Phenyl isocyanate → HCID 68928323, compound

Participants

Reaction Steps

To a solution of methyl (13-cyclohexyl-6,7-dihydro-5H-indolo[1,2-d][1,4]benzodiazepin-10-yl)-carboxylate TFA (80 mg, 0.17 mmol) in triethylamine (0.20 mL) and CH2Cl2 (5 mL) which had been stirred for 5 min. was added phenyl isocyanate (0.20 mL, 1.84 mmol). The reaction solution was stirred for 2 h at rt, diluted with CH2Cl2 (˜10 mL) and MeOH (˜2 mL) and washed with ½ saturated aqueous NH4Cl (10 mL) and brine (10 mL). The organics were concentrated to dryness, dissolved into MeOH/THF (1:1, 3 mL) and treated with 1 M aqueous NaOH (0.80 mL). The reaction mixture was stirred and heated at 80° C. with microwave irradiation for 15 min in a sealed tube. The clear solution was diluted with H2O (3 mL), neutralized with 1M aqueous HCl (0.80 mL) and concentrated to remove organic solvents. The solids were collected by filtration, washed with water and purified by preparative HPLC (MeOH/H2O with NH4OAc buffer) to yield 5H-indolo[1,2-d][1,4]benzodiazepine-10-carboxylic acid, 13-cyclohexyl-6,7-dihydro-5-[(phenylamino)carbonyl] (21 mg, 0.044 mmol, 25%) as an off-white solid. 1H NMR (300 MHz, CD3OD) δ 8.20 (s, 1H), 7.86 (d, J=8.4 Hz, 1H), 7.75–7.59 (m, 5H), 7.19–6.92 (m, 5H), 4.78–4.47 (m, 2H), 4.00–3.51 (m, 2H), 3.10–2.96 (m, 1H), 2.20–1.14 (m, 10H). LCMS: m/e 480 (M+H)+, ret time 1.54 min, column A, 3 minute gradient.

Provenance & Evidence