(S)-2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-5-methyl-2-(((5-methyl-2-((S)-pent-4-en-2-yloxy)benzyl)oxy)methyl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetic acid → (2S)-2-(tert-butoxy)-2-[(20S)-4,15,20,26-tetramethyl-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)-5-methyl-2-(((5-methyl-2-((S)-pent-4-en-2-yloxy)benzyl)oxy)methyl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetic acid (32.7 mg, 0.052 mmol) in DCE (4 mL) were added Hoveyda-Grubbs catalyst 2nd generation (8.07 mg, 0.013 mmol) and copper(I) iodide (9.81 mg, 0.052 mmol) and the mixture was stirred at 90° C. After 3 h, the mixture was cooled to rt and concentrated. The crude material was purified via preparative HPLC to give (2S)-2-(tert-butoxy)-2-[(20S)-4,15,20,26-tetramethyl-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 (2.1 mg, 5.64% yield). 1H NMR (500 MHz, DMSO-d6) δ 7.10 (s, 1H), 7.03 (d, J=6.6 Hz, 1H), 6.88 (d, J=8.4 Hz, 1H), 6.52 (s, 1H), 6.08-5.93 (m, 1H), 5.78 (s, 1H), 5.75-5.67 (m, 1H), 4.82 (d, J=12.1 Hz, 1H), 4.71-4.56 (m, 4H), 4.56-4.39 (m, 2H), 4.01-3.79 (m, 2H), 3.73 (t, J=11.2 Hz, 1H), 3.35 (br. s., 1H), 3.17 (br. s., 1H), 2.74-2.59 (m, 1H), 2.45-2.31 (m, 2H), 2.29-2.14 (m, 5H), 1.89 (t, J=12.5 Hz, 2H), 1.68 (td, J=12.8, 4.0 Hz, 1H), 1.56 (td, J=13.0, 4.4 Hz, 1H), 1.26-1.19 (m, 6H), 1.19-1.01 (m, 9H). LCMS (M+H) calcd for C14H20FN3O4S: 607.35. found: 607.4.

Provenance & Evidence