Synthesis starts with the reaction of the
N-benzyl derivative from
methyl anthranilate with
nitrous acid to give the
N-nitroso derivative. Reduction by means of
sodium thiosulfate leads to the transient hydrazine (
3), which undergoes spontaneous internal hydrazide formation. Treatment of the enolate of this amide with 3-chloro-1-dimethylamino propane gives benzydamine (
5). Please note there is an error in this section: US3318905 states that the nitroso derivative is reduced with sodium hydrosulfite (sodium dithionite) and not with sodium hyposulfite (sodium thiosulfate), as shown in the above scheme and stated in text. An interesting alternative synthesis of this substance starts by sequential reaction of
N-benzylaniline with
phosgene, and then with
sodium azide to produce the corresponding carbonyl azide. On heating, nitrogen is evolved and a separatable mixture of
nitrene insertion product and the desired ketoindazole # results. The latter reaction appears to be a
Curtius rearrangement type product to produce an N-isocyanate #, which then cyclizes. Alkylation of the enol with sodium methoxide and 3-dimethylaminopropyl chloride gives benzydamine. Alternatively, use of
chloroacetamide in the alkylation step followed by acid hydrolysis produces
bendazac instead. ==Research==