Hydrochloric Acid → 2-(Ethylsulfanyl)-4-oxo-3-[4-(2,2,2-trifluoroethoxy)phenyl]-3,4-dihydropyrido[2,3-d]pyrimidine-7-carboxamide

HRID 570725Notes

Reaction equation

HRID 570725 reaction equation
[CH2:1]([S:3][C:4]1[N:5]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:24][C:25]([F:28])([F:27])[F:26])=[CH:19][CH:18]=2)[C:6](=[O:16])[C:7]2[CH:13]=[CH:12][C:11]([CH:14]=[O:15])=[N:10][C:8]=2[N:9]=1)[CH3:2].CC(=CC)C.P([O-])(O)(O)=O.[K+].Cl([O-])=O.[Na+].Cl.[NH4+].O[N:47]1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.O.CC(O)(C)C.O>[CH2:1]([S:3][C:4]1[N:5]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:24][C:25]([F:27])([F:28])[F:26])=[CH:19][CH:18]=2)[C:6](=[O:16])[C:7]2[CH:13]=[CH:12][C:11]([C:14]([NH2:47])=[O:15])=[N:10][C:8]=2[N:9]=1)[CH3:2]

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 105532-Methyl-2-buteneHCID 516951Monobasic potassium phosphateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 220338091-Hydroxybenzotriazole, ammonium saltHCID 23668197Sodium ChloriteHCID 866853852-(Ethylsulfanyl)-4-oxo-3-[4-(2,2,2-trifluoroethoxy)phenyl]-3,4-dihydropyrido[2,3-d]pyrimidine-7-carbaldehyde

Product 1

HCID 680153212-(Ethylsulfanyl)-4-oxo-3-[4-(2,2,2-trifluoroethoxy)phenyl]-3,4-dihydropyrido[2,3-d]pyrimidine-7-carboxamideYield 25.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 714019492-Methylpropan-2-ol--water (1/1)Solvent

Procedure

To a mixture of 2-(ethylsulfanyl)-4-oxo-3-[4-(2,2,2-trifluoroethoxy)phenyl]-3,4-dihydropyrido[2,3-d]pyrimidine-7-carbaldehyde (299 mg), 2-methylbut-2-ene (387 mg), potassium dihydrogen phosphate (88 mg) and 2-methyl-2-propanol/water (4/1, 70 ml) was added sodium chlorite (232 mg) by small portions, and the mixture was stirred at room temperature for 1 hr. To the reaction mixture were added 1M hydrochloric acid and water under ice-cooling, and the mixture was extracted with tetrahydrofuran. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give a pale-yellow residue. The residue (117 mg) and 1-hydroxybenzotriazole ammonium (40 mg) were dissolved in N,N-dimethylformamide (2 ml), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (56 mg) was added thereto, and the mixture was stirred at room temperature for 16 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The extract was washed with water, saturated aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane) and then (NH, ethyl acetate/hexane), and recrystallized from a mixed solvent of ethyl acetate/hexane to give the white title compound (28 mg).

Workup

  1. temperaturecooling
  2. extractionthe mixture was extracted with tetrahydrofuran
  3. washThe extract was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customto give a pale-yellow residue
  7. stirringthe mixture was stirred at room temperature for 16 hr
  8. extractionthe mixture was extracted with ethyl acetate
  9. washThe extract was washed with water, saturated aqueous sodium hydrogen carbonate solution and saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customthe solvent was evaporated under reduced pressure
  12. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane)
  13. custom(NH, ethyl acetate/hexane), and recrystallized from a mixed solvent of ethyl acetate/hexane

Sources & evidence

ORD record
ord-e8b765ec18d1422a8925b752f5f3b04f
Source dataset
uspto-grants-2015_05
Patent number
US09023858B2

Reaction notes

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