(8aS)-2,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-3-one

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared starting from 100 mg (0.187 mmoles) of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide (WO 2005/002577), 79 mg (0.563 mmol) of (8aS)-hexahydropyrrolo[1,2-a]pyrazin-3(4H)-one (D12), 72 mg of copper iodide (0.378 mmol), 40 μl (0.375 mmol) of N,N-dimethylmethanediamine, 112.4 mg (0.375 mmol) of cesium carbonate; the reagents were dissolved in 4 ml of dioxane and heated at 80° C. for 4 h and then at 120° C. overnight. The crude material was purified on SPE cartridge (Silica) eluting with a gradient from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100% and affording 54 mg of the title compound as pale yellow solid. The title compound was prepared at 120° C. overnight The crude material was purified on SPE cartridge (Silica) eluting with a gradient from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100%

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1,1-Dimethylethyl (2S)-2-{[(chloroacetyl)amino]methyl}-1-pyrrolidinecarboxylate (D11; 1.24, 4.5 mmol), was dissolved in 20 ml of DCM and treated with TFA (5 ml) at room temperature. After 1 h complete conversion into the desired material was observed and the reaction mixture was loaded onto a SCX cartridge. The product obtained after elution with 2M NH3 in MeOH was then dissolved in acetonitrile (30 ml) and treated with sodium carbonate (1.43 g, 10.34 mmol). The reaction mixture was heated at 60° C. for 6 hours; the crude obtained after removal is purified by flash-chromatography eluting with dichloromethane/MeOH 95/5 affording 310 mg. The product obtained after elution with 2M NH3 in MeOH was then dissolved in acetonitrile (30 ml) the crude obtained after removal is purified by flash-chromatography eluting with dichloromethane/MeOH 95/5 affording 310 mg

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared starting from 100 mg (0.187 mmoles) of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide (WO 2005/002577), 79 mg (0.563 mmol) of (8aS)-hexahydropyrrolo[1,2-a]pyrazin-3(4H)-one (D12), 72 mg of copper iodide (0.378 mmol), 40 μl (0.375 mmol) of N,N-dimethylmethanediamine, 112.4 mg (0.375 mmol) of cesium carbonate; the reagents were dissolved in 4 ml of dioxane and heated at 80° C. for 4 h and then at 120° C. overnight. The crude material was purified on SPE cartridge (Silica) eluting with a gradient from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100% and affording 54 mg of the title compound as pale yellow solid. The title compound was prepared at 120° C. overnight The crude material was purified on SPE cartridge (Silica) eluting with a gradient from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100%

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1,1-Dimethylethyl (2S)-2-{[(chloroacetyl)amino]methyl}-1-pyrrolidinecarboxylate (D11; 1.24, 4.5 mmol), was dissolved in 20 ml of DCM and treated with TFA (5 ml) at room temperature. After 1 h complete conversion into the desired material was observed and the reaction mixture was loaded onto a SCX cartridge. The product obtained after elution with 2M NH3 in MeOH was then dissolved in acetonitrile (30 ml) and treated with sodium carbonate (1.43 g, 10.34 mmol). The reaction mixture was heated at 60° C. for 6 hours; the crude obtained after removal is purified by flash-chromatography eluting with dichloromethane/MeOH 95/5 affording 310 mg. The product obtained after elution with 2M NH3 in MeOH was then dissolved in acetonitrile (30 ml) the crude obtained after removal is purified by flash-chromatography eluting with dichloromethane/MeOH 95/5 affording 310 mg

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared starting from 100 mg (0.187 mmoles) of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl) -3-pyridinyl]-N,2-dimethylpropanamide (WO 2005/002577), 79 mg (0.563 mmol) of (8aS) -hexahydropyrrolo[1,2-a]pyrazin-3(4H)-one (D12), 72 mg of copper iodide (0.378 mmol), 40 μl (0.375 mmol) of N,N-dimethylmethanediamine, 112.4 mg (0.375 mmol) of cesium carbonate; the reagents were dissolved in 4 ml of dioxane and heated at 80° C. for 4 h and then at 120° C. overnight. The crude material was purified on SPE cartridge (Silica) eluting with a gradient from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100% and affording 54 mg of the title compound as pale yellow solid. The title compound was prepared at 120° C. overnight The crude material was purified on SPE cartridge (Silica) eluting with a gradient from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100%

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared starting from 100 mg (0.187 mmoles) of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl) -3-pyridinyl]-N,2-dimethylpropanamide (WO 2005/002577), 79 mg (0.563 mmol) of (8aS) -hexahydropyrrolo[1,2-a]pyrazin-3(4H)-one (D12), 72 mg of copper iodide (0.378 mmol), 40 μl (0.375 mmol) of N,N-dimethylmethanediamine, 112.4 mg (0.375 mmol) of cesium carbonate; the reagents were dissolved in 4 ml of dioxane and heated at 80° C. for 4 h and then at 120° C. overnight. The crude material was purified on SPE cartridge (Silica) eluting with a gradient from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100% and affording 54 mg of the title compound as pale yellow solid. The title compound was prepared at 120° C. overnight The crude material was purified on SPE cartridge (Silica) eluting with a gradient from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100%

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1,1-Dimethylethyl (2S)-2-{[(chloroacetyl)amino]methyl}-1-pyrrolidinecarboxylate (D 11; 1.24, 4.5 mmol), was dissolved in 20 ml of DCM and treated with TFA (5 ml) at room temperature. After 1 h complete conversion into the desired material was observed and the reaction mixture was loaded onto a SCX cartridge. The product obtained after elution with 2M NH3 in MeOH was then dissolved in acetonitrile (30 ml) and treated with sodium carbonate (1.43 g, 10.34 mmol). The reaction mixture was heated at 60° C. for 6 hours; the crude obtained after removal is purified by flash-chromatography eluting with dichloromethane/MeOH 95/5 affording 310 mg. The product obtained after elution with 2M NH3 in MeOH was then dissolved in acetonitrile (30 ml) the crude obtained after removal is purified by flash-chromatography eluting with dichloromethane/MeOH 95/5 affording 310 mg

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared starting from 100 mg (0.187 mmoles) of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide (WO 2005/002577), 79 mg (0.563 mmol) of (8aS)-hexahydropyrrolo[1,2-a]pyrazin-3(4H)-one (D12), 72 mg of copper iodide (0.378 mmol), 40 μl (0.375 mmol) of N,N-dimethylmethanediamine, 112.4 mg (0.375 mmol) of cesium carbonate; the reagents were dissolved in 4 ml of dioxane and heated at 80° C. for 4 h and then at 120° C. overnight. The crude material was purified on SPE cartridge (Silica) eluting with a gradient from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100% and affording 54 mg of the title compound as pale yellow solid. The title compound was prepared at 120° C. overnight The crude material was purified on SPE cartridge (Silica) eluting with a gradient from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100%

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1,1-Dimethylethyl (2S)-2-{[(chloroacetyl)amino]methyl}-1-pyrrolidinecarboxylate (D11; 1.24, 4.5 mmol), was dissolved in 20 ml of DCM and treated with TFA (5 ml) at room temperature. After 1 h complete conversion into the desired material was observed and the reaction mixture was loaded onto a SCX cartridge. The product obtained after elution with 2M NH3 in MeOH was then dissolved in acetonitrile (30 ml) and treated with sodium carbonate (1.43 g, 10.34 mmol). The reaction mixture was heated at 60° C. for 6 hours; the crude obtained after removal is purified by flash-chromatography eluting with dichloromethane/MeOH 95/5 affording 310 mg. The product obtained after elution with 2M NH3 in MeOH was then dissolved in acetonitrile (30 ml) the crude obtained after removal is purified by flash-chromatography eluting with dichloromethane/MeOH 95/5 affording 310 mg

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared starting from 100 mg (0.187 mmoles) of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide (WO 2005/002577), 79 mg (0.563 mmol) of (8aS)-hexahydropyrrolo[1,2-a]pyrazin-3(4H)-one (D12), 72 mg of copper iodide (0.378 mmol), 40 μl (0.375 mmol) of N,N-dimethylmethanediamine, 112.4 mg (0.375 mmol) of cesium carbonate; the reagents were dissolved in 4 ml of dioxane and heated at 80° C. for 4 h and then at 120° C. overnight. The crude material was purified on SPE cartridge (Silica) eluting with a gradient from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100% and affording 54 mg of the title compound as pale yellow solid. The title compound was prepared at 120° C. overnight The crude material was purified on SPE cartridge (Silica) eluting with a gradient from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100%

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1,1-Dimethylethyl (2S)-2-{[(chloroacetyl)amino]methyl}-1-pyrrolidinecarboxylate (D11; 1.24, 4.5 mmol), was dissolved in 20 ml of DCM and treated with TFA (5 ml) at room temperature. After 1 h complete conversion into the desired material was observed and the reaction mixture was loaded onto a SCX cartridge. The product obtained after elution with 2M NH3 in MeOH was then dissolved in acetonitrile (30 ml) and treated with sodium carbonate (1.43 g, 10.34 mmol). The reaction mixture was heated at 60° C. for 6 hours; the crude obtained after removal is purified by flash-chromatography eluting with dichloromethane/MeOH 95/5 affording 310 mg. The product obtained after elution with 2M NH3 in MeOH was then dissolved in acetonitrile (30 ml) the crude obtained after removal is purified by flash-chromatography eluting with dichloromethane/MeOH 95/5 affording 310 mg