Solvent dependence of optical rotation of (S)-N-[1-(2-fluorophenyl)- 3,4,6,7-tetrahydro-4-oxo-pyrrolo[3,2,1-jk][1,4]benzodiazepine-3-yl]- 1H-indole-2-carboxamide.

A new cholecystokinin-A antagonist, (S)-N-[1-(2-fluorophenyl)- 3,4,6,7-tetrahydro-4-oxo-pyrrolo[3,2,1-jk][1,4]benzodiazepine-3-yl]- 1H-indole-2-carboxamide (FR120480; 1), is a chiral compound that shows considerable solvent dependence of its optical rotation. Not only the absolute values, but also the signs (+ or -) for this compound change in various solvents. The optical rotation of 1 inherently correlated to the electron donating property characterized by donor number of the solvent. The 1H NMR study implied that hydrogen bonds were formed between electron donor groups of the solvents and the NH groups of indole and amide of 1. In accordance with the NMR results, X-ray crystallography of the tetrahydrofuran solvate of 1 showed that hydrogen bond formation occurred between the oxygen atom of tetrahydrofuran and the amide group of 1.