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 2357266노트

반응식

HRID 2357266 반응식
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]

참가 물질

4

반응물 2

HCID 10942334Sodium MethoxideHCID 66893833HCID 66893833, 화합물

생성물 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-one수율 27%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-b5cfd761810244118fb23afd3536a70f
출처 데이터셋
uspto-grants-2010_07
특허 번호
US07759486B2

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