Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[C:10]([O:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:24][CH2:25][C:26]4([C:29]([OH:31])=O)[CH2:28][CH2:27]4)=[C:19]([O:22][CH3:23])[CH:20]=3)[N:15]=[CH:14][CH:13]=2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH3:32])[NH:6]2.C[CH2:34][N:35](C(C)C)[CH:36](C)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.Cl.CNC>C(Cl)Cl>[F:1][C:2]1[C:10]([O:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:24][CH2:25][C:26]4([C:29]([N:35]([CH3:36])[CH3:34])=[O:31])[CH2:28][CH2:27]4)=[C:19]([O:22][CH3:23])[CH:20]=3)[N:15]=[CH:14][CH:13]=2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH3:32])[NH:6]2
Reactant: COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ccnc2cc1OCC1(C(=O)O)CC1
Reactant: CCN(C(C)C)C(C)C
Agent: CNC
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: ClCCl
Product: COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ccnc2cc1OCC1(C(=O)N(C)C)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
The product of Example 10 (100 mg) was mixed with DIPEA (1.5 eq), EDC (1.25 eq), HOBt (1 eq) and dimethylamine hydrochloride (3 eq) in DCM (20 ml). The reaction was stirred at RT overnight and washed with NaHCO3 solution, dried. The solution was evaporated and purified with silica gel column to give the titled product (80 mg). Mass: (M+1), 464
Reaction SMILES: Cl.N1(N)CCCC1.COC(=O)CCC1C(=O)N(N)C(=O)NC=1.[N:23]1([NH:28][C:29]([C:31]2[CH:32]=[N:33][C:34]([C:37]3[CH:42]=[CH:41][CH:40]=[C:39](F)[CH:38]=3)=[N:35][CH:36]=2)=[O:30])[CH2:27][CH2:26][CH2:25][CH2:24]1>>[N:23]1([NH:28][C:29]([C:31]2[CH:36]=[N:35][C:34]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)=[N:33][CH:32]=2)=[O:30])[CH2:24][CH2:25][CH2:26][CH2:27]1
Reactant: O=C(NN1CCCC1)c1cnc(-c2cccc(F)c2)nc1
Agent: COC(=O)CCc1c[nH]c(=O)n(N)c1=O
Agent: Cl
Agent: NN1CCCC1
Product: O=C(NN1CCCC1)c1cnc(-c2ccccc2)nc1

Procedure:
Following procedures similar to those of Example 64 but substituting pyrrolidin-1-ylamine hydrochloride for 3-{3-amino-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-propionic acid methyl ester, there is prepared 2-(3-fluoro-phenyl)-pyrimidine-5-carboxylic acid pyrrolidin 1-yl-amide (67%) as a solid. MS: 269 (M+H); 1H NMR (300 MHz, CDCl3): δ 1.70-2.20 (m, 4H), 2.70-3.46 (m, 4H), 7.55 (s, 3H), 8.42-8.67(m, 2H), 9.14-9.49 (t, 2H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:8][CH3:9].C([Li])CCC.[C:15](=[O:17])=[O:16]>[OH-].[Na+]>[F:1][C:2]1[C:3]([O:8][CH3:9])=[CH:4][CH:5]=[CH:6][C:7]=1[C:15]([OH:17])=[O:16]
Reactant: O=C=O
Reactant: COc1ccccc1F
Agent: [Li]CCCC
Agent: [Na+]
Agent: [OH-]
Product: COc1cccc(C(=O)O)c1F
Temperature: -78 °C

Procedure:
Pentamethylenediethylenetetramine (31.2 ml) was added to a solution of 2-fluoroanisole (15.0 g) in TB (450 ml). The reaction mixture was cooled to −78° C. and n-butyllithium (59.6 ml, 2.5M solution in hexanes) was added dropwise. Stirring was maintained for 2 h before the solution was added in a dropwise fashion to a flask containing solid carbon dioxide pellets. Upon complete addition (30 min) the mixture was allowed to warm to room temperature before removal of the volatiles in vacuo. The residue was dissolved in 10% sodium hydroxide solution (300 ml) and extracted with Et2O (3×). The aqueous was acidified to pH 1 with concentrated hydrochloric acid before extracting with DCM. The organics were washed with H2O, dried (MgSO4) and concentrated in vacuo to afford the subtitle compound as a yellow solid. Yield: 7.1 g.
Reaction SMILES: C([O:3][C:4](=O)[CH2:5][C:6]12[CH2:20][CH:13]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:19]=31)[C:12]1[C:7]2=[CH:8][CH:9]=[CH:10][CH:11]=1)C.[H-].[Al+3].[Li+].[H-].[H-].[H-].O>CCOCC.C(OCC)(=O)C>[OH:3][CH2:4][CH2:5][C:6]12[CH2:20][CH:13]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:19]=31)[C:12]1[C:7]2=[CH:8][CH:9]=[CH:10][CH:11]=1
Reactant: CCOC(=O)CC12CC(c3ccccc31)c1ccccc12
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: CCOCC
Solvent: O
Product: OCCC12CC(c3ccccc31)c1ccccc12
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A mixture of (9,10-dihydro-9,10-methano-9-anthryl)-acetic acid ethyl ester (125 mg) and lithium aluminum hydride (80 mg) in ether (6 ml) was stirred at room temperature for 1 hour. Excess lithium aluminum hydride was decomposed by addition of water. The reaction mixture was diluted with ethyl acetate, dried over anhydrous sodium sulfate and evaporated to dryness to give crystals of 9-β-hydroxyethyl-9,10-dihydro-9,10-methanoanthracene. M.P. 99°-100.5° C.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH2:9])[N:3]=1.[CH3:10][Se:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[S:18]([N:21]=[C:22]=[O:23])(=[O:20])=[O:19]>ClCCl>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH:9][C:22]([NH:21][S:18]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[Se:11][CH3:10])(=[O:19])=[O:20])=[O:23])[N:3]=1
Reactant: Cc1cc(C)nc(N)n1
Reactant: C[Se]c1ccccc1S(=O)(=O)N=C=O
Solvent: ClCCl
Product: C[Se]c1ccccc1S(=O)(=O)NC(=O)Nc1nc(C)cc(C)n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 101.4 %

Procedure:
To a slurry of 4,6-dimethyl-2-pyrimidinamine (0.36 g, 29 mmol) in dry dichloromethane (5 mL) was added a solution of 2-(methylselenyl)benzenesulfonyl isocyanate (1.5 g, crude, 4.2 mmol) in dichloromethane (5 mL). The heterocycle dissolved. The solution was heated at reflux for two hours and stirred at room temperature overnight. The solution was filtered and rotary evaporated to give 1.7 g of yellow solid. This was dissolved in dichloromethane and chromatographed on a column of silica gel using as eluant 320 mL of 15:1, 220 mL of 10:1, 230 mL of 7.5:1, and finally 240 mL of 5:1 dichloromethane-ether, all with 2 mL/L acetic acid. The appropriate fractions were diluted with toluene and rotary evaporated. The residue was dissolved in dichloromethane, diluted with 1-chlorobutane, and rotary evaporated to give a white crystalline solid. This was slurried in hexanes, collected, rinsed with 1-chlorobutane, 1:1 1-chlorobutanehexanes, and hexanes and air dried. The product was isolated as 1.03 g of small white crystalline plates, melting at 205°-207° C. with decomposition.
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([N+:12]([O-])=O)[CH:8]=2)[N:3]=1.[CH3:15][O:16][C:17]1[CH:24]=[C:23]([O:25][CH3:26])[CH:22]=[CH:21][C:18]=1[CH2:19][NH2:20].[CH:27]([N:30]=[C:31]=[O:32])([CH3:29])[CH3:28]>>[CH3:15][O:16][C:17]1[CH:24]=[C:23]([O:25][CH3:26])[CH:22]=[CH:21][C:18]=1[CH2:19][NH:20][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([NH:12][C:31]([NH:30][CH:27]([CH3:29])[CH3:28])=[O:32])[CH:8]=2)[N:3]=1
Reactant: O=[N+]([O-])c1ccc2nc(Cl)ccc2c1
Reactant: CC(C)N=C=O
Reactant: COc1ccc(CN)c(OC)c1
Product: COc1ccc(CNc2ccc3cc(NC(=O)NC(C)C)ccc3n2)c(OC)c1

Procedure:
The title compound, MS: m/e=395.4 (M+H+), was prepared in accordance with the general method of example 14 from 2-chloro-6-nitro-quinoline, 2,4-dimethoxy-benzylamine and isopropyl isocyanate.
Reaction SMILES: [NH2:1][C@@H:2]1[C:10]2[C:5](=[C:6]([C:11]3[N:15]=[C:14]([C:16]4[CH:17]=[CH:18][C:19]([O:24][CH:25]([CH3:27])[CH3:26])=[C:20]([CH:23]=4)[C:21]#[N:22])[O:13][N:12]=3)[CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3]1.[CH3:28][S:29](Cl)(=[O:31])=[O:30]>C(Cl)Cl>[C:21]([C:20]1[CH:23]=[C:16]([C:14]2[O:13][N:12]=[C:11]([C:6]3[CH:7]=[CH:8][CH:9]=[C:10]4[C:5]=3[CH2:4][CH2:3][C@@H:2]4[NH:1][S:29]([CH3:28])(=[O:31])=[O:30])[N:15]=2)[CH:17]=[CH:18][C:19]=1[O:24][CH:25]([CH3:27])[CH3:26])#[N:22]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)Oc1ccc(-c2nc(-c3cccc4c3CC[C@@H]4N)no2)cc1C#N
Solvent: ClCCl
Product: CC(C)Oc1ccc(-c2nc(-c3cccc4c3CC[C@@H]4NS(C)(=O)=O)no2)cc1C#N
Reaction time: 1 h
Yield: 44.7 %

Procedure:
Prepared using General Procedure 8A: To a stirred solution of (S)-5-(3-(1-amino-2,3-dihydro-1H-inden-4-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile 50 (18 mg, 0.05 mmol) in DCM (1 mL) was added TEA (13.9 μL, 0.1 mmol) and methanesulfonyl chloride (19 mg, 0.1 mmol). After 1 h, additional TEA (13.9 μL, 0.1 mmol) and methanesulfonyl chloride (19 mg, 0.1 mmol) were added. After an additional 1 h of stirring the solvent was evaporated and purified by preparative HPLC to afford 9.8 mg (45%) of (S)-N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl) methane sulfonamide 69. LCMS-ESI (m/z) calculated for C22H22N4O4S: 438.1. found 439.1 [M+H]+, tR=3.70 min. 1H NMR (400 MHz, CDCl3) δ 8.41 (d, J=2.2 Hz, 1H), 8.32 (dd, J=8.9, 2.2 Hz, 1H), 8.12 (d, J=7.7 Hz, 1H), 7.60 (d, J=7.6 Hz, 1H), 7.43 (t, J=7.6 Hz, 1H), 7.11 (d, J=9.0 Hz, 1H), 5.07 (dd, J=16.5, 7.8 Hz, 1H), 4.78 (hept, J=6.1 Hz, 1H), 4.48 (d, J=9.3 Hz, 1H), 3.51 (ddd, J=17.5, 8.8, 3.4 Hz, 1H), 3.29-3.12 (m, 1H), 3.09 (s, 3H), 2.74 (dtd, J=12.9, 8.0, 3.5 Hz, 1H), 2.07-1.92 (m, 1H), 1.46 (d, J=6.1 Hz, 6H).
Reaction SMILES: [O:1]1[CH2:3][CH2:2]1.CC([CH2:7][NH2:8])O.[N+:9]([C:12]1([CH2:18][CH:19]2[CH2:21][O:20]2)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)([O-:11])=[O:10]>>[OH:1][CH2:2][CH2:3][N:8]([CH3:7])[CH2:21][CH:19]([OH:20])[CH2:18][C:12]1([N+:9]([O-:11])=[O:10])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1
Reactant: O=[N+]([O-])C1(CC2CO2)CCCCC1
Reactant: CC(O)CN
Reactant: C1CO1
Product: CN(CCO)CC(O)CC1([N+](=O)[O-])CCCCC1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A one neck 100 mL round bottom flask equipped with a stir bar, condenser and nitrogen outlet is charged with 3.24 g (34.6% purity, 0.018 mols) of 24(1-nitrocyclohexyl)methyl)oxirane and 1.31 g (0.018 mols) of monomethylethanolamine. The reaction mixture is stirred at room temperature for 30 minutes followed by heating at 40° C. for 1.5 h. The yellow color oxirane turns to dark orange and the resulting product has high viscosity. GC of the reaction mixture after this time still shows the presence of the epoxide. At this point, 0.7 mL (0.65 g) of additional monomethylethanolamine is added and stirred for additional 1.5 h at 40° C. and overnight at room temperature. GC analysis of the resulting mixture shows the nitro epoxide (12) is fully consumed. At this point, the reaction is deemed complete. Compound (13), 1-((2-hydroxyethyl)(methyl)amino)-3-(1-nitrocyclohexyl)propan-2-ol was identified by LC/MS with [M+H]=261.17. The product mixture from the epoxy ring opening step is used as-is for the hydrogenation step.
Reaction SMILES: [BH4-].[Na+].[NH2:3][C:4]1[CH:16]=[CH:15][C:7]2[N:8]=[C:9]([S:11]([NH2:14])(=[O:13])=[O:12])[S:10][C:6]=2[CH:5]=1.C(O)(=O)C.[H][H].[CH3:23][C:24]([CH3:26])=O>O>[CH3:23][CH:24]([NH:3][C:4]1[CH:16]=[CH:15][C:7]2[N:8]=[C:9]([S:11]([NH2:14])(=[O:13])=[O:12])[S:10][C:6]=2[CH:5]=1)[CH3:26]
Reactant: CC(C)=O
Reactant: [H][H]
Reactant: Nc1ccc2nc(S(N)(=O)=O)sc2c1
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: CC(C)Nc1ccc2nc(S(N)(=O)=O)sc2c1
Temperature: 20 °C

Procedure:
Sodium borohydride (378 mg, 0.01 mole) and 6-amino-2-benzothiazolesulfonamide (459 mg, 0.002 mole) are ground together, then added very slowly to a mixture of glacial acetic acid (5 ml) and acetone (5 ml) with stirring under nitrogen at 20° C. After vigorous evolution of hydrogen, the reaction mixture is stirred at 20° C. for 2 hrs, treated with H2O, filtered, made basic with 10N NaOH solution, then neutralized with aqueous HCl to give 6-(1-methylethyl)amino-2-benzothiazolesulfonamide.
Reaction SMILES: [CH3:1][C:2]1([CH3:21])[CH2:20][N:6]2[C:7]3[CH:8]=[CH:9][C:10]([NH2:19])=[CH:11][C:12]=3[C:13]3([O:18][CH2:17][CH2:16][CH2:15][O:14]3)[C:5]2=[N:4][CH2:3]1.CCN(CC)CC.[C:29]1([S:35](Cl)(=[O:37])=[O:36])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>C(Cl)Cl>[CH3:1][C:2]1([CH3:21])[CH2:20][N:6]2[C:7]3[CH:8]=[CH:9][C:10]([NH:19][S:35]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)(=[O:37])=[O:36])=[CH:11][C:12]=3[C:13]3([O:18][CH2:17][CH2:16][CH2:15][O:14]3)[C:5]2=[N:4][CH2:3]1
Reactant: CC1(C)CN=C2N(C1)c1ccc(N)cc1C21OCCCO1
Reactant: O=S(=O)(Cl)c1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC1(C)CN=C2N(C1)c1ccc(NS(=O)(=O)c3ccccc3)cc1C21OCCCO1
Temperature: 25 °C
Reaction time: 1 h
Yield: 71.3 %

Procedure:
To a solution of 3′,3′-dimethyl-3′,4′-dihydro-2′H-spiro[1,3-dioxane-2,10′-pyrimido[1,2-a]indol]-8′amine (0.060 g 0.21 mmol, 1 eq) in CH2Cl2 (2 mL) was added Et3N (0.060 mL, 0.43 mmol, 2.05 eq) and benzenesulfonyl chloride (0.030 mL, 0.23 mmol, 1.07 eq). The reaction was stirred at rt 1 hour and concentrated. The crude residue purified by column chromatography using acetone/hexanes (30/70) as an eluent to give the title compound as a white solid (0.064 g, 71%). NMR (400 Mz, DMSO-d6): consistent
Reaction SMILES: C[Al](C)C.[NH2:5][CH:6]1[CH2:10][O:9][CH2:8][CH2:7]1.C(O[C:14]([C:16]1[N:17]=[N:18][C:19]([O:22][CH2:23][C:24]2[C:25]([C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[CH:31]=3)=[N:26][O:27][C:28]=2[CH3:29])=[CH:20][CH:21]=1)=[O:15])C.[C:37](C(C(C([O-])=O)O)O)([O-])=O.[K+].[Na+]>O1CCOCC1>[O:9]1[CH2:8][CH2:7][CH:6]([NH:5][C:14]([C:16]2[N:17]=[N:18][C:19]([O:22][CH2:23][C:24]3[C:25]([C:30]4[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[CH:31]=4)=[N:26][O:27][C:28]=3[CH3:29])=[CH:20][CH:21]=2)=[O:15])[CH2:10][CH2:37]1
Reactant: CCOC(=O)c1ccc(OCc2c(-c3cccc(F)c3)noc2C)nn1
Reactant: NC1CCOC1
Reactant: O=C([O-])C(O)C(O)C(=O)[O-]
Agent: C[Al](C)C
Agent: [K+]
Agent: [Na+]
Solvent: C1COCCO1
Product: Cc1onc(-c2cccc(F)c2)c1COc1ccc(C(=O)NC2CCOCC2)nn1
Temperature: 25 °C
Reaction time: 1 h
Yield: 89 %

Procedure:
A solution of trimethylaluminium (2 M in toluene, 800 μL, 1.6 mmol) was added dropwise (exothermic) to a solution of 4-aminotetrahydrofuran (162 mg, 1.6 mmol) in dioxane (10 mL) and the resulting mixture was stirred at room temperature for 1 h. Then a solution of 6-[3-(3-fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-pyridazine-3-carboxylic acid ethyl ester (143 mg, 0.4 mmol) in dioxane (5 mL) was added. The resulting mixture was then heated at 85-95° C. for 4 h, cooled to room temperature, poured into a sodium potassium tartrate solution and extracted with ethyl acetate which was then washed with brine, dried over sodium sulfate and evaporated. Purification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 0:100) afforded the title compound (146 mg, 89%) which was obtained as an off white solid. MS: m/e=413.1 [M+H]−.
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[CH:8]([CH2:12][CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[CH2:7]2.[C:19]1(B(O)O)[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21][CH:20]=1.C(=O)([O-])[O-].[Na+].[Na+].C(O)CO>O>[C:19]1([C:2]2[CH:3]=[CH:4][CH:5]=[C:6]3[C:10]=2[C:9](=[O:11])[CH:8]([CH2:12][CH:13]2[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]2)[CH2:7]3)[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21][CH:20]=1
Reactant: OB(O)c1cccc2ccccc12
Reactant: O=C1c2c(Cl)cccc2CC1CC1CCCCC1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: OCCO
Solvent: O
Product: O=C1c2c(cccc2-c2cccc3ccccc23)CC1CC1CCCCC1
Temperature: 125 °C
Yield: 96.2 %

Procedure:
18.5 g (70.4 mmole) 7-Chloro-2-cyclohexylmethyl-indan-1-one, 14.5 g (1.2 eq.) naphthyl boronic acid, 16.4 g sodium carbonate, 230 ml ethylene glycol and 45 ml water were placed in a 1 l-roundbottom flask equipped with a mechanical stirrer and a reflux condenser. The mixture was degassed three times by slight evacuation and recharging with argon. A premixed catalyst solution consisting of 32 mg (0.2 mole %) palladium acetate, 0.94 ml NaTPPTS (2.6 M in water, 0.8 mole %) and 3 ml of water was added and the mixture was refluxed at 125° C. until complete conversion (approx. 5 h). 100 ml of water were added and the mixture was extracted three times with 100 ml of toluene each. The combined organic layers were washed twice with 100 ml water and once with 100 ml of a saturated sodium chloride solution. Drying over magnesium sulphate and evaporation of the solvent in vacuo yielded 24 g (96%) of the desired product as a yellow sticky oil. 1H-NMR (400 MHz, CDCl3): δ=7.86 (d, 2 h, aromatic), 7.63 (m, 1H, aromatic), 7.52 (m, 2H, aromatic), 7.43 (m, 2H, aromatic), 7.33 (m, 3H, aromatic), 2.39 (m, 1H, (C═O)CH), 2.85, 2.67 (2×m, 2H, benzylic), 1.90-0.80 (m, 13H, aliphatic) ppm.
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[C:10](=[O:17])[NH:11][NH:12][C:13]=2[CH:14]([CH3:16])[CH3:15])=[CH:4][CH:3]=1.N1C=CN=C1.[CH:23]([Si:26](Cl)([CH:30]([CH3:32])[CH3:31])[CH:27]([CH3:29])[CH3:28])([CH3:25])[CH3:24].O>CN(C)C=O>[I:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[C:10]([O:17][Si:26]([CH:30]([CH3:32])[CH3:31])([CH:27]([CH3:29])[CH3:28])[CH:23]([CH3:25])[CH3:24])=[N:11][NH:12][C:13]=2[CH:14]([CH3:15])[CH3:16])=[CH:4][CH:3]=1
Reactant: CC(C)c1[nH][nH]c(=O)c1Cc1ccc(I)cc1
Reactant: CC(C)[Si](Cl)(C(C)C)C(C)C
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)c1[nH]nc(O[Si](C(C)C)(C(C)C)C(C)C)c1Cc1ccc(I)cc1
Reaction time: 3 h
Yield: 99.8 %

Procedure:
To a solution of 1,2-dihydro-4-[(4-iodophenyl)methyl]-5-isopropyl-3H-pyrazol-3-one (5 g) and imidazole (1.19 g) in N,N-dimethylformamide (20 mL) was added triisopropylsilyl chloride (3.1 g) at room temperature, and the mixture was stirred for 3 hours. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give 4-[(4-iodophenyl)methyl]-5-isopropyl-3-triisopropylsilyloxy-1H-pyrazole (7.27 g). To a solution of obtained 4-[(4-iodophenyl)methyl]-5-isopropyl-3-triisopropylsilyloxy-1H-pyrazole (3 g) in N,N-dimethylformamide (10 mL) was added sodium hydride (55%, 0.33 g) under ice-cooling, and the mixture was stirred for 20 minutes. To the reaction mixture were added a solution of 1-benzoyloxy-3-chloropropane (3.0 g) in N,N-dimethylformamide (10 mL) and potassium iodide (0.25 g) at the same temperature, and the resulting mixture was stirred at room temperature overnight. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=20/1-10/1) to give 1-(3-benzoyloxypropyl)-4-[(4-iodophenyl)methyl]-5-isopropyl-3-triisopropylsilyloxy-1H-pyrazole (2.55 g). This material was dissolved in tetrahydrofuran (3 mL). To the solution was added 4 mol/L hydrochloric acid (1,4-dioxane solution, 10 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate, and the resulting mixture was poured into water. The organic layer was separated, and the organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. To the residue was added a mixed solvent of n-hexane and ethyl acetate (20/1) (10 mL), and the mixture was stirred at room temperature for 1 hour. The precipitated crystals were collected by filtration, and washed with a mixed solvent of n-hexane and ethyl acetate (20/1) and dried under reduced pressure to give the title compound (0.85 g).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[N:5][C:6]2[CH:7]([N:13]=[N+]=[N-])[CH2:8][CH2:9][CH2:10][C:11]=2[CH:12]=1.[H][H]>[Pd]>[CH3:1][O:2][C:3]1[CH:4]=[N:5][C:6]2[CH:7]([NH2:13])[CH2:8][CH2:9][CH2:10][C:11]=2[CH:12]=1
Reactant: [H][H]
Reactant: COc1cnc2c(c1)CCCC2N=[N+]=[N-]
Agent: [Pd]
Product: COc1cnc2c(c1)CCCC2N
Yield: 98.2 %

Procedure:
To a solution of (3-methoxy-5,6,7,8-tetrahydroquinolin-8-yl)-azide (0.33 g, 1.6 mmol) in MEOH (16 mL) was added palladium on activated carbon, (10%, 50 mg) and the reaction mixture stirred under 1 atmosphere of hydrogen for 4 h. The mixture was filtered through celite, the cake washed with methanol and the solvent from the eluent removed in vacuo to give crude (3-methoxy-5,6,7,8-tetrahydroquinolin-8-yl)-amine as a yellow oil (0.28 g, 96%). 1H NMR (CDCl3) δ1.75 (m, 2H), 1.97 (m, 1H), 2.17 (m, 1H), 2.77 (m, 2H), 3.81 (s, 3H), 3.98 (t, 1H, J=4.5 Hz), 6.88 (d, 1H, J=1.5 Hz), 8.12 (d, 1H, J=1.5 Hz).
Reaction SMILES: [BH4-].[Na+].[C:3]([O:6][C@@H:7]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH2:8][N:9]1[CH2:14][CH2:13][C:12]([CH2:15][CH2:16][O:17][CH:18]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:11][CH2:10]1)(=[O:5])[CH3:4].[OH-:37].[Na+].OO>C(O)C.O.C1COCC1>[C:3]([O:6][C@@H:7]([C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)[CH2:8][N:9]1[CH2:14][CH2:13][CH:12]([CH2:15][CH2:16][O:17][CH:18]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:11]([OH:37])[CH2:10]1)(=[O:5])[CH3:4]
Reactant: [OH-]
Reactant: CC(=O)O[C@H](CN1CC=C(CCOC(c2ccccc2)c2ccccc2)CC1)c1ccccc1
Agent: OO
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Solvent: CCO
Product: CC(=O)O[C@H](CN1CCC(CCOC(c2ccccc2)c2ccccc2)C(O)C1)c1ccccc1

Procedure:
With reference to FIG. 8, General procedure II was used. The quantities of the chemicals in order of addition are as follows: NaBH4 (0.0191 g, 0.505 mmol), THF (10 ml), BF3-ether complex (0.066 ml, 0.536 mmol), (S)-2-(4-(2-(benzhydryloxy)ethyl)-5,6-dihydropyridin-1(2H)-yl)-1-phenylethyl acetate 7b (0.115 g, 0.252 mmol), water (0.3 ml), ethanol (0.5 ml), 3N NaOH (0.2 ml) and 30% H2O2 (0.2 ml, 1.26 mmol).
Reaction SMILES: [C:1]([O:5][C:6]([C:8]1[CH:12]=[CH:11][NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].BrC[CH:15]([CH2:32]C([O-])=O)[CH2:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])=[CH:20][CH:19]=1>CS(C)=O.[Na+].[Cl-]>[C:1]([O:5][C:6]([C:8]1[CH:12]=[CH:11][N:10]([CH2:32][CH:15]([O:7][C:6](=[O:5])[CH3:8])[CH2:16][O:17][C:18]2[CH:19]=[CH:20][C:21]([CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])=[CH:22][CH:23]=2)[CH:9]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)c1cc[nH]c1
Reactant: CCCCCCCCc1ccc(OCC(CBr)CC(=O)[O-])cc1
Agent: [Cl-]
Agent: [Na+]
Solvent: CS(C)=O
Product: CCCCCCCCc1ccc(OCC(Cn2ccc(C(=O)OC(C)(C)C)c2)OC(C)=O)cc1
Temperature: 110 °C
Reaction time: 0.25 h

Procedure:
0.145 g (0.867 mmol) tert-butylpyrrole-3-carboxylate is dissolved in 10 ml absolute DMSO, mixed with 0.107 g (0.952 mmol) potassium-tert-butylate and stirred at 110° C. for 15 min. A solution of 0.333 g (0.864 mmol) [1-bromo-3-(4-octylphenoxy)propan-2-yl]acetate in 10 ml absolute DMSO is added drop-wise. Following 30 minutes of heating at 110° C. and subsequent cooling, hydrolysis is carried out in saturated NaCl solution. Four extractions with diethyl ether, combination of the organic phases, concentration to half the volume on the rotary evaporator, three wash steps using saturated NaCl solution, drying on sodium sulfate, filtration and reconcentration on the rotary evaporator leave as a crude product a yellow oil which is purified on silica gel by means of flash column chromatography (flow agent: petroleum ether/ethyl acetate 93:7) and yields the product as a colorless oil.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH2:20])[CH:5]=[C:6]([Cl:19])[C:7]=1[S:8][C:9]1[CH:18]=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=1.N1C=CC=CC=1.[Cl:27][C:28]1[CH:33]=[C:32]([Cl:34])[CH:31]=[CH:30][C:29]=1[S:35](Cl)(=[O:37])=[O:36].Cl>C1COCC1>[Cl:27][C:28]1[CH:33]=[C:32]([Cl:34])[CH:31]=[CH:30][C:29]=1[S:35]([NH:20][C:4]1[CH:3]=[C:2]([Cl:1])[C:7]([S:8][C:9]2[CH:18]=[CH:17][C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:10]=2)=[C:6]([Cl:19])[CH:5]=1)(=[O:37])=[O:36]
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1Cl
Reactant: Nc1cc(Cl)c(Sc2ccc3ccccc3c2)c(Cl)c1
Agent: Cl
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: O=S(=O)(Nc1cc(Cl)c(Sc2ccc3ccccc3c2)c(Cl)c1)c1ccc(Cl)cc1Cl
Reaction time: 144 h
Yield: 49 %

Procedure:
To a 0.4M solution of 3,5-dichloro-4-(napthalen-2-ylsulfanyl)phenylamine (90)(153 mg, 0.48 mmol) in THF was added pyridine, obtained from aldrich, (0.19 mL, 2.4 mmol) followed by 2,4-dichlorobenzenesulfonyl chloride, obtained from Maybridge, (129 mg, 0.53 mmol). The resulting mixture was stirred for 6 days. A 1M aqueous solution of HCl (20 mL) was added and the crude reaction mixture was extracted 3× with EtOAc (20 mL). The organic layers were combined and washed once with a brine solution (20 mL), dried over Na2SO4, and concentrated under vacuum. The crude solid was chromatographed (5–15% EtOAc in hexane) to yield 125 mg (49%) of 93 as an off white solid.