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

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared starting from 250 mg (0.47 mmole) of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide (WO 2005/002577), (8aR)-hexahydropyrrolo[1,2-a]pyrazin-4(1H)-one (D4), 164.4 mg (1.17 mmol), 130 mg of potassium carbonate (0.94 mmol); the reagents were dissolved in 1.5 ml of DMSO. The reaction mixture was heated at 150° C. overnight and then added to a saturated NH4Cl solution and back extracted with DCM; the crude material was purified on SPE cartridge (Silica) eluting with a gradient cyclohexane/ethyl acetate 9:1, to ethyl acetate 100% and affording 115 mg of the title compound as pale yellow solid. The title compound was prepared back extracted with DCM the crude material was purified on SPE cartridge (Silica) eluting with a gradient cyclohexane/ethyl acetate 9:1, to ethyl acetate 100%

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

実験手順: 1,1-Dimethylethyl (2R)-2-({[2-(methyloxy)-2-oxoethyl]amino}methyl)-1-pyrrolidinecarboxylate (D3; 800 mg, 2.94 mmol) was dissolved in methylene chloride (10 ml) and treated with trifluoroacetic acid (2.5 ml) for 2 h. The reaction mixture was loaded as such on a SCX column and the non-basic compounds were washed away with methanol. The ninhydrine-positive fractions eluted with 1M methanolic ammonia were concentrated under vacuum at 40° C. for 30 min, isolating the title compound as a pale yellow oil: 410 mg, 2.92 mmol, 99% yield. the non-basic compounds were washed away with methanol The ninhydrine-positive fractions eluted with 1M methanolic ammonia were concentrated under vacuum at 40° C. for 30 min

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared starting from 250 mg (0.47 mmole) of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide (WO 2005/002577), (8aR)-hexahydropyrrolo[1,2-a]pyrazin-4(1H)-one (D4), 164.4 mg (1.17 mmol), 130 mg of potassium carbonate (0.94 mmol); the reagents were dissolved in 1.5 ml of DMSO. The reaction mixture was heated at 150° C. overnight and then added to a saturated NH4Cl solution and back extracted with DCM; the crude material was purified on SPE cartridge (Silica) eluting with a gradient cyclohexane/ethyl acetate 9:1, to ethyl acetate 100% and affording 115 mg of the title compound as pale yellow solid. The title compound was prepared back extracted with DCM the crude material was purified on SPE cartridge (Silica) eluting with a gradient cyclohexane/ethyl acetate 9:1, to ethyl acetate 100%

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared starting from 250 mg (0.47 mmole) of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide (WO 2005/002577), (8aR)-hexahydropyrrolo[1,2-a]pyrazin-4(1H)-one (D4), 164.4 mg (1.17 mmol), 130 mg of potassium carbonate (0.94 mmol); the reagents were dissolved in 1.5 ml of DMSO. The reaction mixture was heated at 150° C. overnight and then added to a saturated NH4Cl solution and back extracted with DCM; the crude material was purified on SPE cartridge (Silica) eluting with a gradient cyclohexane/ethyl acetate 9:1, to ethyl acetate 100% and affording 115 mg of the title compound as pale yellow solid. The title compound was prepared back extracted with DCM the crude material was purified on SPE cartridge (Silica) eluting with a gradient cyclohexane/ethyl acetate 9:1, to ethyl acetate 100%

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

実験手順: 1,1-Dimethylethyl (2R)-2-({[2-(methyloxy)-2-oxoethyl]amino}methyl)-1-pyrrolidinecarboxylate (D3; 800 mg, 2.94 mmol) was dissolved in methylene chloride (10 ml) and treated with trifluoroacetic acid (2.5 ml) for 2 h. The reaction mixture was loaded as such on a SCX column and the non-basic compounds were washed away with methanol. The ninhydrine-positive fractions eluted with 1M methanolic ammonia were concentrated under vacuum at 40° C. for 30 min, isolating the title compound as a pale yellow oil: 410 mg, 2.92 mmol, 99% yield. the non-basic compounds were washed away with methanol The ninhydrine-positive fractions eluted with 1M methanolic ammonia were concentrated under vacuum at 40° C. for 30 min

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

実験手順: 1,1-Dimethylethyl (2R)-2-({[2-(methyloxy)-2-oxoethyl]amino}methyl)-1-pyrrolidinecarboxylate (D3; 800 mg, 2.94 mmol) was dissolved in methylene chloride (10 ml) and treated with trifluoroacetic acid (2.5 ml) for 2 h. The reaction mixture was loaded as such on a SCX column and the non-basic compounds were washed away with methanol. The ninhydrine-positive fractions eluted with 1M methanolic ammonia were concentrated under vacuum at 40° C. for 30 min, isolating the title compound as a pale yellow oil: 410 mg, 2.92 mmol, 99% yield. the non-basic compounds were washed away with methanol The ninhydrine-positive fractions eluted with 1M methanolic ammonia were concentrated under vacuum at 40° C. for 30 min

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared starting from 250 mg (0.47 mmole) of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl) -3-pyridinyl]-N,2-dimethylpropanamide (WO 2005/002577), (8aR)-hexahydropyrrolo[1,2-a]pyrazin-4(1H)-one (D4), 164.4 mg (1.17 mmol), 130 mg of potassium carbonate (0.94 mmol); the reagents were dissolved in 1.5 ml of DMSO. The reaction mixture was heated at 150° C. overnight and then added to a saturated NH4Cl solution and back extracted with DCM; the crude material was purified on SPE cartridge (Silica) eluting with a gradient cyclohexane/ethyl acetate 9:1, to ethyl acetate 100% and affording 115 mg of the title compound as pale yellow solid. The title compound was prepared back extracted with DCM the crude material was purified on SPE cartridge (Silica) eluting with a gradient cyclohexane/ethyl acetate 9:1, to ethyl acetate 100%

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared starting from 250 mg (0.47 mmole) of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl) -3-pyridinyl]-N,2-dimethylpropanamide (WO 2005/002577), (8aR)-hexahydropyrrolo[1,2-a]pyrazin-4(1H)-one (D4), 164.4 mg (1.17 mmol), 130 mg of potassium carbonate (0.94 mmol); the reagents were dissolved in 1.5 ml of DMSO. The reaction mixture was heated at 150° C. overnight and then added to a saturated NH4Cl solution and back extracted with DCM; the crude material was purified on SPE cartridge (Silica) eluting with a gradient cyclohexane/ethyl acetate 9:1, to ethyl acetate 100% and affording 115 mg of the title compound as pale yellow solid. The title compound was prepared back extracted with DCM the crude material was purified on SPE cartridge (Silica) eluting with a gradient cyclohexane/ethyl acetate 9:1, to ethyl acetate 100%

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

実験手順: 1,1-Dimethylethyl (2R)-2-({[2-(methyloxy)-2-oxoethyl]amino}methyl)-1-pyrrolidinecarboxylate (D3; 800 mg, 2.94 mmol) was dissolved in methylene chloride (10 ml) and treated with trifluoroacetic acid (2.5 ml) for 2 h. The reaction mixture was loaded as such on a SCX column and the non-basic compounds were washed away with methanol. The ninhydrine-positive fractions eluted with 1M methanolic ammonia were concentrated under vacuum at 40° C. for 30 min, isolating the title compound as a pale yellow oil: 410 mg, 2.92 mmol, 99% yield. the non-basic compounds were washed away with methanol The ninhydrine-positive fractions eluted with 1M methanolic ammonia were concentrated under vacuum at 40° C. for 30 min

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

実験手順: 1,1-Dimethylethyl (2R)-2-({[2-(methyloxy)-2-oxoethyl]amino}methyl)-1-pyrrolidinecarboxylate (D3; 800 mg, 2.94 mmol) was dissolved in methylene chloride (10 ml) and treated with trifluoroacetic acid (2.5 ml) for 2 h. The reaction mixture was loaded as such on a SCX column and the non-basic compounds were washed away with methanol. The ninhydrine-positive fractions eluted with 1M methanolic ammonia were concentrated under vacuum at 40° C. for 30 min, isolating the title compound as a pale yellow oil: 410 mg, 2.92 mmol, 99% yield. the non-basic compounds were washed away with methanol The ninhydrine-positive fractions eluted with 1M methanolic ammonia were concentrated under vacuum at 40° C. for 30 min

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared starting from 250 mg (0.47 mmole) of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide (WO 2005/002577), (8aR)-hexahydropyrrolo[1,2-a]pyrazin-4(1H)-one (D4), 164.4 mg (1.17 mmol), 130 mg of potassium carbonate (0.94 mmol); the reagents were dissolved in 1.5 ml of DMSO. The reaction mixture was heated at 150° C. overnight and then added to a saturated NH4Cl solution and back extracted with DCM; the crude material was purified on SPE cartridge (Silica) eluting with a gradient cyclohexane/ethyl acetate 9:1, to ethyl acetate 100% and affording 115 mg of the title compound as pale yellow solid. The title compound was prepared back extracted with DCM the crude material was purified on SPE cartridge (Silica) eluting with a gradient cyclohexane/ethyl acetate 9:1, to ethyl acetate 100%

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

実験手順: 1,1-Dimethylethyl (2R)-2-({[2-(methyloxy)-2-oxoethyl]amino}methyl)-1-pyrrolidinecarboxylate (D3; 800 mg, 2.94 mmol) was dissolved in methylene chloride (10 ml) and treated with trifluoroacetic acid (2.5 ml) for 2 h. The reaction mixture was loaded as such on a SCX column and the non-basic compounds were washed away with methanol. The ninhydrine-positive fractions eluted with 1M methanolic ammonia were concentrated under vacuum at 40° C. for 30 min, isolating the title compound as a pale yellow oil: 410 mg, 2.92 mmol, 99% yield. the non-basic compounds were washed away with methanol The ninhydrine-positive fractions eluted with 1M methanolic ammonia were concentrated under vacuum at 40° C. for 30 min