Triethyloxonium tetrafluoroborate → {(S)-1-[6-Fluoro-1-(5-fluoropyridin-3-yl)-1H-benzoimidazol-2-yl]propyl}carbamic acid tert-butyl ester

HRID 243178Notes

Reaction equation

HRID 243178 reaction equation
[C:1]([O:5][C:6](=[O:14])[NH:7][C@H:8]([C:11](=O)[NH2:12])[CH2:9][CH3:10])([CH3:4])([CH3:3])[CH3:2].F[B-](F)(F)F.C([O+](CC)CC)C.[F:27][C:28]1[CH:29]=[C:30]([NH:35][C:36]2[CH:37]=[N:38][CH:39]=[C:40]([F:42])[CH:41]=2)[C:31](N)=[CH:32][CH:33]=1>C(Cl)Cl>[C:1]([O:5][C:6](=[O:14])[NH:7][C@H:8]([C:11]1[N:35]([C:36]2[CH:37]=[N:38][CH:39]=[C:40]([F:42])[CH:41]=2)[C:30]2[CH:29]=[C:28]([F:27])[CH:33]=[CH:32][C:31]=2[N:12]=1)[CH2:9][CH3:10])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 2723982Triethyloxonium tetrafluoroborateHCID 45092008tert-Butyl (S)-(1-amino-1-oxobutan-2-yl)carbamateHCID 681580564-Fluoro-N2-(5-fluoropyridin-3-yl)benzene-1,2-diamine

Product 1

HCID 68157999{(S)-1-[6-Fluoro-1-(5-fluoropyridin-3-yl)-1H-benzoimidazol-2-yl]propyl}carbamic acid tert-butyl esterYield 82.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of ((S)-1-carbamoylpropyl)carbamic acid tert-butyl ester (250 mg, 1.24 mmol) in DCM (5 mL) was added triethyloxonium tetrafluoroborate (228 mg, 1.20 mmol) and the reaction mixture stirred at RT for 1.5 h under argon. The reaction mixture was concentrated in vacuo and the residue dissolved in ethanol (3 mL). 4-Fluoro-N2-(5-fluoropyridin-3-yl)benzene-1,2-diamine (88 mg, 0.40 mmol) was added and the reaction mixture heated at 60° C. for 20 min. The reaction mixture was concentrated in vacuo, and the residue partitioned between DCM and sat. NaHCO3. The organic fraction was washed with brine, dried (Na2SO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si—PPC, gradient 0-50% EtOAc in cyclohexane) to afford the title compound as a white foam (128 mg, 82%). LCMS (Method J): RT=3.42 min, [M+H]+=389.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionthe residue dissolved in ethanol (3 mL)
  3. temperaturethe reaction mixture heated at 60° C. for 20 min
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. customthe residue partitioned between DCM and sat. NaHCO3
  6. washThe organic fraction was washed with brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d1d93f16ecf442acb7cc0992b3dade8a
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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