Isobutyl iodide → 1,3-Dihydro-5-(1,1-dimethylethyl)1-(2-Methylpropyl)-3(R,S)-[(benzyloxycarbonyl)-amino]-2H-1,4benzodiazepin-2-one

Participants

Reaction Steps

A solution of 1,3-dihydro-5-(1,1-dimethylethyl)-3(R,S) -[(benzyloxycarbonyl)-amino]-2H-1,4-benzodiazepin-2-one (500 mg, 1.4 mmol) in dimethylformamide (10 ml) under an atmosphere of nitrogen, was treated with sodium hydride (54 mg of a 57% dispersion in mineral oil, 1.4 mol) in one portion at 0° C. After 1 h, 2-methylpropyl iodide (0.17 ml, 1.45 mmol) was added and the resulting mixture stirred at room temperature for 16 h. The solvent was then evaporated and the crude residue partitioned between water (15 ml) and dichloromethane (2×20 ml). The combined organic phases were washed with brine (2×20 ml), dried (MgSO4) and evaporated. The residue was chromatographed on silica using 2:1 petrol:ethyl acetate as eluent, to afford the title compound as a colourless solid (320 mg, 56%). 1H NMR (250 MHz, D6 -DMSO) δ 0.63 (3H, d, J=7 Hz), 0.77 (3H, d, J=7 Hz), 1.26 (9H, s), 1.49 (1H, m), 3.56 (1H, dd, J=4 Hz, 14 Hz), 4.10 (1H, dd, J=4 Hz, 14 Hz), 4.88 (1H, m), 5.02 (2H, m), 7.20-7.40 (5H, m), 7.58 (1H, t, J=8 Hz), 7.66 (1H, d, J=9 Hz), 7.77 (1H, d, J=8 Hz), 8.18 (1H, d, J=9 Hz).

Provenance & Evidence