Trifluoroacetic acid → 4-fluoro-N-{2-[3-(7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-ureido]-ethyl}-3-trifluoromethyl-benzamide

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Reaction Conditions

Reaction Steps

A solution of {2-[3-(7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-ureido]-ethyl}-carbamic acid tert-butyl ester (170 mg, 0.46 mmol) was treated with trifluoroacetic acid (80 μL, 0.57 mmol). The reaction was stirred at 25° C. for 1 h. The reaction was then concentrated in vacuo, triturated with diethyl ether, collected by filtration and dried in vacuo. A portion of the resulting trifluoroacetic acid salt of 3-amino-pyrrolidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (88 mg, 0.23 mmol) in methylene chloride at 25° C. was treated with 4-fluoro-3-(trifluoromethyl)benzoyl chloride (70 mL, 0.46 mmol). The resulting solution was stirred at 25° C. overnight. Flash chromatography (Merck Silica gel 60, 230-400 mesh, gradient elution 3:1 ethyl acetate/hexanes to 100% ethyl acetate) afforded 4-fluoro-N-{2-[3-(7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-ureido]-ethyl}-3-trifluoromethyl-benzamide (25 mg, 11.8%) as a white solid; ES-HRMS m/e calcd for C17H14F4N6O3S (M+H)+ 459.0857, found 459.0862.

Provenance & Evidence