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

HRID 2202851Notes

Reaction equation

HRID 2202851 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[CH2:30][CH2:29][CH:28]([C:31](O)=O)[CH2:27]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]([CH:28]5[CH2:29][CH2:30][O:26][CH2:27]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 4661317(R)-Tetrahydro-3-furoic acidHCID 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 896909924-((4-Fluorobenzyl)oxy)-1-(1-methyl-2-(tetrahydrofuran-3-yl)-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-fluorobenzyl)oxy)pyridin-2(1H)-one (56.1 mg), tetrahydro-3-furoic acid (0.016 ml), HATU (66.0 mg) and N,N-diisopropylethylamine (0.087 ml) in DMF (1.50 ml) was stirred at room temperature for 1 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 residue was dissolved in AcOH (1.50 ml), and the mixture was stirred at 80° C. for 1 h. The mixture was concentrated in vacuo. The residue was purified by silica gel column chromatography (MeOH/EtOAc). The solid was washed with EtOAc/hexane to give the title compound (34.3 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 residue was dissolved in AcOH (1.50 ml)
  7. stirringthe mixture was stirred at 80° C. for 1 h
  8. concentrationThe mixture was concentrated in vacuo
  9. customThe residue was purified by silica gel column chromatography (MeOH/EtOAc)
  10. washThe solid was washed with EtOAc/hexane

Sources & evidence

ORD record
ord-640dbfc4aae44a79aa7b0bd24a1aef8b
Source dataset
uspto-grants-2016_06
Patent number
US09365540B2

Reaction notes

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