Dimethylacetamide → HCID 86663604, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred mixture of CDI (8.44 g, 52.0 mmol) and dry THF (32 mL), at room temperature under a nitrogen atmosphere, was added a solution of 2-(diethoxyphosphoryl)acetic acid (10.2 g, 52.0 mmol) in THF (28 mL). After addition the reaction mixture was stirred further at 40° C. (bath) for 20 min (whence evolution of gases ceased). A solution of compound 159 (13.4 g, 40.0 mmol) in a mixture of dry THF (45 mL) and DMA (50 mL) was added and the reaction was stirred further at 40° C. The reaction was monitored by TLC (ethyl acetate) and found to be only ca. 70% complete after 1.5 hours. Thus, another batch of reagent was prepared by adding CDI (4.22 g, 26.0 mmol) in dry THF (16 mL) to 2-(diethoxyphosphoryl)acetic acid (5.10 g, 26.0 mmol) in dry THF (7 mL). This additional reagent was added to the reaction mixture before it was stirred further for 2 h at 40° C. and then poured into water (1,000 mL) and stirred with petroleum ether (1,500 mL) at room temperature for 16 h. The petroleum ether layer was then decanted. More petroleum ether (800 mL) was added and the mixture was stirred for 15 min. The solid was collected by filtration, washed with water (5×200 mL) and dried to give diethyl 2-(4-(3-bromo-4-fluorophenylamino)pyrido[3,4-d]pyrimidin-6-ylamino)-2-oxoethylphosphonate (160) (20.1 g, 98%), m.p. 214-217° C. 1H NMR δ (CDCl3) 9.45 (s, 1H), 9.03 (s, 1H), 8.73 (s, 1H), 8.55 (s, 1H), 8.13 (dd, J=6.0, 2.6 Hz, 1H), 7.77 (s, 1H), 7.70-7.63 (m, 1H), 7.18 (dd, J=8.7, 8.2 Hz, 1H), 4.31-4.18 (m, 4H), 3.15 (d, J=21.0 Hz, 2H), 1.39 (t, J=7.1 Hz, 6H). Anal. Calcd for C19H20BrFN5O4P.0.2H2O: C, 44.24; H, 3.99; N, 13.58%. Found C, 44.00; H, 4.09; N, 13.42%.

Provenance & Evidence