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

HRID 60388Notes

Reaction equation

HRID 60388 reaction equation
F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[Br:25][C:26]1[CH:27]=[C:28]([NH:33][CH3:34])[C:29]([NH2:32])=[CH:30][CH:31]=1.C(N(C(C)C)CC)(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.O>[Br:25][C:26]1[CH:31]=[CH:30][C:29]2[N:32]=[C:51]([CH:49]3[CH2:50][CH:48]3[C:46]([O:45][CH3:44])=[O:47])[N:33]([CH3:34])[C:28]=2[CH:27]=1

Participants

7

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 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (554 mg) was added to a solution of 4-bromo-N2-methylbenzene-1,2-diamine (279 mg), diisopropylethylamine (0.727 mL) and (1RS,2SR)-2-(methoxycarbonyl)cyclopropanecarboxylic acid (200 mg) in DMF (5 mL) at room temperature. The mixture was stirred for 1 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with water and brine, dried over magnesium sulfate and concentrated in vacuo. The obtained residue was dissolved in acetic acid (5 mL), and the mixture was stirred at 80° C. for 1 hr. After concentration of the reaction mixture, saturated sodium hydrogen carbonate was added to the residue, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with water and brine, dried over magnesium sulfate and concentrated in vacuo. The obtained residue was purified by silica gel column chromatography (methanol/ethyl acetate) to give the title compound (80 mg) as a pale brown solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe obtained organic layer was washed with water and brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. dissolutionThe obtained residue was dissolved in acetic acid (5 mL)
  6. stirringthe mixture was stirred at 80° C. for 1 hr
  7. additionAfter concentration of the reaction mixture, saturated sodium hydrogen carbonate was added to the residue
  8. extractionthe mixture was extracted with ethyl acetate
  9. washThe obtained organic layer was washed with water and brine
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated in vacuo
  12. customThe obtained residue was purified by silica gel column chromatography (methanol/ethyl acetate)

Sources & evidence

ORD record
ord-f936124670f5473f8f03555c7cbd2473
Source dataset
uspto-grants-2016_09
Patent number
US09440987B2

Reaction notes

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