(S)-2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((2,4-difluoro-6-((S)-pent-4-en-2-yloxy)benzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetic acid → (2S)-2-(tert-butoxy)-2-[(20S)-14,16-difluoro-4,20,26-trimethyl-11,19,25-trioxa-1,5,7,8-tetraazapentacyclo[24.2.2.16,9.02,7.013,18]hentriaconta-2,4,6(31),8,13,15,17,22-octaen-3-yl]acetic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of (S)-2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((2,4-difluoro-6-((S)-pent-4-en-2-yloxy)benzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetic acid (0.030 g, 0.046 mmol) in DCE (4 mL) were added Hoveyda-Grubbs catalyst 2nd generation (7.16 mg, 0.011 mmol) and copper(I) iodide (8.70 mg, 0.046 mmol) and the mixture was stirred at 90° C. After 1.5 h, the mixture was cooled to rt and filtered and concentrated. The crude material was purified via preparative HPLC to afford (2S)-2-(tert-butoxy)-2-[(20S)-14,16-difluoro-4,20,26-trimethyl-11,19,25-trioxa-1,5,7,8-tetraazapentacyclo[24.2.2.16,9.02,7.013,18]hentriaconta-2,4,6(31),8,13,15,17,22-octaen-3-yl]acetic acid (2.4 mg, 5.67% yield). 1H NMR (500 MHz, DMSO-d6) δ: 6.91 (d, J=11.7 Hz, 1H), 6.77 (t, J=9.5 Hz, 1H), 6.51 (s, 1H), 6.09-5.95 (m, 1H), 5.87 (d, J=8.1 Hz, 1H), 5.81-5.62 (m, 1H), 4.81-4.61 (m, 4H), 4.57-4.39 (m, 2H), 3.96-3.70 (m, 3H), 2.61-2.39 (m, 7H), 1.96-1.79 (m, 2H), 1.75-1.61 (m, 1H), 1.61-1.46 (m, 1H), 1.29 (s, 1H), 1.24-1.19 (m, 3H), 1.18-1.12 (m, 9H). LCMS (M+H) calcd for C33H43F2N4O6: 629.31. found: 629.3.

Provenance & Evidence