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Potassium Carbonate → N-(5-(6-(4-cyano-2-(trifluoromethyl)phenyl)imidazo[1,2-b]pyridazin-2-yl)-2-methylphenyl)pivalamide

HRID 539799
ノート
印刷プレビュー

反応式

HRID 539799 の反応式
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][C:13](B(O)O)=[N:12][N:11]3[CH:19]=2)=[CH:4][C:3]=1[NH:20][C:21](=[O:26])[C:22]([CH3:25])([CH3:24])[CH3:23].Br[C:28]1[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[CH:30][C:29]=1[C:36]([F:39])([F:38])[F:37].C([O-])([O-])=O.[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(O)(C)C.O>[C:32]([C:31]1[CH:34]=[CH:35][C:28]([C:13]2[CH:14]=[CH:15][C:10]3[N:11]([CH:19]=[C:8]([C:5]4[CH:6]=[CH:7][C:2]([CH3:1])=[C:3]([NH:20][C:21](=[O:26])[C:22]([CH3:25])([CH3:24])[CH3:23])[CH:4]=4)[N:9]=3)[N:12]=2)=[C:29]([C:36]([F:37])([F:38])[F:39])[CH:30]=1)#[N:33]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 11430Potassium CarbonateHCID 108006474-Bromo-3-(trifluoromethyl)benzonitrileHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 680891592-(4-Methyl-3-pivalamidophenyl)imidazo[1,2-b]pyridazin-6-ylboronic acid

生成物 1

HCID 57406897N-(5-(6-(4-cyano-2-(trifluoromethyl)phenyl)imidazo[1,2-b]pyridazin-2-yl)-2-methylphenyl)pivalamide
収率 48.3%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 21889133Propan-2-ol--water (1/1)溶媒

反応条件

温度
90 °C

実験手順

A 200 mL flask is charged with 2-(4-methyl-3-pivalamidophenyl)imidazo[1,2-b]pyridazin-6-ylboronic acid (11.4 g, 0.0325 mol), 4-bromo-3-(trifluoromethyl)benzonitrile (10.16 g, 0.04 mol), K2CO3 (8.98 g, 0.065 mol), palladium acetate (0.510 g, 2.28 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (1.868 g, 4.55 mmol) and a solution of isopropanol-water (3:1, 80 mL). The mixture is degassed by bubbling N2 through and heated at 90° C. for 5 hours. The mixture is then cooled and filtered through celite, concentrated and purified by silica gel chromatography (0-100% EtOAc in CH2Cl2). The desired fractions are combined and stirred for 24 hours with QuadraSil MP (a mercaptopropyl bound silica gel, 20 g) to scavenge the palladium, filtered and concentrated to give desired title compound (7.5 g). LCMS (m/z)=478.6 [M+H]+, tR=2.97 min.

後処理

  1. customThe mixture is degassed
  2. customby bubbling N2 through and
  3. temperatureThe mixture is then cooled
  4. filtrationfiltered through celite,
  5. concentrationconcentrated
  6. custompurified by silica gel chromatography (0-100% EtOAc in CH2Cl2)
  7. filtrationfiltered
  8. concentrationconcentrated

出典と根拠

ORDレコード
ord-948121cf3db84ae29cbe449ce64a4fc8
出典データセット
uspto-grants-2014_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08871767B2

反応ノート

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