2,6-Lutidine → (R)-N-{1-[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-3-cyclopentyl-2-(4-methanesulfonyl-3-methoxy-phenyl)-propionamide

Participants

Reaction Conditions

Reaction Steps

In a round bottom flask under argon was placed (R)-3-cyclopentyl-2-(4-methanesulfonyl-3-methoxy-phenyl)-propionic acid (prepared in Example 100, 61 mg, 0.19 mmol) which was dissolved in methylene chloride (2 mL) and N,N-dimethylformamide (2 drops). To this solution was then added a solution of oxalyl chloride in methylene chloride (2.0 M solution, 100 μL, 0.20 mmol). Upon addition there was gas evolution. The reaction was stirred for 30 min at 25° C. After such time the reaction was cooled to 0° C. in an ice bath and 2,6-lutidine (47 μL, 0.38 mmol) and the reaction was stirred for 30 min at 0° C. To the solution was then added 1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-ylamine (prepared in Example 67, 45 mg, 0.19 mmol). The reaction was then warmed to 25° C. and stirred for 2 h. After this time, the reaction was quenched with a small amount of methanol and then concentrated with silica gel (2 g) in vacuo and purified on Biotage Flash chromatography system (40S column, silica gel, 50% ethyl acetate/hexanes) to afford (R)—N-{1-[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-3-cyclopentyl-2-(4-methanesulfonyl-3-methoxy-phenyl)-propionamide (15 mg, 15%).

Provenance & Evidence