反应详情

温度

70 °C

A mixture of compound 203 (3.07 g, 8.04 mmol) and 4-methoxybenzylamine (10.6 mL, 80.4 mmol) in dry DMSO (20 mL) was stirred under a nitrogen atmosphere at 70° C. (bath temperature) for 118 h. The mixture was then cooled and petroleum ether (200 mL) was added. It was stirred at room temperature for 15 min. The layers were allowed to separate and the petroleum ether layer was decanted. This procedure was repeated with more petroleum ether (200 ml). Water (200 mL) was added and the mixture was stirred at room temperature overnight (22 h). It was filtered and washed solid with water (5×30 mL), then with petroleum ether (3×30 mL). The sticky yellow/orange solid was stirred with acetone (150 mL) at room temperature for 20 min. Water (150 mL) was added slowly and stirred further at room temperature for 45 min. The fine solid was collected by suction-filtration, washed with water/acetone (1:1) (4×20 mL), petroleum ether (3×20 mL) and dried in vacuum over silica-gel/KOH to give pure N4-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)-N6-(4-methoxybenzyl)pyrido[3,4-d]pyrimidine-4,6-diamine (212) (3.08 g, 77%) as a yellow/orange solid, mp 182-184° C.; 1HNMR δ [(CD3)2SO] 9.60 (s, 1H), 8.72 (s, 1H), 8.64-8.56 (m, 1H), 8.33 (s, 1H), 8.01 (d, J=2.6 Hz, 1H), 7.88 (td, J=7.7, 1.8 Hz, 1H), 7.71 (dd, J=9.0, 2.6 Hz, 1H), 7.58 (d, J=7.7 Hz), 7.42-7.19 (m, 5H), 7.15 (s, 1H), 6.93-6.84 (m, 2H), 5.25 (s, 2H), 4.48 (d, J=6.3 Hz, 2H), 3.71 (s, 3H). Anal. Calcd for C27H23ClN6O2.0.6aCet011e: C, 64.80; H, 5.02; N, 15.74%. Found C, 64.47; H, 5.00; N, 15.95%.

1. temperatureThe mixture was then cooled
2. stirringIt was stirred at room temperature for 15 min
3. customto separate
4. customthe petroleum ether layer was decanted
5. additionWater (200 mL) was added
6. stirringthe mixture was stirred at room temperature overnight (22 h)
7. filtrationIt was filtered
8. washwashed solid with water (5×30 mL)
9. stirringThe sticky yellow/orange solid was stirred with acetone (150 mL) at room temperature for 20 min
10. additionWater (150 mL) was added slowly
11. stirringstirred further at room temperature for 45 min
12. filtrationThe fine solid was collected by suction-filtration
13. washwashed with water/acetone (1:1) (4×20 mL), petroleum ether (3×20 mL)
14. dry with materialdried in vacuum over silica-gel/KOH