Diisopropylethylamine → Methyl-3-(4-chlorophenyl)-2-{[4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzoyl]amino}propanoate

Participants

Reaction Steps

At room temperature, a 2-dram vial, equipped with a magnetic stirrer was charged with 4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzoic acid (153 mg, 0.5 mmol, INTERMEDIATE 2), DL-4-chlorophenylalanine methyl ester hydrochloride (125 mg, 0.5 mmol), bromotrispyrrolidinophosphonium hexafluorophosphate (233 mg, 0.5 mmol) and 5 ml of dimethylformamide. To this was added diisopropylethylamine (524 μl, 3 mmol) dropwise, during which addition the reaction turned a reddish-orange. After a few minutes the reaction mixture faded to a pale yellow clear solution. The reaction mixture was allowed to stir at room temperature for 3 d. The residue was purified by chromatography using a Biotage SP1, 40M silica cartridge, eluting with a linear gradient of hexanes in ethyl acetate from 20% to 100% over 15 column volumes to provide the title compound as a white solid (150 mg). Mass spectrum (ESI) 502.2 (M+1). 1H NMR (600 MHz, CDCl3): δ 8.31 (d, J=8.2 Hz, 2H), 7.93 (d, J=1.2 Hz, 1H), 7.89 (d, J=8.4 Hz, 2H), 7.5 (s, 1H), 7.26 (d, J=8.2 Hz, 2H), 7.1 (d, J=8.3 Hz, 2H), 6.66 (d, J=7.3 Hz, 1H), 3.79 (s, 1H), 3.46 (m, 1H), 3.3 (dd, J=5.9, 5.9 Hz, 1H), 3.21 (dd, J=5.2, 5.0 Hz, 1H), 1.44 (J=6.9 Hz, 6H).

Provenance & Evidence