Tetrahydrofuran → HCID 44227517, compound

HRID 2090830Notes

Reaction equation

HRID 2090830 reaction equation
[CH:1]1([CH:7]([C:9]2[C:10]([CH3:24])=[N:11][N:12]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][N:15]=3)[CH:13]=2)O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.S(Cl)(Cl)=O.[C:29](=[O:32])([O-])[OH:30].[Na+].[OH-].[Na+].[O:36]1[CH2:40][CH2:39][CH2:38][CH2:37]1>C(O)C>[CH:1]1([CH:7]([NH:11][C:10]2[CH:9]=[CH:7][C:39]([C:40]([NH:12][CH2:14][CH2:19][C:29]([OH:30])=[O:32])=[O:36])=[CH:38][CH:37]=2)[C:9]2[C:10]([CH3:24])=[N:11][N:12]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][N:15]=3)[CH:13]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 5

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 24386Thionyl ChlorideHCID 516892Sodium BicarbonateHCID 66778670HCID 66778670, compound

Product 1

HCID 44227517HCID 44227517, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution (10 mL) of cyclohexyl{3-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazol-4-yl}methanol (0.75 g) synthesized above in tetrahydrofuran was added thionyl chloride (0.24 mL) at room temperature, and the mixture was stirred for 30 min. The reaction mixture was poured into aqueous sodium hydrogen carbonate solution at 0° C., and the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in dimethylacetamide (15 mL), and sodium iodide (0.63 g), sodium carbonate (0.45 g) and ethyl 3-{[(4-aminophenyl)carbonyl]amino}propanoate (0.75 g) synthesized in Example 1, (2) were added. The mixture was stirred at 80° C. overnight and allowed to cool. Then, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:1, volume ratio) to give the title object compound in an ethyl ester form (876 mg). This was dissolved in ethanol (4 mL), 1N aqueous sodium hydroxide solution (4 mL) was added at room temperature, and the mixture was stirred for 1 hr. Ethanol was evaporated under reduced pressure, and 1N hydrochloric acid (4 mL) was added to the residue. The precipitate was washed with water to give the title object compound (0.78 g, 70%) as a white solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in dimethylacetamide (15 mL)
  6. additionsodium iodide (0.63 g), sodium carbonate (0.45 g) and ethyl 3-{[(4-aminophenyl)carbonyl]amino}propanoate (0.75 g) synthesized in Example 1, (2) were added
  7. stirringThe mixture was stirred at 80° C. overnight
  8. temperatureto cool
  9. additionThen, water was added to the reaction mixture
  10. extractionthe mixture was extracted with ethyl acetate
  11. concentrationThe extract was concentrated under reduced pressure
  12. customthe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:1, volume ratio)
  13. customto give the title
  14. stirringthe mixture was stirred for 1 hr
  15. customEthanol was evaporated under reduced pressure, and 1N hydrochloric acid (4 mL)
  16. additionwas added to the residue
  17. washThe precipitate was washed with water

Sources & evidence

ORD record
ord-3a903f09d9b0446a80c381e21084da7f
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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