Trifluoroacetic acid → Ethanesulfonamide, N-(1-((4,4-difluorocyclohexyl)methyl)-2-(1,1-dimethylethyl)-1H-benzimidazol-5-yl)-

HRID 230715Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 230715
[C:1]([C:5]1[N:9]([CH2:10][CH:11]2[CH2:16][CH2:15][C:14]([F:18])([F:17])[CH2:13][CH2:12]2)[C:8]2[CH:19]=[CH:20][C:21]([NH2:23])=[CH:22][C:7]=2[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:24]([S:26](Cl)(=[O:28])=[O:27])[CH3:25].C(O)(C(F)(F)F)=O>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:1]([C:5]1[N:9]([CH2:10][CH:11]2[CH2:16][CH2:15][C:14]([F:18])([F:17])[CH2:13][CH2:12]2)[C:8]2[CH:19]=[CH:20][C:21]([NH:23][S:26]([CH2:24][CH3:25])(=[O:28])=[O:27])=[CH:22][C:7]=2[N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Komponenten

6

Edukt 3

HCID 6422Trifluoroacetic acidHCID 11667Ethanesulfonyl chlorideHCID 577232132-tert-Butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazol-5-amine

Produkt 1

HCID 11675994Ethanesulfonamide, N-(1-((4,4-difluorocyclohexyl)methyl)-2-(1,1-dimethylethyl)-1H-benzimidazol-5-yl)-

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

2-tert-Butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazol-5-amine (440 mg, 1.37 mmol) and DMAP (165 mg, 1.37 mmol) were dissolved in 50 mL of DCM. Ethanesulfonyl chloride (0.170 mL, 1.78 mmol) was added dropwise and the solution was stirred at rt for 2.5 h. The solution washed with saturated aqueous NaHCO3 solution, saturated aqueous NaCl solution and dried over anhydrous Na2SO4. The product was purified by silica gel flash chromatography using EtOAc as eluent. The fractions were concentrated and the residue was dissolved in 25 mL of MeOH. TFA (0.155 mL, 2.06 mmol) was added dropwise and the solution was stirred at rt for 30 min. The solvent was evaporated and the product was precipitated in ether affording the title compound as its corresponding TFA salt. Yield: 565 mg (78%). 1H NMR (400 MHz, METHANOL-D4) δ 1.29 (t, J=7.42 Hz, 3H), 1.48-1.60 (m, 2H), 1.64 (s, 9H), 1.66-1.72 (m, 2H), 1.73-1.82 (m, 2H), 1.99-2.09 (m, 2H), 2.18-2.28 (m, 1H), 3.11 (m, 2H), 4.50 (d, J=7.62 Hz, 2H), 7.38 (dd, J=9.08, 2.05 Hz, 1H), 7.72 (d, J=2.15 Hz, 1H), 7.85 (d, J=8.98 Hz, 1H); MS (ESI) (M+H)+ 414.0.

Aufarbeitung

  1. washThe solution washed with saturated aqueous NaHCO3 solution, saturated aqueous NaCl solution
  2. dry with materialdried over anhydrous Na2SO4
  3. customThe product was purified by silica gel flash chromatography
  4. concentrationThe fractions were concentrated
  5. dissolutionthe residue was dissolved in 25 mL of MeOH
  6. stirringthe solution was stirred at rt for 30 min
  7. customThe solvent was evaporated
  8. customthe product was precipitated in ether affording the title compound as its corresponding TFA salt

Quellen und Nachweise

ORD-Eintrag
ord-70e32c9550ab4931833d0502d8019097
Quelldatensatz
uspto-grants-2009_07
Patentnummer
US07566788B2

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