tert-Butyl acrylate → (E)-tert-butyl 3-(6,6-dimethyl-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 6-bromo-3,3-dimethyl-3,4-dihydro-1,8-naphthyridin-2(1H)-one (Intermediate-7) (1.3 g, 5.10 mmol), tert-butyl acrylate (3.26 g, 25.50 mmol) in DMF/propionitrile (5 mL/20 mL) was added DIPEA (2.7 mL, 15.30 mmol) at 20-35° C. and the mixture was degassed with N2 for 10 minutes. Then Pd(OAc)2 (114 mg, 0.51 mmol), P(o-tolyl)3 (310 mg, 1.02 mmol) were added, again degassed with N2 for another 10 minutes and heated at 125° C. for 16 h. The reaction mixture was cooled to 20-35° C. and filtered through Celite®. The filtrate was rotary evaporated under vacuum to get residue which was purified by column chromatography using a mixture of 80% ethyl acetate/hexane as an eluent to get the desired compound as a pale yellow solid (1.2 g, 78%); 1H NMR (400 MHz, DMSO-d6) δ 10.66 (s, 1H), 8.37 (d, J=2.0 Hz, 1H), 8.02 (d, J=1.0 Hz, 1H), 7.50 (d, J=15.6 Hz, 1H), 6.51 (d, J=16.1 Hz, 1H), 2.78 (s, 2H), 1.48 (s, 9H), 1.07 (s, 6H).

Provenance & Evidence