2-Aminopyridine → 3-cyclopentyl-N-pyridin-2-yl-2-(4-pyridin-3-yl-phenyl)-propionamide

Temperature

0 °C

A solution of triphenylphosphine (133 mg, 0.51 mmol) in methylene chloride (5 mL) was cooled to 0° C. and then slowly treated with N-bromosuccinimide (90 mg, 0.51 mmol). The reaction mixture was stirred at 0° C. for 20 min and then treated with 3-cyclopentyl-2-(4-pyridin-3-yl-phenyl)-propionic acid (125 mg, 0.42 mmol). The resulting reaction mixture was stirred at 0° C. for 5 min and then allowed to warm to 25° C. where it was stirred for 20 min. The reaction mixture was then treated with 2-aminopyridine (88 mg, 0.93 mmol). The resulting reaction mixture was stirred at 25° C. for 15 h. The crude reaction mixture was then directly purified by flash chromatography (Merck Silica gel 60, 230-400 mesh, 1/2 hexanes/ethyl acetate) to afford impure 3-cyclopentyl-N-pyridin-2-yl-2-(4-pyridin-3-yl-phenyl)-propionamide as a pink foam. The impure foam was dissolved in methylene chloride (40 mL) and washed with a saturated aqueous sodium bicarbonate solution (1×40 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo to afford pure 3-cyclopentyl-N-pyridin-2-yl-2-(4-pyridin-3-yl-phenyl)-propionamide (75 mg, 48%) as a pink foam: mp 139-140° C.; EI-HRMS m/e calcd for C24H25N3O (M+) 371.1998, found 371.2006.

1. customThe resulting reaction mixture
2. stirringwas stirred at 0° C. for 5 min
3. temperatureto warm to 25° C. where it
4. stirringwas stirred for 20 min
5. customThe resulting reaction mixture
6. stirringwas stirred at 25° C. for 15 h
7. customThe crude reaction mixture
8. customwas then directly purified by flash chromatography (Merck Silica gel 60, 230-400 mesh, 1/2 hexanes/ethyl acetate)

ORD record

ord-d414c95f4ca740c991c0ebc3c6dbc083

Source dataset

uspto-grants-2002_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06384220B2