Lithium Hexamethyldisilazide → 4-(2-fluoro-4-(methylthio)phenylamino)-1-methyl-6-oxo-N-(2-(vinyloxy)ethoxy)-1,6-dihydropyridazine-3-carboxamide

HRID 15960

반응식

HRID 15960 반응식
[F:1][C:2]1[CH:7]=[C:6]([S:8][CH3:9])[CH:5]=[CH:4][C:3]=1[NH:10][C:11]1[C:12]([C:19]([O:21]C)=O)=[N:13][N:14]([CH3:18])[C:15](=[O:17])[CH:16]=1.[CH:23]([O:25][CH2:26][CH2:27][O:28][NH2:29])=[CH2:24].[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[F:1][C:2]1[CH:7]=[C:6]([S:8][CH3:9])[CH:5]=[CH:4][C:3]=1[NH:10][C:11]1[C:12]([C:19]([NH:29][O:28][CH2:27][CH2:26][O:25][CH:23]=[CH2:24])=[O:21])=[N:13][N:14]([CH3:18])[C:15](=[O:17])[CH:16]=1

참가 물질

5

반응물 3

HCID 2733832Lithium HexamethyldisilazideHCID 21867017O-(2-(Vinyloxy)ethyl)hydroxylamineHCID 66673411Methyl 4-(2-fluoro-4-(methylthio)phenylamino)-1-methyl-6-oxo-1,6-dihydropyridazine-3-carboxylate

생성물 1

HCID 866016154-(2-fluoro-4-(methylthio)phenylamino)-1-methyl-6-oxo-N-(2-(vinyloxy)ethoxy)-1,6-dihydropyridazine-3-carboxamide수율 99%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of methyl 4-(2-fluoro-4-(methylthio)phenylamino)-1-methyl-6-oxo-1,6-dihydropyridazine-3-carboxylate (25 mg, 0.077 mmol) and O-(2-vinyloxy-ethyl)-hydroxylamine (24 mg, 0.23 mmol) in THF (2 mL) at 0° C. was added LiHMDS (0.54 mL, 0.54 mmol, 1 M in THF). The reaction mixture was warmed to room temperature and stirred for 1 hour. The reaction mixture was quenched with saturated aqueous NaHCO3 and diluted with EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure to give the crude material that was purified by silica gel flash column chromatography (100% CH2Cl2 to 1.5% MeOH in CH2Cl2) to afford 30 mg (99%) of the desired product.

후처리

  1. customThe reaction mixture was quenched with saturated aqueous NaHCO3
  2. additiondiluted with EtOAc
  3. washThe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give the crude material that
  8. customwas purified by silica gel flash column chromatography (100% CH2Cl2 to 1.5% MeOH in CH2Cl2)

출처 및 근거

ORD 기록
ord-3b25464ef122462787f2fbae1dbb57ee
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07732616B2

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