Propionic Acid → 1-(2-Ethyl-1-methyl-1H-benzimidazol-6-yl)-4-((4-fluorobenzyl)oxy)pyridin-2(1H)-one

HRID 2202898Notes

Reaction equation

HRID 2202898 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]([F: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=N[C:36]2C=CC=N[C:35]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:50](O)(=O)CC.C(N(CC)C(C)C)(C)C.[Cl-].[Cl-].[Ca+2]>CN(C=O)C>[CH2:35]([C:25]1[N:24]([CH3:50])[C:3]2[CH:4]=[C:5]([N:8]3[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]4[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=4)=[CH:10][C:9]3=[O:23])[CH:6]=[CH:7][C:2]=2[N:1]=1)[CH3:36]

Participants

7

Reactant 5

HCID 1032Propionic AcidHCID 81531DiisopropylethylamineHCID 5284359Calcium ChlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 896902791-(4-Amino-3-(methylamino)phenyl)-4-((4-fluorobenzyl)oxy)pyridin-2(1H)-one

Product 1

HCID 716609141-(2-Ethyl-1-methyl-1H-benzimidazol-6-yl)-4-((4-fluorobenzyl)oxy)pyridin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 1-(4-amino-3-(methylamino)phenyl)-4-((4-fluorobenzyl)oxy)pyridin-2(1H)-one (90 mg), HATU (106 mg), propionic acid (0.040 ml), N,N-diisopropylethylamine (0.136 ml) and DMF (2 ml) was stirred at room temperature under a dry atmosphere (CaCl2 tube) for 1 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 resulting residue was dissolved in AcOH (2 ml), and the mixture was stirred at 90° C. for 1 h. After evaporation of the solvent, the residue was purified by NH silica gel column chromatography (hexane/EtOAc). The resulting solid was recrystallized from EtOAc/MeOH to give the title compound (44.9 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 resulting residue was dissolved in AcOH (2 ml)
  8. customAfter evaporation of the solvent
  9. customthe residue was purified by NH silica gel column chromatography (hexane/EtOAc)
  10. customThe resulting solid was recrystallized from EtOAc/MeOH

Sources & evidence

ORD record
ord-5352d093cd54494593ea81ec5a336de4
Source dataset
uspto-grants-2016_06
Patent number
US09365540B2

Reaction notes

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