Dichloromethane → [2-((S)-1-Aminoethyl)-5-fluoro-3-phenyl-3H-benzoimidazol-4-yl]acetonitrile dihydrochloride

HRID 243244Notes

Reaction equation

HRID 243244 reaction equation
C(OC(=O)[NH:7][C@H:8]([C:10](=O)N)[CH3:9])(C)(C)C.F[B-](F)(F)F.C([O+](CC)CC)C.[NH2:26][C:27]1[C:28]([NH:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)=[C:29]([CH2:34][C:35]#[N:36])[C:30]([F:33])=[CH:31][CH:32]=1.C(Cl)[Cl:45]>>[ClH:45].[ClH:45].[NH2:7][C@H:8]([C:10]1[N:37]([C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[C:28]2[C:29]([CH2:34][C:35]#[N:36])=[C:30]([F:33])[CH:31]=[CH:32][C:27]=2[N:26]=1)[CH3:9]

Participants

5

Reactant 4

HCID 6344DichloromethaneHCID 2723982Triethyloxonium tetrafluoroborateHCID 7015295Boc-Ala-NH2HCID 68158122(3-Amino-6-fluoro-2-phenylaminophenyl)acetonitrile

Product 1

HCID 68156958[2-((S)-1-Aminoethyl)-5-fluoro-3-phenyl-3H-benzoimidazol-4-yl]acetonitrile dihydrochloride

Procedure

To a suspension of ((S)-1-carbamoylethyl)carbamic acid tert-butyl ester (435 mg, 2.31 mmol) in DCM (5 mL) was added triethyloxonium tetrafluoroborate (369 mg, 1.94 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 (5 mL). (3-Amino-6-fluoro-2-phenylaminophenyl)acetonitrile (223 mg, 0.92 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) LCMS (Method C): RT=3.36 min, [M+H]+=395. The product was dissolved in HCl in dioxane (4N, 10 mL) and the reaction stirred at RT for 1 h. The reaction mixture was concentrated in vacuo to give the title product as an off white solid (227 mg, 67%). LCMS (Method C): RT=1.88 min, [M+H]+=295.

Workup

  1. dissolutiondissolved
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionthe residue dissolved in ethanol (5 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) LCMS (Method C)
  12. dissolutionThe product was dissolved in HCl in dioxane (4N, 10 mL)
  13. stirringthe reaction stirred at RT for 1 h
  14. concentrationThe reaction mixture was concentrated in vacuo

Sources & evidence

ORD record
ord-6bd440c1bdd34bb68fa17ea295e6e4c2
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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