반응 #44117

반응 방정식

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

수율 45.0%

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

수율 45.0%

용매

dichloromethane

dichloromethane

반응 조건

후처리

1. 1
   workup.STIRRINGThe solution was stirred for 2 h at 0° C.
2. 2
   기타then partitioned between saturated aqueous ammonium chloride solution and ethyl acetate
3. 3
   건조The organic phase was dried over sodium sulfate
4. 4
   농축the 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
   기타then partitioned between saturated aqueous ammonium chloride solution and dichloromethane
8. 8
   건조The organic phase was dried over sodium sulfate
9. 9
   농축concentrated under reduced pressure
10. 10
    기타The residue was purified by chromatography (SPE cartridge, Silica)
11. 11
    세척eluting with a gradient from dichloromethane-methanol (100:2) to (98:2)

실험 절차

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%).

출처