Oxalyl chloride → 3-cyclopentyl-N-pyrimidin-4-yl-2-(3-trifluoromethyl-phenyl)-propionamide

Temperature

0 °C

A solution of 3-cyclopentyl-2-(3-trifluoromethyl-phenyl)-propionic acid (prepared as in Example 88, 152 mg, 0.532 mmol) in methylene chloride (10 mL) was treated with dry N,N-dimethylformamide (3 drops). The reaction mixture was cooled to 0° C. and then treated dropwise with a 2M solution of oxalyl chloride in methylene chloride (0.30 mL, 0.58 mmol). The reaction mixture was stirred at 0° C. for 10 min and then stirred at 25° C. for 30 min. The reaction mixture was then treated with N,N-diisopropylethylamine (0.22 mL, 1.26 mmol) followed by a solution of 4-aminopyrimidine (106 mg, 1.12 mmol) in dry tetrahydrofuran (5 mL). The resulting reaction mixture was stirred at 25° C. for 17 h. The reaction mixture was concentrated in vacuo. The resulting residue was adsorbed onto silica gel (Merck Silica gel 60, 230–400 mesh) and then purified via Biotage chromatography (FLASH 40S, Silica, 1/1 hexanes/ethyl acetate) to afford 3-cyclopentyl-N-pyrimidin-4-yl-2-(3-trifluoromethyl-phenyl)-propionamide (170 mg, 88%) as a white solid: mp 113–115° C.; EI-HRMS m/e calcd for C19H20F3N3O (M+) 363.1558, found 363.1553.

1. stirringstirred at 25° C. for 30 min
2. customThe resulting reaction mixture
3. stirringwas stirred at 25° C. for 17 h
4. concentrationThe reaction mixture was concentrated in vacuo
5. custompurified via Biotage chromatography (FLASH 40S, Silica, 1/1 hexanes/ethyl acetate)

ORD record

ord-0fce22c5a907405686cc788437233756

Source dataset

uspto-grants-2007_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07223868B2