Formaldehyde → HCID 131719553, compound

Participants

Reaction Conditions

Reaction Steps

To a cooled (0° C.) and stirred solution of N-[3(R,S)-5-cyclohexyl-2,3-dihydro-2-oxo-1-propyl-1H-1,4-benzodiazepin-3-yl]N'-[4-(N-piperazinyl)phenyl]urea (96 mg) in methanol (4 ml) and glacial acetic add (49 μl) was added sodium cyanoborohydride (24 mg) followed by dropwise addition of a solution of formaldehyde (37 μl of a 38% (w/v) solution in water) in methanol (2 ml). The solution was stirred at 0° C. for 20 min then at room temperature for 1 h. After this time the solvent was removed in vacuo and the residue partitioned between dichloromethane (20 ml) and saturated potassium carbonate solution (20 ml). The organic phase was separated and the aqueous layer washed with dichloromethane (2×20 ml). The combined organic layers were washed with brine (20 ml), dried (Na2SO4) and evaporated in vacuo to afford a white solid. This was then chromatographed on silica gel, eluting with 90:10:1:1 dichloromethane:methanol:acetic acid:water to afford the title compound (60 mg) as a white solid. 1H NMR (360 MHz, D6 -DMSO) δ 0.73 (3H, t, J=7.4 Hz), 0.89-0.95 (1H, m), 1.10-1.70 (11H, m), 2.20 (3H, s), 2.40-2.43 (4H, m), 2.94-3.01 (5H, m), 3.60-3.70 (1H, m), 4.15-4.22 (1H, m), 5.02 (1H, d, J=8.9 Hz), 6.81 (2H, d, J=9 Hz), 7.12 (1H, d, J=8.6 Hz), 7.17 (2H, d, J=9 Hz), 7.35-7.39 (1H, m), 7.61-7.63 (2H, m), 7.76 (1H, d, J=7.8), 8.74 (1H, s). MS (CI, NH3) 517 (M+1).

Provenance & Evidence