Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:8]1[CH:31]=[CH:30][CH:29]=[CH:28][C:9]=1[C:10]([NH:12][CH2:13][C:14]1[CH:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[C:16]([C:24]([F:27])([F:26])[F:25])[CH:15]=1)=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:32][Si](C)(C)[N-][Si](C)(C)C.[K+].CI.C(OCC)(=O)C>CN(C)C=O>[CH2:1]([C:8]1[CH:31]=[CH:30][CH:29]=[CH:28][C:9]=1[C:10]([N:12]([CH2:13][C:14]1[CH:15]=[C:16]([C:24]([F:25])([F:26])[F:27])[CH:17]=[C:18]([C:20]([F:22])([F:23])[F:21])[CH:19]=1)[CH3:32])=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Reactant: O=C(NCc1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1ccccc1Cc1ccccc1
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CI
Solvent: CN(C)C=O
Product: CN(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)C(=O)c1ccccc1Cc1ccccc1
Yield: 86.7 %

Procedure:
To a solution of 100 mg (0.23 mmol) 2-benzyl-N-(3,5-bis-trifluoromethyl-benzyl)-benzamide in 1 ml N,N-dimethylformamide at 0° C. were added 50 mg (0.25 mmol) potassium hexamethyldisilazide. Stirring was continued for 1 h at this temperature and 0.016 ml (0.25 mmol) methyl iodide were added. After stirring for 3 h at room temperature, ethyl acetate was added. The mixture was washed with brine, dried (magnesium sulfate) and evaporated. The solvent was removed in vacuo and the residue was purified by flash chromatography to give 90 mg (87%) of the title compound as a colourless oil.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][C@H:9]1[CH2:15][O:16][C:17]([N:19]1[CH2:24][CH2:23][N:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:21][CH2:20]1)=[O:18])=O)(C)(C)C.[ClH:31].CCOCC>CO>[ClH:31].[ClH:31].[ClH:31].[C:25]1([N:22]2[CH2:23][CH2:24][N:19]([C:17]([O:16][CH2:15][C@@H:9]3[CH2:10][N:11]([CH3:14])[CH2:12][CH2:13][NH:8]3)=[O:18])[CH2:20][CH2:21]2)[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1
Reactant: CN1CCN(C(=O)OC(C)(C)C)[C@H](COC(=O)N2CCN(c3ccccc3)CC2)C1
Agent: Cl
Solvent: CCOCC
Solvent: CO
Product: CN1CCN[C@H](COC(=O)N2CCN(c3ccccc3)CC2)C1
Temperature: 25 °C
Reaction time: 72 h
Yield: 96 %

Procedure:
To a solution of (S)-4-methyl-2-(4-phenyl-piperazine-1-carbonyloxymethyl)-piperazine-1-carboxylic acid tert-butyl ester (1.65 g, 3.9 mmol) in MeOH (10 mL) was added 2M HCl in Et2O solution (11.8 mL, 23.6 mmol). The reaction was stirred at room temperature for 3 days. The reaction mixture was concentrated in vacuo. The residue was purified by reverse phase column chromatography (LiChroprep RP-18, 40-63 μm, 460×26 mm (100 g), 30 mL/min, gradient 0% to 15% (over 75 min) MeOH in water with 0.1% TFA. The material was then purified further by reverse phase HPLC(YMC ODS-A 100×20 mm, 5 μm, 25 mL/min, gradient 50% to 100% (over 7 min) then 100% (3 min) MeOH in 10% MeOH/water). The pure product was stirred in 4M aq HCl solution (10 mL) for 4 hours before being concentrated in vacuo. The resulting oil was washed with heptane, concentrated in vacuo and then dried in a vacuum oven overnight to afford the [(2S)-4-methylpiperazin-2-yl]methyl 4-phenylpiperazine-1-carboxylate trihydrochloride salt (1.63 g, 96%) as a pale brown solid.
Reaction SMILES: [O-:1][N+:2]1[C:7]2[CH:8]=[C:9]3[C:14](=[CH:15][C:6]=2[N:5]=[C:4]([NH:16][CH2:17][CH2:18][N:19]([CH3:21])[CH3:20])[N:3]=1)[CH2:13][CH2:12][CH2:11][CH2:10]3.C[OH:23]>>[O-:1][N+:2]1[C:7]2[CH:8]=[C:9]3[C:14](=[CH:15][C:6]=2[N+:5]([O-:23])=[C:4]([NH:16][CH2:17][CH2:18][N:19]([CH3:21])[CH3:20])[N:3]=1)[CH2:13][CH2:12][CH2:11][CH2:10]3
Reactant: CO
Reactant: CN(C)CCNc1nc2cc3c(cc2[n+]([O-])n1)CCCC3
Product: CN(C)CCNc1n[n+]([O-])c2cc3c(cc2[n+]1[O-])CCCC3

Procedure:
H2O2 (70%, 0.27 mL, ca. 5.3 mmol) was added dropwise to a stirred solution of TFAA (0.8 mL, 5.3 mmol) in DCM (10 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 177 (153 mg, 0.5 mmol) and TFA (0.20 mL, 2.7 mmol) in DCM (10 mL) at 0° C. The solution was stirred at 20° C. for 16 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH/DCM, to give (i) starting material 177 (37 mg, 24%) and (ii) 1,4-dioxide 178 (47 mg, 29%) as a red solid: mp (MeOH) 148-151° C.; 1H NMR δ 8.02 (s, 1H, H-10), 7.98 (s, 1H, H-5), 7.35 (br s, 1H, NH), 3.63 (br t, J=6.0 Hz, 2H, CH2N), 2.98-3.04 (m, 2H, CH2), 2.91-2.96 (m, 2H, CH2), 2.61 (br t, J=6.0 Hz, 2H, CH2N), 2.30 [s, 6H, N(CH3)2], 1.83-1.92 (m, 4H, H-7, H-8); 13C NMR δ 149.4, 148.7, 138.8, 136.5, 128.9, 120.1, 115.8, 57.6, 45.2 (2), 38.9, 30.3, 29.4, 22.3, 22.0. Anal. calcd for C15H21N5O2.1½H2O: C, 54.5; H, 7.3; N, 21.2. Found: C, 54.4; H, 6.3; N, 20.7%.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[C:9]([OH:11])[C:8]([N+:12]([O-:14])=[O:13])=[CH:7][C:3]=1[C:4](O)=[O:5].S(Cl)([Cl:17])=O>CN(C)C=O>[OH:1][C:2]1[CH:10]=[C:9]([OH:11])[C:8]([N+:12]([O-:14])=[O:13])=[CH:7][C:3]=1[C:4]([Cl:17])=[O:5]
Reactant: O=C(O)c1cc([N+](=O)[O-])c(O)cc1O
Reactant: O=S(Cl)Cl
Solvent: CN(C)C=O
Product: O=C(Cl)c1cc([N+](=O)[O-])c(O)cc1O

Procedure:
A mixture of 2,4-dihydroxy-5-nitrobenzoic acid (14.2 g, 92.1 mmol), thionyl chloride (100 mL, 1.15 mol) and dimethylformamide (4 drops) is refluxed for 4 h. The solvents are removed under reduced pressure and the resulting gum is stripped once with toluene and dried under reduced pressure to afford 2,4-dihydroxy-5-nitrobenzoyl chloride as a gum, which is used without further purification.
Reaction SMILES: [OH:1][N:2]1[C:7]([CH3:9])([CH3:8])[CH2:6][CH:5]([O:10][C:11](=[O:18])[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:4][C:3]1([CH3:20])[CH3:19].[C:21](Cl)(=[O:39])[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38]>>[C:11]([O:10][CH:5]1[CH2:6][C:7]([CH3:9])([CH3:8])[N:2]([O:1][C:21](=[O:39])[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])[C:3]([CH3:20])([CH3:19])[CH2:4]1)(=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: CCCCCCCCCCCCCCCCCC(=O)Cl
Reactant: CC1(C)CC(OC(=O)c2ccccc2)CC(C)(C)N1O
Product: CCCCCCCCCCCCCCCCCC(=O)ON1C(C)(C)CC(OC(=O)c2ccccc2)CC1(C)C
Yield: 60 %

Procedure:
Using 1-hydroxy-4-benzoyloxy-2,2,6,6-tetramethylpiperidine, prepared as described by Kurumada T. et. al., loc. cit., and stearoyl chloride in a procedure otherwise similar to the preparation of the compound 101 gives a 60% yield of the compound 109 which is obtained in the form of colourless crystals; melting point: 85-89° C. (acetonitrile).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:38]=[CH:37][CH:36]=[CH:35][C:4]=1[CH2:5][NH:6][CH2:7][CH:8]([NH:19][C:20](=O)[CH2:21][N:22]1[CH2:27][CH2:26][N:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:24][CH2:23]1)[CH2:9][C:10]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[NH:12][CH:11]=1>ClC1C=CC=CC=1Cl>[CH3:1][O:2][C:3]1[CH:38]=[CH:37][CH:36]=[CH:35][C:4]=1[CH2:5][N:6]1[CH2:7][CH:8]([CH2:9][C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[NH:12][CH:11]=2)[N:19]=[C:20]1[CH2:21][N:22]1[CH2:27][CH2:26][N:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:24][CH2:23]1
Reactant: COc1ccccc1CNCC(Cc1c[nH]c2ccccc12)NC(=O)CN1CCN(c2ccccc2)CC1
Solvent: Clc1ccccc1Cl
Product: COc1ccccc1CN1CC(Cc2c[nH]c3ccccc23)N=C1CN1CCN(c2ccccc2)CC1

Procedure:
A stirring solution of (RS) 1-[N-(2-methoxybenzyl)amino]-3-(1H-indol-3-yl)-2-[N-(2-((4-phenyl)piperazin-1-yl)acetyl)amino]propane (50 mg, 0.098 mmol), prepared as described in Preparation 4, supra, dissolved in 6 ml of 1,2-dichlorobenzene was heated to reflux under a nitrogen atmosphere. The solution was allowed to reflux overnight. The progress of the reaction was monitored by thin layer chromatography. The solution was then refluxed for an additional eight hours. The desired title product was then purified by chromatography. (Yield: 40.0 mg, 83%).
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]([O:10]CC)=O)=[CH:6][N:5]=[C:4]([S:13][CH3:14])[N:3]=1.[H-].[Na+].[Cl:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[C:19]=1[N:25]=[C:26]=[O:27].Cl>CN(C)C=O.C(OCC)(=O)C>[Cl:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[C:19]=1[N:25]1[C:8](=[O:10])[C:7]2[C:2](=[N:3][C:4]([S:13][CH3:14])=[N:5][CH:6]=2)[NH:1][C:26]1=[O:27]
Reactant: CCOC(=O)c1cnc(SC)nc1N
Reactant: O=C=Nc1c(Cl)cccc1Cl
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CSc1ncc2c(=O)n(-c3c(Cl)cccc3Cl)c(=O)[nH]c2n1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 85.9 %

Procedure:
To a solution of 1.0 g of ethyl 4-amino-2-(methylsulfanyl)pyrimidine-5-carboxylate in 15 mL of N,N-dimethylformamide, 315 mg of sodium hydride was added, and the resulting mixture was stirred at room temperature for 5 minutes. To the reaction mixture, 970 mg of 2,6-dichlorophenyl isocyanate was added, and the resulting mixture was stirred at room temperature for 1 hour. To the reaction mixture, ethyl acetate and a 1 N aqueous hydrochloric acid solution were added and the organic layer was separated. The organic layer was washed with saturated saline and dried over anhydrous sodium sulfate, and then, the solvent was distilled off. The precipitated solid was solidified with methanol and collected by filtration, whereby 1.43 g of the title compound was obtained as a white solid.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:17])=[C:6]([CH:16]=1)[CH2:7][O:8][Si:9]([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10].C([O-])([O-])=O.[K+].[K+].O.[CH3:25][C:26]1(C)C(C)(C)OB(C=C)O1>COCCOC.CCOCC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:12]([Si:9]([O:8][CH2:7][C:6]1[CH:16]=[C:2]([CH:25]=[CH2:26])[CH:3]=[CH:4][C:5]=1[Cl:17])([CH3:11])[CH3:10])([CH3:15])([CH3:14])[CH3:13]
Reactant: CC(C)(C)[Si](C)(C)OCc1cc(Br)ccc1Cl
Reactant: C=CB1OC(C)(C)C(C)(C)O1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOCC
Solvent: O
Solvent: COCCOC
Product: C=Cc1ccc(Cl)c(CO[Si](C)(C)C(C)(C)C)c1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 97.5 %

Procedure:
Pd(PPh3)4 (173 mg, 0.149 mmol) was added to a sol. of (5-bromo-2-chloro-benzyloxy)-tert-butyl-dimethyl-silane (1.00 g, 2.98 mmol) in DME (30 mL). The mixture was stirred at rt for 20 min, and K2CO3 (411 mg, 2.98 mmol), water (10 mL) and 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (0.53 mL, 2.98 mmol) were added. The mixture was heated rapidly to reflux, and stirred under reflux for 2 h. The mixture was allowed to cool to rt, and was diluted with Et2O (100 mL). The mixture was washed with water, and the aq. layer was extracted back with Et2O (3×). The combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (EtOAc/heptane 5:95) yielded the title compound (822 mg, 98%). LC-MS: tR=1.22 min.
Reaction SMILES: CC([O-])(C)C.[Na+].[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][NH:17][C@@H:16]([CH:20]([CH3:22])[CH3:21])[CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].[CH2:23]([C:30]1[CH:35]=[CH:34][CH:33]=[C:32](Br)[CH:31]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(Cl)Cl.CO>C1(C)C=CC=CC=1.CCOCC.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].C1(P(C2C=CC=CC=2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)C=CC=CC=1>[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][N:17]([C:32]2[CH:33]=[CH:34][CH:35]=[C:30]([CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH:31]=2)[C@@H:16]([CH:20]([CH3:22])[CH3:21])[CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8]
Reactant: Brc1cccc(Cc2ccccc2)c1
Reactant: CC(C)[C@H]1CN(C(=O)OC(C)(C)C)CCN1
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: CN(C)c1ccccc1-c1ccccc1P(c1ccccc1)c1ccccc1
Solvent: CCOCC
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: CC(C)[C@H]1CN(C(=O)OC(C)(C)C)CCN1c1cccc(Cc2ccccc2)c1
Temperature: 80 °C
Yield: 59322 %

Procedure:
9.4 mg (10.3 μmol, 0.013 eq.) Pd2(dba)3 and 11.4 mg (29.9 μmol, 0.04 eq.) 2-Diphenylphosphino-2′-dimethylamino-biphenyl were dissolved in 6 ml dry toluene. Then 170.7 mg (1.78 mmol, 2.32 eq.) NaOt-Bu was added, followed by a solution of 175.0 mg (0.77 mmol) 3-(S)-Isopropyl-piperazine-1-carboxylic acid tert-butyl ester (85) and 290.6 mg (1.18 μmol, 1.54 eq.) 1-Benzyl-3-bromo-benzene (87). The resulting mixture was heated at 80° C. for 22 h. After cooling to room temperature the mixture was diluted with ether and washed with brine. The comb. org. fractions were dried over Na2SO4 and evaporated. Column chromatography (hexanes/EtOAc (3+1)) yielded 276.5 mg (0.70 mmol, 91.49%) 4-(3′-Benzylphenyl)-3-(S)-iso-propyl-piperazine-1-carboxylic acid tert-butyl ester (88).
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][O:7][CH:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10](=[O:17])[N:9]1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[CH:24]([NH2:27])([CH3:26])[CH3:25].[OH-].[Na+].[C:30]([OH:37])(=[O:36])/[CH:31]=[CH:32]/[C:33]([OH:35])=[O:34]>C1(C)C=CC=CC=1.C(O)(C)C.C(OCC)C.O>[C:30]([OH:37])(=[O:36])/[CH:31]=[CH:32]/[C:33]([OH:35])=[O:34].[CH:24]([NH:27][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][O:7][CH:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10](=[O:17])[N:9]1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)([CH3:26])[CH3:25]
Reactant: O=C1c2ccccc2C(OCCCCCCl)N1c1ccccc1
Reactant: CC(C)N
Agent: O=C(O)/C=C/C(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)O
Solvent: CCOCC
Solvent: Cc1ccccc1
Product: CC(C)NCCCCCOC1c2ccccc2C(=O)N1c1ccccc1

Procedure:
A solution of 3-(5-chloropentyloxy)-2-phenyl-isoindolin-1-one (31.6 g.) and isopropylamine (83 cc.) in toluene (50 cc.) is heated in an autoclave at 140° C. for 48 hours. After cooling, the reaction mixture is poured into water (200 cc.) and diethyl ether (200 cc.). The organic phase is separated. The aqueous solution is washed with diethyl ether (2 × 50 cc.). The organic solutions obtained are combined and washed with water (5 × 25 cc.) and are then extracted with 4N hydrochloric acid (3 × 35 cc.). The acid solutions obtained are combined and rendered alkaline by adding 10N sodium hydroxide solution (45 cc.). The resulting insoluble oil is extracted with methylene chloride (3 × 80 cc.) and the organic solution obtained is dried over sodium sulphate and concentrated to dryness under reduced pressure. An oil (30 g.) is obtained and is dissolved in isopropanol (250 cc.). Fumaric acid (9.3 g.) is added to the solution and the mixture is then heated to the boiling point. A slight amount of insoluble matter is removed by carrying out a hot filtration. The product which crystallises on cooling is filtered off and then washed with isopropanol (50 cc.) and acetone (50 cc.). After drying, 3-(5-isopropylaminopentyloxy)-2-phenyl-isoindolin-1-one hydrogen fumarate (30.6 g.), which melts at 150° C., is obtained.
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[C:12]2[C:7]([CH2:8][CH2:9][CH2:10][C:11]2=[O:14])=[CH:6][CH:5]=1)([O-:3])=[O:2].B.CSC>C1COCC1>[N+:1]([C:4]1[CH:13]=[C:12]2[C:7]([CH2:8][CH2:9][CH2:10][CH:11]2[OH:14])=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: O=C1CCCc2ccc([N+](=O)[O-])cc21
Agent: B
Solvent: CSC
Solvent: C1CCOC1
Product: O=[N+]([O-])c1ccc2c(c1)C(O)CCC2
Temperature: 0 °C
Yield: 99.2 %

Procedure:
7-Nitro-3,4-dihydro-1(2H)-naphthalenone (5.0 g, 26.1 mmol) was stirred with 2M borane-dimethylsulfide in THF (14.4 mL, 28.8 mmol) in THF (200 mL) at rt for 15 h. The reaction was cooled to 0° C. and quenched with MeOH. The solvent and reaction byproducts were removed under vacuum and afforded 5.0 g (99%) of the desired alcohol as a brown powder. 1H NMR (400 MHz, DMSO-d6) δ 8.25 (d, J=2.6 Hz, 1 H), 7.98 (dd, J=8.5, 2.6 Hz, 1H), 7.34 (d, J=8.5 Hz, 1H), 5.55 (d, J=5.7 Hz, 1H), 4.63 (m, 1H), 2.87-2.73 (m, 2H), 2.00-1.83 (m, 2H), 1.75-1.60 (m, 2H).
Reaction SMILES: [H-].[Na+].[CH3:3][S:4]([NH2:7])(=[O:6])=[O:5].F[C:9]1[C:10]([CH3:29])=[N:11][C:12]2[C:17]([N:18]=1)=[C:16]([C:19]1[NH:27][C:26]3[CH2:25][CH2:24][NH:23][C:22](=[O:28])[C:21]=3[CH:20]=1)[CH:15]=[CH:14][CH:13]=2.[C:30]([OH:36])([C:32]([F:35])([F:34])[F:33])=[O:31]>CN(C=O)C.CS(C)=O>[F:33][C:32]([F:35])([F:34])[C:30]([OH:36])=[O:31].[CH3:29][C:10]1[C:9]([NH:7][S:4]([CH3:3])(=[O:6])=[O:5])=[N:18][C:17]2[C:12]([N:11]=1)=[CH:13][CH:14]=[CH:15][C:16]=2[C:19]1[NH:27][C:26]2[CH2:25][CH2:24][NH:23][C:22](=[O:28])[C:21]=2[CH:20]=1
Reactant: CS(N)(=O)=O
Reactant: Cc1nc2cccc(-c3cc4c([nH]3)CCNC4=O)c2nc1F
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CS(C)=O
Solvent: O=C(O)C(F)(F)F
Product: Cc1nc2cccc(-c3cc4c([nH]3)CCNC4=O)c2nc1NS(C)(=O)=O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 17.9 %

Procedure:
To a slurry of NaH (60% in mineral oil; 0.064 g, 1.606 mmol) in 1 mL DMF at 0° C. was added methanesulfonamide (TCI America, Portland, Oreg.; 0.153 g, 1.606 mmol) in portions. The ice/water bath was removed and the reaction warmed to RT. 2-(3-fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 126; 0.068 g, 0.229 mmol) was added. After 30 min, the reaction was cooled to 0° C., TFA (0.177 ml, 2.295 mmol) was added (dropwise via syringe), and 1 mL DMSO was added. The solution was filtered through a 0.45 micron syringe filter and purified by rpHPLC (Phenomenex Gemini 150×30 mm C18 column, 10-70% ACN/H2O with 0.1% TFA); product-containing fractions were concentrated in vacuo, to give N-(3-methyl-8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinoxalin-2-yl)methanesulfonamide 2,2,2-trifluoroacetate (0.020 g, 0.041 mmol, 18% yield) as a brown solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 12.09 (1H, br. s.), 10.98 (1H, br. s), 8.11 (1H, d, J=7.6 Hz), 7.74 (1H, dt, J=8.0, 0.8 Hz), 7.54-7.66 (1H, m), 7.05-7.15 (1H, m), 7.01 (1H, br. s.), 3.44 (2H, t, J=7.0 Hz), 3.39 (3H, s), 2.91 (2H, t, J=6.9 Hz), 2.68 (3H, s). m/z (ESI, +ve) 372.0 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([SH:8])=[CH:4][CH:3]=1.Br[CH2:10][CH2:11][CH2:12][O:13][C:14]1[C:19]([Cl:20])=[CH:18][C:17]([O:21][CH2:22][CH:23]=[C:24]([Cl:26])[Cl:25])=[CH:16][C:15]=1[Cl:27].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:10][CH2:11][CH2:12][O:13][C:14]2[C:15]([Cl:27])=[CH:16][C:17]([O:21][CH2:22][CH:23]=[C:24]([Cl:26])[Cl:25])=[CH:18][C:19]=2[Cl:20])=[CH:4][CH:3]=1
Reactant: ClC(Cl)=CCOc1cc(Cl)c(OCCCBr)c(Cl)c1
Reactant: Sc1ccc(Cl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: ClC(Cl)=CCOc1cc(Cl)c(OCCCSc2ccc(Cl)cc2)c(Cl)c1
Temperature: 25 °C
Reaction time: 24 h
Yield: 80.7 %

Procedure:
A mixture of 0.47 g of 4-chlorothiophenol, 1.33 g of 1-(3-bromopropyloxy)-2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)benzene, 0.49 g of potassium carbonate and 20 ml of N,N-dimethylformamide was stirred at room temperature for 24 hours. The reaction mixture was poured into ice-water, and extracted twice with 50 ml of diethyl ether. The combined ether layer was washed with water, dried with anhydrous magnesium sulfate, and concentrated to obtain a crude product. The crude product was subjected to silica gel chromatography, which afforded 1.24 g of 1-(3-(4-chlorophenylthio) propyloxy)-2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)benzene (81% yield), nD26.0 1.6035.
Reaction SMILES: [CH3:1][C:2]([CH3:5])([O-])C.[K+].BrCC=C.[CH3:11][N:12]([CH:14]=[N:15][C:16]1[NH:17][CH:18]=[CH:19][N:20]=1)[CH3:13].O>CN(C=O)C>[CH3:11][N:12]([CH:14]=[N:15][C:16]1[N:17]([CH2:1][CH:2]=[CH2:5])[CH:18]=[CH:19][N:20]=1)[CH3:13]
Reactant: CN(C)C=Nc1ncc[nH]1
Reactant: CC(C)(C)[O-]
Agent: [K+]
Solvent: C=CCBr
Solvent: O
Solvent: CN(C)C=O
Product: C=CCn1ccnc1N=CN(C)C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 120.2 %

Procedure:
Potassium t-butoxide (0.37 g) and 3-bromo-1-propene (0.3 ml) were added to a solution of 2-(dimethylaminomethylene)aminoimidazole (0.2 g) in DMF (3 ml) under ice-cooling. After warming to room temperature, the mixture was stirred for 30 minutes. Water was added to the reaction mixture, and the product was extracted with chloroform. The extract was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by column chromatography on silica gel (eluent: chloroform-methanol-ammonia water=40:1:0.1) to give 2-(dimethylaminomethylene)amino-1-(2-propenyl)imidazole (0.31 g, Yield: 80%) as a brown oil.
Reaction SMILES: [CH:1]([NH2:3])=[O:2].C#N.C(#N)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>>[C:1]([NH2:3])(=[O:2])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: N#Cc1ccccc1
Reactant: NC=O
Agent: C#N
Product: NC(=O)c1ccccc1

Procedure:
A solution of formamide (0.5047 g, 11.2 retool), PdBr2 (0.165 g, 0.62 mmol) in 25 mL of benzonitrile was stirred at reflux for 16 hours. At the end of this time, it was found that 0.29 mmol of HCN was produced. Benzamide was also produced.
Reaction SMILES: [CH2:1]([Cl:4])[C:2]#[CH:3].[CH2:5]([O:7][SiH:8]([O:12][CH2:13][CH3:14])[O:9][CH2:10][CH3:11])[CH3:6]>C([Si](C)(C)O[Si](C=C)(C)C)=C.[Pt]>[Cl:4][CH2:1][CH:2]=[CH:3][Si:8]([O:12][CH2:13][CH3:14])([O:9][CH2:10][CH3:11])[O:7][CH2:5][CH3:6]
Reactant: C#CCCl
Reactant: CCO[SiH](OCC)OCC
Agent: [Pt]
Agent: C=C[Si](C)(C)O[Si](C)(C)C=C
Product: CCO[Si](C=CCCl)(OCC)OCC
Reaction time: 1 h

Procedure:
A 250 ml 3-neck round-bottom flask was equipped with a reflux condenser, addition funnel and stir bar. Propargyl chloride (50 g, 0.671 mol) and 0.15 g of Platinum (0)-1,3-divinyl-1,1,3,3-tetramethyldisiloxane complex (3% Weight in xylenes) were added to the flask. Triethoxysilane (115.6 g, 0.705 mol) was added dropwise from the addition funnel to the reaction mixture. The flask quickly became warm. After the completion of addition, the flask was kept at 100° C. for one hour. The final product 103 g was purified by distillation (108° C./49 mmHg) as a mixture of isomers. NMR showed a ratio of 1:0.13 of the two isomers.
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]([CH3:29])=[C:5]([C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24])[CH:6]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([N+:20]([O-:22])=[O:21])[CH:15]=2)[C:7]=1[C:8]([O:10][CH2:11][CH2:12][OH:13])=[O:9].[N+]([O-])(O)=O.[OH-].[Na+]>O>[CH3:1][C:2]1[C:7]([C:8]([O:10][CH2:11][CH2:12][OH:13])=[O:9])=[C:6]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([N+:20]([O-:22])=[O:21])[CH:15]=2)[C:5]([C:23]([O:25][CH:26]([CH3:27])[CH3:28])=[O:24])=[C:4]([CH3:29])[N:3]=1
Reactant: CC1=C(C(=O)OCCO)C(c2cccc([N+](=O)[O-])c2)C(C(=O)OC(C)C)=C(C)N1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: O=[N+]([O-])O
Product: Cc1nc(C)c(C(=O)OC(C)C)c(-c2cccc([N+](=O)[O-])c2)c1C(=O)OCCO
Reaction time: 1 h

Procedure:
20 g (49.5 mmol) of 2-hydroxyethyl isopropyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate were introduced into a mixture of 83 ml of 96% strength nitric acid in 660 ml of water and heated to boiling for 1 hour. The mixture was then cooled down to 5° to 10° C. and made weakly alkaline with dilute sodium hydroxide solution. The oil which had separated out was extracted with methylene chloride, the extracts were dried over sodium sulphate and evaporated in vacuo. The oily residue was induced to crystallize by trituration with ether/petroleum ether, filtered off with suction and recrystallized from methanol.