m-Tolyl isocyanate → HCID 57309341, compound

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Reaction Steps

5-Cyclohexyl-1,3-dihydro-1-methyl-3(R,S)-[(benzyloxycarbonyl)amino]-2H-1,4-benzodiazepin-2-one (0.34 g, 0.84 mmol) was dissolved in formic acid/methanol (50 ml of a 4.5% (v/v) solution), and added, over 5 min, to a stirred suspension of 10% palladium on carbon (100 mg, 30% (w/w)) in formic acid/methanol (10 ml of a 4.5% (v/v)) solution). After 45 min the catalyst was filtered off and washed sequentially with methanol and acetone. The flitrate was evaporated in vacuo and the residue partitioned between ethyl acetate (100 ml) and 10% sodium carbonate solution (100 ml). The organic phase was separated, dried (Na2SO4) and evaporated to give a clear oil, which was used without further purification. A solution of the crude amine (167 mg, 0.61 mmol) in anhydrous tetrahydrofuran (10 ml) was treated with m-tolylisocyanate (79 μl, 0.61 mmol) dropwise over 5 min. After stirring at ambient temperature for 1.5 h the solvent was removed under reduced pressure to leave a white solid. The solid was recrystallised from methanol to give the urea (70 mg, 28%) as a white solid. mp 207°-209° C. 1H NMR (360 MHz, CDCl3) δ 1.07-2.04 (10H, m), 2.29 (3H, s), 2.79 (1H, m), 3.40 (3H, m), 5.40 (1H, d, J=8 Hz), 6.71 (1H, d, J=8 Hz), 6.84 (2H, m), 7.07-7.30 (5H, m), 7.55 (2H, m).

Provenance & Evidence