Tri-o-tolylphosphine → (E)-3-(3,3-Dimethyl-2,3-dihydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)-N-methyl-N-(3-methylbenzofuran-2-ylmethyl)acrylamide

Participants

Reaction Steps

A suspension of 7-bromo-3,3-dimethyl-2,3-dihydro-1H-pyrido[2,3-e][1,4]diazepine (255 mg, 1.00 mmol) and N-methyl-N-(3-methylbenzofuran-2-ylmethyl)acrylamide (0.28 g, 1.2 mmol) in propionitrile (5.0 mL) and DMF (1.3 mL) was de-oxygenated with Ar for 10 min. The mixture was treated with (i-Pr)2EtN (0.38 mL, 2.2 mmol) and was de-oxygenated with Ar for 5 min. Pd(OAc)2 (22 mg, 0.10 mmol) and P(o-tol)3 (63 mg, 0.21 mmol) were added simultaneously, and the mixture was de-oxygenated a third time for 5 min. The mixture was heated to reflux overnight, then allowed to cool. The mixture was diluted with EtOAc (50 mL) and washed with H2O (25 mL). The organic layer was dried over Na2SO4, filtered and concentrated to an orange oil. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH, 96:4) followed by trituration with Et2O gave the title compound (85 mg, 21%) as a yellow powder and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ8.44-8.43 (m, 1H), 8.25 (s, 1H), 8.19-8.15 (m, 1H), 8.06 (s, 1H), 7.58-7.08 (m, 6H), 4.99-4.79 (m, 2H), 3.18-2.92 (m, 5H), 2.27 (s, 3H), 1.16 (s, 6H); MS (ESI) m/e 403 (M+H)+.

Provenance & Evidence