(S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((4-(2-((allyloxy)methyl)phenyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate → ethyl (2S)-2-(4,28-dimethyl-22,27-dioxa-1,5,7,8,11,12,13-heptazahexacyclo[26.2.2.16,9.111,14.02,7.015,20]tetratriaconta-2,4,6(34),8,12,14(33),15,17,19,24-decaen-3-yl)-2-[(2-methylpropan-2-yl)oxy]acetate

Participants

Reaction Steps

To a stirred solution of (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((4-(2-((allyloxy)methyl)phenyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.055 g, 0.082 mmol) in 1,2-dichloroethane (20 mL) was added at once Hoveyda-Grubbs catalyst 2nd generation (2.56 mg, 4.09 μmol) at 70° C. and refluxed for 5 h. Then, cooled, concentrated and purified by prep-HPLC to afford a mixture of products and one major isomer. Trans-isomer (0.0089 g, 0.014 mmol, 16.89% yield), off-white solid. 1H NMR (500 MHz, CDCl3) δ 8.37 (s, 1H), 7.94 (dd, J=1.1, 7.7 Hz, 1H), 7.39-7.46 (m, 2H), 7.32-7.36 (m, 1H), 6.73 (s, 1H), 6.00-6.13 (m, 2H), 5.98 (s, 1H), 5.89 (d, JAB=14.3 Hz, 1H), 5.65 (d, JAB=14.3 Hz, 1H), 4.58 (dt, J=2.3, 12.4 Hz, 1H), 4.49 (d, JAB=10.5 Hz, 1H), 4.40 (d, JAB=10.5 Hz, 1H), 4.08-4.22 (m, 4H), 3.95-4.05 (m, 2H), 3.75-3.82 (m, 1H), 3.03 (td, J=2.0, 11.5 Hz, 1H), 2.73-2.79 (m, 1H), 2.61 (s, 3H), 2.00 (dd, J=2.4, 13.6 Hz, 1H), 1.90 (dd, J=2.1, 13.7 Hz, 1H), 1.67-1.74 (m, 2H), 1.31 (s, 3H), 1.24 (s, 9H), 1.18 (t, J=7.1 Hz, 3H). LCMS (M+H)=644.6. This is contaminated with minor isomer.

Provenance & Evidence