Diisopropylethylamine → 4-((4-Chlorobenzyl)oxy)-1-(1-methyl-2-(2-methylcyclopropyl)-1H-benzimidazol-6-yl)pyridin-2(1H)-one

HRID 2202926Notes

Reaction equation

HRID 2202926 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([N:32]2[CH:37]=[CH:36][C:35]([O:38][CH2:39][C:40]3[CH:45]=[CH:44][C:43]([Cl:46])=[CH:42][CH:41]=3)=[CH:34][C:33]2=[O:47])=[CH:28][C:27]=1[NH:48][CH3:49].C(N(CC)C(C)C)(C)C.[CH3:59][CH:60]1[CH2:62][CH:61]1[C:63](O)=O>CN(C=O)C>[Cl:46][C:43]1[CH:42]=[CH:41][C:40]([CH2:39][O:38][C:35]2[CH:36]=[CH:37][N:32]([C:29]3[CH:30]=[CH:31][C:26]4[N:25]=[C:63]([CH:61]5[CH2:62][CH:60]5[CH3:59])[N:48]([CH3:49])[C:27]=4[CH:28]=3)[C:33](=[O:47])[CH:34]=2)=[CH:45][CH:44]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 998732-Methylcyclopropanecarboxylic acidHCID 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 896912804-((4-Chlorobenzyl)oxy)-1-(1-methyl-2-(2-methylcyclopropyl)-1H-benzimidazol-6-yl)pyridin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of HATU (101 mg), 1-(4-amino-3-(methylamino)phenyl)-4-((4-chlorobenzyl)oxy)pyridin-2(1H)-one (90 mg), N,N-diisopropylethylamine (0.130 ml), 2-methylcyclopropanecarboxylic acid (0.049 ml) and DMF (2 ml) was stirred at room temperature 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 residue was dissolved in AcOH (2.00 ml), and the mixture was stirred at 90° C. for 2 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 (3 mg) as a diastereomeric mixture. The filtrate was concentrated in vacuo and the precipitate was recrystallized from THF to give the title compound (17 mg) as a diastereomeric mixture.

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 (2.00 ml)
  8. stirringthe mixture was stirred at 90° C. for 2 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-63311f951bd4401286d5a6dc2fcae569
Source dataset
uspto-grants-2016_06
Patent number
US09365540B2

Reaction notes

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