1,1-dioxothian-4-amine

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-Benzyl-1,1-dioxotetrahydro-2H-thiopyran-4-amine (2.00 g) was added to ethanol (40 mL) in a pressure bottle. Palladium hydroxide on carbon (0.587 g) was added and the solution was stirred under 30 psi of hydrogen at room temperature for 2 hours. The mixture was filtered though a nylon membrane and the solvent was removed under vacuum. The mixture was filtered though a nylon membrane the solvent was removed under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-Benzyl-1,1-dioxotetrahydro-2H-thiopyran-4-amine (2.00 g) was added to ethanol (40 mL) in a pressure bottle. Palladium hydroxide on carbon (0.587 g) was added and the solution was stirred under 30 psi of hydrogen at room temperature for 2 hours. The mixture was filtered though a nylon membrane and the solvent was removed under vacuum. The mixture was filtered though a nylon membrane the solvent was removed under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N,N-Diisopropylethylamine (137 μL, 0.81 mmol), 4-dimethylaminopyridine (27 mg, 0.22 mmol) and 4-nitrophenyl chloroformate (45 mg, 0.22 mmol) is added to a solution of (R)-4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]-pyrimidin-4-yl)benzonitrile (example 1A, 80 mg, 0.20 mmol) in acetonitrile (2.0 mL), and the mixture is stirred at room temperature over night. 1,1-Dioxotetrahydro-2H-thiopyran-4-amine (74 mg, 0.40 mmol) is added, and the mixture is stirred for 1 h and purified by reversed phase HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA). Yield: 72 mg; ESI mass spectrum [M+H]+=573; Retention time HPLC: 1.01 min (Z018_S04). the mixture is stirred for 1 h purified by reversed phase HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA) 1.01 min (Z018_S04)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-Benzyl-1,1-dioxotetrahydro-2H-thiopyran-4-amine (2.00 g) was added to ethanol (40 mL) in a pressure bottle. Palladium hydroxide on carbon (0.587 g,) was added and the solution was stirred under 30 psi of hydrogen at room temperature for 2 hours. The mixture was filtered though a nylon membrane and the solvent was removed under vacuum. The mixture was filtered though a nylon membrane the solvent was removed under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-Benzyl-1,1-dioxotetrahydro-2H-thiopyran-4-amine (2.00 g) was added to ethanol (40 mL) in a pressure bottle. Palladium hydroxide on carbon (0.587 g,) was added and the solution was stirred under 30 psi of hydrogen at room temperature for 2 hours. The mixture was filtered though a nylon membrane and the solvent was removed under vacuum. The mixture was filtered though a nylon membrane the solvent was removed under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-Benzyl-1,1-dioxotetrahydro-2H-thiopyran-4-amine (2.00 g) was added to ethanol (40 mL) in a pressure bottle. Palladium hydroxide on carbon (0.587 g,) was added and the solution was stirred under 30 psi of hydrogen at room temperature for 2 hours. The mixture was filtered though a nylon membrane and the solvent was removed under vacuum. The mixture was filtered though a nylon membrane the solvent was removed under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of [6-(4,4-dimethylcyclohexyl)-2-methylthieno[2,3-d]pyrimidin-4-yl]methyl methanesulfonate (200 mg), DIPEA (139 μL), and DMF (3.0 mL) was added tetrahydro-2H-thiopyran-4-amine-1,1-dioxide (97 mg), followed by stirring at room temperature for 4 hours. To the reaction mixture was added a saturated aqueous NH4Cl solution, followed by extraction with EtOAc. The organic layer was washed sequentially with water and brine, dried over MgSO4, and then concentrated under reduced pressure. The residue was purified by silica gel column and dissolved in EtOAc, and 4 M HCl/EtOAc (137 μL) was added dropwise. The precipitate was collected by filtration and then dried to obtain N-{[6-(4,4-dimethylcyclohexyl)-2-methylthieno[2,3-d]pyrimidin-4-yl]methyl}tetrahydro-2H-thiopyran-4-amine-1,1-dioxide hydrochloride (165 mg). followed by extraction with EtOAc The organic layer was washed sequentially with water and brine dried over MgSO4 concentrated under reduced pressure The residue was purified by silica gel column dissolved in EtOAc 4 M HCl/EtOAc (137 μL) was added dropwise The precipitate was collected by filtration dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-Benzyl-1,1-dioxotetrahydro-2H-thiopyran-4-amine (2.00 g) was added to ethanol (40 mL) in a pressure bottle. Palladium hydroxide on carbon (0.587 g,) was added and the solution was stirred under 30 psi of hydrogen at room temperature for 2 hours. The mixture was filtered through a nylon membrane and the solvent was removed under vacuum. The mixture was filtered through a nylon membrane the solvent was removed under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-Benzyl-1,1-dioxotetrahydro-2H-thiopyran-4-amine (2.00 g) was added to ethanol (40 mL) in a pressure bottle. Palladium hydroxide on carbon (0.587 g) was added and the solution was stirred under 30 psi of hydrogen at room temperature for 2 hours. The mixture was filtered though a nylon membrane and the solvent was removed under vacuum. The mixture was filtered though a nylon membrane the solvent was removed under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound, MS: m/e=438.3 (M+H+), was prepared in accordance with the general method of example 3 from 2-chloro-5-iodo-quinoline (CAS 455955-26-7), 7-amino-2,3-dihydro-2,2-dimethylbenzofuran (CAS 68298-46-4) and 1,1-dioxo-tetrahydro-2H-thiopyran-4-amine.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-Benzyl-1,1-dioxotetrahydro-2H-thiopyran-4-amine (2.00 g) was added to ethanol (40 mL) in a pressure bottle. Palladium hydroxide on carbon (0.587 g) was added and the solution was stirred under 30 psi of hydrogen at room temperature for 2 hours. The mixture was filtered though a nylon membrane and the solvent was removed under vacuum. The mixture was filtered though a nylon membrane the solvent was removed under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N,N-Diisopropylethylamine (137 μL, 0.81 mmol), 4-dimethylaminopyridine (27 mg, 0.22 mmol) and 4-nitrophenyl chloroformate (45 mg, 0.22 mmol) is added to a solution of (R)-4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]-pyrimidin-4-yl)benzonitrile (example 1A, 80 mg, 0.20 mmol) in acetonitrile (2.0 mL), and the mixture is stirred at room temperature over night. 1,1-Dioxotetrahydro-2H-thiopyran-4-amine (74 mg, 0.40 mmol) is added, and the mixture is stirred for 1 h and purified by reversed phase HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA). Yield: 72 mg; ESI mass spectrum [M+H]+=573; Retention time HPLC: 1.01 min (Z018_S04). the mixture is stirred for 1 h purified by reversed phase HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA) 1.01 min (Z018_S04)