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 (0.060 g, 0.094 mmol), dimethyl (2-(but-3-en-1-yl)phenyl)boronate (0.029 g, 0.141 mmol), and 2.0 M aqueous K2CO3 (0.094 ml, 0.188 mmol) in DMF (1 ml). The reaction was sparged with nitrogen for 10 minutes, treated with Pd(Ph3P)4 (10.83 mg, 9.38 pmol), then sparged for 15 min. The reaction tube was sealed and then heated (90° C., heating block) for 2.5 h. The reaction was cooled, then diluted with Et2O (20 mL) and washed with water, then brine (20 mL). The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure to an orange oil (˜80 mg). The crude was purified by Biotage column chromatography, and 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′-(but-3-en-1-yl)-[1,1′-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.039 g, 0.056 mmol, 60.2% yield). 1H NMR (500 MHz, CDCl3) δ: 7.85 (d, J=7.8 Hz, 1H), 7.78-7.82 (m, 1H), 7.42 (t, J=7.7 Hz, 1H), 7.30-7.35 (m, 2H), 7.25 (t, J=3.4 Hz, 2H), 6.93-7.01 (m, 2H), 6.89 (s, 1H), 5.97-6.10 (m, 1H), 5.69 (ddt, J=16.9, 10.3, 6.7 Hz, 1H), 5.32 (m, J=17.2, 1.4 Hz, 1H), 5.23 (m, J=10.3, 1.3 Hz, 1H), 4.81-4.94 (m, 2H), 4.25 (t, J=4.4 Hz, 2H), 3.66-3.75 (m, 1H), 3.65 (s, 3H), 3.55-3.62 (m, 1H), 3.19 (q, J=3.9 Hz, 2H), 2.84 (s, 3H), 2.64-2.71 (m, 2H), 2.18-2.28 (m, 2H), 1.25-1.33 (m, 1H), 1.17 (s, 9H). LCMS (M+H)=691.5.
