反应详情

6-Bromo-8-ethyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-8H-pyrido[2,3-d]pyrimidin-7-one (5, 120 mg, 0.27 mmol), 4-methylsulfonylphenylboronic acid (60 mg, 0.30 mmol), K3PO4 (64 mg, 0.30 mmol) and PdCl2(dppf) (25 mg, 0.03 mmol) were mixed under argon in a degassed mixture of dimethylformamide and water (20:1, 4 mL). The resulting suspension was irradiated for 30 min at 140° C. in a microwave reactor. After completion, the reaction mixture was evaporated and the residue purified by ISCO eluting with chloroform:methanol (100:0→98:2). The partially purified product (50 mg) was recrystallized from ethyl acetate. The title compound (21 mg, 0.04 mmol, 15%) was obtained as a yellow solid. ESMS m/z 519 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 8.60 (s, 1H) 7.99 (d, J=8.3 Hz, 2H) 7.90 (d, J=8.3 Hz, 2H) 7.71 (s, 1H) 7.55 (d, J=8.8 Hz, 2H) 7.30 (br. s, 1H) 6.98 (d, J=8.8 Hz, 2H) 4.51 (q, J=7.0 Hz, 2H) 3.18-3.27 (m, 4H) 3.07 (s, 3H) 2.54-2.67 (m, 4H) 2.37 (s, 3H) 1.39 (t, J=7.0 Hz, 3H).

1. customThe resulting suspension was irradiated for 30 min at 140° C. in a microwave reactor
2. customAfter completion, the reaction mixture was evaporated
3. customthe residue purified by ISCO
4. washeluting with chloroform:methanol (100:0→98:2)
5. customThe partially purified product (50 mg) was recrystallized from ethyl acetate