反应详情

A solution of N-(2-ethoxy-3-isopropylbenzyl)-N-methylacrylamide (0.281 g, 1.07 mmol) in propionitrile (4 mL) and DMF (0.8 mL) was deoxygenated with Ar for 20 min. The solution was treated with diisopropylethylamine (0.30 mL, 1.73 mmol) and 7-bromo-4-(4-methoxy-benzyl)-1,3,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-2-one (0.300 g, 0.828 mmol). The solution was deoxygenated with Ar for 20 min. Pd(OAc)2 (0.018 g, 0.082 mmol) and P(o-tol)3 (0.050 g, 0.16 mmol) were then added and the solution was deoxygenated again with Ar for 10 min. The mixture was heated to reflux for 1.5 h, then allowed to cool. The mixture was diluted with H2O (100 mL) and then was washed with EtOAc (3×50 mL). The organic layer was washed with brine (2×100 mL), dried (Na2SO4) and concentrated to an orange oil. Purification by column chromatography (silica gel, CH2Cl2 to CH2Cl2/MeOH, 100 to 99.5:0.5) gave the title compound (0.20 g, 44%) as a light yellow solid and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ 10.43-10.41 (m, 1H), 8.55-8.49 (m, 1H), 8.10-8.01 (m, 1H), 7.55-7.50 (m, 1H), 7.35-7.17 (m, 4H), 7.12-7.04 (m, 1H), 6.91-6.85 (m, 3H), 4.80-4.66 (m, 2H), 3.83-3.70 (m, 7H), 3.65-3.62 (m, 2H), 3.41-3.38 (m, 2H), 3.29-3.90 (m, 1H), 2.56-2.51 (m, 3H), 1.39-1.37 (m, 3H), 1.25-1.11 (m, 6H); MS (ESI) m/e 543 (M+H)+.

1. customThe solution was deoxygenated with Ar for 20 min
2. customthe solution was deoxygenated again with Ar for 10 min
3. temperatureThe mixture was heated
4. temperatureto reflux for 1.5 h
5. temperatureto cool
6. additionThe mixture was diluted with H2O (100 mL)
7. washwas washed with EtOAc (3×50 mL)
8. washThe organic layer was washed with brine (2×100 mL)
9. dry with materialdried (Na2SO4)
10. concentrationconcentrated to an orange oil
11. customPurification by column chromatography (silica gel, CH2Cl2 to CH2Cl2/MeOH, 100 to 99.5:0.5)