Quaternization of 2-aziridino-5-chlorobenzophenone,an efficient synthesis of medazepam

Quaternization of 2-aziridino-5-chlorobenzophenone (1) with methyl iodide resulted in formation of 2-(N-β-iodoethyl-N-methyl)aminobenzophenone ( 2 ), via an unstable quaternary compound. Rate constants for 1 → 2 conversion, as determined by an nmr method at 35 ± 0.1°, varied between 0.22 × 10^?3 sec^?1 in DMSO-d₆, and 0.95 × 10^?6 sec^?1 in methanol-d₄. Ammonolysis with hexamine, and subsequent cyclization afforded 7-chloro-l-methyl-5-phenyl-2,3-dihydro-lH-1,4-benzodiazepine (3, generic name medazepam) in 92% over-all yield.