Methanesulfonyl chloride → 8-Chloro-1-(2,4-dichlorophenyl)-5-(1-ethylpropyl)-2,3-dihydro-1H-imidazo[1,2-a]benzimidazole

HRID 1398964Notes

Reaction equation

HRID 1398964 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=3[Cl:19])[N:7]([CH2:20][CH2:21]O)[C:6]=2[C:5]([CH:23]([CH2:26][CH3:27])[CH2:24][CH3:25])=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.CS(Cl)(=O)=O>O1CCCC1.C(OCC)(=O)C>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:12]4[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=4[Cl:19])[CH2:21][CH2:20][N:7]3[C:6]=2[C:5]([CH:23]([CH2:26][CH3:27])[CH2:24][CH3:25])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 31297Methanesulfonyl chloride2×HCID 81531Diisopropylethylamine2×HCID 249676592-[4-Chloro-2-[(2,4-dichlorophenyl)amino]-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]ethanol

Product 1

HCID 577863538-Chloro-1-(2,4-dichlorophenyl)-5-(1-ethylpropyl)-2,3-dihydro-1H-imidazo[1,2-a]benzimidazoleYield 23.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-{4-chloro-2-[(2,4-dichlorophenyl)amino]-7-(1-ethylpropyl)-1H-benzimidazol-1-yl}ethanol (Reference Example 19; 66 mg, 0.155 mmol) in tetrahydrofuran (0.8 mL) were added diisopropylethylamine (0.053 ml, 0.310 mmol) and methanesulfonyl chloride (0.013 ml, 0.170 mmol) at 0° C., and the mixture was stirred at room temperature for 2 hr. Additional diisopropylethylamine (0.053 ml, 0.310 mmol) and methanesulfonyl chloride (0.013 mL, 0.170 mmol) were added at 0° C., followed by stirring at room temperature for 15 hr. The reaction mixture was diluted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with a 10-25% ethyl acetate/n-hexane gradient mixture. The desired fractions were concentrated in vacuo, and the resulting solid was washed with n-hexane to give the title compound (15 mg, 0.0360 mmol, 23%) as a colorless solid.

Workup

  1. stirringby stirring at room temperature for 15 hr
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel column chromatography
  6. washeluting with a 10-25% ethyl acetate/n-hexane gradient mixture
  7. concentrationThe desired fractions were concentrated in vacuo
  8. washthe resulting solid was washed with n-hexane

Sources & evidence

ORD record
ord-98e1971e35aa4283978a8c14943e2e42
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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