Tri-o-tolylphosphine → (E)-3-(7,7-Dimethyl-8-oxo-6,7,8,9-tetrahydro-5-oxa-1,9-diaza-benzocyclohepten-3-yl)-N-(3-methoxy-2-propoxy-benzyl)-N-methylacrylamide

Participants

Reaction Steps

To a solution of 3-bromo-7,7-dimethyl-6,7-dihydro-9H-5-oxa-1,9-diaza-benzocyclohepten-8-one (200 mg, 0.738 mmol) in propionitrile (24 mL) and DMF (6 mL) were added N-(3-methoxy-2-propoxy-benzyl)-N-methylacrylamide (253 mg, 0.959 mmol), (i-Pr)2EtN (0.26 mL, 1.5 mmol), Pd(OAc)2 (17 mg, 0.074 mmol) and P(o-tol)3 (45 mg, 0.15 mmol), and the mixture was de-oxygenated with argon for 15 min. The mixture was heated to reflux overnight, allowed to cool and then diluted with water (60 mL). The mixture was extracted with CH2Cl2 (3×50 mL). The combined extracts were washed with water and brine, dried (Na2SO4) and the solvent was removed in vacuo. Purification by column chromatography (silica gel, CH2Cl2/MeOH, 97:3) then by slow precipitation from CH2Cl2/hexanes gave the title compound (150 mg, 45%) as a pale-yellow solid and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ 10.12-10.10 (m, 1H), 8.28-8.22 (m, 1H), 7.95-7.85 (m, 1H), 7.54-7.47 (m, 1H), 7.33-7.27 (m, 1H), 7.07-6.93 (m, 2H), 6.68-6.61 (m, 1H), 4.80-4.63 (m, 2H), 4.08-4.04 (m, 2H), 3.91-3.84 (m, 2H), 3.79 (s, 3H), 3.10-2.73 (m, 3H), 1.74-1.67 (m, 2H), 1.20-1.17 (m, 6H), 1.01-0.93 (m, 3H); MS (ESI) m/e 454 (M+H)+.

Provenance & Evidence