Reaction Steps
To a 2-5 ml microwave tube was added (2S)-methyl 2-(7-(4-allyl-5-chloro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.240 g, 0.375 mmol), 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (0.124 g, 0.563 mmol), and 2M aqueous K2CO3 (0.375 ml, 0.750 mmol) in 1,4-dioxane (3.0 ml) and water (0.75 ml). The reaction was sparged with nitrogen for 10 minutes, treated with Pd(Ph3P)4 (0.043 g, 0.038 mmol), then sparged for 15 min. The reaction tube was sealed and heated (90° C., heating block) for 90 min. The reaction was cooled, diluted with water (5 mL) and extracted with Et2O. The ether layer was washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was adsorbed onto silica gel, then purified by biotage column chromatography (5%-55% EtOAc in hexanes). The product fractions were pooled and concentrated under reduced pressure to afford (2S)-methyl 2-(7-(4-allyl-5-chloro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-2-(2′-hydroxy-[1,1′-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate. 1H NMR (500 MHz, CDCl3) δ 7.94 (t, J=1.5 Hz, 1H), 7.86 (dt, J=7.7, 1.4 Hz, 1H), 7.47-7.52 (m, 1H), 7.39-7.45 (m, 1H), 7.25 (s, 1H), 6.95-7.02 (m, 5H), 6.88-6.92 (m, 1H), 5.96-6.10 (m, 1H), 5.51 (br. s., 1H), 5.29-5.37 (m, 1H), 5.24 (dd, J=10.3, 1.5 Hz, 1H), 5.04-5.09 (m, 1H), 4.24 (t, J=4.4 Hz, 2H), 3.67-3.76 (m, 1H), 3.65 (s, 2H), 3.58 (dd, J=15.2, 6.1 Hz, 1H), 3.16-3.23 (m, 2H), 2.84 (s, 3H), 1.95 (s, 1H), 1.17 (s, 9H). LCMS (M+H)=653.4.
