1-Hydroxybenzotriazole → HCID 21947899, compound

Participants

Reaction Steps

To a stirred solution of 10-{[2′-chloro-6-chloro-3-methoxy-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Example 16, Step C (0.250 g, 0.49 mmol) was added 1-methyl-4-(methylamino)piperidine (0.076 g, 0.59 mmol) followed by 1-hydroxybenzotriazole (0.073 g, 0.54 mmol), 1-[3-(dimethylamino)propyl]-3-ethyl carbodiimide hydrochloride (0.093 g, 0.54 mmol), and N,N-diisopropylethyl amine (0.096 g, 0.74 mmol). After stirring overnight, the reaction mixture was diluted with chloroform, washed with saturated aqueous sodium bicarbonate and brine, dried over anhydrous magnesium sulfate, filtered and evaporated to dryness. The residue was flash chromatographed over silica gel eluting with 5% methanol in chloroform containing 0.5% ammonium hydroxide, to provide the title compound as white powder (0.100 g), 92.95% pure by analytical HPLC [Primesphere C-18 column (2.0×150 mm); mobile phase:gradient from 10 to 90% acetonitrile/water containing 0.1% phosphoric acid, 2 to 20 minute gradient].

Provenance & Evidence