(S)-2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((4-chloro-2-((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)-16-chloro-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-(((4-chloro-2-((S)-pent-4-en-2-yloxy)benzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetic acid (41.4 mg, 0.063 mmol) in DCE (2 mL) were added Hoveyda-Grubbs catalyst 2nd generation (9.90 mg, 0.016 mmol) and copper(I) iodide (12.03 mg, 0.063 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)-16-chloro-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 (2.9 mg, 4.62 μmol, 7.32% yield). 1H NMR (500 MHz, DMSO-d6) δ 7.31 (d, J=8.1 Hz, 1H), 7.10 (s, 1H), 6.94 (d, J=7.0 Hz, 1H), 6.48 (s, 1H), 6.34 (d, J=5.9 Hz, 1H), 5.65 (br. s., 1H), 4.75 (d, J=11.7 Hz, 1H), 4.67-4.47 (m, 5H), 4.34-4.22 (m, 1H), 3.64 (d, J=12.8 Hz, 1H), 3.39-3.27 (m, 6H), 2.49 (s, 3H), 2.41 (d, J=3.3 Hz, 1H), 2.27-2.15 (m, 1H), 1.82 (d, J=5.5 Hz, 3H), 1.68-1.55 (m, 1H), 1.32 (s, 3H), 1.20 (s, 12H). LCMS (M+H) calcd for C33H44ClN4O6: 627.29. found: 627.5.

Provenance & Evidence