(S)-2-(3-哌啶基)乙酸甲酯

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 6-chloro-N-methyl-2-(propylthio)-N-(tetrahydro-2H-pyran-4-yl)nicotinamide (0.398 g, 1.21 mmol) was added to (S)-methyl 2-(piperidin-3-yl)acetate.HCl (0.353 g, 1.82 mmol) and potassium carbonate (0.753 g, 5.45 mmol) in butyronitrile (3 mL) was heated at 150° C. for 4 hours. The reaction mixture was diluted with DCM (60 mL), and washed sequentially with water (20 mL) and brine (20 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in DCM. Pure fractions were evaporated to dryness to afford methyl [(3S)-1-{5-[methyl(tetrahydro-2H-pyran-4-yl)carbamoyl]-6-(propylthio)pyridin-2-yl}piperidin-3-yl]acetate (0.310 g, 57%) as a white solid. washed sequentially with water (20 mL) and brine (20 mL) The organic layer was dried over MgSO4 filtered evaporated to afford crude product The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in DCM Pure fractions were evaporated to dryness

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: N-adamantan-1-yl-6-chloro-2-(propylthio)nicotinamide (0.365 g, 1 mmol) was added to (S)-methyl 2-(piperidin-3-yl)acetate.HCl (0.194 g, 1 mmol) and potassium carbonate (0.415 g, 3 mmol) in butyronitrile (4 mL) was heated at 150° C. for 2 hours. The reaction mixture was diluted with EtOAc (50 mL), and washed sequentially with water (20 mL) and brine (20 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in hexane. Pure fractions were evaporated to dryness to afford methyl {(3S)-1-[5-(adamantan-1-ylcarbamoyl)-6-(propylthio)pyridin-2-yl]piperidin-3-yl}acetate (0.215 g, 44%) as a white solid. washed sequentially with water (20 mL) and brine (20 mL) The organic layer was dried over MgSO4 filtered evaporated to afford crude product The crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in hexane Pure fractions were evaporated to dryness

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 6-chloro-N-methyl-2-(propylthio)-N-(tetrahydro-2H-pyran-4-yl)nicotinamide (0.398 g, 1.21 mmol) was added to (S)-methyl 2-(piperidin-3-yl)acetate.HCl (0.353 g, 1.82 mmol) and potassium carbonate (0.753 g, 5.45 mmol) in butyronitrile (3 mL) was heated at 150° C. for 4 hours. The reaction mixture was diluted with DCM (60 mL), and washed sequentially with water (20 mL) and brine (20 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in DCM. Pure fractions were evaporated to dryness to afford methyl [(3S)-1-{5-[methyl(tetrahydro-2H-pyran-4-yl)carbamoyl]-6-(propylthio)pyridin-2-yl}piperidin-3-yl]acetate (0.310 g, 57%) as a white solid. washed sequentially with water (20 mL) and brine (20 mL) The organic layer was dried over MgSO4 filtered evaporated to afford crude product The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in DCM Pure fractions were evaporated to dryness

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: N-adamantan-1-yl-6-chloro-2-(propylthio)nicotinamide (0.365 g, 1 mmol) was added to (S)-methyl 2-(piperidin-3-yl)acetate.HCl (0.194 g, 1 mmol) and potassium carbonate (0.415 g, 3 mmol) in butyronitrile (4 mL) was heated at 150° C. for 2 hours. The reaction mixture was diluted with EtOAc (50 mL), and washed sequentially with water (20 mL) and brine (20 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in hexane. Pure fractions were evaporated to dryness to afford methyl {(3S)-1-[5-(adamantan-1-ylcarbamoyl)-6-(propylthio)pyridin-2-yl]piperidin-3-yl}acetate (0.215 g, 44%) as a white solid. washed sequentially with water (20 mL) and brine (20 mL) The organic layer was dried over MgSO4 filtered evaporated to afford crude product The crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in hexane Pure fractions were evaporated to dryness