(E)-3-[4-(2,6-difluoro-phenylamino)-6-(4-fluoro-2-methyl-phenyl)-2-methylsulfanyl-pyrimidin-5-yl]-acrylic acid ethyl ester → HCID 59639576, compound

HRID 2357254Notes

Reaction equation

HRID 2357254 reaction equation
C(O[C:4](=[O:32])/[CH:5]=[CH:6]/[C:7]1[C:8]([NH:23][C:24]2[C:29]([F:30])=[CH:28][CH:27]=[CH:26][C:25]=2[F:31])=[N:9][C:10](SC)=[N:11][C:12]=1[C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=1[CH3:20])C.[CH3:33][O-:34].[Na+]>CO>[F:30][C:29]1[CH:28]=[CH:27][CH:26]=[C:25]([F:31])[C:24]=1[N:23]1[C:8]2[N:9]=[C:10]([O:34][CH3:33])[N:11]=[C:12]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=3[CH3:20])[C:7]=2[CH:6]=[CH:5][C:4]1=[O:32]

Participants

4

Reactant 2

HCID 10276274(E)-3-[4-(2,6-difluoro-phenylamino)-6-(4-fluoro-2-methyl-phenyl)-2-methylsulfanyl-pyrimidin-5-yl]-acrylic acid ethyl esterHCID 10942334Sodium Methoxide

Product 1

HCID 59639576HCID 59639576, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of the product of Example 30 (90 mg, 0.2 mmol) in methanol (5 mL) was added sodium methoxide (1 mL of 25% w/w solution in methanol, excess). The reaction mixture turned yellow and was heated under reflux for 2 h evaporated and H2O (5 mL), then EtOAc (20 mL), was added. The layers were separated. The organic layer was washed with satd aq NaCl, dried (MgSO4), filtered and evaporated. The yellow residue was then purified by Flash chromatography to afford 71 mg (83% yield) of 8-(2,6-difluoro-phenyl)-4-(4-fluoro-2-methyl-phenyl)-2-methoxy-8H-pyrido[2,3-d]pyrimidin-7-one. 1H-NMR (CDCl3) δ 2.30 (s, 3H), 3.82 (s, 3H), 6.61 (d, 1H, J=9.7 Hz), 7.01-7.18 (m, 4H), 7.25 (m, 1H), 7.52 (m, 2H); LC MS (m/e)=398 (MH+).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 2 h
  3. customevaporated
  4. additionH2O (5 mL), then EtOAc (20 mL), was added
  5. customThe layers were separated
  6. washThe organic layer was washed with satd aq NaCl
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customevaporated
  10. customThe yellow residue was then purified by Flash chromatography

Sources & evidence

ORD record
ord-0767bf41da1c47ef8ccbad2466578353
Source dataset
uspto-grants-2010_07
Patent number
US07759486B2

Reaction notes

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