Tetrabutylammonium Fluoride → (S)-ethyl 2-(tert-butoxy)-2-(2-(3-(4,5-difluoro-2-hydroxyphenyl)propyl)-7-(4-(((R)-5-hydroxyhexyl)oxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate

Participants

Reaction Steps

To a solution of (S)-ethyl 2-(2-(3-(2-(benzyloxy)-4,5-difluorophenyl)prop-1-en-1-yl)-7-(4-(((R)-5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (190 mg, 0.190 mmol) in ethanol (4 mL) was added 10% Pd—C (60.6 mg, 0.057 mmol) and the resulting mixture was stirred under balloon hydrogen atmosphere for 16 h. At this point LCMS indicates completion of reaction. Mixture was then filtered through a pad of celite, concentrated and dried under high vacuum. The residue was then treated with 1M TBAF (0.949 mL, 0.949 mmol) in THF (4 mL) for 16 h. Mixture was then concentrated and purified by Biotage (5-70% EtOAc/hexane) to afford to afford (S)-ethyl 2-(tert-butoxy)-2-(2-(3-(4,5-difluoro-2-hydroxyphenyl)propyl)-7-(4-(((R)-5-hydroxyhexyl)oxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (85 mg, 0.126 mmol, 66.4% yield) as thick paste. 1H NMR (500 MHz, CDCl3) 6.96-6.89 (m, 1H), 6.68 (dd, J=11.7, 7.1 Hz, 1H), 6.34 (s, 1H), 5.90 (br. s., 1H), 4.31-4.09 (m, 2H), 3.93-3.81 (m, 1H), 3.44 (br. s., 2H), 2.88-2.70 (m, 4H), 2.63 (s, 4H), 2.12-1.94 (m, 4H), 1.90 (br. s., 2H), 1.57-1.42 (m, 6H), 1.41-1.31 (m, 3H), 1.27-1.18 (m, 18H). LCMS (M+H)=675.6.

Provenance & Evidence