2,6-Lutidine → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(2-hydroxy-propyl)-1H-pyrazol-3-yl]-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in PCT WO 2004/052869 A1, Example 1, 106 mg, 0.32 mmol) was dissolved in methylene chloride (2 mL) and N,N-dimethylfomamide (two drops) at 25° C. under argon. To this solution was added dropwise a solution of oxalyl chloride in methylene chloride (2 M solution, 170 μL, 0.33 mmol) which produced gas evolution and it was then stirred at 25° C. for 30 minutes. After this time, the reaction was cooled to 0° C. and 2,6-lutidine (80 μL, 0.64 mmol) was added to the flask and it was stirred for 15 min. To this was then added a solution of 1-(3-amino-pyrazol-1-yl)-propan-2-ol (45 mg, 0.32 mmol) in methylene chloride (1 mL) and the reaction was allowed to warm up to 25° C. and stirred for 45 minutes. After this time the reaction was diluted with a small amount of methanol in methylene chloride and washed with aqueous 1 N hydrochloric acid solution (1×15 mL) and then a saturated aqueous brine solution (1×15 mL). The organics were then dried over sodium sulfate, filtered and concentrated in vacuo with silica gel (2 g) and purified by Biotage Flash Chromatography (40S column, Silica gel, 50% ethyl acetate/hexanes to 100% ethyl acetate) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(2-hydroxy-propyl)-1H-pyrazol-3-yl]-propionamide (88 mg, 61%, diastereomeric mixture 1:1) as a white foam: ES-HRMS m/e calcd for C21H28N3O4SCl (M+H)+ 454.1562, observed 454.1559.

Provenance & Evidence