The reaction of indoline (I) with formic acid in refluxing toluene gives N-formylindoline (II), which is treated with chlorosulfonic acid to yield 5-(chlorosulfonyl)indoline-1-carbaldehyde (III). The reaction of (III) with 3,4,5-trimethoxyaniline (IV) and pyridine in THF affords the sulfonamide (V), which is deformylated to sulfonamide (VI) with HCl in methanol. The reaction of indoline (VI) with salcomine and O2 in methanol provides the corresponding indole derivative (VII), which is finally methylated with methyl iodide and NaHMDS in THF to give the target 1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide.
The condensation of 3-aminno-4-phenylsulfonyl fluoride (II) with 3,4,5-trimethoxyphenol (I) in the presence of triethylamine furnished the sulfonate ester (III). The amino group of (III) was then acylated with N-Boc-beta-alanine (IV) using EDC and HOBt to yield amide (V). Finally, acid cleavage of the N-Boc protecting group of (V) provided the title aminopropionamide.
The reaction of indoline (I) with formic acid in refluxing toluene gives N-formylindoline (II), which is treated with chlorosulfonic acid to yield 5-(chlorosulfonyl)indoline-1-carbaldehyde (III). The reaction of (III) with 3,4,5-trimethoxyaniline (IV) and pyridine in THF affords the sulfonamide (V), which is deformylated to sulfonamide (VI) with HCl in methanol. The reaction of indoline (VI) with salcomine and O2 in methanol provides the corresponding indole derivative (VII), which is methylated with methyl iodide and NaHMDS in THF to give 1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide (VIII). Finally, this compound is condensed with N,N-dimethylglycine (IX) by means of DCC and 4-(1-pyrrolidinyl)pyridine (pypyr) in dichloromethane.