5-Amino-3-methylisoxazole (I) was chlorinated with N-chlorosuccinimide (NCS) in chloroform to afford 5-amino-4-chloro-3-methylisoxazole (II). Condensation of this isoxazole (II) with 3-(chlorosulfonyl)thiophene-2-carboxylic acid methyl ester (III) was effected in the presence of sodium hydride in THF to give sulfonamide (IV), which was then hydrolyzed to the acid (V) on treatment with methanolic sodium hydroxide. This acid (V) was activated by reaction with carbonyldiimidazole (CDI) in DMF, and the resulting solution of acylimidazole was then cannulated into a cooled mixture of 2-amino-4,5-(methylenedioxy)benzonitrile (VI) and sodium hydride in DMF to yield the title amide.

The condensation of 3-(chlorosulfonyl)thiophene-2-carboxylic acid methyl ester (I) with 4-chloro-3-methylisoxazol-5-amine by means of NaH in THF gives the corresponding sulfonamide (III), which is hydrolyzed with NaOH in methanol to yield the expected carboxylic acid (IV). The reaction of (IV) with N,O-dimethylhydroxylamine and carbonyldiimidazole (CDI) in THF affords the corresponding amide (V), which is finally condensed with the Grignard reagent 6-methyl-1,3-benzodioxol-5-ylmethyl magnesium chloride (VI) in THF. The intermediate Grignard reagent (VI) is obtained by chloromethylation of 5-methyl-1,3-benzodioxole (VII) with formaldehyde and HCl, giving 5-(chloromethyl)-6-methyl-1,3-benzodioxole (VIII), followed by reaction of this compound with Mg in THF.

5-Amino-3-methylisoxazole (I) was chlorinated with N-chlorosuccinimide (NCS) in chloroform to afford 5-amino-4-chloro-3-methylisoxazole (II) (1). Condensation of this isoxazole (II) with 3-(chlorosulfonyl)thiophene-2-carboxylic acid methyl ester (III) was effected in the presence of sodium hydride in THF to give sulfonamide (IV), which was then hydrolyzed to the acid (V) on treatment with methanolic sodium hydroxide. This acid (V) was activated by reaction with carbonyldiimidazole (CDI) in DMF, and the resulting solution of acylimidazole was then cannulated into a cooled mixture of 2-amino-4,5-(methylenedioxy)benzonitrile (VI) and sodium hydride in DMF to yield the title amide.

5-Amino-3-methylisoxazole (I) was chlorinated with N-chlorosuccinimide (NCS) in chloroform to afford 5-amino-4-chloro-3-methylisoxazole (II). Condensation of this isoxazole (II) with 3-(chlorosulfonyl)thiophene-2-carboxylic acid methyl ester (III) was effected in the presence of sodium hydride in THF to give sulfonamide (IV), which was then hydrolyzed to the acid (V) on treatment with methanolic sodium hydroxide. This acid (V) was activated by reaction with carbonyldiimidazole (CDI) in DMF, and the resulting solution of acylimidazole was then cannulated into a cooled mixture of 2-amino-4,5-(methylenedioxy)benzonitrile (VI) and sodium hydride in DMF to yield the title amide.