Trifluoroacetic acid → HCID 72489373, compound

Participants

Reaction Steps

A suspension of the trifluoroacetic acid salt of 3-Amino-pyrrolidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-b]pyridine-2-yl)-amide (160 mg, 0.39 mmol) in methanol was treated with N,N-diisopropylethylamine (0.28 mL, 1.57 mmol). Stir the reaction at 25° C. for 30 min. The methanol is then removed in vacuo. 4-fluoro-3-(trifluoromethyl)benzaldehyde (0.08 mL, 0.59 mmol) and toluene are then added to the flask and the resulting mixture was stirred at 60° C. for 1 h and was then concentrated in vacuo. This procedure was repeated until the reaction mixture became homogenous when dissolved in toluene. After the final concentration to remove toluene, the reaction mixture was diluted with dichloroethane (15 mL) and then was treated with acetic acid (94 mg) and sodium triacetoxyborohydride (250 mg, 1.18 mmol). The resulting reaction mixture was allowed to stir at 25° C. overnight. At this time, the reaction mixture was poured into 1N NaOH and extracted into methylene chloride. The organics were washed with a saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 98:2 methylene chloride/methanol) afforded a colorless oil. The oil was dissolved in diethyl ether and then was concentrated in vacuo to afford 3-(4-Fluoro-3-trifluoromethyl-benzylamino)-pyrrolidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-b]pyridin-2-yl)-amide (19 mg, 25%) as a white solid. LRMS for C20H19F4N5O2S (M+H)30 at m/z=469. The NMR spectrum obtained on the sample is compatible with its structure.

Provenance & Evidence