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

HRID 750359Notes

Reaction equation

HRID 750359 reaction equation
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

Participants

11

Reactant 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, compound

Product 2

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

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Conditions

Temperature
-20 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-6e30e1853e6043458b744c32723f3cc7
Source dataset
uspto-grants-2008_07
Patent number
US07402595B2

Reaction notes

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