3-methylpyrrolidine

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-[3-(3-bromo-pyridin-2-yl)-azetidin-1-yl]-quinoline (339 mg, 1 mmol), 3-methyl-pyrrolidine (93.5 mg, 1.1 mmol), BINAP (31.1 mg, 0.05 mmol), t-BuONa (196 mg, 2 mmol) in dioxane (25 mL) was added Pd2(dba)3 (45.75 mg, 0.05 mmol) then the reaction mixture was stirred at 90° C. under nitrogen atmosphere overnight. The reaction mixture was filtered through CELITE® and washed with EtOAc (50 mL). The filtrate was concentrated and the crude product was purified by ISCO silica gel column (10% to 80% EtOAc in petroleum ether) to give 2-{3-[3-(3-methyl-pyrrolidin-1-yl)-pyridin-2-yl]-azetidin-1-yl}-quinoline (64 mg, 0.19 mmol, yield 19%). The reaction mixture was filtered through CELITE® washed with EtOAc (50 mL) The filtrate was concentrated the crude product was purified by ISCO silica gel column (10% to 80% EtOAc in petroleum ether)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-(3-chloro-pyrazin-2-yl)-azetidine-1-carboxylic acid tert-butyl ester (7) (200 mg, 0.74 mmol, Preparation 2) and 3-methyl-pyrrolidine (42) (69.2 mg, 0.84 mmol) in DMSO (5 mL) was added Et3N (149.5 mg, 1.48 mmol). The reaction mixture was stirred at 100° C. overnight. The reaction mixture was diluted with water, extracted with EtOAc (30 mL×3). The combined organic extracts were washed with water (30 mL) and brine (30 mL), dried over Na2SO4 and filtered. The filtrate was evaporated in vacuo and the residue was purified by flash column chromatography on silica gel to give 3-[3-(3-methyl-pyrrolidin-1-yl)-pyrazin-2-yl]-azetidine-1-carboxylic acid tert-butyl ester (43) (194 mg, 0.56 mmol, yield 75.99%). extracted with EtOAc (30 mL×3) The combined organic extracts were washed with water (30 mL) and brine (30 mL) dried over Na2SO4 filtered The filtrate was evaporated in vacuo the residue was purified by flash column chromatography on silica gel