Triethyloxonium tetrafluoroborate → [(S)-1-(6-Fluoro-7-methyl-1-pyridin-2-yl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tert-butyl ester

HRID 243061Notes

Reaction equation

HRID 243061 reaction equation
[C:1]([O:5][C:6](=[O:13])[NH:7][C@H:8]([C:10](=O)[NH2:11])[CH3:9])([CH3:4])([CH3:3])[CH3:2].F[B-](F)(F)F.C([O+](CC)CC)C.[F:26][C:27]1[C:28]([CH3:41])=[C:29]([NH:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=2)[C:30](N)=[CH:31][CH:32]=1>C(Cl)Cl>[C:1]([O:5][C:6](=[O:13])[NH:7][C@H:8]([C:10]1[N:34]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=2)[C:29]2[C:28]([CH3:41])=[C:27]([F:26])[CH:32]=[CH:31][C:30]=2[N:11]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 2723982Triethyloxonium tetrafluoroborateHCID 7015295Boc-Ala-NH2HCID 681580774-Fluoro-3-methyl-N2-pyridin-2-yl-benzene-1,2-diamine

Product 1

HCID 68157743[(S)-1-(6-Fluoro-7-methyl-1-pyridin-2-yl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tert-butyl esterYield 76%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of ((S)-1-carbamoylethyl)carbamic acid tert-butyl ester (1.52 g, 8.1 mmol) in DCM (15 mL) was added triethyloxonium tetrafluoroborate (1.63 g, 8.6 mmol) and the reaction mixture stirred at RT for 2 h, during which the solids dissolved. The reaction mixture was concentrated in vacuo and the residue dissolved in ethanol (15 mL). 4-fluoro-3-methyl-N2-pyridin-2-yl-benzene-1,2-diamine (1.0 g, 5.1 mmol) was added and the reaction heated at 75° C. for 16 h. The reaction mixture was concentrated in vacuo, the residue dissolved in water and the product extracted with EtOAc (3×20 mL). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, eluting with 0-100% EtOAc in cyclohexane) to yield the title compound as a white solid (1.29 g, 76%). LCMS (Method C): RT=3.22 min, [M+H]+=371.

Workup

  1. dissolutiondissolved
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionthe residue dissolved in ethanol (15 mL)
  4. temperaturethe reaction heated at 75° C. for 16 h
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. dissolutionthe residue dissolved in water
  7. extractionthe product extracted with EtOAc (3×20 mL)
  8. washThe combined organic extracts were washed with brine
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated in vacuo
  11. washThe resultant residue was subjected to flash chromatography (SiO2, eluting with 0-100% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-8716166c3c9c410b84e9e062f6855d6a
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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