p-Toluenesulfonic acid → 2-Methyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridine

Participants

Reaction Steps

In one aspect, the invention provides a method for making 2-methyl-1-(2-methylpropyl)-5-oxido-1H-imidazo[4,5-c][1,5]naphthyridine. The method includes: providing N4-(2-methylpropyl)-3-nitro[1,5]naphthyridin-4-amine in a carrier including toluene; combining the N4-(2-methylpropyl)-3-nitro[1,5]naphthyridin-4-amine in the carrier with a hydrogenation catalyst and isopropanol to form a mixture; subjecting the mixture that includes the N4-(2-methylpropyl)-3-nitro[1,5]naphthyridin-4-amine and the hydrogenation catalyst to a hydrogen atmosphere under conditions effective to form N4-(2-methylpropyl)[1,5]naphthyridine-3,4-diamine; removing at least a portion of the hydrogenation catalyst from the N4-(2-methylpropyl)[1,5]naphthyridine-3,4-diamine; removing at least a portion of the isopropanol from the mixture of N4-(2-methylpropyl)[1,5]naphthyridine-3,4-diamine in a carrier that includes toluene and isopropanol; heating the N4-(2-methylpropyl)[1,5]naphthyridine-3,4-diamine in the carrier to a temperature of 20° C. to 55° C.; combining the N4-(2-methylpropyl)[1,5]naphthyridine-3,4-diamine in the carrier with p-toluenesulfonic acid to form a mixture; combining the mixture that includes the N4-(2-methylpropyl)[1,5]naphthyridine-3,4-diamine and p-toluenesulfonic acid with a trialkyl orthoacetate at a temperature of 70° C. to 100° C.; maintaining the temperature at 70° C. to 100° C. for a period of time sufficient to form 2-methyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridine; cooling the mixture that includes 2-methyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridine to a temperature of 45° C. to 55° C.; combining the 2-methyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridine in the carrier with an oxidizing agent including peracetic acid to form a mixture; maintaining the mixture that includes the 2-methyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridine and peracetic acid at a temperature of 45° C. to 55° C. for a time sufficient to form 2-methyl-1-(2-methylpropyl)-5-oxido-1H-imidazo[4,5-c][1,5]naphthyridine; and isolating at least a portion of the 2-methyl-1-(2-methylpropyl)-5-oxido-1H-imidazo[4,5-c][1,5]naphthyridine.

Provenance & Evidence