Hydrochloric Acid → 7-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-thioxo-3-[4-(2,2,2-trifluoroethoxy)phenyl]-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-one

HRID 570722Notes

Reaction equation

HRID 570722 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([O:10]C)=O)=[CH:6][CH:5]=[C:4]([CH2:12][OH:13])[N:3]=1.[C:14]([Si:18](Cl)([CH3:20])[CH3:19])([CH3:17])([CH3:16])[CH3:15].N1C=CN=C1.[N:27]([C:30]1[CH:35]=[CH:34][C:33]([O:36][CH2:37][C:38]([F:41])([F:40])[F:39])=[CH:32][CH:31]=1)=[C:28]=[S:29].[H-].[Na+].Cl>CN(C)C=O.O>[Si:18]([O:13][CH2:12][C:4]1[CH:5]=[CH:6][C:7]2[C:8](=[O:10])[N:27]([C:30]3[CH:31]=[CH:32][C:33]([O:36][CH2:37][C:38]([F:41])([F:39])[F:40])=[CH:34][CH:35]=3)[C:28](=[S:29])[NH:1][C:2]=2[N:3]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:20])[CH3:19]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 795ImidazoleHCID 24758Sodium hydrideHCID 28928tert-Butyldimethylsilyl chlorideHCID 866436111-Isothiocyanato-4-(2,2,2-trifluoroethoxy)benzeneHCID 86685381Methyl 2-amino-6-(hydroxymethyl)pyridine-3-carboxylate

Product 1

HCID 866853837-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-thioxo-3-[4-(2,2,2-trifluoroethoxy)phenyl]-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-oneYield 67.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

A mixture of methyl 2-amino-6-(hydroxymethyl)pyridine-3-carboxylate (296 mg), tert-butyl(chloro)dimethylsilane (298 mg), imidazole (218 mg) and N,N-dimethylformamide (8 ml) was stirred at room temperature for 15 min. To the reaction solution was added water, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give a white solid. The white solid was added to a mixture of 1-isothiocyanato-4-(2,2,2-trifluoroethoxy)benzene (670 mg), sodium hydride (60% in oil, 132 mg) and N,N-dimethylformamide (15 ml) under ice-cooling, and the mixture was stirred for 30 min. The reaction mixture was acidified with 1M hydrochloric acid, and extracted with ethyl acetate. The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (547 mg) as a white solid.

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. customto give a white solid
  6. temperaturecooling
  7. stirringthe mixture was stirred for 30 min
  8. extractionextracted with ethyl acetate
  9. washThe extract was washed with water and saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-7815b904bd4d4dafb7671e5d39dec7cc
Source dataset
uspto-grants-2015_05
Patent number
US09023858B2

Reaction notes

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