Phosphorus oxychloride → 4-Chloro-3-nitro-1,5-naphthyridine

Participants

Reaction Steps

In a preferred embodiment, providing 2-methyl-1-(2-methylpropyl)-5-oxido-1H-imidazo[4,5-c][1,5]naphthyridine (referred to above) includes: providing 3-nitro[1,5]naphthyridin-4-ol in a carrier including N,N-dimethylformamide; combining the 3-nitro[1,5]naphthyridin-4-ol in the carrier with phosphorous oxychloride under conditions effective to form 4-chloro-3-nitro[1,5]naphthyridine; combining the mixture that includes the 4-chloro-3-nitro[1,5]naphthyridine with water under conditions effective to form solid 4-chloro-3-nitro[1,5]naphthyridine; separating at least a portion of the solid 4-chloro-3-nitro[1,5]naphthyridine from at least a portion of the mixture that includes the water; combining the separated solid 4-chloro-3-nitro[1,5]naphthyridine with a carrier that includes a water-miscible organic liquid; combining the 4-chloro-3-nitro[1,5]naphthyridine in the carrier with isobutylamine under conditions effective to form a mixture that includes N4-(2-methylpropyl)-3-nitro[1,5]naphthyridin-4-amine; combining the mixture that includes the N4-(2-methylpropyl)-3-nitro[1,5]naphthyridin-4-amine with water to form solid N4-(2-methylpropyl)-3-nitro[1,5]naphthyridin-4-amine; separating at least a portion of solid N4-(2-methylpropyl)-3-nitro[1,5]naphthyridin-4-amine from at least a portion of the mixture that includes the water; and converting the solid N4-(2-methylpropyl)-3-nitro[1,5]naphthyridin-4-amine to 2-methyl-1-(2-methylpropyl)-5-oxido-1H-imidazo[4,5-c][1,5]naphthyridine.

Provenance & Evidence