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

HRID 1987211

반응식

HRID 1987211 반응식
[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]

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매

실험 절차

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 was 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, 3 H), 1.48-1.60 (m, 2 H), 1.64 (s, 9 H), 1.66-1.72 (m, 2 H), 1.73-1.82 (m, 2 H), 1.99-2.09 (m, 2 H), 2.18 (m, 1 H), 3.11 (m, 2 H), 4.50 (d, J=7.62 Hz, 2 H), 7.38 (dd, J=9.08, 2.05 Hz, 1 H), 7.72 (d, J=2.15 Hz, 1 H), 7.85 (d, J=8.98 Hz, 1 H); MS (ESI) (M+H)+ 414.0.

후처리

  1. washThe solution was 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

출처 및 근거

ORD 기록
ord-04868f1b93824ea298aab0aa6eb51da1
출처 데이터셋
uspto-grants-2009_06
특허 번호
US07550495B2

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