Ethyl Acetate → HCID 68678952, compound

HRID 387485Notes

Reaction equation

HRID 387485 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:10]=[N:11][CH:12]=[C:13](C3C=CC(O)=CC=3)[N:14]=2)=[CH:4][C:3]=1C(F)(F)F.[CH3:26][C:27](C)([O-:29])[CH3:28].[K+].[CH3:32][NH:33][C:34]([C:36]1[CH:41]=[C:40](Cl)[CH:39]=[CH:38][N:37]=1)=[O:35].[C:43]([O-])([O-])=O.[K+].[K+].C(O[CH2:53][CH3:54])(=O)C>CN(C=O)C.O>[CH3:32][NH:33][C:34]([C:36]1[CH:41]=[C:40]([O:29][C:27]2[CH:28]=[CH:54][C:53]([C:12]3[N:11]=[N:10][C:9]([NH:8][C:5]4[CH:4]=[CH:3][CH:2]=[CH:7][CH:6]=4)=[N:14][CH:13]=3)=[CH:43][CH:26]=2)[CH:39]=[CH:38][N:37]=1)=[O:35]

Participants

8

Reactant 5

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 14768144-Chloro-N-methylpicolinamideHCID 23665647Potassium tert-butoxideHCID 136179697HCID 136179697, compound

Product 1

HCID 68678952HCID 68678952, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
100 °C

Procedure

7.23 g (19.73 mmol) of 4-(3-{[4-chloro-3-(trifluoromethyl)phenyl]amino}-1,2,4-triazin-5-yl)phenol can be dissolved in 80 mL of anhydrous DMF under argon atmosphere. 2.44 g (21.71 mmol, 1.1 equivalent) of solid potassium tert-butoxide can be added to the solution. The resulting mixture can be heated to about 100° C. and stirred at that temperature for 15 min. Then a solution of 3.7 g (21.71 mmol, 1.1 equivalent) of 4-chloro-pyridine-2-carboxylic acid methylamide in 10 mL of anhydrous DMF can be added, followed by 3.28 g (23.68 mmol, 1.2 equivalent) of anhydrous K2CO3. The reaction mixture can be heated at 140° C. for 30 hrs. The progress of the reaction can be monitored by LC/MS. Then it can be allowed to cool down to ambient temperature. The resulting mixture can be poured into 500 mL of water and 100 mL of ethyl acetate. The aqueous layer can be extracted with a number of solvents, such as ethyl acetate, methylene chloride or ether. The combined extracts can be washed 3 times with 100 mL of water, then with brine and dried over anhydrous sodium sulfate. Solvent can be removed in vacuum to yield crude 4-[4-(3-phenylamino-[1,2,4]triazin-6-yl)-phenoxy]-pyridine-2-carboxylic acid methylamide. The product can be than purified using silica gel column chromatography. Those having ordinary skill in the art can determine which solvent system can be used as an eluents in the chromatographic purification.

Workup

  1. temperatureThe reaction mixture can be heated at 140° C. for 30 hrs
  2. customThe progress of the reaction
  3. temperatureto cool down to ambient temperature
  4. extractionThe aqueous layer can be extracted with a number of solvents, such as ethyl acetate, methylene chloride or ether
  5. washThe combined extracts can be washed 3 times with 100 mL of water
  6. dry with materialwith brine and dried over anhydrous sodium sulfate
  7. customSolvent can be removed in vacuum

Sources & evidence

ORD record
ord-6d2496db1d994d6f867d102869ad0f8c
Source dataset
uspto-grants-2013_02
Patent number
US08372971B2

Reaction notes

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