Pyridine → 1-methyl-2-(3-methylpyridin-4-yl)-5-trifluoromethyl-1H-benzimidazole

HRID 2390469Notes

Reaction equation

HRID 2390469 reaction equation
[CH3:1][NH:2][C:3]1[C:4]([NH2:13])=[CH:5][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:7][CH:8]=1.[CH3:14][C:15]1[CH:23]=[N:22][CH:21]=[CH:20][C:16]=1[C:17](O)=O.CCN=C=NCCCN(C)C.N1C=CC=CC=1>O>[CH3:1][N:2]1[C:3]2[CH:8]=[CH:7][C:6]([C:9]([F:11])([F:10])[F:12])=[CH:5][C:4]=2[N:13]=[C:17]1[C:16]1[CH:20]=[CH:21][N:22]=[CH:23][C:15]=1[CH3:14]

Participants

6

Reactant 4

HCID 1049PyridineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 715666N1-Methyl-4-(trifluoromethyl)benzene-1,2-diamineHCID 15020033-Methyl-isonicotinic acid

Product 1

HCID 666638951-methyl-2-(3-methylpyridin-4-yl)-5-trifluoromethyl-1H-benzimidazoleYield 82.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 0.38 g of N1-methyl-4-trifluoromethylbenzene-1,2-diamine, 0.33 g of 3-methylisonicotinic acid, 0.46 g of WSC and 10 ml of pyridine was stirred for 5 hours while heating at 120° C. After cooling down to room temperature, water was poured, and the mixture was extracted three times with ethyl acetate. The combined organic layers were dried over magnesium sulfate, then, concentrated under reduced pressure. To the residue were added a mixture of 0.57 g of p-toluenesulfonic acid monohydrate and 10 ml of toluene, and the mixture was stirred for 1 hour while heating at 80° C., and stirred for 2 hours while heating at 120° C. After cooling down to room temperature, a saturated sodium hydrogen carbonate aqueous solution was poured, and the mixture was extracted three times with ethyl acetate. The combined organic layers were dried over magnesium sulfate, then, concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 0.48 g of 1-methyl-2-(3-methylpyridin-4-yl)-5-trifluoromethyl-1H-benzimidazole (hereinafter, referred to as present active compound 6).

Workup

  1. temperatureAfter cooling down to room temperature
  2. extractionthe mixture was extracted three times with ethyl acetate
  3. dry with materialThe combined organic layers were dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. additionTo the residue were added
  6. additiona mixture of 0.57 g of p-toluenesulfonic acid monohydrate and 10 ml of toluene
  7. stirringthe mixture was stirred for 1 hour
  8. temperaturewhile heating at 80° C.
  9. stirringstirred for 2 hours
  10. temperaturewhile heating at 120° C
  11. temperatureAfter cooling down to room temperature
  12. additiona saturated sodium hydrogen carbonate aqueous solution was poured
  13. extractionthe mixture was extracted three times with ethyl acetate
  14. dry with materialThe combined organic layers were dried over magnesium sulfate
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-5f1264b6ba3e4c738f50ddaafbea1867
Source dataset
uspto-grants-2012_09
Patent number
US08273764B2

Reaction notes

Loading…