Hydrochloric Acid → 2-thioxo-3-[4-(2,2,2-trifluoroethoxy)phenyl]-2,3,5,6-tetrahydropyrido[2,3-d]pyrimidine-4,7(1H,8H)-dione

HRID 570704Notes

Reaction equation

HRID 570704 reaction equation
[N:1]([C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]([F:15])([F:14])[F:13])=[CH:6][CH:5]=1)=[C:2]=[S:3].[H-].[Na+].[C:18]([CH:21]([CH2:27][CH2:28][C:29]([O:31]CC)=O)[C:22](OCC)=[O:23])(=[NH:20])[NH2:19].Cl>CN(C)C=O>[S:3]=[C:2]1[NH:19][C:18]2[NH:20][C:29](=[O:31])[CH2:28][CH2:27][C:21]=2[C:22](=[O:23])[N:1]1[C:4]1[CH:5]=[CH:6][C:7]([O:10][CH2:11][C:12]([F:13])([F:15])[F:14])=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 866436111-Isothiocyanato-4-(2,2,2-trifluoroethoxy)benzeneHCID 86685366Diethyl 2-carbamimidoylpentane-1,5-dioate

Product 1

HCID 866853672-thioxo-3-[4-(2,2,2-trifluoroethoxy)phenyl]-2,3,5,6-tetrahydropyrido[2,3-d]pyrimidine-4,7(1H,8H)-dioneYield 26.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-isothiocyanato-4-(2,2,2-trifluoroethoxy)benzene (1.77 g) in N,N-dimethylformamide (25 mL) was added sodium hydride (60% in oil, 0.478 g) under ice-cooling. The reaction mixture was stirred for 5 min under ice-cooling, diethyl 2-carbamimidoylpentane-1,5-dioate (2.5 g) was added thereto, and the mixture was stirred for 30 min under ice-cooling. To the reaction mixture was added 1M hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in ethanol (25 mL), sodium ethoxide (20% ethanol solution, 10.6 mL) was added thereto, and the mixture was stirred for 30 min. To the reaction mixture was added 1M hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (0.75 g).

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringthe mixture was stirred for 30 min under ice-
  4. temperaturecooling
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe extract was washed with saturated brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe solvent was evaporated under reduced pressure
  9. dissolutionThe residue was dissolved in ethanol (25 mL)
  10. additionsodium ethoxide (20% ethanol solution, 10.6 mL) was added
  11. stirringthe mixture was stirred for 30 min
  12. additionTo the reaction mixture was added 1M hydrochloric acid
  13. extractionthe mixture was extracted with ethyl acetate
  14. washThe extract was washed with saturated brine
  15. dry with materialdried over anhydrous sodium sulfate
  16. customThe solvent was evaporated under reduced pressure
  17. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-0ef33096d8fb4e048fad284df6524667
Source dataset
uspto-grants-2015_05
Patent number
US09023858B2

Reaction notes

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