Diisopropylethylamine → 4-((4-Fluorobenzyl)oxy)-1-(1-methyl-2-(1,3-oxazol-5-yl)-1H-benzimidazol-6-yl)pyridin-2(1H)-one

HRID 2202905Notes

Reaction equation

HRID 2202905 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].[O:26]1[C:30]([C:31](O)=O)=[CH:29][N:28]=[CH:27]1.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.C([O-])(O)=O.[Na+]>CN(C=O)C>[F: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:31]([C:30]5[O:26][CH:27]=[N:28][CH:29]=5)[N:24]([CH3:25])[C:3]=4[CH:4]=3)[C:9](=[O:23])[CH:10]=2)=[CH:21][CH:20]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 16340557Oxazole-5-carboxylic AcidHCID 896902791-(4-Amino-3-(methylamino)phenyl)-4-((4-fluorobenzyl)oxy)pyridin-2(1H)-one

Product 1

HCID 896902954-((4-Fluorobenzyl)oxy)-1-(1-methyl-2-(1,3-oxazol-5-yl)-1H-benzimidazol-6-yl)pyridin-2(1H)-oneYield 33.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 1-(4-amino-3-(methylamino)phenyl)-4-((4-fluorobenzyl)oxy)pyridin-2(1H)-one (100 mg), oxazole-5-carboxylic acid (33.3 mg), HATU (118 mg), N,N-diisopropylethylamine (0.154 ml) and DMF (2 ml) was stirred at room temperature for 2 h. The mixture was poured into saturated NaHCO3 solution and extracted with EtOAc. The organic layer was separated, washed with brine, dried over MgSO4 and concentrated in vacuo. The resulting residue was dissolved in AcOH (2 ml), and the mixture was stirred at 80° C. for 2 h. The mixture was concentrate in vacuo. The residue was purified by NH silica gel column chromatography (MeOH/EtOAc). The resulting solid was washed with EtOAc/hexane to give the title compound (40.7 mg) as an off-white solid.

Workup

  1. extractionextracted with EtOAc
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. dissolutionThe resulting residue was dissolved in AcOH (2 ml)
  7. stirringthe mixture was stirred at 80° C. for 2 h
  8. concentrationThe mixture was concentrate in vacuo
  9. customThe residue was purified by NH silica gel column chromatography (MeOH/EtOAc)
  10. washThe resulting solid was washed with EtOAc/hexane

Sources & evidence

ORD record
ord-1c8c7164b4224003bb454c57d2d5146f
Source dataset
uspto-grants-2016_06
Patent number
US09365540B2

Reaction notes

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