Tri-o-tolylphosphine → (E)-3-(3,4-Dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)-N-methyl-N-(3-methylbenzofuran-2-ylmethyl)acrylamide

Participants

Reaction Steps

A solution of N-methyl-N-(3-methylbenzofuran-2-ylmethyl)acrylamide (0.190 g, 0.637 mmol) in propionitrile (3 mL) and DMF (0.6 mL) was deoxygenated with Ar for 20 min. The solution was treated with diisopropylethylamine (0.34 mL, 1.97 mmol) and 7-bromo-2,2-dimethyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine (0.188 g, 0.828 mmol). The solution was deoxygenated with Ar for 20 min. Pd(OAc)2 (0.014 g, 0.078 mmol) and P(o-tol)3 (0.038 g, 0.15 mmol) were then added and the solution was deoxygenated again with Ar for 20 min. The mixture was heated to reflux for 2 h, then allowed to cool. The mixture was diluted with H2O (200 mL) and the resulting solution was washed with EtOAc (3×50 mL). The combined organic layers were washed with brine (2×30 mL), dried (Na2SO4) and concentrated to a dark green oil. Column chromatography (silica gel, CH2Cl2/MeOH, 100 to 98:2) gave the title compound (0.12 g, 52%) as a light yellow solid and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ 7.83 (br s, 1H), 7.62-7.60 (m, 1H), 7.56-7.51 (m, 2H), 7.48-7.41 (m, 1H), 7.38-7.69 (m, 4H), 5.01-4.95 (m, 2H), 4.03 (s, 2H), 3.48 (s, 2H), 3.06-2.90 (m, 3H), 2.18 (s, 3H); MS (ESI) m/e 364 (M+H)+.

Provenance & Evidence