Potassium Carbonate → ethyl 8-(4-chloro-3-fluorophenoxy)-3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-8-carboxylate

HRID 71082Notes

Reaction equation

HRID 71082 reaction equation
Cl[C:2]1([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:7][CH2:6][CH2:5][N:4]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([N:17]4[CH:21]=[C:20]([CH3:22])[N:19]=[CH:18]4)=[C:13]([O:23][CH3:24])[N:12]=3)=[N:9][N:10]=[C:3]12.[Cl:30][C:31]1[CH:36]=[CH:35][C:34]([OH:37])=[CH:33][C:32]=1[F:38].C(=O)([O-])[O-].[K+].[K+].[Cl-].[NH4+]>CN(C=O)C>[Cl:30][C:31]1[CH:36]=[CH:35][C:34]([O:37][C:2]2([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:7][CH2:6][CH2:5][N:4]3[C:8]([C:11]4[CH:16]=[CH:15][C:14]([N:17]5[CH:21]=[C:20]([CH3:22])[N:19]=[CH:18]5)=[C:13]([O:23][CH3:24])[N:12]=4)=[N:9][N:10]=[C:3]23)=[CH:33][C:32]=1[F:38]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 27245234-Chloro-3-fluorophenolHCID 66607848ethyl 8-chloro-3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-8-carboxylate

Product 1

HCID 66608593ethyl 8-(4-chloro-3-fluorophenoxy)-3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-8-carboxylateYield 73.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of ethyl 8-chloro-3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-8-carboxylate (200 mg), 4-chloro-3-fluorophenol (73.8 mg) and potassium carbonate (66.3 mg) in DMF (2 mL) was stirred at 100° C. for 2 hr. The reaction mixture was cooled to room temperature, saturated aqueous ammonium chloride solution was added, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane) to give the title compound (73.5% mg).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with water and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane)

Sources & evidence

ORD record
ord-2215c1a27795429b83b72896b980f14b
Source dataset
uspto-grants-2014_09
Patent number
US08822699B2

Reaction notes

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