Sodium Methoxide → 8-(2,6-difluoro-phenyl)-4-(4-fluoro-2-methyl-phenyl)-2-methylsulfanyl-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one

HRID 2249784Notes

Reaction equation

HRID 2249784 reaction equation
CO[C:3](=[O:31])[CH2:4][CH2:5][C:6]1[C:7]([NH:22][C:23]2[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=2[F:30])=[N:8][C:9]([S:20][CH3:21])=[N:10][C:11]=1[C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=1[CH3:19].C[O-].[Na+]>CO>[F:30][C:24]1[CH:25]=[CH:26][CH:27]=[C:28]([F:29])[C:23]=1[N:22]1[C:7]2[N:8]=[C:9]([S:20][CH3:21])[N:10]=[C:11]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=3[CH3:19])[C:6]=2[CH2:5][CH2:4][C:3]1=[O:31]

Participants

4

Reactant 2

HCID 10942334Sodium MethoxideHCID 66893833HCID 66893833, compound

Product 1

HCID 596396668-(2,6-difluoro-phenyl)-4-(4-fluoro-2-methyl-phenyl)-2-methylsulfanyl-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-oneYield 27%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 3-[4-(2,6-difluoro-phenylamino)-6-(4-fluoro-2-methyl-phenyl)-2-methylsulfanyl-pyrimidin-5-yl]-propionic acid methyl ester (45 mg, 0.1 mmol) in methanol (5 mL) was added a solution of sodium methoxide (0.5 mL) and the reaction mixture was heated under reflux for 1 h. The reaction mixture was then evaporated, and EtOAc (20 mL) followed by H2O (10 mL) were added. Layers were separated, organic washed with satd aq NaCl, dried (MgSO4), filtered and the solvent was evaporated. Dichloromethane (5 mL) was added followed by 0.5 mL of oxalyl chloride and 0.1 mL of Et3N. The reaction mixture was then stirred for 2 h at 23°, H2O (5 mL) was then added followed by dichloromethane (15 mL). Layers were separated, organic layer was washed with sat'd aq. NaCl, dried (MgSO4), filtered and solvent was evaporated. The yellow residue was purified by Flash chromatography to give 11.2 mg (21% yield) of pure 8-(2,6-difluoro-phenyl)-4-(4-fluoro-2-methyl-phenyl)-2-methylsulfanyl-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one. 1H-NMR (CDCl3): δ 2.20 (s, 3H), 2.29 (s, 3H), 3.85 (m, 4H), 7.02 (m, 4H), 7.21 (m, 1H), 7.42 (m, 1H). LC MS (m/e)=416.2 (MH+). Rt=2.44 min.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureunder reflux for 1 h
  3. customThe reaction mixture was then evaporated
  4. additionwere added
  5. customLayers were separated
  6. washorganic washed with satd aq NaCl
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customthe solvent was evaporated
  10. additionDichloromethane (5 mL) was added
  11. additionH2O (5 mL) was then added
  12. customLayers were separated
  13. washorganic layer was washed with sat'd aq. NaCl
  14. dry with materialdried (MgSO4)
  15. filtrationfiltered
  16. customsolvent was evaporated
  17. customThe yellow residue was purified by Flash chromatography

Sources & evidence

ORD record
ord-6f3ca563156f48608cb9ffeda6cac7ca
Source dataset
uspto-grants-2008_01
Patent number
US07314881B2

Reaction notes

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