1-(2-Fluoro-5-iodophenyl)-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide → 3-Acetyl-1-(2-fluoro-5-iodophenyl)-5-methoxypyridazin-4(1H)-one

HRID 1805566ノート

反応式

HRID 1805566 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([I:8])=[CH:4][C:3]=1[N:9]1[CH:14]=[C:13]([O:15][CH3:16])[C:12](=[O:17])[C:11]([C:18](N(OC)C)=[O:19])=[N:10]1.[CH3:24][Mg+].[Br-]>C1COCC1>[C:18]([C:11]1[C:12](=[O:17])[C:13]([O:15][CH3:16])=[CH:14][N:9]([C:3]2[CH:4]=[C:5]([I:8])[CH:6]=[CH:7][C:2]=2[F:1])[N:10]=1)(=[O:19])[CH3:24]

参加物

4

反応物 2

HCID 594362381-(2-Fluoro-5-iodophenyl)-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamideHCID 178418689HCID 178418689、化合物

生成物 1

HCID 594361593-Acetyl-1-(2-fluoro-5-iodophenyl)-5-methoxypyridazin-4(1H)-one収率 92.2%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

To a mixture of 1-(2-fluoro-5-iodophenyl)-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide (4.33 g, 10.0 mmol) in THF (1.0 L) was added MeMgBr (1.0 M in THF, 20.0 mL, 20.0 mmol) at −78° C. under N2. The mixture was stirred at −78° C. for 2 h. The reaction was quenched with saturated NH4Cl aqueous solution at −78° C. The mixture was diluted with saturated NaHCO3 aqueous solution, extracted with EtOAc, dried over Na2SO4, filtered, concentrated in vacuo, purified by column chromatography on silica gel (hexane/EtOAc=50/50 to 0/100 and EtOAc/MeOH=100/0 to 0/100) and triturated with EtOAc/hexane to yield the title compound (3.58 g, 92% yield) as a pale yellow solid: 1H NMR (DMSO-d6, 300 MHz): δ ppm 2.50 (3H, s), 3.80 (3H, s), 7.38 (1H, dd, J=11.0, 8.7 Hz), 7.95 (1H, ddd, J=8.7, 4.5, 2.3 Hz), 8.15 (1H, dd, J=7.2, 2.3 Hz), 8.52 (1H, d, J=1.5 Hz).

後処理

  1. customThe reaction was quenched with saturated NH4Cl aqueous solution at −78° C
  2. additionThe mixture was diluted with saturated NaHCO3 aqueous solution
  3. extractionextracted with EtOAc
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. custompurified by column chromatography on silica gel (hexane/EtOAc=50/50 to 0/100 and EtOAc/MeOH=100/0 to 0/100)
  8. customtriturated with EtOAc/hexane

出典と根拠

ORDレコード
ord-867d194023ee4b6f993aa813a3181bac
出典データセット
uspto-grants-2013_01
特許番号
US08354411B2

反応ノート

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