Reaktion #44117

Reaktionsgleichung

trimethylaluminium

3-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}aniline

3-{2-[4-(2-Methyl-5-quinolinyl)-1-piperazinyl]ethyl}aniline

phthalide

N,N-diisopropylethylamine

methanesulfonyl chloride

→

title compound

Ausbeute 45.0%

2-(3-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}phenyl)-2,3-dihydro-1H-isoindol-1-one

Ausbeute 45.0%

Lösungsmittel

dichloromethane

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe solution was stirred for 2 h at 0° C.
2. 2
   Sonstigethen partitioned between saturated aqueous ammonium chloride solution and ethyl acetate
3. 3
   TrocknenThe organic phase was dried over sodium sulfate
4. 4
   Einengenthe solution was concentrated under reduced pressure
5. 5
   workup.DISSOLUTIONThe crude 2-(hydroxymethyl)-N-(3-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}phenyl)benzamide was dissolved in dichloromethane
6. 6
   workup.STIRRINGThe reaction mixture was stirred for 2 hours at room temperature
7. 7
   Sonstigethen partitioned between saturated aqueous ammonium chloride solution and dichloromethane
8. 8
   TrocknenThe organic phase was dried over sodium sulfate
9. 9
   Einengenconcentrated under reduced pressure
10. 10
    SonstigeThe residue was purified by chromatography (SPE cartridge, Silica)
11. 11
    Wascheneluting with a gradient from dichloromethane-methanol (100:2) to (98:2)

Vorschrift

A solution of trimethylaluminium (2.0 M in hexane, 1 eq) was added slowly to a stirred solution of 3-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}aniline (D6, 1 eq) in dichloromethane (0.1 M) at 0° C. The reaction mixture was stirred for 15 min then a solution of phthalide (1 eq) in dichloromethane was added dropwise. The solution was stirred for 2 h at 0° C. then partitioned between saturated aqueous ammonium chloride solution and ethyl acetate. The organic phase was dried over sodium sulfate and the solution was concentrated under reduced pressure. The crude 2-(hydroxymethyl)-N-(3-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}phenyl)benzamide was dissolved in dichloromethane then N,N-diisopropylethylamine (1 eq.) and methanesulfonyl chloride (1 eq.) were added successively. The reaction mixture was stirred for 2 hours at room temperature then partitioned between saturated aqueous ammonium chloride solution and dichloromethane. The organic phase was dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by chromatography (SPE cartridge, Silica) eluting with a gradient from dichloromethane-methanol (100:2) to (98:2) affording the title compound (yield 45%).

Quelle