Water → HCID 178456934, compound

HRID 1620661Notes

Reaction equation

HRID 1620661 reaction equation
Cl.Cl.[CH2:3]([NH:6][C:7]1=[N:8][C:9](=[O:19])[S:10]/[C:11]/1=[CH:12]\[CH:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1)[C:4]#[CH:5].C(=O)([O-])[O-].[K+].[K+].C([O:29][C:30]1[CH:35]=[CH:34][C:33]([CH2:36]Br)=[C:32]([C:38]([F:41])([F:40])[F:39])[CH:31]=1)(=O)C.O>CN(C=O)C>[OH:29][C:30]1[CH:35]=[CH:34][C:33]([CH2:36][N:16]2[CH2:17][CH2:18][CH:13](/[CH:12]=[C:11]3/[C:7]([NH:6][CH2:3][C:4]#[CH:5])=[N:8][C:9](=[O:19])[S:10]/3)[CH2:14][CH2:15]2)=[C:32]([C:38]([F:39])([F:40])[F:41])[CH:31]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 86678825HCID 86678825, compoundHCID 178456897HCID 178456897, compound

Product 1

HCID 178456934HCID 178456934, compoundYield 28.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (5Z)-4-(prop-2-yn-1-ylamino)-5-(piperidin-4-ylmethylidene)-1,3-thiazol-2(5H)-one dihydrochloride (2 g) in DMF (20 mL) were added potassium carbonate (3.45 g) and 4-(bromomethyl)-3-(trifluoromethyl)phenyl acetate (1.84 g). The reaction mixture was stirred at room temperature for 2 hr. Water was added to the reaction mixture, 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. To a solution of the residue in methanol (20 mL) was added potassium carbonate (858 mg), and the mixture was stirred at room temperature for 2 hr. To the reaction mixture was added saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The extract was washed with 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 (hexane/ethyl acetate), and the solid was recrystallized from ethyl acetate/heptane to give the title compound (0.75 g).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with water and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. additionTo a solution of the residue in methanol (20 mL) was added potassium carbonate (858 mg)
  6. stirringthe mixture was stirred at room temperature for 2 hr
  7. additionTo the reaction mixture was added saturated aqueous ammonium chloride solution
  8. extractionthe mixture was extracted with ethyl acetate
  9. washThe extract was washed with saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customthe solvent was evaporated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)
  13. customthe solid was recrystallized from ethyl acetate/heptane

Sources & evidence

ORD record
ord-88b7896b67064bd38dcd0729a054281f
Source dataset
uspto-grants-2014_07
Patent number
US08772277B2

Reaction notes

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