Triethyloxonium tetrafluoroborate → [1-(6-Fluoro-1-pyridin-4-yl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tert-butyl ester

HRID 243100Notes

Reaction equation

HRID 243100 reaction equation
[C:1]([NH:8][C@H:9]([C:11](N)=O)[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].F[B-](F)(F)F.C([O+](CC)CC)C.[F:26][C:27]1[CH:28]=[C:29]([NH:34][C:35]2[CH:40]=[CH:39][N:38]=[CH:37][CH:36]=2)[C:30]([NH2:33])=[CH:31][CH:32]=1>C(Cl)Cl.CCO>[C:4]([O:3][C:1](=[O:2])[NH:8][CH:9]([C:10]1[N:34]([C:35]2[CH:36]=[CH:37][N:38]=[CH:39][CH:40]=2)[C:29]2[CH:28]=[C:27]([F:26])[CH:32]=[CH:31][C:30]=2[N:33]=1)[CH3:11])([CH3:7])([CH3:6])[CH3:5]

Participants

6

Reactant 3

HCID 2723982Triethyloxonium tetrafluoroborateHCID 7015295Boc-Ala-NH2HCID 681579954-Fluoro-N2-pyridin-4-yl-benzene-1,2-diamine

Product 1

HCID 68157623[1-(6-Fluoro-1-pyridin-4-yl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tert-butyl esterYield 58%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of (S)-Boc-alaninamide (385 mg, 2.05 mmol) in DCM (5 mL) was added triethyloxonium tetrafluoroborate (389 mg, 2.05 mmol) in one portion under a nitrogen atmosphere. The resulting mixture was left to stir at RT for 1 h. The volatiles were removed under reduced pressure and to the resulting residue was added 4-fluoro-N2-pyridin-4-yl-benzene-1,2-diamine (208 mg, 1.02 mmol) in absolute EtOH (5 mL) and the mixture was stirred at 80° C. for 16 h. The volatiles were removed under reduced pressure and the resulting residue partitioned between DCM and a saturated aqueous solution of NaHCO3. The organic fraction was dried, concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-10% MeOH in EtOAc) to afford the title compound as a pale yellow oil (210 mg, 58%). LCMS (Method C): RT 2.84 min [M+H]+ 357.15

Workup

  1. waitThe resulting mixture was left
  2. customThe volatiles were removed under reduced pressure and to the resulting residue
  3. stirringthe mixture was stirred at 80° C. for 16 h
  4. customThe volatiles were removed under reduced pressure
  5. customthe resulting residue partitioned between DCM
  6. customThe organic fraction was dried
  7. concentrationconcentrated in vacuo
  8. customthe resulting residue purified by column chromatography (Si—PCC, gradient 0-10% MeOH in EtOAc)

Sources & evidence

ORD record
ord-e686fe91e9f849fba42218a90d327dd3
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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