73 (m, 1H).
Reaction SMILES: C[Si](C)(C)CCOC[N:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[CH:16]=O.[N:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[CH2:26][NH:27][S:28]([C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([CH2:37][NH:38][CH:39]2[C:48]3[N:47]=[CH:46][CH:45]=[CH:44][C:43]=3[CH2:42][CH2:41][CH2:40]2)[CH:32]=1)(=[O:30])=[O:29].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1>[NH:9]1[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[N:7]=[C:8]1[CH2:16][N:38]([CH2:37][C:33]1[CH:32]=[C:31]([S:28]([NH:27][CH2:26][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][N:20]=2)(=[O:29])=[O:30])[CH:36]=[CH:35][CH:34]=1)[CH:39]1[C:48]2[N:47]=[CH:46][CH:45]=[CH:44][C:43]=2[CH2:42][CH2:41][CH2:40]1
Reactant: C[Si](C)(C)CCOCn1c(C=O)nc2ccccc21
Reactant: O=S(=O)(NCc1ccccn1)c1cccc(CNC2CCCc3cccnc32)c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: O=S(=O)(NCc1ccccn1)c1cccc(CN(Cc2nc3ccccc3[nH]2)C2CCCc3cccnc32)c1
Yield: 46.9 %

Procedure:
Using general procedure B: Reaction of 1-(2-Trimethylsilanyl-ethoxymethyl)-1H-benzimidazole-2-carbaldehyde (192 mg, 0.70 mmol), N-Pyridin-2-ylmethyl-3-[(5,6,7,8-tetrahydro-quinolin-8-ylamino)-methyl]-benzenesulfonamide (284 mg, 0.70 mmol), acetic acid (0.2 mL) and sodium triacetoxyborohydride (442 mg, 2.08 mmol) in THF (7 mL) at room temperature under N2 for 40 min., followed by purification of the crude material by chromatography on silica gel (1:1:98 CH3OH—NH3H2O—CH2Cl2,), afforded the title compound (177 mg, 38%) as a white foam.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[C:9]2[C:19]2[CH:24]=[CH:23][C:22](/[CH:25]=[CH:26]/[N:27](C)C)=[C:21]([N+]([O-])=O)[CH:20]=2)=[CH:4][CH:3]=1>CCO.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[C:9]2[C:19]2[CH:24]=[C:23]3[C:22]([CH:25]=[CH:26][NH:27]3)=[CH:21][CH:20]=2)=[CH:6][CH:7]=1
Reactant: CN(C)/C=C/c1ccc(-c2nc3ccccc3c(=O)n2-c2ccc(Cl)cc2)cc1[N+](=O)[O-]
Solvent: CCO
Solvent: CN(C)C=O
Product: O=c1c2ccccc2nc(-c2ccc3cc[nH]c3c2)n1-c1ccc(Cl)cc1
Yield: 37.2 %

Procedure:
A solution of (E)-3-(4-chlorophenyl)-2-(4-(2-(dimethylamino)vinyl)-3-nitrophenyl)quinazolin-4(3H)-one (0.340 g, 0.76 mmol) in a 3:1 mixture of EtOH/DMF (50 mL) was flushed with N2. Pd/C (0.034 g, 10 wt %) was added the reaction was flushed with H2 for 1.5 hours. After filtering through diatomaceous earth, the filtrate was concentrated. Purification by flash chromatography on silica gel, eluting with 5% to 70% EtOAc in heptane, afforded the title compound as a white solid (0.105 g, 37%). 1H-NMR (300 MHz, DMSO-d6, mixture of rotamers): δ11.34 (s, 0.5H), 11.25 (s, 0.5H), 8.16-8.29 (m, 1H), 7.86-8.00 (m, 1H), 7.71-7.82 (m, 1H), 7.49-7.67 (m, 3H), 7.29-7.48 (m, 5H), 6.87-7.05 (m, 1H), 6.37-6.42 (m, 0.5H), 6.25-6.26 (m, 0.5H). MS (APCI) m/z: 372 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:21])[C:4]([CH3:20])([NH:6][S:7]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[C:16]([F:19])([F:18])[F:17])(=[O:9])=[O:8])[CH3:5].[CH2:22](I)[CH2:23][CH3:24].O>CN(C=O)C>[CH3:1][O:2][C:3](=[O:21])[C:4]([CH3:5])([N:6]([CH2:22][CH2:23][CH3:24])[S:7]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[C:16]([F:19])([F:17])[F:18])(=[O:8])=[O:9])[CH3:20]
Reactant: COC(=O)C(C)(C)NS(=O)(=O)c1ccccc1C(F)(F)F
Reactant: CCCI
Solvent: O
Solvent: CN(C)C=O
Product: CCCN(C(C)(C)C(=O)OC)S(=O)(=O)c1ccccc1C(F)(F)F
Temperature: 25 °C
Reaction time: 12 h
Yield: 97.9 %

Procedure:
Methyl-2-methyl-2-(2-(trifluoromethyl)phenylsulfonamido)propanoate (310 mg, 0.95 mmol) was dissolved in DMF (8 ml), and added with propyl iodide (0.32 ml, 3.34 mmol) at 0° C., followed by stirring at room temperature for 12 hours. The resultant solution was added with H2O and extracted with EA (×2). The organic solution was washed with H2O, dried with MgSO4, and filtered. Through vacuum distillation, the solvent was removed. The resultant mixture was purified with column chromatography so as to obtain methyl-2-methyl-2-(N-propyl-2-(trifluoromethyl)phenylsulfonamido)propanoate (340 mg, 0.93 mmol, 97%).
Reaction SMILES: [CH2:1]([O:3][C:4]([CH2:6][CH2:7][CH2:8][CH:9]1[CH2:14][CH2:13][N:12](C(OC(C)(C)C)=O)[CH2:11][CH2:10]1)=[O:5])[CH3:2]>FC(F)(F)C(O)=O>[NH:12]1[CH2:13][CH2:14][CH:9]([CH2:8][CH2:7][CH2:6][C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:10][CH2:11]1
Reactant: CCOC(=O)CCCC1CCN(C(=O)OC(C)(C)C)CC1
Solvent: O=C(O)C(F)(F)F
Product: CCOC(=O)CCCC1CCNCC1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 144.3 %

Procedure:
tert-Butyl 4-(3-ethoxycarbonylpropyl)piperidine-1-carboxylate (1.2 g, 4.0 mmol, Production example 43-1) was dissolved in trifluoroacetic acid (30 ml), and the reaction mixture was stirred at room temperature for 20 minutes. This was concentrated under reduced pressure, and was further azeotropically distilled with toluene. The obtained residue was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The organic layer was dried over anhydrous magnesium sulfate. In addition, the aqueous layer was concentrated under reduced pressure to dryness; the obtained solid was suspended in tetrahydrofuran; insoluble portion were filtered off, and this solution was added to the previously obtained organic layer. This was purified by silica gel column chromatography (Fuji Silysia NH, hexane-ethyl acetate-methanol system) to yield the title compound (1.15 g, quantitative) as a yellow oil.
Reaction SMILES: [C:1]([C:4]1[NH:5][CH:6]=[CH:7][CH:8]=1)(=[O:3])[CH3:2].[CH:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=[CH:11][C:10]=1[C:19](Cl)=[O:20].[Cl-].[Al+3].[Cl-].[Cl-]>ClCCCl>[CH:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=[CH:11][C:10]=1[C:19]([C:7]1[CH:8]=[C:4]([C:1](=[O:3])[CH3:2])[NH:5][CH:6]=1)=[O:20]
Reactant: CC(=O)c1ccc[nH]1
Reactant: O=C(Cl)c1ccc2ccccc2c1
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCCl
Product: CC(=O)c1cc(C(=O)c2ccc3ccccc3c2)c[nH]1
Temperature: 65 °C
Reaction time: 4 h
Yield: 50.9 %

Procedure:
A mixture of 7.5 g (0.069 mole) of 2-acetylpyrrole, 17 g (0.089 mole) of 2-naphthalenoyl chloride and 18.3 (0.14 mole) of aluminum chloride in 200 mL of 1,2-dichloroethane was stirred for 4 h and then heated at 65° C. for 1.5 h. After cooling, the reaction mixture was poured into 2N HCl/ice. The organics were separated, washed with water, NaHCO3, water, brine and dried (MgSO4). The solvent was evaporated in vacuo and the residue recrystallized from EtOAc to give 9.25 g (51%) of 1-[4-(2-naphthalenoyl)-1H-pyrrol-2-yl]ethanone. mp 172-174° C. CIMS m/z 264 (MH+). 1H NMR (300 MHz, CDCl3) δ 8.4 (Ar, 1H); 8.0-7.9 (Ar, 4H); 7.7-7.55 (Ar, 3H); 7.5 (Ar, 1H); 2.55 (s, 3H).