Tri-o-tolylphosphine → (E)-N-(3-Isopropyl-2-propoxybenzyl)-N-methyl-3-(2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylamide

Participants

Reaction Steps

A solution of N-(3-isopropyl-2-propoxybenzyl)-N-methylacrylamide (0.385 g, 1.40 mmol) in propionitrile (5 mL) and DMF (1 mL) was deoxygenated with Ar for 20 min. The solution was treated with diisopropylethylamine (0.39 mL, 2.25 mmol) and 7-bromo-1,3,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-2-one (0.300 g, 1.07 mmol). The solution was deoxygenated with Ar for 20 min. Pd(OAc)2 (0.024 g, 0.10 mmol) and P(o-tol)3 (0.065 g, 0.21 mmol) were then added and the solution deoxygenated with Ar for 20 min. The solution was heated to reflux for 18 h, then allowed to cool. The solution was diluted with H2O (30 mL) and the mixture was washed with EtOAc (3×50 mL). The combined organics were washed with brine (2×100 mL), dried (Na2SO4) and concentrated. Purification by column chromatography (silica gel, CH2Cl2/MeOH, 100 to 95:5) gave the title compound (0.15 g, 33%) as an off-white solid and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ 10.08-10.05 (m, 1H), 8.45-8.39 (m, 1H), 8.03-7.93 (m, 1H), 7.55-7.49 (m, 1H), 7.32-7.20 (m, 2H), 7.13-7.04 (m, 1H), 6.88-6.86 (m, 1H), 4.81-4.66 (m, 2H), 3.91-3.86 (m, 2H), 3.76-3.69 (m, 2H), 3.63-3.60 (m, 2H), 3.30-3.25 (m, 1H), 3.12-2.90 (m, 4H), 1.83-1.75 (m, 2H), 1.24-1.17 (m, 6H), 1.06-1.01 (m, 3H).

Provenance & Evidence