反应详情

A solution of N-(2-isobutoxy-3-methoxybenzyl)-N-methyl-acrylamide (0.475 g, 1.71 mmol) in propionitrile (6 mL) and DMF (1.2 mL) was deoxygenated with Ar for 20 min. The solution was treated with diisopropylethylamine (0.48 mL, 2.77 mmol) and 6-bromo-3,4-dihydro-1H-[1,8]naphthyridin-2-one (0.300 g, 1.32 mmol). The solution was deoxygenated with Ar for 20 min. Pd(OAc)2 (0.029 g, 0.13 mmol) and P(o-tol)3 (0.080 g, 0.26 mmol) were then added and the mixture was deoxygenated with Ar for 20 min. The mixture was heated to reflux for 18 h. Upon cooling, a precipitate formed. The solids were collected by filtration and washed with water. Purification by column chromatography (silica gel, CH2Cl2/MeOH 9:1) gave an orange solid. The solid was dissolved in CH2Cl2 and the solution was diluted with hexanes. The resulting precipitate was collected by filtration, washed with Et2O (50 mL) and dried to yield the title compound (0.18 g, 32%) as an off-white solid and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ 10.66-10.64 (m, 1H), 8.36-8.32 (m, 1H), 8.09-8.00 (m, 1H), 7.53-7.47 (m, 1H), 7.27-7.20 (m, 1H), 7.04-7.96 (m, 2H), 6.66-6.60 (m, 1H), 4.79-4.64 (m, 2H), 3.79 (s, 3H), 3.72-3.67 (m, 2H), 3.10-2.85 (m, 5H), 2.56-2.49 (m, 2H), 2.03-1.97 (m, 1H), 1.00-0.97 (m, 6H); MS (ESI) m/e 424 (M+H)+.

1. customThe solution was deoxygenated with Ar for 20 min
2. customthe mixture was deoxygenated with Ar for 20 min
3. temperatureThe mixture was heated
4. temperatureto reflux for 18 h
5. temperatureUpon cooling
6. customa precipitate formed
7. filtrationThe solids were collected by filtration
8. washwashed with water
9. customPurification by column chromatography (silica gel, CH2Cl2/MeOH 9:1)
10. customgave an orange solid
11. filtrationThe resulting precipitate was collected by filtration
12. washwashed with Et2O (50 mL)
13. customdried