反应详情

温度

40 °C

To a stirred mixture of CDI (2.25 g, 13.9 mmol) and dry THF (9 mL), at room temperature and under a nitrogen atmosphere, was added a solution of 2-(diethoxyphosphoryl)acetic acid (2.43 g, 12.4 mmol) in THF (7 mL). After addition the reaction mixture was stirred further at 40° C. (bath) for 15 min (whence evolution of gases ceased). A mixture of compound 221 (1.88 g, 4.96 mmol) in a mixed solvents of dry THF (10 mL) and DMA (16 mL) was added and stirred further at 40° C. The reaction was monitored by TLC (dichloromethane-MeOH=15:1). After stirred for 17 h, it was poured into water (300 mL) and stirred with petroleum ether (300 mL) at room temperature for 30 min. Petroleum ether layer was decanted. It was repeated once more with petroleum ether (300 mL). The solid was collected by suction filtration; washed with water (5×20 mL) and dried to give diethyl 2-(4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)pyrido[3,4-d]pyrimidin-6-ylamino)-2-oxoethylphosphonate (230) (2.56 g, 93%); mp 113-116° C.; 1H NMR δ [(CD3)2SO]: 10.82 (s, 1H), 10.25 (s, 1H), 8.99 (s, 1H), 8.84 (s, 1H), 8.63-8.56 (m, 214), 7.96 (d, J=2.6 Hz, 1H), 7.88 (td, J=7.7, 1.8 Hz, 1H), 7.70 (dd, J=8.9, 2.6 Hz, 1H), 7.59 (br d, J=7.8 Hz, 1H), 7.41-7.34 (m, 1H), 7.28 (d, J=9.0 Hz, 4.16-4.03 (m, 4H), 3.31 (d, partially obscured by water peak, 211), 1.26 (t, J=7.0 Hz, 6H). Anal. Calcd for C25H26ClN6O5P.1.2H2O: C, 51.90; H, 4.95; N, 14.53%. Found C, 51.85; H, 4.94; N, 14.52%.

1. additionAfter addition the reaction mixture
2. additionwas added
3. stirringstirred further at 40° C
4. stirringAfter stirred for 17 h
5. customPetroleum ether layer was decanted
6. filtrationThe solid was collected by suction filtration
7. washwashed with water (5×20 mL)
8. customdried