Cyclobutanecarboxylic acid → 4-((4-Chlorobenzyl)oxy)-1-(2-cyclobutyl-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one

HRID 2202936Notes

Reaction equation

HRID 2202936 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)=[CH:10][C:9]2=[O:23])=[CH:4][C:3]=1[NH:24][CH3:25].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.[CH:59]1([C:63](O)=O)[CH2:62][CH2:61][CH2:60]1>CN(C=O)C>[Cl:22][C:19]1[CH:18]=[CH:17][C:16]([CH2:15][O:14][C:11]2[CH:12]=[CH:13][N:8]([C:5]3[CH:6]=[CH:7][C:2]4[N:1]=[C:63]([CH:59]5[CH2:60][CH2:61][CH2:62]5)[N:24]([CH3:25])[C:3]=4[CH:4]=3)[C:9](=[O:23])[CH:10]=2)=[CH:21][CH:20]=1

Participants

6

Reactant 4

HCID 19494Cyclobutanecarboxylic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 896902584-(4-Chlorobenzyloxy)-1-(4-amino-3-(methylamino)phenyl)pyridin-2(1h)-one

Product 1

HCID 896912054-((4-Chlorobenzyl)oxy)-1-(2-cyclobutyl-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 1-(4-amino-3-(methylamino)phenyl)-4-((4-chlorobenzyl)oxy)pyridin-2(1H)-one (90 mg), HATU (101 mg), N,N-diisopropylethylamine (0.130 ml), cyclobutanecarboxylic acid (0.024 ml) and DMF (2 ml) was stirred at room temperature for 2 h. The mixture was quenched with water and extracted with EtOAc. The organic layer was separated, washed with water and brine, dried over MgSO4 and concentrated in vacuo. The residue was dissolved in AcOH (2 ml), and the mixture was stirred at 90° C. for 1 h. After evaporation, the residue was purified by NH silica gel column chromatography (hexane/EtOAc). The resulting solid was recrystallized from EtOH to give the title compound (22.72 mg) as an off-white solid.

Workup

  1. customThe mixture was quenched with water
  2. extractionextracted with EtOAc
  3. customThe organic layer was separated
  4. washwashed with water and brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in AcOH (2 ml)
  8. stirringthe mixture was stirred at 90° C. for 1 h
  9. customAfter evaporation
  10. customthe residue was purified by NH silica gel column chromatography (hexane/EtOAc)
  11. customThe resulting solid was recrystallized from EtOH

Sources & evidence

ORD record
ord-dd8c36cff9404a55a5e14d711a2448df
Source dataset
uspto-grants-2016_06
Patent number
US09365540B2

Reaction notes

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