A new synthetic procedure for azosemide has been reported: The condensation of 2-formylthiophene (I) with 2-chloro-4-amino-5-(5-tetrazolyl)benzenesulfonamide (II) by means of polyphosphoric acid (PPA) in DMSO gives the corresponding Schiff base (III), which is reduced with KBH4 in the same solvent.

The reaction of 2-fluoro-4-chloro-5-sulfamoylbenzoic acid (I) with refluxing SOCl2 gives the corresponding acyl chloride (II), which by reaction with aqueous NH3 is transformed into the amide (III). The dehydration of (III) with refluxing POCl3 affords the nitrile (IV), which is then condensed with thenylamine (V) to yield 4-chloro-2-thenylamino-5-sulfamoylbenzonitrile (VI). Finally, this compound is cyclized with sodium azide in DMF at 100 C.

The reaction of 2-fluoro-4-chloro-5-sulfamoylbenzoic acid (I) with refluxing SOCl2 gives the corresponding acyl chloride (II), which by reaction with aqueous NH3 is transformed into the amide (III). The dehydration of (III) with refluxing POCl3 affords the nitrile (IV), which is then condensed with thenylamine (V) to yield 4-chloro-2-thenylamino-5-sulfamoylbenzonitrile (VI). Finally, this compound is cyclized with sodium azide in DMF at 100 C.