4-Methoxybenzylamine → N4-(3-bromo-4-chlorophenyl)-N6-(4-methoxybenzyl)pyrido[3,4-d]pyrimidine-4,6-diamine

Participants

Reaction Conditions

Reaction Steps

A mixture of compound 205 (3.09 g, 8.74 mmol) and 4-methoxybenzylamine (11.5 mL, 87.4 mmol) in dry DMSO (20 mL) was stirred under a nitrogen atmosphere at 58-60° C. (bath temperature) for a week. The solution was then cooled and petroleum ether (300 mL) was added. It was stirred at room temperature for 20 min. The layers were allowed to separate and the petroleum ether layer was decanted. This procedure was repeated once more with petroleum ether (300 mL). Water (250 mL) was added and the mixture was stirred at room temperature for 20 h. The yellow/orange solid was collected by filtration and washed with water (5×20 mL), then with petroleum ether (3×30 mL). The sticky yellow/orange solid was dissolved in acetone (150 mL) at 45° C. (bath temperature). It was filtered to remove insoluble impurities. To the filtrate was added water (400 mL) and stirred at room temperature for 1 h. The solid was collected by suction-filtration, washed with water (5×25 mL), petroleum ether (3×30 mL), and dried in vacuum over silica-gel/KOH to give pure N4-(3-bromo-4-chlorophenyl)-N6-(4-methoxybenzyl)pyrido[3,4-d]pyrimidine-4,6-diamine (214) (3.01 g, 73%) as a greenish yellow solid, mp 207-210° C.; 1H NMR δ [(CD)2SO] 9.74 (s, 1H), 8.77 (s, 1H), 8.41 (s, 1H), 8.39 (d, J=2.4 Hz, 1H), 7.96 (dd, J=8.8, 2.4 Hz, 1H), 7.64 (d, J=8.8 Hz, 1H), 7.38-7.25 (m, 3H), 7.17 (s, 1H), 6.92-6.85 (m, 2H), 4.49 (d, J=6.3 Hz, 3.71 (s, 3H). Anal. Calcd for C21H17BrClN5O: C, 53.58; H, 3.64; N, 14.88%. Found C, 53.84; H, 3.55; N, 14.63%.

Provenance & Evidence