Toluene → 1-(4-(3-(4-(5-Methylpyridin-2-ylamino)phenoxy)pyrazin-2-yl)piperidin-1-yl)ethanone

HRID 473702

반응식

HRID 473702 반응식
Cl[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N:3]=1.[NH2:9][C:10]1[CH:31]=[CH:30][C:13]([O:14][C:15]2[C:16]([CH:21]3[CH2:26][CH2:25][N:24]([C:27](=[O:29])[CH3:28])[CH2:23][CH2:22]3)=[N:17][CH:18]=[CH:19][N:20]=2)=[CH:12][CH:11]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2C)CCCCC1.CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>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]>[CH3:8][C:5]1[CH:6]=[CH:7][C:2]([NH:9][C:10]2[CH:31]=[CH:30][C:13]([O:14][C:15]3[C:16]([CH:21]4[CH2:26][CH2:25][N:24]([C:27](=[O:29])[CH3:28])[CH2:23][CH2:22]4)=[N:17][CH:18]=[CH:19][N:20]=3)=[CH:12][CH:11]=2)=[N:3][CH:4]=1

참가 물질

8

반응물 5

HCID 1140TolueneHCID 5813932-Chloro-5-methyl-pyridineHCID 27349382-(Dicyclohexylphosphino)-2'-methylbiphenylHCID 23676156Sodium t-butoxideHCID 59374162HCID 59374162, 화합물

생성물 1

HCID 462205171-(4-(3-(4-(5-Methylpyridin-2-ylamino)phenoxy)pyrazin-2-yl)piperidin-1-yl)ethanone

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 6344Dichloromethane용매

반응 조건

온도
100 °C

실험 절차

Into a sealed tube were added 2-chloro-5-methylpyridine (0.055 g, 0.431 mmol), 1-(4-(3-(4-aminophenoxy)pyrazin-2-yl)piperidin-1-yl)ethanone (0.148 g, 0.474 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.024 g, 0.026 mmol), 2-(dicyclohexylphosphino)-2′-methylbiphenyl (0.016 g, 0.043 mmol), sodium tert-butoxide (0.124 g, 1.293 mmol), and toluene (2.16 mL, 0.431 mmol). After the mixture was degassed for 5 min, the reaction was stirred at 100° C. for 18 h. The cooled reaction was diluted with CH2Cl2 and washed with water. The organic layer was dried (MgSO4), filtered, and concentrated in vacuo. ISCO purification (20% to 80% EtOAc (10% MeOH)/Hexanes), followed by reverse phase HPLC (Shimadzu) afforded 1-(4-(3-(4-(5-methylpyridin-2-ylamino)phenoxy)pyrazin-2-yl)piperidin-1-yl)ethanone as a white amorphous solid. MS (ESI, pos. ion) m/z: 404.0 (M+1). IC50 (uM) 0.00004.

후처리

  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
  7. customISCO purification (20% to 80% EtOAc (10% MeOH)/Hexanes)

출처 및 근거

ORD 기록
ord-55520cf068464924b82101a379953731
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08637500B2

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