4-Methylmorpholine → HCID 10369746, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of racemic 2,3-cis-3-amino-2-(2,5-difluorophenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one (1d) (300 mg) in dichloromethane (40 mL) at 0° C. under nitrogen was added N-[(3,5-difluorophenyl)acetyl]-L-alanine (1e) (238 mg), HOBt-hydrate (330 mg), EDAC-HCl (282 mg) and NMM (165 mg). The reaction mixture was stirred 1 h at 0° C., concentrated in vacuo and partitioned between water (100 mL) and ethyl acetate (125 mL). The organic phase was collected and consecutively washed with water, saturated aqueous sodium bicarbonate, and brine, dried, filtered and evaporated to yield a mixture of the title compound and N2-[(3,5-difluorophenyl)acetyl]-N1-[(2S,3S)-2-(2,5-difluorophenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-3-yl]-L-alaninamide. The crude product (500 mg) was purified by flash chromatography (50% ethyl acetate/hexanes) to afford the title compound (180 mg, 69%) as an off-white solid. 1H NMR (300 MHz, CDCl3) δ1.22 (d, 3H), 3.48 (s, 2H), 4.29 (m, 1H), 4.93 (t, 1H), 5.68 (d, 1H), 6.01 (d, 1H), 6.50 (d, 1H), 6.73-6.80 (m, 3H), 6.93-7.02 (m, 2H), 7.15 (d, 1H), 7.30 (t, 1H), 7.43 (t, 1H),7.5-7.6 (m, 1H), 7.73 (d, 1H), 7.74 (s, 1H). MS APCI, m/z=532 (M+1). LC/MS: 2.53 min.

Provenance & Evidence