Water → N-[4-(4-amino-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)butyl]-4-[[2-(dimethylamino)ethoxy](phenyl)methyl]benzamide

HRID 11379Notes

Reaction equation

HRID 11379 reaction equation
[CH3:1][N:2]([CH3:22])[CH2:3][CH2:4][O:5][CH:6]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:7]1[CH:15]=[CH:14][C:10]([C:11](Cl)=[O:12])=[CH:9][CH:8]=1.[NH2:23][C:24]1[C:29]2[N:30]=[CH:31][N:32]([CH2:33][CH2:34][CH2:35][CH2:36][NH2:37])[C:28]=2[C:27]([CH3:38])=[C:26]([CH3:39])[N:25]=1.C(N(CC)CC)C.O>CN(C)C=O.CN(C)C1C=CN=CC=1>[NH2:23][C:24]1[C:29]2[N:30]=[CH:31][N:32]([CH2:33][CH2:34][CH2:35][CH2:36][NH:37][C:11](=[O:12])[C:10]3[CH:14]=[CH:15][C:7]([CH:6]([O:5][CH2:4][CH2:3][N:2]([CH3:22])[CH3:1])[C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)=[CH:8][CH:9]=3)[C:28]=2[C:27]([CH3:38])=[C:26]([CH3:39])[N:25]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 121091334-[[2-(Dimethylamino)ethoxy](phenyl)methyl]benzoyl chlorideHCID 219738081-(4-aminobutyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-4-amine

Product 1

HCID 10239351N-[4-(4-amino-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)butyl]-4-[[2-(dimethylamino)ethoxy](phenyl)methyl]benzamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

4-[[2-(Dimethylamino)ethoxy](phenyl)methyl]benzoyl chloride (1 equivalent) was added dropwise to a suspension of 4-(4-amino-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)butan-1-amine (0.22 g) in N,N-dimethylformamide (7 ml). At 1 hour, triethylamine (2 equivalents) was added followed by the addition at 2 hours of a small amount (approx. 10 mole %) of 4-dimethyaminopyridine. The reaction was maintained at room temperature overnight. The resulting mixture was poured into water and the pH was adjusted to 13. The aqueous fraction was extracted with chloroform (3×). The combined organic fractions were sequentially washed with water and brine; dried (magnesium sulfate); filtered; and concentrated to yield a yellow oil. The crude product was submitted to flash column chromatography [30 g silica gel, gradient elution: dichloromethane:methanol: triethylamine (100:0:0 to 97:2:1 to 92:7:1). A final HPLC purification using the method described above provided 83 mg of N-[4-(4-amino-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)butyl]-4-[[2-(dimethylamino)ethoxy](phenyl)methyl]benzamide as a trifluoroacetate salt.

Workup

  1. extractionThe aqueous fraction was extracted with chloroform (3×)
  2. washThe combined organic fractions were sequentially washed with water and brine
  3. dry with materialdried (magnesium sulfate)
  4. filtrationfiltered
  5. concentrationand concentrated
  6. customto yield a yellow oil
  7. wash30 g silica gel, gradient elution
  8. customA final HPLC purification

Sources & evidence

ORD record
ord-38834526cadc4d40971a9b48554cd939
Source dataset
uspto-grants-2006_08
Patent number
US07098221B2

Reaction notes

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