Reaction Steps
.(S,E)-Methyl 2-(7-(4-(buta-1,3-dien-1-yl)-4-methylpiperidin-1-yl)-2-(5′-chloro-2′-hydroxy-[1,1′-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (90 mg, 0.143 mmol) was dissolved in DMF (3 mL). Solid K2CO3 (39.5 mg, 0.286 mmol) was added and the mixture was heated to 90° C. for 1 h. The reaction was then cooled to rt and treated with 3-bromoprop-1-ene (0.024 mL, 0.286 mmol) and allowed to stir at rt for 18 h. The reaction was partitioned between EtOAc and water. The organic phase was washed with water, dried (Na2SO4), filtered, and concentrated in vacuo to yield (S,E)-methyl 2-(2-(2′-(allyloxy)-5′-chloro-[1,1′-biphenyl]-3-yl)-7-(4-(buta-1,3-dien-1-yl)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (90 mg, 0.134 mmol, 94% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.18 (br. s., 1H), 8.07-8.00 (m, 1H), 7.60-7.48 (m, 2H), 7.42 (d, J=2.7 Hz, 1H), 7.31 (d, J=2.7 Hz, 1H), 6.95 (d, J=8.8 Hz, 1H), 6.85 (s, 1H), 6.39 (dt, J=17.0, 10.1 Hz, 1H), 6.16 (dd, J=15.5, 10.1 Hz, 1H), 6.08 (s, 1H), 5.98 (ddt, J=17.3, 10.6, 4.8 Hz, 1H), 5.88 (d, J=15.7 Hz, 1H), 5.40-5.33 (m, 1H), 5.25-5.15 (m, 2H), 5.03 (d, J=10.0 Hz, 1H), 5.00-2.50 (m, 4 H), 4.56 (dt, J=4.8, 1.6 Hz, 2H), 3.74 (s, 3H), 2.64 (s, 3H), 1.97-1.63 (m, 4H), 1.32-1.23 (m, 12H). LCMS (M+1)=669.3.
