Triethyloxonium tetrafluoroborate → {(S)-1-[6-fluoro-1-(1-methyl-1H-pyrazol-4-yl)-1H-benzoimidazol-2-yl]ethyl}carbamic acid tert-butyl ester

HRID 243191Notes

Reaction equation

HRID 243191 reaction equation
F[B-](F)(F)F.C([O+](CC)CC)C.[C:13]([O:17][C:18](=[O:25])[NH:19][C@H:20]([C:22](=O)[NH2:23])[CH3:21])([CH3:16])([CH3:15])[CH3:14].[F:26][C:27]1[CH:28]=[C:29]([NH:34][C:35]2[CH:36]=[N:37][N:38]([CH3:40])[CH:39]=2)[C:30](N)=[CH:31][CH:32]=1>C(Cl)Cl>[C:13]([O:17][C:18](=[O:25])[NH:19][C@H:20]([C:22]1[N:34]([C:35]2[CH:36]=[N:37][N:38]([CH3:40])[CH:39]=2)[C:29]2[CH:28]=[C:27]([F:26])[CH:32]=[CH:31][C:30]=2[N:23]=1)[CH3:21])([CH3:16])([CH3:15])[CH3:14]

Participants

5

Reactant 3

HCID 2723982Triethyloxonium tetrafluoroborateHCID 7015295Boc-Ala-NH2HCID 681577154-Fluoro-N2-(1-methyl-1H-pyrazol-4-yl)-benzene-1,2-diamine

Product 1

HCID 68158164{(S)-1-[6-fluoro-1-(1-methyl-1H-pyrazol-4-yl)-1H-benzoimidazol-2-yl]ethyl}carbamic acid tert-butyl esterYield 86%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Triethyloxonium tetrafluoroborate (0.35 g, 1.86 mmol) was added to a solution of ((S)-1-carbamoylethyl)carbamic acid tert-butyl ester (0.41 g, 2.22 mmol) in DCM (10 mL) at 20° C. under nitrogen and the resultant mixture stirred for 3 h then was concentrated in vacuo. The residue was dissolved in ethanol (10 mL) and 4-fluoro-N2-(1-methyl-1H-pyrazol-4-yl)-benzene-1,2-diamine (0.183 g, 0.89 mmol) added. The resultant solution was stirred at reflux for 16 h under nitrogen. The reaction mixture was concentrated in vacuo and the residue partitioned between DCM (×3) and saturated aqueous NaHCO3. The combined DCM extracts were dried (Na2SO4) and concentrated in vacuo. The resultant residue was purified by chromatography (SiO2, 0-5% (2M ammonia in methanol) in DCM) to give the title compound as a brown oil (0.274 g, 86%). LCMS (Method C): RT 2.77 min [M+H]+ 360.2.

Workup

  1. concentrationthen was concentrated in vacuo
  2. dissolutionThe residue was dissolved in ethanol (10 mL)
  3. temperatureat reflux for 16 h under nitrogen
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. customthe residue partitioned between DCM (×3) and saturated aqueous NaHCO3
  6. dry with materialThe combined DCM extracts were dried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe resultant residue was purified by chromatography (SiO2, 0-5% (2M ammonia in methanol) in DCM)

Sources & evidence

ORD record
ord-9228f06dd5d948b2bd4c6096ec3f6614
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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