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

HRID 2090166Notes

Reaction equation

HRID 2090166 reaction equation
[CH3:1][CH:2]([CH3:16])[CH2:3][NH:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][N:13]=2)[N:8]=[CH:7][C:6]=1[NH2:15].[C:17]1(C)C=CC(S(O)(=O)=O)=C[CH:18]=1>>[CH3:17][C:18]1[N:4]([CH2:3][CH:2]([CH3:16])[CH3:1])[C:5]2[C:14]3[N:13]=[CH:12][CH:11]=[CH:10][C:9]=3[N:8]=[CH:7][C:6]=2[N:15]=1

Participants

3

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 53699038N4-Isobutyl-1,5-naphthyridine-3,4-diamine

Product 1

HCID 221726862-Methyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridine

Procedure

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.

Workup

  1. customremoving at least a portion of the hydrogenation catalyst from the N4-(2-methylpropyl)[1,5]naphthyridine-3,4-diamine
  2. customremoving at least a portion of the isopropanol
  3. additionfrom the mixture of N4-(2-methylpropyl)[1,5]naphthyridine-3,4-diamine in a carrier that
  4. temperatureheating the N4-(2-methylpropyl)[1,5]naphthyridine-3,4-diamine in the carrier to a temperature of 20° C. to 55° C.
  5. customto form a mixture
  6. customat a temperature of 70° C. to 100° C.
  7. temperaturemaintaining the temperature at 70° C. to 100° C. for a period of time sufficient

Sources & evidence

ORD record
ord-e3f846976ec746e485923287ed14bea4
Source dataset
uspto-grants-2013_05
Patent number
US08436176B2

Reaction notes

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