Hydrochloric Acid → 7-chloro-2-thioxo-3-[4-(2,2,2-trifluoroethoxy)phenyl]pyrido[2,3-d]pyrimidin-4(3H)-one

HRID 570717Notes

Reaction equation

HRID 570717 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+].[NH2:18][C:19]1[C:24]([C:25](OC)=[O:26])=[CH:23][CH:22]=[C:21]([Cl:29])[N:20]=1.Cl>CN(C)C=O.C(OCC)C>[Cl:29][C:21]1[CH:22]=[CH:23][C:24]2[C:25](=[O:26])[N:1]([C:4]3[CH:5]=[CH:6][C:7]([O:10][CH2:11][C:12]([F:13])([F:15])[F:14])=[CH:8][CH:9]=3)[C:2](=[S:3])[NH:18][C:19]=2[N:20]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 57415887Methyl 2-amino-6-chloronicotinateHCID 866436111-Isothiocyanato-4-(2,2,2-trifluoroethoxy)benzene

Product 1

HCID 866853777-chloro-2-thioxo-3-[4-(2,2,2-trifluoroethoxy)phenyl]pyrido[2,3-d]pyrimidin-4(3H)-oneYield 17.9%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×

Procedure

1-Isothiocyanato-4-(2,2,2-trifluoroethoxy)benzene (4.06 g) was dissolved in N,N-dimethylformamide (50 ml), and sodium hydride (60% in oil, 1.39 g) was added thereto under ice-cooling. Methyl 2-amino-6-chloropyridine-3-carboxylate (2.95 g) was dissolved in N,N-dimethylformamide (25 ml), the solution was added dropwise to the reaction mixture under ice-cooling, and the mixture was stirred for 20 min, and then at room temperature for 1 hr and 30 min. The reaction mixture was poured into 0.5M hydrochloric acid (80 ml), and the white precipitate was collected by filtration. The precipitate was dissolved in tetrahydrofuran (100 ml), and the solution was diluted with ethyl acetate (200 ml), washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give a white residue. The residue was suspended in diethyl ether (100 ml), and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane), and washed with diethyl ether to give the white title compound (1.1 g).

Workup

  1. temperatureunder ice-cooling
  2. additionthe solution was added dropwise to the reaction mixture under ice-
  3. temperaturecooling
  4. waitat room temperature for 1 hr
  5. custom30 min
  6. filtrationthe white precipitate was collected by filtration
  7. dissolutionThe precipitate was dissolved in tetrahydrofuran (100 ml)
  8. additionthe solution was diluted with ethyl acetate (200 ml)
  9. washwashed with saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customThe solvent was evaporated under reduced pressure
  12. customto give a white residue
  13. concentrationthe filtrate was concentrated under reduced pressure
  14. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane)
  15. washwashed with diethyl ether

Sources & evidence

ORD record
ord-4c42da94ca21452c8dee551c733d83c1
Source dataset
uspto-grants-2015_05
Patent number
US09023858B2

Reaction notes

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