Acetic Acid → 4-(3-Trifluoromethyl-benzyl)-piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide

Participants

Reaction Conditions

Reaction Steps

A solution of piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide hydrochloride (2 g, 6.0 mmol) in methanol (200 mL) was treated with N,N-diisopropylethylamine (2.2 mL, 12.6 mmol). The mixture was stirred at 25° C. for 10 min until a clear solution formed. At this time, the reaction was treated with acetic acid (1.75 mL, 30.6 mmol), 3-trifluoromethy-benzaldehyde (2.4 mL, 17.9 mmol) and sodium cyanoborohydride (1.1 g, 17.7 mmol). This mixture was stirred at 25° C. overnight. The reaction was then concentrated in vacuo and partitioned between methylene chloride and an aqueous phosphate buffer (pH=7). The organics were washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated in vacuo to give a solid. This solid was dissolved in methanol and absorbed onto silica gel (4 g). ISCO chromatography (330 g, Silica, gradient elution 5/95 methanol/methylene chloride) afforded 4-(3-trifluoromethyl-benzyl)-piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (1.56 g, 58%) as a white solid; LRMS for C19H19F3N6O2S (M+H)+ at m/z=453. The NMR spectrum obtained on the sample is compatible with its structure.

Provenance & Evidence