反应详情

温度

59 °C

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%.

1. temperatureThe solution was then cooled
2. stirringIt was stirred at room temperature for 20 min
3. customto separate
4. customthe petroleum ether layer was decanted
5. additionWater (250 mL) was added
6. stirringthe mixture was stirred at room temperature for 20 h
7. filtrationThe yellow/orange solid was collected by filtration
8. washwashed with water (5×20 mL)
9. dissolutionThe sticky yellow/orange solid was dissolved in acetone (150 mL) at 45° C. (bath temperature)
10. filtrationIt was filtered
11. customto remove insoluble impurities
12. additionTo the filtrate was added water (400 mL)
13. stirringstirred at room temperature for 1 h
14. filtrationThe solid was collected by suction-filtration
15. washwashed with water (5×25 mL), petroleum ether (3×30 mL)
16. dry with materialdried in vacuum over silica-gel/KOH