p-Toluenesulfonic acid → Ethyl 4-[4-chloro-2-[(4-chloro-2-methoxy-6-methylphenyl)amino]-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoate

HRID 1628436Notes

Reaction equation

HRID 1628436 reaction equation
Cl[C:2]1[N:6]([CH2:7][CH2:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:5]2[C:15]([CH:20]([CH2:23][CH3:24])[CH2:21][CH3:22])=[CH:16][CH:17]=[C:18]([Cl:19])[C:4]=2[N:3]=1.[Cl:25][C:26]1[CH:32]=[C:31]([CH3:33])[C:29]([NH2:30])=[C:28]([O:34][CH3:35])[CH:27]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C(C)=CC=CC=1>[Cl:19][C:18]1[C:4]2[N:3]=[C:2]([NH:30][C:29]3[C:31]([CH3:33])=[CH:32][C:26]([Cl:25])=[CH:27][C:28]=3[O:34][CH3:35])[N:6]([CH2:7][CH2:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:5]=2[C:15]([CH:20]([CH2:23][CH3:24])[CH2:21][CH3:22])=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 591919724-Chloro-2-methoxy-6-methylanilineHCID 68761768Ethyl 4-[2,4-dichloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoate

Product 1

HCID 68773857Ethyl 4-[4-chloro-2-[(4-chloro-2-methoxy-6-methylphenyl)amino]-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoateYield 22.8%

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Procedure

A mixture of ethyl 4-[2,4-dichloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoate (Reference Example 33; 470 mg, 1.27 mmol), 4-chloro-2-methoxy-6-methylaniline (650 mg, 3.81 mmol) and p-toluenesulfonic acid (241 mg, 1.27 mmol) and xylene (5.0 mL) was irradiated by microwave at 150° C. for 4 hr. After cooling, the reaction mixture was extracted with ethyl acetate (×3). The organics were dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with a 10-50% ethyl acetate/n-hexane gradient mixture to give the title compound (120 mg, 0.289 mmol, 18.7%) as a brown amorphous.

Workup

  1. customwas irradiated by microwave at 150° C. for 4 hr
  2. temperatureAfter cooling
  3. extractionthe reaction mixture was extracted with ethyl acetate (×3)
  4. dry with materialThe organics were dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography
  8. washeluting with a 10-50% ethyl acetate/n-hexane gradient mixture

Sources & evidence

ORD record
ord-0b4bc9bb63744866b7c639b42cd5ede6
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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