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

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 8 ml sealed vial was charged with 100 mg (0.187 mmol) of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide (WO 2005/002577), 78.6 mg (0.561 mmol) of (8aS)-hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one (WO 2003/066635), 52 mg (0.374 mmol) of potassium carbonate; the reagents were dissolved in 0.8 ml of DMSO. The reaction mixture was heated at 180° C. for 36-48 hrs 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 from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100% and affording 23 mg of the desired compound. A 8 ml sealed vial back extracted with DCM the crude material was purified on SPE cartridge (Silica) eluting with a gradient from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100%

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared starting from 50 mg (0.094 mmoles) of 1-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]cyclopropanecarboxamide (D2), 39 mg (0.278 mmol) of (8aS)-hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one (WO 2003/066635), 26.2 mg (0.189 mmol) of potassium carbonate; the reagents were dissolved in 0.4 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 from cyclohexane/ethyl acetate 1:1, to ethyl acetate 100% and affording 26 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 from cyclohexane/ethyl acetate 1:1, to ethyl acetate 100%

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 8 ml sealed vial was charged with 100 mg (0.161 mmoles) of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide (WO 2005/002577), 67 mg (0.483 mmol) of (8aS)-hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one (WO 2003/066635), 44.5 mg (0.322 mmol) of potassium carbonate; the reagents were dissolved in 0.8 ml of DMSO. The reaction mixture was heated at 180° C. for 36-48 hrs 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 from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100% and affording 56 mg of the title compound as pale yellow solid. A 8 ml sealed vial back extracted with DCM the crude material was purified on SPE cartridge (Silica) eluting with a gradient from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100%

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 8 ml sealed vial was charged with 100 mg (0.187 mmol) of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide (WO 2005/002577), 78.6 mg (0.561 mmol) of (8aS)-hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one (WO 2003/066635), 52 mg (0.374 mmol) of potassium carbonate; the reagents were dissolved in 0.8 ml of DMSO. The reaction mixture was heated at 180° C. for 36-48 hrs and then added to a saturated NH4Cl solution and back extracted with dichloromethane; 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 52 mg of the title compound as pale yellow solid. A 8 ml sealed vial back extracted with dichloromethane the crude material was purified on SPE cartridge (Silica) eluting with a gradient from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100%

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 8 ml sealed vial was charged with 100 mg (0.187 mmol) of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide (WO 2005/002577), 78.6 mg (0.561 mmol) of (8aS)-hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one (WO 2003/066635), 52 mg (0.374 mmol) of potassium carbonate; the reagents were dissolved in 0.8 ml of DMSO. The reaction mixture was heated at 180° C. for 36-48 hrs 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 from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100% and affording 23 mg of the desired compound. A 8 ml sealed vial back extracted with DCM the crude material was purified on SPE cartridge (Silica) eluting with a gradient from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100%

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 8 ml sealed vial was charged with 100 mg (0.187 mmol) of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide (WO 2005/002577), 78.6 mg (0.561 mmol) of (8aS)-hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one (WO 2003/066635), 52 mg (0.374 mmol) of potassium carbonate; the reagents were dissolved in 0.8 ml of DMSO. The reaction mixture was heated at 180° C. for 36-48 hrs 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 from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100% and affording 23 mg of the desired compound. A 8 ml sealed vial back extracted with DCM the crude material was purified on SPE cartridge (Silica) eluting with a gradient from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100%

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared starting from 50 mg (0.094 mmoles) of 1-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]cyclopropanecarboxamide (D2), 39 mg (0.278 mmol) of (8aS)-hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one (WO 2003/066635), 26.2 mg (0.189 mmol) of potassium carbonate; the reagents were dissolved in 0.4 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 from cyclohexane/ethyl acetate 1:1, to ethyl acetate 100% and affording 26 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 from cyclohexane/ethyl acetate 1:1, to ethyl acetate 100%

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 8 ml sealed vial was charged with 100 mg (0.161 mmoles) of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide (WO 2005/002577), 67 mg (0.483 mmol) of (8aS)-hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one (WO 2003/066635), 44.5 mg (0.322 mmol) of potassium carbonate; the reagents were dissolved in 0.8 ml of DMSO. The reaction mixture was heated at 180° C. for 36-48 hrs 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 from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100% and affording 56 mg of the title compound as pale yellow solid. A 8 ml sealed vial back extracted with DCM the crude material was purified on SPE cartridge (Silica) eluting with a gradient from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100%

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 8 ml sealed vial was charged with 100 mg (0.187 mmol) of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide (WO 2005/002577), 78.6 mg (0.561 mmol) of (8aS)-hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one (WO 2003/066635), 52 mg (0.374 mmol) of potassium carbonate; the reagents were dissolved in 0.8 ml of DMSO. The reaction mixture was heated at 180° C. for 36-48 hrs and then added to a saturated NH4Cl solution and back extracted with dichloromethane; 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 52 mg of the title compound as pale yellow solid. A 8 ml sealed vial back extracted with dichloromethane the crude material was purified on SPE cartridge (Silica) eluting with a gradient from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100%

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 8 ml sealed vial was charged with 100 mg (0.187 mmol) of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide (WO 2005/002577), 78.6 mg (0.561 mmol) of (8aS)-hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one (WO 2003/066635), 52 mg (0.374 mmol) of potassium carbonate; the reagents were dissolved in 0.8 ml of DMSO. The reaction mixture was heated at 180° C. for 36-48 hrs and then added to a saturated NH4Cl solution and back extracted with dichloromethane; 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 52 mg of the title compound as pale yellow solid. A 8 ml sealed vial back extracted with dichloromethane the crude material was purified on SPE cartridge (Silica) eluting with a gradient from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100%

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 8 ml sealed vial was charged with 100 mg (0.187 mmol) of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide (WO2005/002577), 78.6 mg (0.561 mmol) of (8aS) -hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one (WO 2003/066635), 52 mg (0.374 mmol) of potassium carbonate; the reagents were dissolved in 0.8 ml of DMSO. The reaction mixture was heated at 180° C. for 36-48 hrs 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 from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100% and affording 23 mg of the desired compound. A 8 ml sealed vial back extracted with DCM the crude material was purified on SPE cartridge (Silica) eluting with a gradient from cyclohexane/ethyl acetate 9:1, to ethyl acetate 100%

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared starting from 50 mg (0.094 mmoles) of 1-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl) -3-pyridinyl]cyclopropanecarboxamide (D2), 39 mg (0.278 mmol) of (8aS) -hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one (WO 2003/066635), 26.2 mg (0.189 mmol) of potassium carbonate; the reagents were dissolved in 0.4 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 from cyclohexane/ethyl acetate 1:1, to ethyl acetate 100% and affording 26 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 from cyclohexane/ethyl acetate 1:1, to ethyl acetate 100%