Reaction Steps
To a solution of (S)-4-bromo-3-(pent-4-en-2-yloxy)benzonitrile (0.136 g, 0.51 mmol, 1.5 equiv) in THF (3.4 mL) was added Reike zinc (0.67 mL of a 10 g/100 mL slurry in THF, 1.03 mmol, 3 equiv). The reaction was then heated at 60° C. for 2 h. Upon cooling to ambient temperature, the zincate solution was filtered and added to a solution of (S)-methyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.20 g, 0.34 mmol, 1 equiv) in THF (1.7 mL). The reaction was then heated at 60° C. for 18 h. Upon cooling to ambient temperature, the reaction was diluted with EtOAc and washed with a saturated aqueous solution of NaHCO3. The EtOAc layer was dried (Na2SO4) and concentrated in vacuo. The crude product was purified by flash column chromatography (0-100% EtOAc in hexane) to provide the product as a colorless oil (0.14 g, 59%). 1H NMR (400 MHz, CDCl3) [note: 4H of piperidine not observed] δ 8.12 (s, 1H), 8.07 (d, J=6.8 Hz, 1H), 7.56-7.48 (m, 3H), 7.36 (dd, J=7.8, 1.3 Hz, 1H), 7.24 (s, 1H), 6.85 (br. s., 1H), 6.06-5.92 (m, J=11.2, 11.2, 5.0 Hz, 2H), 5.72 (s, 1H), 5.40 (dd, J=17.1, 1.5 Hz, 1H), 5.13-5.05 (m, J=3.5 Hz, 2H), 5.03 (s, 1H), 4.52-4.43 (m, J=5.8 Hz, 1H), 4.01 (d, J=4.5 Hz, 2H), 3.75 (s, 3H), 2.63 (s, 3H), 2.48-2.39 (m, 1H), 2.38-2.28 (m, J=7.5 Hz, 1H), 2.05-1.94 (m, 2H), 1.78-1.68 (m, 1H), 1.59 (br. s., 1H), 1.36 (br. s., 3H), 1.30 (d, J=6.0 Hz, 3H), 1.26 (s, 9H). LCMS (M+1)=692.35.
