Cesium carbonate → 6-chloro-2-methyl-4-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridazin-3(2H)-one

HRID 407800ノート

反応式

HRID 407800 の反応式
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]2[N:8]=[C:9]([NH2:11])[CH:10]=[C:4]2[CH2:3]1.Br[C:13]1[C:14](=[O:21])[N:15]([CH3:20])[N:16]=[C:17]([Cl:19])[CH:18]=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:19][C:17]1[CH:18]=[C:13]([NH:11][C:9]2[CH:10]=[C:4]3[CH2:3][N:2]([CH3:1])[CH2:7][CH2:6][N:5]3[N:8]=2)[C:14](=[O:21])[N:15]([CH3:20])[N:16]=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 580439335-methyl-4H,5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-amineHCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-one

生成物 1

HCID 666346996-chloro-2-methyl-4-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridazin-3(2H)-one収率 60%

試薬・触媒・溶媒 2

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

反応条件

温度
90 °C

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 (30 mL), 5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-amine 128b (1.70 g, 11.2 mmol), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (2.68 g, 12.0 mmol), and cesium carbonate (7.30 g, 22.4 mmol). After bubbling nitrogen through the suspension for 30 minutes, Xantphos (0.59 g, 1.02 mmol) and tris(dibenzylideneacetone)dipalladium(0) (467 mg, 0.51 mmol) were added. The system was subjected to three cycles of vacuum/argon flush and heated at 90° C. for 2 h. It was then cooled to room temperature and filtered. The filtrate was evaporated in vacuo. The residue was purified by silica-gel column chromatography eluting with 30:1 dichloromethane/methanol to afford 153a (1.9 g, 60%) as a brown solid. LCMS: [M+H]+ 295.1

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 30 minutes
  3. customflush
  4. temperatureIt was then cooled to room temperature
  5. filtrationfiltered
  6. customThe filtrate was evaporated in vacuo
  7. customThe residue was purified by silica-gel column chromatography
  8. washeluting with 30:1 dichloromethane/methanol

出典と根拠

ORDレコード
ord-992bd8d4466b4b8dad3d1b5ada20a360
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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