反应详情

温度

85 °C

(R,Z)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one oxime (Compound 86c) was prepared as described in Example 85 above. A mixture of 86c (36.5 mg, 0.1 mmol and 2-(6-methoxypyridin-2-yl)-6-phenyl-1,3,6,2-dioxazaborocane (86f, 149 mg, 0.5 mmol), Pd(dppf)2Cl2 (8.12 mg, 0.01 mmol), and 2N Na2CO3 (0.25 mL, 0.5 mmol) in DMA (3 mL) was degassed with N2 and heated at 85° C. overnight. The reaction mixture was cooled to ambient temperature, diluted with ethyl acetate and filtered through Celite. The filtrate was concentrated to afford brown oil which was purified by preparative HPLC to afford (R,Z)-2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one oxime (86 g or 61), 13.2 mg, 33%) as white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.78 (s, 3H) 3.14-3.31 (m, 1H) 3.43-3.46 (m, 1H) 3.89 (s, 3H) 5.08 (d, J=7.58 Hz, 1H) 6.78 (d, J=8.34 Hz, 1H) 7.05 (d, J=7.07 Hz, 2H) 7.18 (d, J=8.84, 2H) 7.70 (t, J=7.71, 1H). MS (ES) [M+H] calculated for C20H20FN6O2, 395.16. found 395.20.

1. customwas degassed with N2
2. temperatureThe reaction mixture was cooled to ambient temperature
3. additiondiluted with ethyl acetate
4. filtrationfiltered through Celite
5. concentrationThe filtrate was concentrated
6. customto afford brown oil which
7. customwas purified by preparative HPLC