Aniline → (6S)-N-Phenyl-3-[3-(trifluoromethyl)benzyl(benzyloxycarbonyl)amino]-4-oxo-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrimidine-6alpha-carboxamide

Participants

Reaction Steps

To a solution of 12a (6.18 g, 12.7 mmol) and aniline (1.64 mL, 19.0 mmol) in 60 mL 5:1 CH2Cl2/DMF at 0° C., was added HOAt (1.90 g, 14.0 mmol), NaHCO3 (2.13 g, 25.4 mmol), and EDCI (3.41 g, 17.8 mmol). The mixture was stirred and allowed to warm to rt over 15 h. The reaction was diluted with EtOAc and the organic phase was washed with H2O, sat. NaHCO3, H2O, 1N HCl, H2O, and brine. The organic phase was dried (Na2SO4) and concentrated. The residue obtained was purified by flash chromatography (50 to 60 to 70% EtOAc/hexanes) to afford 4.60 g (60%, 2 steps) of 12b as an off-white solid. 1H NMR (300 MHz, CDCl3) δ9.35 (br s, 1H), 7.68 (br s, 1H), 7.52-7.21 (m, 13H), 7.07 (t, J=7.5, 1H), 5.28 (dd, J=8.7, 0.5, 1H), 5.22-5.11 (m, 2H), 4.84 (br s, 2H), 3.47-3.34 (m, 1H), 3.04-2.95 (m, 1H), 2.80 (br t, J=10.5, 1H), 2.44-2.30 (m, 1H). MS (ESI) 563.5 (M+H+), 35 585.5 (M+Na+), 561.4 (M−H+).

Provenance & Evidence