Dichloromethane → N,N'-bis-Boc-(2R)-2,5-diamino-N-[(1R)-1-[(RS)-(5-tert-butyl-2-benzoxazolyl)-hydroxymethyl]-3-phenylpropyl]-valeramide

Participants

Reaction Conditions

Reaction Steps

A mixture of (1R)-1-[(RS)-(5-tert-butyl-2-benzoxazolyl)hydroxymethyl]-3-phenyl-propylamine (108 mg), N,N′-bis-Boc-D-ornithine (130 mg), dichloromethane (3 mL), PyBrop (164 mg) and triethylamine (195 μL) was stirred at 0° C. for 1 h, then at 25° C. for 10 h. The reaction mixture is poured into ethyl acetate, washed successively with water, 1 N HCl, saturated aqueous bicarbonate and brine. The organic layer is dried (Na2SO4), concentrated and the residue is purified by chromatography over silica gel (30% ethyl acetate/ hexane) afforded N,N′bis-Boc-(2R)-2,5-diamino-N-[(1R)-1-[(RS)-(5-tert-butyl-2-benzoxazolyl)-hydroxymethyl]-3-phenylpropyl]-valeramide (130 mg) which was deprotected (trifluoroacetic acid) to give the title product (107 mg) as a white powder: 1H NMR (300 MHz, D2O) δ1.35 and 1.26 (2s, 9H), 1.54 (m, 2H), 1.85-2.19 (m, 2H), 2.77 (m, 4H), 4.79 (m, 1H), 4.42 (m, 1H), 5.02 (s, 0.2H), 5.14 (d, J=3.3 Hz, 0.8H), 7.21-7.38 (m, 5H), and 7.78 (m, 1H).

Provenance & Evidence