Diisopropylethylamine → Methyl(1RS,2SR)-2-(6-bromo-1-methyl-1H-benzimidazol-2-yl)cyclopropanecarboxylate

HRID 2202919Notes

Reaction equation

HRID 2202919 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Br:25][C:26]1[CH:31]=[C:30]([NH:32][CH3:33])[C:29]([NH2:34])=[CH:28][CH:27]=1.C(N(CC)C(C)C)(C)C.[CH3:44][O:45][C:46]([CH:48]1[CH2:50][CH:49]1[C:51](O)=O)=[O:47]>CN(C=O)C>[Br:25][C:26]1[CH:27]=[CH:28][C:29]2[N:34]=[C:51]([CH:49]3[CH2:50][CH:48]3[C:46]([O:45][CH3:44])=[O:47])[N:32]([CH3:33])[C:30]=2[CH:31]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 121982705-Bromo-N1-methylbenzene-1,2-diamineHCID 125109711-Ethoxycarbonylcyclopropanecarboxylic acid

Product 1

HCID 121386226Methyl(1RS,2SR)-2-(6-bromo-1-methyl-1H-benzimidazol-2-yl)cyclopropanecarboxylateYield 18.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (554 mg) was added to a solution of 5-bromo-N1-methylbenzene-1,2-diamine (279 mg), N,N-diisopropylethylamine (0.727 ml) and (1RS,2SR)-2-(methoxycarbonyl)cyclopropanecarboxylic acid (200 mg) in DMF (5 ml) at room temperature. The mixture 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 (5 ml), and the mixture was stirred at 80° C. for 1 h. After concentration of the mixture, the residue was neutralized with saturated NaHCO3 solution and extracted with EtOAc. The organic layer was separated, washed with water and brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography (MeOH/EtOAc) to give the title compound (80 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 residue was dissolved in AcOH (5 ml)
  8. stirringthe mixture was stirred at 80° C. for 1 h
  9. extractionextracted with EtOAc
  10. customThe organic layer was separated
  11. washwashed with water and brine
  12. dry with materialdried over MgSO4
  13. concentrationconcentrated in vacuo
  14. customThe residue was purified by silica gel column chromatography (MeOH/EtOAc)

Sources & evidence

ORD record
ord-9f4f62d2868744009fb0ff7ecb3efc3d
Source dataset
uspto-grants-2016_06
Patent number
US09365540B2

Reaction notes

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