反应详情

温度

90 °C

To (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 (0.24 g, 0.41 mmol, 1 equiv), (5-fluoro-2-hydroxyphenyl)boronic acid (96 mg, 0.62 mmol, 1.5 equiv), and Pd(PPh3)4 (47 mg, 0.041 mmol, 0.1 equiv) was added DMF (4.1 mL that had been degassed by sparging with nitrogen for 10 min) Na2CO3 (0.41 mL of a 2 M aqueous solution, 0.82 mmol, 2 equiv) was added and the reaction was heated to 90° C. for 3 h. Upon cooling to ambient temperature, the reaction was diluted with EtOAc and washed with water. The EtOAc layer was dried (Na2SO4) and concentrated in vacuo. The crude product was purified by flash column chromatography (0-60% acetone in hexane) to provide the product as a yellow foam (0.19 g, 75%). 1H NMR (400 MHz, CDCl3) δ 8.13-8.08 (m, 1H), 8.05-8.00 (m, 1H), 7.67-7.48 (m, 3H), 7.09-6.94 (m, 4H), 6.07-5.92 (m, 1H), 5.45-5.36 (m, 1H), 5.22-5.07 (m, 2H), 4.04-3.97 (m, 2H), 3.81-3.77 (m, 3H), 3.77-3.74 (m, 4H), 2.74-2.65 (m, 3H), 2.08-1.94 (m, 3H), 1.80-1.68 (m, 1H), 1.36 (s, 3H), 1.24 (s, 9H). LCMS (M+1)=617.35.

1. additionwas added
2. temperatureUpon cooling to ambient temperature
3. washwashed with water
4. dry with materialThe EtOAc layer was dried (Na2SO4)
5. concentrationconcentrated in vacuo
6. customThe crude product was purified by flash column chromatography (0-60% acetone in hexane)