2-Methylpyridine → 6-bromo-3-(1-hydroxy-2-pyridin-2-ylethyl)-2-(4-methanesulfonylbenzyl)-4-phenyl-2H-isoquinolin-1-one

HRID 750359노트

반응식

HRID 750359 반응식
C([Li])CCC.[CH3:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1.[Br-].[Mg+2].[Br-].[Br:16][Mg:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1.[Br:25][C:26]1[CH:27]=[C:28]2[C:33](=[CH:34][CH:35]=1)[C:32](=[O:36])[N:31]([CH2:37][C:38]1[CH:43]=[CH:42][C:41]([S:44]([CH3:47])(=[O:46])=[O:45])=[CH:40][CH:39]=1)[C:30]([CH:48]=[O:49])=[C:29]2[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1.C(=O)([O-])O.[Na+]>CCCCCC.C1COCC1.O>[Br:16][Mg:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1.[Br:25][C:26]1[CH:27]=[C:28]2[C:33](=[CH:34][CH:35]=1)[C:32](=[O:36])[N:31]([CH2:37][C:38]1[CH:39]=[CH:40][C:41]([S:44]([CH3:47])(=[O:45])=[O:46])=[CH:42][CH:43]=1)[C:30]([CH:48]([OH:49])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1)=[C:29]2[C:50]1[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=1

참가 물질

11

반응물 6

HCID 79752-MethylpyridineHCID 82241Magnesium BromideHCID 516892Sodium BicarbonateHCID 230608166-Bromo-2-(4-methanesulfonylbenzyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbaldehydeHCID 178418339ButyllithiumHCID 178419667HCID 178419667, 화합물

생성물 2

HCID 230609606-bromo-3-(1-hydroxy-2-pyridin-2-ylethyl)-2-(4-methanesulfonylbenzyl)-4-phenyl-2H-isoquinolin-1-oneHCID 178419667HCID 178419667, 화합물

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매3회HCID 8058Hexane용매

반응 조건

온도
-20 °C

실험 절차

Under a nitrogen stream, a solution (1.61M, 15.8 ml) of n-butyllithium in hexane was added to THF (15 ml) at −50° C. or below, and a solution (2.5 ml) of 2-methylpyridine (2.5 g) in THF was added dropwise at −50° C. or below. The reaction mixture was allowed to warm to −20° C. and stirred for 10 min. and then cooled to −50° C. and magnesium bromide (2.5 g) was added. The reaction mixture was allowed to warm to room temperature, stirred for 30 min. and bromo(pyridin-2-ylmethyl)magnesium was prepared. The obtained suspension (4 ml) of bromo(pyridin-2-ylmethyl)magnesium was added to a solution of 6-bromo-2-(4-methanesulfonylbenzyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbaldehyde (500 mg) in THF (5 ml), and the mixture was stirred at room temperature for 10 min. To the reaction mixture were added water and saturated aqueous sodium hydrogen carbonate, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel column chromatography (ethyl acetate) to give the title compound (400 mg).

후처리

  1. temperaturecooled to −50° C.
  2. temperatureto warm to room temperature
  3. stirringstirred for 30 min.
  4. stirringthe mixture was stirred at room temperature for 10 min
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe organic layer was washed with water and saturated brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe solvent was evaporated under reduced pressure
  9. customthe obtained residue was purified by silica gel column chromatography (ethyl acetate)

출처 및 근거

ORD 기록
ord-6e30e1853e6043458b744c32723f3cc7
출처 데이터셋
uspto-grants-2008_07
특허 번호
US07402595B2

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