Tri-o-tolylphosphine → (E)-tert-butyl 2-oxo-6-(3-oxo-3-(4-(thiazol-2-ylmethyl)-5,6-dihydropyridin-1(2H)-yl)prop-1-en-1-yl)-2,4-dihydro-1H-spiro[[1,8]naphthyridine-3,4'-piperidine]-1'-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 1-(4-(thiazol-2-ylmethyl)-5,6-dihydropyridin-1(2H)-yl)prop-2-en-1-one (Intermediate-4) (350 mg, 1.50 mmol) and tert-butyl 6-bromo-2-oxo-2,4-dihydro-1H-spiro[[1,8]naphthyridine-3,4′-piperidine]-1′-carboxylate (Intermediate-6) (500 mg, 1.20 mmol) in DMF/propionitrile (4 mL/16 mL) was added DIPEA (0.55 mL, 3.16 mmol) at 20-35° C. and the mixture was degassed with N2 for 10 minutes. Then Pd(OAc)2 (28 mg, 0.12 mmol) and P(o-tolyl)3 (77 mg, 0.25 mmol) were added, again degassed with N2 for another 10 minutes and heated at 110° 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 mixture of 3% MeOH/DCM as an eluent to get the desired compound as a light yellow solid (150 mg, 22%); 1H NMR (400 MHz, DMSO-d6) δ 10.73 (s, 1H), 8.37 (d, J=1.5 Hz, 1H), 8.09 (s, 1H), 7.71 (d, J=3.4 Hz, 1H), 7.61 (d, J=3.5 Hz, 1H), 7.45 (d, J=15.1 Hz, 1H), 7.28-7.16 (m, 1H), 5.68-5.64 (m, 1H), 4.24-4.21 (m, 1H), 4.08-4.03 (m, 1H), 3.75 (s, 2H), 3.64-3.61 (m, 1H), 3.57-3.52 (m, 3H), 3.27-3.21 (m, 2H), 2.94 (s, 2H), 2.18-2.13 (m, 2H), 1.80-1.68 (m, 2H), 1.39 (s, 9H), 1.40-1.31 (m, 2H); ES-MS: 548.2 (M−1)+.

Provenance & Evidence