反应详情

温度

40 °C

To a stirred mixture of CDI (1.98 g, 12.2 mmol) and dry THF (8 mL), at room temperature and under a nitrogen atmosphere, was added a solution of 2-(diethoxyphosphoryl)acetic acid (2.18 g, 11.1 mmol) in THF (6 mL). After addition the reaction mixture was stirred further at 40° C. (bath) for 15 min (whence evolution of gases ceased). A solution of compound 222 (1.70 g, 5.56 mmol) in a mixed solvents of dry THF (6 mL) and DMA (7 mL) was added and stirred further at 40° C. The reaction was monitored by TLC (dichloromethane-MeOH=15:1). After stirred overnight (17 h), the reaction mixture was poured into water (300 mL) and stirred with petroleum ether (400 mL) at room temperature for 20 min. Petroleum ether layer was decanted. It was repeated once more with petroleum ether (400 mL). The solid was collected by suction filtration; washed with water (5×30 mL) and dried to give diethyl 2-(4-(3,4-dichlorophenylamino)pyrido[3,4-d]pyrimidin-6-ylamino)-2-oxoethylphosphonate (231) (2.56 g, 95%); mp 121-124° C.; 1H NMR δ [(CD3)2SO]: 10.86 (s, 10.42 (s, 1H), 9.04 (s, 1H), 8.87 (s, 1H), 8.67 (s, 1 H), 8.24 (d, J=2.2 Hz, 1H), 7.89 (dd, J=8.8, 2.2 Hz, 1H), 7.65 (d, J=8.8 Hz, 1H), 4.16-4.04 (m, 4H), 3.32 (d, partially obscured by water peak, 2H), 1.26 (t, J=7.0 Hz, 6H). Anal. Calcd for C19H20Cl2N5O4P.H2O: C, 45.43; H, 4.42; N, 13.94%. Found C, 45.37; H, 4.20; N, 13.81%.

1. additionAfter addition the reaction mixture
2. stirringstirred further at 40° C
3. stirringAfter stirred overnight (17 h)
4. customPetroleum ether layer was decanted
5. filtrationThe solid was collected by suction filtration
6. washwashed with water (5×30 mL)
7. customdried