1-Hydroxybenzotriazole → 10-[4-((3R)-3-Hydroxy-2-methyl-cyclohex-1-en-1-yl)-3-methyl-benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid methyl-pyridin-3-yl methyl-amide

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Reaction Steps

10-[4-((3R)-3-hydroxy-2-methyl-cyclohex-1-en-1-yl)-3-methyl-benzoyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Step C (0.250 g, 0.548 mmol), 3-(methylaminomethyl)pyridine (0.080 mL, 0.658 mmol), 1-hydroxy benzotriazole (0.081 g, 0.603 mmol) and 1-[(3-dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.116 g, 0.603 mmol) were combined in amine-free N,N-dimethylformamide (2.2 mL), followed by addition of N,N-diisopropylethyl amine (0.143 mL, 0.822 mmol). The reaction was stirred at room temperature for 18 hours, then diluted with ethyl acetate and washed with water, saturated aqueous sodium bicarbonate and brine. The combined aqueous washings were saturated with sodium chloride and extracted with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by flash column chromatography on silica gel eluting with a solvent gradient from 0 to 8% of methanol in chloroform, to afford 0.270 g of the title compound as an oil which was dissolved in diethyl ether and precipitated with petroleum ether to afford a white solid, m.p.100-144° C., [α]589=+18.49 (c=1.0, chloroform).

Provenance & Evidence