Tri-o-tolylphosphine → (E)-3-(7,7-Dimethyl-6,7,8,9-tetrahydro-5-oxa-1,9-diaza-benzocyclohepten-3-yl)-N-methyl-N-(3-methyl-benzofuran-2-ylmethyl)acrylamide

Participants

Reaction Steps

To a solution of 3-bromo-7,7-dimethyl-6,7,8,9-tetrahydro-5-oxa-1,9-diaza-benzocycloheptene (250 mg, 0.972 mmol) in propionitrile (24 mL) and DMF (6 mL) were added N-methyl-N-(3-methyl-benzofuran-2-ylmethyl)acrylamide (290 mg, 1.26 mmol), (i-Pr)2EtN (0.34 mL, 1.94 mmol), Pd(OAc)2 (22 mg, 0.097 mmol) and P(o-tol)3 (59 mg, 0.19 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, 97:4) and then by slow precipitation from CH2Cl2/hexanes gave the title compound (60 mg, 15%) as a pale yellow solid and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ7.92 (s, 1H), 7.60-7.55 (m, 2H), 7.50-7.38 (m, 2H), 7.31-6.96 (m, 3H), 6.68-6.65 (m, 1H), 4.96-4.76 (m, 2H), 3.77 (s, 2H), 3.15-2.91 (m, 5H), 2.26 (s, 3H), 0.96 (s, 6H); MS (ESI) m/e 406 (M+H)+.

Provenance & Evidence