Cesium carbonate → 6-Chloro-2-methyl-4-(5-methyl-1H-pyrazol-3-ylamino)pyridazin-3(2H)-one

HRID 407697ノート

反応式

HRID 407697 の反応式
[CH2:1]([C:3]1[NH:7][N:6]=[C:5]([NH2:8])[CH:4]=1)C.Br[C:10]1[C:11](=[O:18])[N:12]([CH3:17])[N:13]=[C:14]([Cl:16])[CH:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Cl:16][C:14]1[CH:15]=[C:10]([NH:8][C:5]2[CH:4]=[C:3]([CH3:1])[NH:7][N:6]=2)[C:11](=[O:18])[N:12]([CH3:17])[N:13]=1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 219910953-ethyl-1H-pyrazol-5-amineHCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-one

生成物 1

HCID 866839736-Chloro-2-methyl-4-(5-methyl-1H-pyrazol-3-ylamino)pyridazin-3(2H)-one収率 75.1%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

実験手順

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 1,4-dioxane (20 mL), 5-ethyl-1H-pyrazol-3-amine (971 mg, 10.0 mmol), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (2.46 g, 11.0 mmol), and cesium carbonate (6.52 g, 20.0 mmol). After bubbling nitrogen through the suspension for 10 minutes, xantphos (1.74 g, 3.0 mmol) and tris(dibenzylideneacetone)dipalladium(0) (1.37 g, 1.5 mmol) were added. The system was subjected to three cycles of vacuum/argon flush and heated at reflux for 2 h. It was then filtered immediately when the reaction mixture was still hot. The solid was washed with dioxane (3×30 mL) and the combined filtrate was concentrated under reduced pressure. The residue was purified by silica-gel chromatography eluting with 6:1 petroleum ether/ethyl acetate to afford 127a (1.8 g, 75%) as a yellow solid. MS-ESI: [M+H]+ 239.9

後処理

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter bubbling nitrogen through the suspension for 10 minutes
  3. customflush
  4. temperatureheated
  5. temperatureat reflux for 2 h
  6. filtrationIt was then filtered immediately when the reaction mixture
  7. washThe solid was washed with dioxane (3×30 mL)
  8. concentrationthe combined filtrate was concentrated under reduced pressure
  9. customThe residue was purified by silica-gel chromatography
  10. washeluting with 6:1 petroleum ether/ethyl acetate

出典と根拠

ORDレコード
ord-e9d4b8e6fc6b4e9fbba73c34e2b16a66
出典データセット
uspto-grants-2014_06
特許番号
US08754077B2

反応ノート

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