反应详情

温度

95 °C

A mixture of 7-fluoro-4-(3-bromoanilino)-pyrido[4,3-d]pyrimidine (74 mg, 0.23 mmol), triethylamine (7 mL, 50 mmol) and methylamine hydrochloride (3.0 g, 44 mmol) in isopropanol (30 mL) contained in a steel bomb is stirred at 95° C. (oil bath) for 5 h. The resulting mixture is concentrated under vacuum, basified with aqueous Na2CO3, diluted with water and extracted with EtOAc (3×100 mL). Chromatography of this extract on silica gel (3% MeOH/CH2Cl2) gives 4-(3-bromoanilino)-7-methylaminopyrido[4,3-d]pyrimidine (50 mg, 65%) as a pale yellow solid. 1H NMR (DMSO) δ 9.93 (1H, brs), 9.37 (1H, s), 8.47 (1H, s), 8.18 (1H, s), 7.84 (1H, d, J=7.8 Hz), 7.34 (1H, t, J=7.9 Hz), 7.30 (1H, brd, J=8.1 Hz), 7.19 (1H, q, J=4.7 Hz), 6.35 (1H, s), 2.85 (3H, d, J=4.8 Hz)

1. concentrationThe resulting mixture is concentrated under vacuum
2. additiondiluted with water
3. extractionextracted with EtOAc (3×100 mL)
4. extractionChromatography of this extract on silica gel (3% MeOH/CH2Cl2)