反应详情

A suspension of N-methyl-N-(3-methyl-benzo[b]thiophen-2-ylmethyl)acrylamide (500 mg, 2.04 mmol), 6-bromo-2-oxo-1,2-dihydro-[1,8]naphthyridine-3-carboxylic acid ethyl ester (665 mg, 2.24 mmol), (o-tol)3P (135 mg, 0.44 mmol) and DIEA (0.4 mL, 2.45 mmol) in EtCN (10 mL) and DMF (10 mL) was deoxygenated with argon for 30 min. Pd(OAc)2 (50 mg, 0.22 mmol) was added, the mixture was deoxygenated with argon for 20 min and then heated to reflux overnight. The mixture was cooled to room temperature and concentrated. The residue was partitioned between CH2Cl2 and H2O. The organic layer was washed with satd NaCl, dried (Na2SO4) and concentrated. Purification by column chromatography (silica gel, 89:10:1 CH2Cl2/MeOH/conc NH4OH) gave the title compound (530 mg, 56%) as a yellow solid and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ 12.63 (s, 1H), 8.98 (d, J=2.1 Hz, 1H), 8.67 (s, 1H), 8.44-8.42 (m, 1H), 7.88 (d, J=7.6 Hz, 1H), 7.75-7.52 (m, 2H), 7.43-7.31 (m, 3H), 5.14-4.91 (m, 2H), 4.32-4.25 (m, 2H), 3.18-2.96 (m, 3H), 2.43 (s, 3H), 1.33-1.27 (m, 3H); MS (ESI) m/e 462 (M+H)+.

1. customwas deoxygenated with argon for 30 min
2. customthe mixture was deoxygenated with argon for 20 min
3. temperatureheated
4. temperatureto reflux overnight
5. concentrationconcentrated
6. customThe residue was partitioned between CH2Cl2 and H2O
7. washThe organic layer was washed with satd NaCl
8. dry with materialdried (Na2SO4)
9. concentrationconcentrated
10. customPurification by column chromatography (silica gel, 89:10:1 CH2Cl2/MeOH/conc NH4OH)