Trifluoroacetic acid → N-{2-tert-Butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazol-5-yl}cyclopropanesulfonamide

HRID 1987212Notes

Reaction equation

HRID 1987212 reaction equation
[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].[CH:24]1([S:27](Cl)(=[O:29])=[O:28])[CH2:26][CH2:25]1.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:27]([CH:24]3[CH2:26][CH2:25]3)(=[O:29])=[O:28])=[CH:22][C:7]=2[N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 2760919Cyclopropanesulfonyl chlorideHCID 577232132-tert-Butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazol-5-amine

Product 1

HCID 11589941N-{2-tert-Butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazol-5-yl}cyclopropanesulfonamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

2-tert-Butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazol-5-amine (300 mg, 0.934 mmol) and DMAP (115 mg, 0.934 mmol) were dissolved in 10 mL of DCM. Cyclopropanesulfonyl chloride (170 mg, 1.21 mmol) was added and the solution was stirred at rt for 2 h. The solution was washed with saturated aqueous NaHCO3 solution, brine and dried over anhydrous MgSO4. 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 (0.143 mL, 1.86 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: 390 mg (77%). 1H NMR (400 MHz, METHANOL-D4) δ 0.91-0.97 (m, 2 H), 1.02-1.08 (m, 2 H), 1.48-1.60 (m, 2 H), 1.65 (s, 9 H), 1.67-1.75 (m, 3 H), 1.75-1.82 (m, 1 H), 2.00-2.10 (m, 2 H), 2.18-2.28 (m, 1 H), 2.53-2.61 (m, 1 H), 4.50 (d, J=7.42 Hz, 2 H), 7.42 (dd, J=8.98, 2.15 Hz, 1 H), 7.74 (d, J=1.56 Hz, 1 H), 7.85 (d, J=8.79 Hz, 1 H); MS (ESI) (M+H)+ 426.0; Anal. Calcd (%) for C21H29N3O2SF2+1.0 TFA; C, 51.20; H, 5.60; N, 7.79. Found: C, 51.38; H, 5.66; N, 7.56.

Workup

  1. washThe solution was washed with saturated aqueous NaHCO3 solution, brine
  2. dry with materialdried over anhydrous MgSO4
  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

Sources & evidence

ORD record
ord-ab911f2563cb424f8489dffc2e22414c
Source dataset
uspto-grants-2009_06
Patent number
US07550495B2

Reaction notes

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