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

Participants

Reaction Steps

To a solution of (S)-ethyl 2-(2-(3-(2-(benzyloxy)-3,5-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 (40.4 mg, 0.038 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 vac to afford (S)-ethyl 2-(tert-butoxy)-2-(7-(4-(((R)-5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidin-1-yl)-2-(3-(3,5-difluoro-2-hydroxyphenyl)propyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (140 mg, 0.153 mmol, 81% yield) as thick paste. Used as is in the next step without further purification. 1H NMR (500 MHz, CDCl3) δ 7.70 (d, J=7.3 Hz, 4H), 7.45-7.34 (m, 6H), 6.75-6.63 (m, 2H), 6.34 (s, 1H), 5.90 (br. s., 1H), 4.33-4.10 (m, 3H), 3.95-3.79 (m, 1H), 3.35 (br. s., 2H), 2.92-2.76 (m, 3H), 2.73 (br. s., 1H), 2.61 (s, 3H), 2.16-2.04 (m, 3H), 1.92 (br. s., 1H), 1.87 (br. s., 1H), 1.53-1.46 (m, 3H), 1.45-1.26 (m, 9H), 1.24 (s, 9H), 1.07 (s, 9H). LCMS (M+H)=913.9.

Provenance & Evidence