Diisopropylethylamine → 1-(6-(4-((4-Fluorobenzyl)oxy)-2-oxopyridin-1(2H)-yl)-1-methyl-1H-benzimidazol-2-yl)cyclopropanecarbonitrile

HRID 2202876Notes

Reaction equation

HRID 2202876 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].[C:26]([C:28]1([C:31](O)=O)[CH2:30][CH2:29]1)#[N:27].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O.CCOC(C)=O>[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:28]5([C:26]#[N:27])[CH2:29][CH2:30]5)[N:24]([CH3:25])[C:3]=4[CH:4]=3)[C:9](=[O:23])[CH:10]=2)=[CH:21][CH:20]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 27332591-Cyanocyclopropanecarboxylic 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 896911641-(6-(4-((4-Fluorobenzyl)oxy)-2-oxopyridin-1(2H)-yl)-1-methyl-1H-benzimidazol-2-yl)cyclopropanecarbonitrileYield 9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-(4-amino-3-(methylamino)phenyl)-4-((4-fluorobenzyl)oxy)pyridin-2(1H)-one (73 mg), 1-cyanocyclopropanecarboxylic acid (25.1 mg) and N,N-diisopropylethylamine (0.11 ml) in DMF (2 ml) was added HATU (86 mg), and the mixture was stirred at room temperature overnight. The mixture was poured into a mixture of EtOAc and water, and the organic layer was washed with brine, dried over MgSO4, and concentrated. Then the resulting residue was heated in AcOH (1 ml) at 90° C. for 1 h. The mixture was concentrated, and poured into saturated NaHCO3. The mixture was extracted with EtOAc, and the organic layer was washed with brine, dried over MgSO4, concentrated, and purified by NH silica gel column chromatography (hexane/EtOAc) to give the title compound (8 mg) as a white solid.

Workup

  1. washthe organic layer was washed with brine
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. temperatureThen the resulting residue was heated in AcOH (1 ml) at 90° C. for 1 h
  5. concentrationThe mixture was concentrated
  6. additionpoured into saturated NaHCO3
  7. extractionThe mixture was extracted with EtOAc
  8. washthe organic layer was washed with brine
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated
  11. custompurified by NH silica gel column chromatography (hexane/EtOAc)

Sources & evidence

ORD record
ord-2d6e5c4b264d46b5b168b790d3d570b3
Source dataset
uspto-grants-2016_06
Patent number
US09365540B2

Reaction notes

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