Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([Si:7]2(CCC)[CH2:12][CH2:11][CH:10]([CH:13]3[CH2:18][CH2:17][CH:16]([C:19]([OH:21])=[O:20])[CH2:15][CH2:14]3)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:25]1(P(C2C=CC=CC=2)C2C=CC=CC=2)[CH:30]=CC=C[CH:26]=1.[F:44][C:45]1[CH:50]=[CH:49][C:48](O)=[CH:47][CH:46]=1.Cl>CN(C)C1C=CN=CC=1.N1C=CC=CC=1.C(Cl)(Cl)(Cl)Cl>[C:1]1([SiH:7]2[CH2:8][CH2:9][C:10]([CH2:26][CH2:25][CH3:30])([CH:13]3[CH2:14][CH2:15][CH:16]([C:19]([O:21][C:48]4[CH:49]=[CH:50][C:45]([F:44])=[CH:46][CH:47]=4)=[O:20])[CH2:17][CH2:18]3)[CH2:11][CH2:12]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: Oc1ccc(F)cc1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: CCC[Si]1(c2ccccc2)CCC(C2CCC(C(=O)O)CC2)CC1
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: c1ccncc1
Solvent: ClC(Cl)(Cl)Cl
Product: CCCC1(C2CCC(C(=O)Oc3ccc(F)cc3)CC2)CC[SiH](c2ccccc2)CC1
Yield: 70.2 %

Procedure:
A mixture of 3.58 g of 4-(4-phenyl-4-n-propyl-4-silacyclohexyl)cyclohexanecarboxylic acid, 3.0 g of triphenylphosphine and 50 ml of carbon tetrachloride was agitated under reflux for 6 hours. Then, a mixture of 1.50 g of 4-fluorophenol and 10 ml of pyridine was added to the mixture, followed by further addition of 50 mg of 4-dimethylaminopyridine and agitation at room temperature for 18 hours. The resultant reaction mixture was poured into dilute hydrochloric acid, followed by extraction with ethyl acetate. The ethyl acetate solution was washed with brine, dried and concentrated, followed by purification of the resultant residue with silica gel chromatography to obtain 3.20 g (yield: 70%) of 4-fluorophenyl 4-(4-phenyl-n-propyl-4-silacyclohexyl)cyclohexanecarboxylate. The results of
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=1)[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])=[CH:9][CH:8]=1.[CH2:22]([O:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1B(O)O)[CH3:23].C(=O)([O-])[O-].[K+].[K+].C(O)C>C(OCC)(=O)C.C1(C)C=CC=CC=1>[CH2:22]([O:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:2]1[CH:21]=[CH:20][CH:19]=[C:4]([CH2:5][O:6][C:7]2[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])=[CH:9][CH:8]=2)[CH:3]=1)[CH3:23]
Reactant: COC(=O)CCc1ccc(OCc2cccc(Br)c2)cc1
Reactant: CCOc1ccccc1B(O)O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: CCOc1ccccc1-c1cccc(COc2ccc(CCC(=O)OC)cc2)c1
Yield: 62.5 %

Procedure:
A mixture of methyl 3-[4-[(3-bromobenzyl)oxy]phenyl]propanoate (0.30 g, 0.86 mmol), 2-ethoxyphenylboronic acid (0.16 g, 0.95 mmol), tetrakistriphenylphosphine palladium (40 mg, 0.034 mmol), 2N potassium carbonate aqueous solution (0.3 mL), ethanol (0.3 mL) and toluene (3 mL) was heated under reflux overnight under an argon atmosphere. The reaction mixture was cooled, diluted with ethyl acetate, washed with water, dried, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-2/1) to give methyl 3-(4-((2′-ethoxybiphenyl-3-yl)methoxy)phenyl)propanoate (0.21 g, 63%) as a colorless oil.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][NH:5][C:6]=1[C:7]([CH3:15])([CH3:14])[O:8][SiH2:9][C:10]([CH3:13])([CH3:12])[CH3:11].[O:16]1[CH:21]=[CH:20][CH2:19][CH2:18][CH2:17]1.[H-].[Na+]>C(O)(C(F)(F)F)=O>[Br:1][C:2]1[C:6]([C:7]([CH3:15])([CH3:14])[O:8][SiH2:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[N:5][N:4]([CH:17]2[CH2:18][CH2:19][CH2:20][CH2:21][O:16]2)[CH:3]=1.[Br:1][C:2]1[CH:3]=[N:4][N:5]([CH:17]2[CH2:18][CH2:19][CH2:20][CH2:21][O:16]2)[C:6]=1[C:7]([CH3:15])([CH3:14])[O:8][SiH2:9][C:10]([CH3:13])([CH3:12])[CH3:11]
Reactant: C1=COCCC1
Reactant: CC(C)(C)[SiH2]OC(C)(C)c1[nH]ncc1Br
Agent: [H-]
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Product: CC(C)(C)[SiH2]OC(C)(C)c1c(Br)cnn1C1CCCCO1
Product: CC(C)(C)[SiH2]OC(C)(C)c1nn(C2CCCCO2)cc1Br
Temperature: 90 °C
Reaction time: 18 h
Yield: 111.8 %

Procedure:
4-Bromo-5-(tert-butyl-dimethyl-silanyloxymethyl)-1H-pyrazole (1 g, 3.45 mmol) is dissolved in 3,4-dihydro-2H-pyran (0.944 mL, 10.34 mmol) in the presence of a catalytic amount of TFA (0.0026 mL, 0.035 mmol). The reaction mixture is stirred at 90° C. for 18 hours, cooled and then quenched using NaH (4.69 mg, 0.206 mmol). After removing the solvent, the residue is purified by silica gel column chromatography eluting with a mixture of 95:5 petroleum ether-ethyl acetate, followed by 90:10 petroleum ether-ethyl acetate. The fractions containing the desired compounds are collected and concentrated in vacuo to afford 4-bromo-3-(tert-butyl-dimethyl-silanyloxymethyl)-1-(tetrahydro-pyran-2-yl)-1H-pyrazole and 4-bromo-5-(tert-butyl-dimethyl-silanyloxymethyl)-1-(tetrahydro-pyran-2-yl)-1H-pyrazole (724 mg, 56%).
Reaction SMILES: [CH2:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:14]3[CH2:15][CH2:16][C:17]4[C:22]([C:13]=3[O:12][N:11]=2)=[CH:21][CH:20]=[C:19]([CH:23]=C)[CH:18]=4)=[CH:6][CH:5]=1)[CH2:2][CH3:3].C[N+]1([O-])CC[O:29]CC1.I([O-])(=O)(=O)=O.[Na+]>C1COCC1.O.[Os](=O)(=O)(=O)=O>[CH2:1]([C:4]1[CH:5]=[CH:6][C:7]([C:10]2[C:14]3[CH2:15][CH2:16][C:17]4[C:22]([C:13]=3[O:12][N:11]=2)=[CH:21][CH:20]=[C:19]([CH:23]=[O:29])[CH:18]=4)=[CH:8][CH:9]=1)[CH2:2][CH3:3]
Reactant: C[N+]1([O-])CCOCC1
Reactant: C=Cc1ccc2c(c1)CCc1c(-c3ccc(CCC)cc3)noc1-2
Agent: O=[Os](=O)(=O)=O
Agent: [Na+]
Agent: [O-][I+3]([O-])([O-])[O-]
Solvent: O
Solvent: C1CCOC1
Product: CCCc1ccc(-c2noc3c2CCc2cc(C=O)ccc2-3)cc1
Temperature: 25 °C
Reaction time: 85 h
Yield: 92.2 %

Procedure:
To 3-(4-propylphenyl)-7-vinyl-4,5-dihydronaphtho[2,1-d]isoxazole (Preparation 20D, 0.205 g, 0.650 mmol) in THF (2 mL) were added sequentially N-methylmorpholine-N-oxide (0.3 mL, 0.650 mmol) and osmium tetroxide (0.102 mL, 0.013 mmol) at room temperature. The contents were stirred at room temperature for 85 h. Next, sodium periodate (0.209 g, 0.975 mmol) dissolved in 1.5 mL of water was added at room temperature and the reaction mixture was stirred at room temperature for 1 h. The reaction mixture was partitioned between ethyl acetate (20 mL) and brine (20 mL). The ethyl acetate layer was dried over sodium sulfate and concentrated to yield 3-(4-propylphenyl)-4,5-dihydronaphtho[2,1-d]isoxazole-7-carbaldehyde (0.19 g, 0.599 mmol, 92% yield) as a tan solid. LCMS M+1=318.2.
Reaction SMILES: [CH2:1]([C:3]1[C:4]([CH3:23])=[C:5]([C:9]([NH:12][S:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2F)(=[O:15])=[O:14])=[CH:10][CH:11]=1)[C:6]([OH:8])=[O:7])[CH3:2].C(N(CC)CC)C.[CH2:31]([N:33]([CH2:38][CH3:39])[CH2:34][CH2:35][CH2:36][NH2:37])[CH3:32]>C(#N)C>[CH2:31]([N:33]([CH2:38][CH3:39])[CH2:34][CH2:35][CH2:36][NH:37][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[S:13]([NH:12][C:9]1[C:5]([C:6]([OH:8])=[O:7])=[C:4]([CH3:23])[C:3]([CH2:1][CH3:2])=[CH:11][CH:10]=1)(=[O:15])=[O:14])[CH3:32]
Reactant: CCN(CC)CCCN
Reactant: CCc1ccc(NS(=O)(=O)c2ccccc2F)c(C(=O)O)c1C
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CCc1ccc(NS(=O)(=O)c2ccccc2NCCCN(CC)CC)c(C(=O)O)c1C
Yield: 10.8 %

Procedure:
A solution of Example 230C (40 mg, 0.12 mmol), triethylamine (0.1 mL), and N,N-diethyl-1,3-propanediamine (0.1 mL) in acetonitrile (1.0 mL) was heated to 200° C. for 1 hour on a Personal Chemistry microwave instrument. The mixture was then purified by reverse phase HPLC to provide the desired product (5.8 mg, 10.8%). 1H NMR (DMSO-d6) δ 1.07 (t, 3H), 1.12 (t, 6H), 2.19 (s, 3H), 2.53 (q, 2H), 3.05-3.12 (m, 8H), 6.02 (br s, 1H), 6.62-6.66 (m, 2H), 6.84 (d, 1H), 7.03 (d, 1H), 7.40 (t, 1H), 7.52 (d, 1H), 8.98 (br s, 1H), 9.50 (br s, 1H); MS (ESI(+)) m/e 448 (M+H)+.
Reaction SMILES: [F:1][CH2:2][CH2:3]I.C(=O)([O-])[O-].[K+].[K+].[C:11]([O:15][C:16]([NH:18][C@@H:19]([CH2:27][CH2:28][CH:29]([CH2:37][C:38]1[CH:43]=[CH:42][C:41]([OH:44])=[CH:40][N:39]=1)[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[O:17])([CH3:14])([CH3:13])[CH3:12]>CN(C)C=O>[C:11]([O:15][C:16]([NH:18][C@@H:19]([CH2:27][CH2:28][CH:29]([CH2:37][C:38]1[CH:43]=[CH:42][C:41]([O:44][CH2:3][CH2:2][F:1])=[CH:40][N:39]=1)[C:30]([O:32][C:33]([CH3:34])([CH3:35])[CH3:36])=[O:31])[C:20]([O:22][C:23]([CH3:26])([CH3:24])[CH3:25])=[O:21])=[O:17])([CH3:12])([CH3:13])[CH3:14]
Reactant: CC(C)(C)OC(=O)N[C@@H](CCC(Cc1ccc(O)cn1)C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Reactant: FCCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N[C@@H](CCC(Cc1ccc(OCCF)cn1)C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 20 h

Procedure:
To a solution of 54 mg 1-fluoro-2-iodoethane (0.31 mmol) in N,N-dimethylformamide (10 mL) was subsequently added 101 mg potassium carbonate (0.73 mmol), followed by 100 mg of di-tert-butyl (2S)-2-[(tert-butoxycarbonyl)amino]-5-[(5-hydroxypyridin-2-yl)methyl]hexanedioate (0.21 mmol), and the resulting mixture was stirred for 20 h at room temperature. The mixture was then partitioned between water and ethyl acetate, the aqueous layer was then extracted with ethyl acetate again. The combined organic layers were washed with brine, dried over sodium sulfate, and evaporated. The residue was purified by preparative HPLC, method A to give 56 mg (approx. 90% purity, 46% purity adjusted yield) of the target compound.
Reaction SMILES: [Br:1][C:2]1[C:3]([C@H:10]([NH:20][C:21](=[O:36])[CH2:22][N:23]2[C:31]3[CH2:30][CH2:29][CH2:28][CH2:27][C:26]=3[C:25]([C:32]([F:35])([F:34])[F:33])=[N:24]2)[CH2:11][C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[C:14]([F:19])[CH:13]=2)=[N:4][C:5]([S:8][CH3:9])=[N:6][CH:7]=1.ClC1C=C(C=CC=1)C(OO)=[O:42].[OH2:48]>ClCCl>[Br:1][C:2]1[C:3]([C@H:10]([NH:20][C:21](=[O:36])[CH2:22][N:23]2[C:31]3[CH2:30][CH2:29][CH2:28][CH2:27][C:26]=3[C:25]([C:32]([F:35])([F:34])[F:33])=[N:24]2)[CH2:11][C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[C:14]([F:19])[CH:13]=2)=[N:4][C:5]([S:8]([CH3:9])(=[O:42])=[O:48])=[N:6][CH:7]=1
Reactant: CSc1ncc(Br)c([C@@H](Cc2cc(F)cc(F)c2)NC(=O)Cn2nc(C(F)(F)F)c3c2CCCC3)n1
Reactant: O
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: CS(=O)(=O)c1ncc(Br)c([C@@H](Cc2cc(F)cc(F)c2)NC(=O)Cn2nc(C(F)(F)F)c3c2CCCC3)n1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
Compound 11G (198 mg, 0.33 mmol) was charged in dichloromethane (2 ml) at 0° C. mCPBA (meta-chloroperoxybenzoic acid) (185 mg, 0.8 mmol, content 77 percent; 2.5 eq.) was added a little at a time. The mixture was slowly warmed to room temperature and stirred for 4 h and then water was added. The reaction mixture was partitioned between dichloromethane and saturated NaHCO3 aqueous solution. The organic layer was separated and concentrated to afford the title product. MS (m/z) 622.98 [M+H]+.
Reaction SMILES: ClC1C=CC(C2N(C3C=CC(Cl)=CC=3Cl)N=C([C:21](=[O:29])/[CH:22]=[C:23](\[OH:28])/[C:24]([CH3:27])([CH3:26])[CH3:25])C=2C)=CC=1.Cl.[NH2:32]O>CCO>[C:24]([C:23]1[O:28][N:32]=[CH:21][CH:22]=1)([CH3:27])([CH3:26])[CH3:25].[C:24]([C:23]1[CH:22]=[CH:21][O:29][N:32]=1)([CH3:27])([CH3:26])[CH3:25]
Reactant: NO
Reactant: Cc1c(C(=O)/C=C(\O)C(C)(C)C)nn(-c2ccc(Cl)cc2Cl)c1-c1ccc(Cl)cc1
Agent: Cl
Solvent: CCO
Product: CC(C)(C)c1ccno1
Product: CC(C)(C)c1ccon1
Yield: 34 %
Yield: 14 %

Procedure:
A solution of diketone (87) (200 mg, 0.43 mmol) and hydroxylamine hydrochloride (60 mg, 0.86 mmol) in EtOH (5 mL) was irradiated in a microwave reactor (Biotage) for 20 min. at 140° C. Purification by Prep-LC (Gilson) provided 67 mg (34%) of 5-t-butylisoxazole and 28 mg (14%) of 3-t-butylisoxazole as solid.
Reaction SMILES: [Cl:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12](/[CH:16]=[C:17]4/[C:18](=[O:30])[N:19]([CH2:23][C@H:24]5[O:29][CH2:28][CH2:27][NH:26][CH2:25]5)[C:20](=[O:22])[S:21]/4)=[CH:13][CH:14]=3)[CH:9]=[N:8]2)=[C:4]([C:33]([F:36])([F:35])[F:34])[CH:3]=1.[CH2:37]=O>>[Cl:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12](/[CH:16]=[C:17]4/[C:18](=[O:30])[N:19]([CH2:23][C@H:24]5[O:29][CH2:28][CH2:27][N:26]([CH3:37])[CH2:25]5)[C:20](=[O:22])[S:21]/4)=[CH:13][CH:14]=3)[CH:9]=[N:8]2)=[C:4]([C:33]([F:36])([F:35])[F:34])[CH:3]=1
Reactant: O=C1S/C(=C\c2ccc3c(cnn3Cc3ccc(Cl)cc3C(F)(F)F)c2)C(=O)N1C[C@@H]1CNCCO1
Reactant: C=O
Product: CN1CCO[C@H](CN2C(=O)S/C(=C\c3ccc4c(cnn4Cc4ccc(Cl)cc4C(F)(F)F)c3)C2=O)C1

Procedure:
(5Z)-5-({1-[4-Chloro-2-(trifluoromethyl)benzyl]-1H-indazol-5-yl}methylidene)-3-{[(2S)-4-methylmorpholin-2-yl]methyl}-1,3-thiazolidine-2,4-dione was prepared from (5Z)-5-({1-[4-chloro-2-(trifluoromethyl)-benzyl]-1H-indazol-5-yl}methylidene)-3-[(2S)-morpholin-2-ylmethyl]-1,3-thiazolidine-2,4-dione (Example 183) and formaldehyde following General Procedure R.
Reaction SMILES: C([NH:5][S:6]([C:9]1[S:10][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]3[N:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[C:22]([C:30]4[CH:31]=[N:32][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:34][CH:35]=4)[N:21]=3)[CH:15]=2)=[CH:12][CH:13]=1)(=[O:8])=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O>ClCCl>[F:29][C:26]([F:27])([F:28])[C:24]1[CH:23]=[C:22]([C:30]2[CH:31]=[N:32][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:34][CH:35]=2)[N:21]=[C:20]([C:16]2[CH:15]=[C:14]([C:11]3[S:10][C:9]([S:6]([NH2:5])(=[O:8])=[O:7])=[CH:13][CH:12]=3)[CH:19]=[CH:18][CH:17]=2)[N:25]=1
Reactant: CC(C)(C)NS(=O)(=O)c1ccc(-c2cccc(-c3nc(-c4ccc(C(F)(F)F)nc4)cc(C(F)(F)F)n3)c2)s1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: NS(=O)(=O)c1ccc(-c2cccc(-c3nc(-c4ccc(C(F)(F)F)nc4)cc(C(F)(F)F)n3)c2)s1
Temperature: 25 °C
Reaction time: 15 h
Yield: 49.1 %

Procedure:
To a cooled and stirred solution of N-tert-butyl-5-{3-[4-trifluoromethyl-6-(6-trifluoromethyl-pyridin-3-yl)-pyrimidin-2-yl]-phenyl}-thiophene-2-sulfonic acid amide (0.45 g) in dichloromethane (6 ml) was added TFA (6 ml) and the reaction mixture was allowed to stir at room temperature for 15 h. The mixture was evaporated to dryness, poured into 2N Na2CO3 solution (25 ml) and extracted with ethyl acetate (3×50 ml). The combined organic layers were washed with brine (50 ml), dried (MgSO4) and evaporated. Further purification by flash chromatography on silica gel (ethyl acetate/heptane) and crystallization (ethyl acetate/heptane) yielded the title compound as a light yellow solid (0.2 g, 38%). MS (ISP) 531.0 [(M+H)+]; mp 250.5° C.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]([NH:13][CH2:14][CH2:15][CH2:16][N:17]2[CH:21]=[CH:20][N:19]=[CH:18]2)(=[O:12])=[O:11])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[CH3:22][O:23][C:24]1[CH:31]=[C:30]([O:32][CH3:33])[C:29]([N:34]2[CH2:38][CH2:37][CH2:36][CH2:35]2)=[CH:28][C:25]=1[CH:26]=O.C[O-].[Li+]>CN(C=O)C.CO>[CH3:22][O:23][C:24]1[CH:31]=[C:30]([O:32][CH3:33])[C:29]([N:34]2[CH2:38][CH2:37][CH2:36][CH2:35]2)=[CH:28][C:25]=1/[CH:26]=[CH:2]/[C:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]([NH:13][CH2:14][CH2:15][CH2:16][N:17]2[CH:21]=[CH:20][N:19]=[CH:18]2)(=[O:12])=[O:11])=[CH:6][CH:5]=1)=[O:3]
Reactant: CC(=O)c1ccc(S(=O)(=O)NCCCn2ccnc2)cc1
Reactant: COc1cc(OC)c(N2CCCC2)cc1C=O
Agent: C[O-]
Agent: [Li+]
Solvent: CO
Solvent: CN(C)C=O
Product: COc1cc(OC)c(N2CCCC2)cc1/C=C/C(=O)c1ccc(S(=O)(=O)NCCCn2ccnc2)cc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 41.3 %

Procedure:
A solution 4-acetyl-N-(3-imidazol-1-ylpropyl)benzenesulfonamide (Ex-23A, 653 mg, 2.13 mmol) and 2,4-dimethoxy-5-pyrrolidin-1-yl-benzaldehyde (Ex-38B, 500 mg, 2.13 mmol) in DMF (9.3 mL) and MeOH (4.0 mL) was treated with lithium methoxide (162 mg, 4.26 mmol) and stirred for 20 h at room temperature under nitrogen atmosphere. The reaction mixture was quenched with water (75 mL) and extracted ethyl acetate (3×50 mL). The organic phase was brined, dried over sodium sulfate, and concentrated to a red solid. Crystallization from hot ethanol (10 mL) and water (12 mL) gave 461 mg (41%) of the title compound as a red solid, mp 140–143° C. 1H-NMR (300 MHz, DMSO-d6) 8.23 (d, 2H, J=8.7 Hz), 8.05 (d, 1H, J=15.3 Hz), 7.88 (d, 2H, J=9.3 Hz), 7.64 (d, 1H, J=15.3 Hz), 7.51 (s, 1H), 7.17 (s, 1H), 7.05 (s, 1H), 6.81 (s, 1H), 6.67 (s, 1H), 3.92 (t, 2H, J=6.9 Hz), 3.86 (s, 6H), 3.15 (m, 4H), 2.68 (t, 2H, J=6.3 Hz), 1.80 (m, 6H). HRMS (ESI) Calcd. for C27H32N4O5S: 525.2172 (M+H)+; Found; 525.2179.
Reaction SMILES: [CH:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]3[CH:20]=[CH:19][C:15]4[NH:16][CH:17]=[N:18][C:14]=4[CH:13]=3)[CH:10]=2)[NH:5][CH:4]=1)=O.C([O-])(=O)C.[NH4+].[N+:26]([CH3:29])([O-:28])=[O:27].CN(C)C=O>CS(C)=O>[N+:26]([CH:29]=[CH:1][C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]3[CH:20]=[CH:19][C:15]4[NH:16][CH:17]=[N:18][C:14]=4[CH:13]=3)[CH:10]=2)[NH:5][CH:4]=1)([O-:28])=[O:27]
Reactant: O=Cc1c[nH]c2ccc(-c3ccc4[nH]cnc4c3)cc12
Reactant: C[N+](=O)[O-]
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: CN(C)C=O
Solvent: CS(C)=O
Product: O=[N+]([O-])C=Cc1c[nH]c2ccc(-c3ccc4[nH]cnc4c3)cc12
Temperature: 25 °C
Yield: 86 %

Procedure:
A mixture of 5-(3-formylindol-5-yl)-1H-benzimidazole (0.40 g, 1.53 mmol) and ammonium acetate (50 mg) in a solution of nitromethane (10 mL), N,N-dimethylformamide (5 mL), and dimethyl sulfoxide (1 mL) was heated at reflux under nitrogen for 4 hours. The resulting reaction mixture was cooled to room temperature and filtered to afford the title compound (0.40 g, 86%) as a yellow solid: mp >280° C.; 13C NMR (DMSO-d6) δ 146.9, 145.3, 144.3, 137.4, 136.6, 135.5, 134.2, 132.1, 129.8, 127.8, 125.0, 119.9, 118.7, 115.9, 113.4, 108.7. Anal. calcd for C16H11N5O2.0.125 H2O: C, 62.49; H, 3.69; N, 22.77. Found: C, 62.34; H, 3.51; N, 22.45.
Reaction SMILES: [N+:1](/[CH:4]=[CH:5]/[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)([O-:3])=[O:2].[CH:12](=[O:16])[CH:13]([CH3:15])[CH3:14].CC(O)C.CCCCCC>C(Cl)(Cl)Cl>[CH3:14][C:13]([CH3:15])([C@H:5]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH2:4][N+:1]([O-:3])=[O:2])[CH:12]=[O:16]
Reactant: O=[N+]([O-])/C=C/c1ccccc1
Reactant: CC(C)C=O
Solvent: CC(C)O
Solvent: ClC(Cl)Cl
Solvent: CCCCCC
Product: CC(C)(C=O)[C@@H](C[N+](=O)[O-])c1ccccc1

Procedure:
The title compound was prepared from (E)-(2-nitrovinyl)benzene and isobutyraldehyde according to the general procedure. The enantiomeric ratio were determined by HPLC with Chiralpak OD-H column at 210 nm (2-propanol:hexane=15:85), 1 mL/min, tmajor=19.7 min, tminor=13.9 min, [α]D20=−4.3 (c=1.6, CHCl3).
Reaction SMILES: [C:1]([O:5][C:6]([O:8][C:9]1[CH:18]=[CH:17][C:16]2[C:11](=[C:12]([O:57][C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59])[CH:13]=[CH:14][C:15]=2[C@@H:19]([O:49][Si:50]([C:53]([CH3:56])([CH3:55])[CH3:54])([CH3:52])[CH3:51])[CH2:20][N:21]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][O:35][CH2:36][CH2:37][CH2:38][CH2:39][C:40]2[CH:45]=[CH:44][C:43]([N+:46]([O-])=O)=[CH:42][CH:41]=2)[C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(OCC)(=O)C.[H][H]>CO.[Pd]>[NH2:46][C:43]1[CH:44]=[CH:45][C:40]([CH2:39][CH2:38][CH2:37][CH2:36][O:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][N:21]([CH2:20][C@@H:19]([C:15]2[CH:14]=[CH:13][C:12]([O:57][C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59])=[C:11]3[C:16]=2[CH:17]=[CH:18][C:9]([O:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[N:10]3)[O:49][Si:50]([C:53]([CH3:56])([CH3:55])[CH3:54])([CH3:51])[CH3:52])[C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:41][CH:42]=1
Reactant: [H][H]
Reactant: CC(C)(C)OC(=O)Oc1ccc2c([C@H](CN(CCCCCCOCCCCc3ccc([N+](=O)[O-])cc3)C(=O)OC(C)(C)C)O[Si](C)(C)C(C)(C)C)ccc(OC(=O)OC(C)(C)C)c2n1
Agent: [Pd]
Solvent: CO
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)Oc1ccc2c([C@H](CN(CCCCCCOCCCCc3ccc(N)cc3)C(=O)OC(C)(C)C)O[Si](C)(C)C(C)(C)C)ccc(OC(=O)OC(C)(C)C)c2n1

Procedure:
Intermediate 41 (175 mg, 0.19 mmol) was dissolved in methanol (4 mL) and ethyl acetate (1 mL) and treated with palladium on carbon (10% w/w, wet Degussa-type, catalytic amount). The suspension was stirred under a balloon of hydrogen gas for 45 minutes. The mixture was then filtered through a pad of Celite diatomaceous earth, and the filtrate was concentrated to dryness under reduced pressure to provide the title material. ES/MS calcd. for C48H76N3O10Si+882.5. found m/z=882.5 (M+H)+.
Reaction SMILES: [C:1]([O:5][C:6](=[O:31])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18](=O)[C:19]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:20]N(C)C)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[N:32]1[N:33]=[C:34]([NH2:38])[NH:35][C:36]=1[NH2:37]>C(O)(=O)C.C(O)C.C(Cl)Cl>[C:1]([O:5][C:6](=[O:31])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19]([C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=4)=[CH:20][N:32]4[N:33]=[C:34]([NH2:38])[N:35]=[C:36]4[N:37]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:3])([CH3:2])[CH3:4]
Reactant: CN(C)C=C(C(=O)c1ccc(C2(NC(=O)OC(C)(C)C)CCC2)cc1)c1ccccc1
Reactant: Nc1nnc(N)[nH]1
Solvent: ClCCl
Solvent: CCO
Solvent: CC(=O)O
Product: CC(C)(C)OC(=O)NC1(c2ccc(-c3nc4nc(N)nn4cc3-c3ccccc3)cc2)CCC1

Procedure:
A mixture of 1 (250 mg, 0.59 mmol) and 4H-[1,2,4]Triazole-3,5-diamine (58.91 mg, 0.59 mmol) in acetic acid (0.4 mL) and ethanol (1.6 mL) was heated under reflux for 6 hours. After cooling, the mixture was diluted with 15 mL of DCM, the combined organic phase was washed with NaHCO3 aq. and brine, dried over anhydrous Na2SO4 and concentrated. The residue was purified by prep.TLC to give 6-1. MS (ESI) m/e (M+H+) 457.3
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[C:7]([C:12]([F:15])([F:14])[F:13])[CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:16]([F:19])([F:18])[F:17])[CH:3]=1.[NH:20]1[CH:24]=[N:23][CH:22]=[N:21]1.C(=O)([O-])[O-].[K+].[K+].CC(C)=O>O>[N:20]1([C:2]2[C:11]3[C:6](=[C:7]([C:12]([F:15])([F:14])[F:13])[CH:8]=[CH:9][CH:10]=3)[N:5]=[C:4]([C:16]([F:19])([F:18])[F:17])[CH:3]=2)[CH:24]=[N:23][CH:22]=[N:21]1
Reactant: FC(F)(F)c1cc(Cl)c2cccc(C(F)(F)F)c2n1
Reactant: c1nc[nH]n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: O
Product: FC(F)(F)c1cc(-n2cncn2)c2cccc(C(F)(F)F)c2n1
Reaction time: 23 h
Yield: 72.7 %

Procedure:
A mixture of 3.0 g of 4-chloro-2,8-bis-trifluoromethyl-quinoline, 1.38 g of 1,2,4-triazole, 1.38 g of potassium carbonate and 30 ml of acetone is heated to boiling for 23 hours whereupon the reaction mixture is poured into 100 ml of water. The precipitated product is filtered, dissolved in 5 ml of ethanol, whereupon 5 ml of water are added. The precipitated product is filtered. Thus 2.42 g of the desired compound are obtained, yield: 73%, mp.: 106°-107° C.
Reaction SMILES: F[C:2](F)(F)[C:3](O)=[O:4].[CH3:8][O:9][C:10](=[O:21])[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([NH:19][NH2:20])=[S:18])[CH:12]=1.Cl.C(OC(=N)CCl)C>CCO.CCOC(C)=O>[CH3:8][O:9][C:10](=[O:21])[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]2[S:18][C:2]([CH2:3][OH:4])=[N:20][N:19]=2)[CH:12]=1
Reactant: O=C(O)C(F)(F)F
Reactant: COC(=O)c1cccc(C(=S)NN)c1
Agent: CCOC(=N)CCl
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CCO
Product: COC(=O)c1cccc(-c2nnc(CO)s2)c1
Temperature: 80 °C
Yield: 39.7 %

Procedure:
A mixture of 3-hydrazinothiocarbonyl-benzoic acid methyl ester trifluoroacetate (0.49 g) and 2-chloro-acetimidic acid ethyl ester hydrochloride (0.47 g) in EtOH (6 mL) was heated to 80° C. for 2.5 h. The mixture was diluted with AcOEt and washed with 1N HCl and with brine. The organic layer was dried and evaporated. The residual oil (0.8 g) was dissolved in MeOH (5 mL), MeONa (0.08 g) was added and the solution was heated to 65° C. for 0.5 h. The mixture was diluted with AcOEt and washed with 1N HCl and with brine. The organic layer was dried and evaporated and the residue was crystallized from AcOEt/hexane to give 3-(5-hydroxymethyl-[1,3,4]thiadiazol-2-yl) -benzoic acid methyl ester (0.15 g) as a white solid, MS (ISP) 251.2 [(M+H)+].