N′-benzyl-5-methylisoxazole-3-carbohydrazide, which is known by the INN name Isocarboxazid, is a monoamine oxidase (MAO) inhibitor used for the treatment of depression, especially depressions that do not respond to other drugs.
Isocarboxazid, having the following chemical formula (I):

and CAS RN 59-63-2, is marketed under the brand name Marplan©.
U.S. Pat. No. 2,908,688 describes a process for making Isocarboxazid by reacting, in absence of any solvent, methyl 5-methylisoxazole-3-carboxylate with benzyl hydrazine at a temperature in the range from 60° to 100° C. The crude Isocarboxazid so obtained was extensively purified, initially by crystallisation in methanol followed by preparation of its hydrochloride salt, which was successively re-crystallised.
U.S. Pat. No. 6,518,254 discloses a process for preparing Isocarboxazid by adding benzylhydrazine to a solution of methyl 5-methylisoxazole-3-carboxylate in isopropanol, at a temperature of 45° C. The compound was obtained in molar 38% yield by filtration at 10° C. and treatment with cold isopropanol.
The above processes, due to one or more reasons, e.g. unfavourable impurity profile, multiple steps, low yield and difficult isolation procedures are not particularly convenient and suitable for industrial scale production.
Thus, there is an apparent need to develop improved processes for the preparation of substantially pure Isocarboxazid, which may be cost-effective, industrially amenable, with good % of yield and which may overcome the drawbacks of various prior disclosed processes.
USPTO Backgrounds
USPTO Backgrounds