Pyridine → 3-cyclopentyl-2(R)-(3,4-dichlorophenyl)-N-pyrimidin-4-yl-propionamide

Temperature

0 °C

A solution of 3-cyclopentyl-2(R)-(3,4-dichlorophenyl)-propionic acid (prepared as in Example 54A, 200 mg, 0.69 mmol) in methylene chloride (5 mL) was treated with 1 drop of N,N-dimethylformamide and then cooled to 0° C. The reaction mixture was then treated with a 2.0M solution of oxalyl chloride in methylene chloride (0.52 mL, 1.04 mmol). The reaction mixture was stirred at 0° C. for 30 min and then treated with a solution of 4-aminopyrimidine (131 mg, 1.38 mmol) in tetrahydrofuran (10 mL) and pyridine (0.28 mL, 3.45 mmol). The resulting reaction mixture was stirred at 23° C. for 14 h. The reaction mixture was then diluted with water (10 mL) and extracted with methylene chloride (3×15 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 3/2 hexanes/ethyl acetate) afforded 3-cyclopentyl-2(R)-(3,4-dichloro-phenyl)-N-pyrimidin-4-yl-propionamide (147 mg, 60%) as a white solid: mp 166.5-169.3° C.; EI-HRMS m/e calcd for C18H19Cl2N3O (M+) 363.0905, found 363.0909.

1. customThe resulting reaction mixture
2. stirringwas stirred at 23° C. for 14 h
3. extractionextracted with methylene chloride (3×15 mL)
4. dry with materialThe combined organic layers were dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo

ORD record

ord-eb61848511db4c0084ef7c982024ced8

Source dataset

uspto-grants-2003_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06610846B1