Dimethylacetamide → Diethyl (2-((4-((3-bromo-4-chlorophenyl)amino)pyrido[3,4-d]pyrimidin-6-yl)amino)-2-oxoethyl)phosphonate

Participants

Reaction Conditions

Reaction Steps

To a stirred mixture of CDI (1.20 g, 7.42 mmol) and dry THF (5 mL), at room temperature and under a nitrogen atmosphere, was added a solution of 2-(diethoxyphosphoryl)acetic acid (1.45 g, 7.42 mmol) in THF (4 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 223 (2.00 g, 5.71 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=10:1) and found only ca. 60% reaction occurred after 1 h. Thus, another batch of reagent was prepared from CDI [0.87 g, 5.37 mmol; dry THF (2.5 mL)] and 2-(diethoxyphosphoryl)acetic acid [0.72 g, 5.37 mmol); THF (3 mL)] and added to the reaction. It was stirred further for 3 h at 40° C. 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-bromo-4-chlorophenylamino)pyrido[3,4-d]pyrimidin-6-ylamino)-2-oxoethylphosphonate (232) (2.85 g, 94%); mp 113-116° C.; 1H NMR δ [(CD3)2SO]: 10.86 (s, 1H), 10.40 (s, 1H), 9.04 (s, 1H), 8.87 (s, 1H), 8.67 (s, 1 H), 8.34 (d, J=2.3 Hz, 1H), 7.94 (dd, J=8.8, 2.3 Hz, 1H), 7.65 (d, J=8.8 Hz, 1H), 4.16-4.03 (m, 4H), 3.32 (d, partially obscured by water peak, 2H), 1.26 (t, J=7.1 Hz, 6H). Anal. Calcd for C19H20BrClN5O4P.H2O: C, 41.74; H, 4.06; N, 12.81%. Found C, 42.01; H, 3.90; N, 12.78%.

Provenance & Evidence