tert-Butyl acrylate → (E)-3-[4-(2-Morpholin-4-yl-ethyl)-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl]acrylic acid tert-butyl ester

Participants

Reaction Steps

A suspension of 7-bromo-4-(2-morpholin-4-yl-ethyl)-1,3,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-2-one (0.18 g, 0.52 mmol) in propionitrile (4 mL) and DMF (1 mL) was de-oxygenated with Ar for 15 min. The mixture was treated with tert-butyl acrylate (0.3 mL, 2 mmol) and (i-Pr)2EtN (0.2 mL, 1 mmol) and was de-oxygenated with Ar for 10 min. Pd(OAc)2 (12 mg, 0.053 mmol) and P(o-tol)3 (32 mg, 0.10 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 Et2O (50 mL) and the resulting solution washed with H2O (20 mL). The organic layer was dried over Na2SO4, filtered and the solvent was removed in vacuo. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH, 97:3) gave the title compound (92 mg, 44%) as an off-white solid: 1H NMR (300 MHz, DMSO-d6) δ 9.51 (s, 1H), 8.52 (s, 1H), 7.61-7.49 (m, 2H), 6.36 (d, J=16.0 Hz, 1H), 4.07 (s, 2H), 3.90 (s, 2H), 3.70-3.67 (m, 4H), 2.78-2.74 (m, 2H), 2.52-2.49 (m, 6H), 1.53 (s, 9H); MS (ESI) m/e 403 (M+H)+.

Provenance & Evidence