Cesium carbonate → 4-(1-Ethoxyvinyl)-N-(3-methoxy-4-(6-methylpyridazin-4-yl)phenyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-2-amine

HRID 59097

反応式

HRID 59097 の反応式
Cl[C:2]1[N:7]=[C:6]([C:8]([O:10][CH2:11][CH3:12])=[CH2:9])[CH:5]=[C:4]([CH2:13][O:14][CH2:15][C:16]([F:19])([F:18])[F:17])[N:3]=1.[CH3:20][O:21][C:22]1[CH:23]=[C:24]([CH:26]=[CH:27][C:28]=1[C:29]1[CH:34]=[C:33]([CH3:35])[N:32]=[N:31][CH:30]=1)[NH2:25].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:11]([O:10][C:8]([C:6]1[CH:5]=[C:4]([CH2:13][O:14][CH2:15][C:16]([F:19])([F:18])[F:17])[N:3]=[C:2]([NH:25][C:24]2[CH:26]=[CH:27][C:28]([C:29]3[CH:34]=[C:33]([CH3:35])[N:32]=[N:31][CH:30]=3)=[C:22]([O:21][CH3:20])[CH:23]=2)[N:7]=1)=[CH2:9])[CH3:12]

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 668590663-Methoxy-4-(6-methylpyridazin-4-yl)anilineHCID 1178207992-Chloro-4-(1-ethoxyvinyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidine

生成物 1

HCID 1178210484-(1-Ethoxyvinyl)-N-(3-methoxy-4-(6-methylpyridazin-4-yl)phenyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-2-amine収率 63%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

2-Chloro-4-(1-ethoxyvinyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidine (0.70 g, 2.36 mmol), 3-methoxy-4-(6-methylpyridazin-4-yl)aniline (0.508 g, 2.36 mmol), cesium carbonate (1.538 g, 4.72 mmol), palladium(II) acetate (0.079 g, 0.35 mmol) and 2-(dicyclohexylphosphino)biphenyl (0.124 g, 0.35 mmol) were mixed in dioxane (16 mL). The vial was capped, evacuated and flushed with nitrogen. The reaction mixture was heated at 120° C. for 1.5 h. The mixture was filtered and the filter was washed with mixtures of methanol and DCM. The filtrate was concentrated. The residue was purified by column chromatography on silica column eluting with a gradient of methanol and DCM to give the title compound as a solid 702 mg (63%).

後処理

  1. customThe vial was capped
  2. customevacuated
  3. customflushed with nitrogen
  4. filtrationThe mixture was filtered
  5. washthe filter was washed with mixtures of methanol and DCM
  6. concentrationThe filtrate was concentrated
  7. customThe residue was purified by column chromatography on silica column
  8. washeluting with a gradient of methanol and DCM

出典と根拠

ORDレコード
ord-625d0562a5f0403d9273f1fdee12028b
出典データセット
uspto-grants-2016_09
特許番号
US09439904B2

関連ノート

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