(S)-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one → 2-(4-Fluoro-phenyl)-4-oxo-3,4-dihydro-2H-pyridine-1-carboxylic acid (2-fluoro-5-methoxy-4-methyl-phenyl)-amide

HRID 1691816ノート

反応式

HRID 1691816 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:13][C:12](=[O:14])[CH:11]=[CH:10][NH:9]2)=[CH:4][CH:3]=1.[Li]CCCC.[F:20][C:21]1[CH:26]=[C:25]([CH3:27])[C:24]([O:28][CH3:29])=[CH:23][C:22]=1[N:30]=[C:31]=[O:32]>C1COCC1>[F:20][C:21]1[CH:26]=[C:25]([CH3:27])[C:24]([O:28][CH3:29])=[CH:23][C:22]=1[NH:30][C:31]([N:9]1[CH:10]=[CH:11][C:12](=[O:14])[CH2:13][CH:8]1[C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)=[O:32]

参加物

5

反応物 3

HCID 59377679(S)-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-oneHCID 593778971-Fluoro-2-isocyanato-4-methoxy-5-methyl-benzeneHCID 178418339Butyllithium

生成物 1

HCID 669077172-(4-Fluoro-phenyl)-4-oxo-3,4-dihydro-2H-pyridine-1-carboxylic acid (2-fluoro-5-methoxy-4-methyl-phenyl)-amide収率 24.9%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

(S)-2-(4-Fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one (95 mg, 0.50 mmol) was dissolved in THF and cooled to −40° C. n-BuLi (1.1 eq, 0.34 ml of 2.5M solution) was added dropwise, forming a purple suspension. The mixture was allowed to stir for 30 minutes until the purple color changed to white. 1-Fluoro-2-isocyanato-4-methoxy-5-methyl-benzene (1 eq, 90 mg) was added. The mixture was allowed to stir for 1 hour at −40° C., then allowed to warm to room temperature and stirred for 2 hours. The reaction was quenched with saturated ammonium chloride solution. The mixture was diluted with water and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by flash chromatography (gradient 9:1 to 1:1 hexanes/ethyl acetate) to give 2-(4-Fluoro-phenyl)-4-oxo-3,4-dihydro-2H-pyridine-1-carboxylic acid (2-fluoro-5-methoxy-4-methyl-phenyl)-amide (46 mg, 24.7%) as a foam. MS (ES+) m/z 373 (M+H).

後処理

  1. additionwas added dropwise
  2. customforming a purple suspension
  3. stirringto stir for 1 hour at −40° C.
  4. stirringstirred for 2 hours
  5. customThe reaction was quenched with saturated ammonium chloride solution
  6. additionThe mixture was diluted with water
  7. extractionextracted with ethyl acetate
  8. washThe combined organic extracts were washed with brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by flash chromatography (gradient 9:1 to 1:1 hexanes/ethyl acetate)

出典と根拠

ORDレコード
ord-f3b554c6d21340be9342ca7aae6fc32b
出典データセット
uspto-grants-2012_04
特許番号
US08153809B2

反応ノート

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