Anisole → HCID 10640427, compound

Participants

Reaction Steps

To a stirred homogeneous solution of compound 165 (15.9 g, 34.9 mmol) in trifluoroacetic acid (80 mL) was added anisole (7.58 mL, 69.8 mmol). The mixture was then stirred at room temperature for 20 h. Most of the trifluoroacetic acid was evaporated under reduced pressure at 35° C. (bath temperature). The resultant red-brown oil was stirred with petroleum ether (400 mL) at room temperature for ca. 10 min. The petroleum ether layer was then decanted and the process was repeated with more petroleum ether (2×300 mL). The residue was then stirred with 5M NH3 at 0° C. for 5 min, then at room temperature for another 45 min. The solid thus obtained was collected by filtration and washed with water (3×60 mL) before being dried in vacuo. The solid was then stirred with warm acetone (500 mL) for 30 min. Water (800 mL) was added and the suspension was stirred at room temperature for 1 h. The solid was again collected by filtration and washed successively with water (6×70 mL) and then petroleum ether/ethyl acetate (3:1, 4×100 mL) before being dried under reduced pressure, to give N4-(3-bromo-4-fluorophenyl)pyrido[3,4-d]pyrimidine-4,6-diamine (159) (11.5 g, 99%), mp 269-271° C. (literature mp 268-270° C.). 1H NMR identical with that reported (Smaill et al. J Med Chem, 1999, 42, 1803-1815).

Provenance & Evidence