2-Chloro-5-methyl-pyridine → 1-(4-(2-(4-(5-Methylpyridin-2-ylamino)phenoxy)pyridin-3-YL)piperidin-1-YL)ethanone

HRID 473695

反応式

HRID 473695 の反応式
[NH2:1][C:2]1[CH:23]=[CH:22][C:5]([O:6][C:7]2[C:12]([CH:13]3[CH2:18][CH2:17][N:16]([C:19](=[O:21])[CH3:20])[CH2:15][CH2:14]3)=[CH:11][CH:10]=[CH:9][N:8]=2)=[CH:4][CH:3]=1.Cl[C:25]1[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][N:26]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2C)CCCCC1.CC(C)([O-])C.[Na+]>C(Cl)Cl.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].C1(C)C=CC=CC=1>[CH3:31][C:28]1[CH:29]=[CH:30][C:25]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([O:6][C:7]3[C:12]([CH:13]4[CH2:18][CH2:17][N:16]([C:19](=[O:21])[CH3:20])[CH2:15][CH2:14]4)=[CH:11][CH:10]=[CH:9][N:8]=3)=[CH:22][CH:23]=2)=[N:26][CH:27]=1

参加物

8

反応物 4

HCID 5813932-Chloro-5-methyl-pyridineHCID 27349382-(Dicyclohexylphosphino)-2'-methylbiphenylHCID 23676156Sodium t-butoxideHCID 593739391-(4-(2-(4-Aminophenoxy)pyridin-3-yl)piperidin-1-yl)ethanone

生成物 1

HCID 593740041-(4-(2-(4-(5-Methylpyridin-2-ylamino)phenoxy)pyridin-3-YL)piperidin-1-YL)ethanone

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
100 °C

実験手順

Into a sealed tube were added 1-(4-(2-(4-aminophenoxy)pyridin-3-yl)piperidin-1-yl)ethanone (0.11 g, 0.37 mmol), 2-chloro-5-methylpyridine (0.043 g, 0.33 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.019 g, 0.02 mmol), 2-(dicyclohexylphosphino)-2′-methylbiphenyl (0.012 g, 0.034 mmol), sodium tert-butoxide (0.097 g, 1.01 mmol), and toluene (1.6 mL). After the mixture was degassed for 5 min, the reaction was stirred at 100° C. for 16 h. The cooled reaction was diluted with CH2Cl2 and washed with water. The organic layer was dried (MgSO4), filtered, and concentrated in vacuo. Flash column chromatography (20% to 80% EtOAc(10% MeOH)/Hexanes) gave a crude crop of the desired product. Further purification via reverse phase HPLC afforded 1-(4-(2-(4-(5-methylpyridin-2-ylamino)phenoxy)pyridin-3-yl)piperidin-1-yl)ethanone as a white amorphous solid. MS (ESI, pos. ion) m/z: 403.0 (M+1). IC50 (uM) 0.002844.

後処理

  1. customAfter the mixture was degassed for 5 min
  2. customThe cooled reaction
  3. washwashed with water
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-e4dcd4250c9c408180e8ee132d212f7a
出典データセット
uspto-grants-2014_01
特許番号
US08637500B2

関連ノート

読み込み中…