Triethyloxonium tetrafluoroborate → {(S)-1-[7-Cyano-6-fluoro-1-(5-fluoropyridin-3-yl)-1H-benzoimidazol-2-yl]-ethyl}carbamic acid tert-butyl ester

HRID 243247Notes

Reaction equation

HRID 243247 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.N[C:27]1[C:28]([NH:36][C:37]2[CH:38]=[N:39][CH:40]=[C:41]([F:43])[CH:42]=2)=[C:29]([C:32]([F:35])=[CH:33][CH:34]=1)[C:30]#[N:31]>C(Cl)Cl>[C:1]([O:5][C:6](=[O:13])[NH:7][C@H:8]([C:10]1[N:36]([C:37]2[CH:38]=[N:39][CH:40]=[C:41]([F:43])[CH:42]=2)[C:28]2[C:29]([C:30]#[N:31])=[C:32]([F:35])[CH:33]=[CH:34][C:27]=2[N:11]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 2723982Triethyloxonium tetrafluoroborateHCID 7015295Boc-Ala-NH2HCID 68157539HCID 68157539, compound

Product 1

HCID 68158144{(S)-1-[7-Cyano-6-fluoro-1-(5-fluoropyridin-3-yl)-1H-benzoimidazol-2-yl]-ethyl}carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of ((S)-1-carbamoyl-ethyl)carbamic acid tert-butyl ester (1.81 g, 9.63 mmol) in DCM (20 mL) was added triethyloxonium tetrafluoroborate (1.54 g, 8.08 mmol) and the reaction mixture stirred at RT for 2 hours, during which the solids dissolved. The reaction mixture was concentrated in vacuo and the residue dissolved in ethanol (20 mL). 3-Amino-6-fluoro-2-(5-fluoropyridin-3-ylamino)benzonitrile (948 mg, 3.86 mmol) was added and the reaction heated at 70° C. for 1 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 give the title compound as an off white solid. LCMS (Method C): RT=3.20 min, [M+H-tBu]+=344, 100%, [M+H]+=400, 10%.

Workup

  1. dissolutiondissolved
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionthe residue dissolved in ethanol (20 mL)
  4. temperaturethe reaction heated at 70° C. for 1 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-9e670d4905334fee81c8b8bf1bb43f52
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

Loading…