Metaclazepam can be prepared by a cyclization reaction of the acyl diamine (I) with phosphorus oxychloride, thus yielding a mixture of two isomeric compounds (II) and (III). This mixture is directly converted into 1-methyl-2-methoxymethyl-5-(2'-chlorophenyl)-2,3-dihydro-1H-1,4-benzodiazepine (IV) by means of sodium methoxide in methanol. The nucleophilic attack of the methoxide ion on compound (III) affords nearly complete ring contraction to form (IV) as the main product. Finally, (IV) is halogenated by treatment with N-bromosuccinimide in methylene chloride at reflux temperature.

Metaclazepam can be prepared by a cyclization reaction of the acyl diamine (I) with phosphorus oxychloride, thus yielding a mixture of two isomeric compounds (II) and (III). This mixture is directly converted into 1-methyl-2-methoxymethyl-5-(2'-chlorophenyl)-2,3-dihydro-1H-1,4-benzodiazepine (IV) by means of sodium methoxide in methanol. The nucleophilic attack of the methoxide ion on compound (III) affords nearly complete ring contraction to form (IV) as the main product. Finally, (IV) is halogenated by treatment with N-bromosuccinimide in methylene chloride at reflux temperature.