Pyridine → 2-(3-ethylpyridin-4-yl-)-3-methyl-6-trifluoromethyl-3H-imidazo[4,5-b]pyridine

HRID 1256606Notes

Reaction equation

HRID 1256606 reaction equation
[CH3:1][NH:2][C:3]1[C:8]([NH2:9])=[CH:7][C:6]([C:10]([F:13])([F:12])[F:11])=[CH:5][N:4]=1.[CH2:14]([C:16]1[CH:24]=[N:23][CH:22]=[CH:21][C:17]=1[C:18](O)=O)[CH3:15].CCN=C=NCCCN(C)C.N1C=CC=CC=1>O>[CH2:14]([C:16]1[CH:24]=[N:23][CH:22]=[CH:21][C:17]=1[C:18]1[N:2]([CH3:1])[C:3]2=[N:4][CH:5]=[C:6]([C:10]([F:11])([F:12])[F:13])[CH:7]=[C:8]2[N:9]=1)[CH3:15]

Participants

6

Reactant 4

HCID 1049PyridineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 2735930N2-Methyl-5-(trifluoromethyl)pyridine-2,3-diamineHCID 450847433-Ethylisonicotinic acid

Product 1

HCID 666003732-(3-ethylpyridin-4-yl-)-3-methyl-6-trifluoromethyl-3H-imidazo[4,5-b]pyridineYield 15.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 0.40 g of N2-methyl-5-trifluoromethylpyridine-2,3-diamine, 0.41 g of 3-ethylisonicotinic acid, 0.44 g of WSC and 10 ml of pyridine was stirred for 2.5 hours at 120° C. The reaction mixture was cooled down to room temperature. Into the reaction mixture was poured water, and the mixture was extracted three times with ethyl acetate. The organic layer was dried over magnesium sulfate, then, concentrated under reduced pressure. To the residue was added a mixture of 0.60 g of p-toluenesulfonic acid monohydrate and 10 ml of toluene, and the mixture was stirred for 7 hours at 120° C. The reaction mixture was cooled down to room temperature. Into the reaction mixture was poured water, and the mixture was extracted three times with ethyl acetate. The organic layer was dried over magnesium sulfate, then, concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 0.10 g of 2-(3-ethylpyridin-4-yl-)-3-methyl-6-trifluoromethyl-3H-imidazo[4,5-b]pyridine (hereinafter, referred to as present active compound 217).

Workup

  1. temperatureThe reaction mixture was cooled down to room temperature
  2. extractionthe mixture was extracted three times with ethyl acetate
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. additionTo the residue was added
  6. additiona mixture of 0.60 g of p-toluenesulfonic acid monohydrate and 10 ml of toluene
  7. stirringthe mixture was stirred for 7 hours at 120° C
  8. temperatureThe reaction mixture was cooled down to room temperature
  9. additionInto the reaction mixture was poured water
  10. extractionthe mixture was extracted three times with ethyl acetate
  11. dry with materialThe organic layer was dried over magnesium sulfate
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-714dc097d2b849d2b79b0e39ef050be1
Source dataset
uspto-grants-2013_06
Patent number
US08461181B2

Reaction notes

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