反应详情

The preparation of N4-(5-amino-2-methoxyphenyl)-N6-(3-chloro-4-fluorophenyl)pyrimidine-4,6-diamine (1) is described in Example 7 (Int-G). To a stirred solution of 1 (150 mg, 0.41 mmol) in DMF (8 mL) was added 2 (137 mg, 0.83 mmol), HATU (317 mg, 0.83 mmol) and DIPEA (215 mg, 1.67 mmol) at 0° C. The reaction mixture was stirred for 18 h at RT. After the completion of reaction (monitored by TLC), the crude mixture was diluted with water and extracted with EtOAc (4×100 mL). The organic layers were dried over anhydrous Na2SO4 and concentrated under vacuo to afford 3 (100 mg, 47.3%) as off-white solid, which was used in the next step without further purification. 1H NMR (CDCl3, 500 MHz): δ 8.35 (s, 1H), 8.12 (s, 1H), 7.48-7.43 (m, 1H), 7.24 (s, 1H), 7.16-7.10 (m, 2H), 7.03 (s, 1H), 6.84 (t, J=9.0 Hz, 2H), 6.49 (s, 1H), 6.15 (s, 1H), 5.29 (s, 1H), 3.85 (s, 3H), 3.33 (d, J=5.0 Hz, 2H), 2.80 (s, 3H). Mass: m/z 506 (M++1).

1. customAfter the completion of reaction (monitored by TLC)
2. extractionextracted with EtOAc (4×100 mL)
3. dry with materialThe organic layers were dried over anhydrous Na2SO4
4. concentrationconcentrated under vacuo