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‐d 6 , and 0.95 × 10 −6 sec −1 in methanol‐d 4 . Ammonolysis with hexamine, and subsequent cyclization afforded 7‐chloro‐l‐methyl‐5‐phenyl‐2,3‐dihydro‐l H ‐1,4‐benzodiazepine (3, generic name medazepam) in 92% over‐all yield.