Methyl iodide → 1-(3-Fluoro-5-chloropyridin-2-yl)-3-methyl-4-trifluoromethylpyrimidin-2,6-dione

HRID 843563Notes

Reaction equation

HRID 843563 reaction equation
[F:1][C:2]([F:12])([F:11])[C:3]([NH2:10])=[CH:4][C:5]([O:7]CC)=O.[H-].[Na+].[H][H].C([O:19][C:20]([NH:22][C:23]1[C:28]([F:29])=[CH:27][C:26]([Cl:30])=[CH:25][N:24]=1)=O)C.[CH3:31]I>CN1CCCC1.C(OCC)(=O)C>[F:29][C:28]1[C:23]([N:22]2[C:5](=[O:7])[CH:4]=[C:3]([C:2]([F:1])([F:11])[F:12])[N:10]([CH3:31])[C:20]2=[O:19])=[N:24][CH:25]=[C:26]([Cl:30])[CH:27]=1

Participants

8

Reactant 5

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 136209Ethyl 3-amino-4,4,4-trifluoro-2-butenoateHCID 226109302-Ethoxycarbonylamino-3-fluoro-5-chloropyridineHCID 178418361HCID 178418361, compound

Product 1

HCID 226109291-(3-Fluoro-5-chloropyridin-2-yl)-3-methyl-4-trifluoromethylpyrimidin-2,6-dione

Reagents, catalysts & solvents 2

HCID 84541-MethylpyrrolidineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 22.7 g of ethyl 4,4,4-trifluoro-3-amino-2-butenoate is added dropwise with stirring and cooling at 0-5° C. under a nitrogen atmosphere to 5.1 g of a previously introduced sodium hydride dispersion (60%) in 60 ml of n-methylpyrrolidine, and stirring is continued at 22° C. until the evolution of hydrogen has ceased. Then, 23.7 g of 2-ethoxycarbonylamino-3-fluoro-5-chloropyridine (Example H1) are added and the reaction mixture is heated for approx. 5 hours at 120° C. It is then cooled, 16.7 9 of methyl iodide are added dropwise, and stirring is continued overnight at 22° C. After the reaction mixture has been taken up in ethyl acetate, it is washed with ice-water, dried over sodium sulfate, filtered and evaporated. The residue obtained is recrystallized from ethyl acetate/n-hexane. This gives the desired title compound of m.p. 133-134° C.

Workup

  1. stirringstirring
  2. temperatureIt is then cooled
  3. stirringstirring
  4. washit is washed with ice-water
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue obtained
  9. customis recrystallized from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-31e15cfe84a5443582ff510b31ea4c24
Source dataset
uspto-grants-2002_04
Patent number
US06380134B1

Reaction notes

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