This compound can be prepared by two similar ways: 1) The monoacylation of ethylene glycol (I) with chloroacetyl chloride (II) and triethylamine gives 2-hydroxyethyl chloroacetate (III), which is condensed with saccharine (IV) by means of NaOH in ethylene glycol yielding 2-hydroxyethyl 3-oxo-1,2-benzisothiazoline-2-acetate 1,1-dioxide (V). Isomerization of (V) by means of potassium tert-butoxide in DMSO affords2-hydroxyethyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide (VI), which is methylated with NaOH and methyl iodide in aqueous ethanol giving the corresponding N-methyl derivative (VII). Hydrolysis of (VII) with NaOH in ethanol - water yields the corresponding free acid (VIII), which is acylated with cinnamoyl chloride (IX) by means of triethylamine in dichloromethane to afford the biscinnamoyl derivative (X). Finally, this compound is treated with 2-aminopyridine (XI) in dichloromethane. 2) The preceding sequence can also be carried out with cyclohexanol (XII) instead of ethylene glycol (I), then producing compounds (XIII), (XIV), (XV) and (XVI), which by hydrolysis affords the free acid (VIII).
The condensation of sodium saccharin (I) with tert-butyl chloroacetate (II) in hot DMF gives the benzoisothiazolin-acetic ester (III), which is rearranged by means of potassium tert-butoxide in THF to yield 4-hydroxy-2H-1,2-benzothiazine-3-carboxylic acid tert-butyl ester 1,1-dioxide (IV). The methylation of (IV) with dimethyl sulfate and NaOH in water affords the 2-methyl derivative (V), which is acylated with cinnamoyl chloride (VI) and TEA in DMF to provide the 4-cinnamoyloxy derivative (VII). The cleavage of the tert-butyl group of (VII) by means of Tms-Cl, NaI and sodium thiosulfate gives the expected free acid (VIII), which is finally condensed with 2-aminopyridine (IX), previous activation with Cl2SO or ethyl chloroformate, and TEA in chloroform or dichloromethane to give rise to the target amide.