Tetrahydrofuran → HCID 86668944, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred mixture of CDI (2.01 g, 12.4 mmol) and dry THE (9 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 THE (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 226 (1.24 g, 4.44 mmol) in a mixed solvents of dry THF (5 mL) and DMA (6 mL) was added and stirred further at 40° C. The reaction was monitored by TLC (dichloromethane-MeOH=30:1). After stirred for 22 h, it was poured into water (200 mL) and the residue washed down with MeOH. Petroleum ether (300 mL) was added and stirred at room temperature for 1 h. Petroleum ether layer was decanted. It was repeated once more with petroleum ether (150 mL). The solid was collected by suction filtration; washed with water (5×20 mL) and dried to give diethyl 2-(4-(3-ethynyl-4-fluorophenylamino)pyrido[3,4-d]-pyrimidin-6-ylamino)-2-oxoethylphosphonate (235) (1.85 g, 91%); mp 103-106° C.; 1H NMR δ [(CD3)2SO]: 10.84 (s, 1H), 10.33 (s, 1H), 9.01 (s, 1H), 8.86 (s, 1H), 8.61 (s, 1H), 8.01 (dd, J=6.4, 2.7 Hz, 1H), 7.92-7.83 (m, 1H), 7.35 (t, J=9.1 Hz, 1H), 4.51 (s, 1H), 4.17-4.03 (m, 4H), 3.32 (d, partially obscured by water peak, 2H), 1.26 (t, J=7.0 Hz, 6H). Anal. Calcd for C21H21FN3O4P.MeOH: C, 53.99; H, 5.15; N, 14.31%. Found C, 54.21; H, 4.94; N, 14.43%.

Provenance & Evidence