Sodium hydride → 3(R,S)-[(Benzyloxycarbonyl)amino]-5-cyclohexyl-1,3-dihydro-1-propyl-2H-1,4-benzodiazepin-2-one

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Reaction Steps

A solution of 5-cyclohexyl-1,3-dihydro-3(R,S)-[(benzyloxycarbonyl)amino]-2H-1,4-benzodiazepin-2-one ( 2 g, 5.1 mmol) in anhydrous dimethylformamide (15 ml), under an atmosphere of nitrogen, was treated with sodium hydride (0.22 g of a 55-60% dispersion in mineral oil, 5.1 mmol) in one portion, at 0° C. After 45 min at 0° C., 1-iodopropane (0.55ml, 5.6 mmol) was added in one portion and the solution allowed to reach ambient temperature and stirred overnight. After this time the solvent was removed under reduced pressure, and the crude residue partitioned between water (25 ml) and dichloromethane (25 ml). The organic phase was separated and the aqueous phase extracted with dichloromethane (3×25 ml). The combined organic layers were washed with brine (50 ml), dried (MgSO4) and evaporated in vacuo. The residue was triturated with diethyl ether to give the title compound (1.74 g, 79%) as a colourless solid. mp 160°-163° C. 1H NMR (360 MHz, CDCl3) δ 0.82 (3H, t, J=10.5 Hz), 0.94-1.48 (5H, m), 1.50-1.76 (5H, m), 1.79-1.90 (1H, m), 1.96-2.08 (1H, m), 2,70-2.84 (1H, m), 3.46-3.59 (1H, m), 4.22-4.35 (1H, m), 5.06-5.16 (3H, m), 5.07 (1H, d, J=12.0 Hz), 7.21-7.40 (7H, m), 7.44-7.59 (2H, m).

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