Ethanesulfonic acid → n-{2-Tert-butyl-1-[(4,4-difluorocyclohexyl)methyl]-1h-benzimidazol-5-yl}ethanesulfonamide esylate

HRID 230718

Reaction equation

HRID 230718 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]([NH:23][S:24]([CH2:27][CH3:28])(=[O:26])=[O:25])=[CH:22][C:7]=2[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:29]([S:31]([OH:34])(=[O:33])=[O:32])[CH3:30].C(C(C)=O)C(C)C.C(S(O)(=O)=O)C>C(C(C)=O)C(C)C>[S:31]([CH2:29][CH3:30])([OH:34])(=[O:33])=[O:32].[C:1]([C:5]1[N:9]([CH2:10][CH:11]2[CH2:12][CH2:13][C:14]([F:18])([F:17])[CH2:15][CH2:16]2)[C:8]2[CH:19]=[CH:20][C:21]([NH:23][S:24]([CH2:27][CH3:28])(=[O:25])=[O:26])=[CH:22][C:7]=2[N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 11668Ethanesulfonic acidHCID 11675994Ethanesulfonamide, N-(1-((4,4-difluorocyclohexyl)methyl)-2-(1,1-dimethylethyl)-1H-benzimidazol-5-yl)-HCID 131727546Methyl iso-butyl ketone ethane sulphonic acid

Product 1

HCID 16742587n-{2-Tert-butyl-1-[(4,4-difluorocyclohexyl)methyl]-1h-benzimidazol-5-yl}ethanesulfonamide esylateYield 85%

Reagents, catalysts & solvents 1

HCID 7909Methyl Isobutyl KetoneSolvent2×

Procedure

N-{2-tert-butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazol-5-yl}ethanesulfonamide (210 mg) was dissolved in methyl iso-butyl ketone (2.1 ml). A solution was made of ethansulphonic acid (43.7 μl) and methyl iso-butyl ketone (1.0 ml). The methyl iso-butyl ketone/ethane sulphonic acid solution was added in a controlled manner over three hours. Thus, initially, to the base solution was added 2×20 μl acid solution. Then after 30 minutes three more additions were made (3×20 μl). Approximately 20 minutes later three additions of 40 μl acid solution was made and after 40 minutes 400 μl was added. Finally, 20 minutes later the remaining amount of acid solution was added. The resulting slurry was left 2.5 days with stirring before it was filtered off and washed with methyl iso-butyl ketone (2×200 μl). The product was dried at 40° C. under vacuum yielding 227 mg crystalline N-{2-tert-butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazol-5-yl}ethanesulfonamide esylate salt. (yield 85%)

Workup

  1. addition400 μl was added
  2. additionFinally, 20 minutes later the remaining amount of acid solution was added
  3. waitThe resulting slurry was left 2.5 days
  4. filtrationwas filtered off
  5. washwashed with methyl iso-butyl ketone (2×200 μl)
  6. customThe product was dried at 40° C. under vacuum

Sources & evidence

ORD record
ord-6a4f742e715f4a0d93e9f15a5c1ccd9c
Source dataset
uspto-grants-2009_07
Patent number
US07566788B2

Linked notes

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