反応 #46139

反応方程式

4-chlorobutanoyl chloride

3-(2-aminoethyl)-6-methoxy-2-methyl-4-phenylisoquinolin-1(2H)-one hydrochloride

triethylamine

→

titled product

6-Methoxy-2-methyl-3-[2-(2-oxopyrrolidin-1-yl)ethyl]-4-phenylisoquinolin-1(2H)-one

溶媒

dichloromethane

反応条件

後処理

1. 1
   濃縮the mixture was concentrated in vacuo
2. 2
   workup.ADDITIONTetrahydrofuran was added (15 mL)
3. 3
   workup.ADDITIONSodium hydride was added (58 mg, 60% dispersion in mineral oil, 1.45 mmol)
4. 4
   workup.WAITat 50° C. for 2 hours
5. 5
   その他The solution was partitioned between EtOAc and saturated NaHCO3 solution
6. 6
   洗浄the organic layer was washed with brine
7. 7
   乾燥dried over Na2SO4
8. 8
   ろ過filtered
9. 9
   濃縮concentrated in vacuo
10. 10
    その他The crude residue was purified by preparative reversed phase HPLC

実験手順

To a solution of 3-(2-aminoethyl)-6-methoxy-2-methyl-4-phenylisoquinolin-1(2H)-one hydrochloride (125 mg, 0.362 mmol) in 15 mL of dichloromethane was added triethylamine (0.202 mL, 1.45 mmol), followed by 4-chlorobutanoyl chloride (0.045 mL, 0.40 mmol). After 45 minutes, the mixture was concentrated in vacuo. Tetrahydrofuran was added (15 mL), and the solution was cooled to 0° C. Sodium hydride was added (58 mg, 60% dispersion in mineral oil, 1.45 mmol). The reaction mixture was stirred at 0° C. for 30 minutes, at room temperature for 16 hours, then at 50° C. for 2 hours. The solution was partitioned between EtOAc and saturated NaHCO3 solution, and the organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by preparative reversed phase HPLC to provide the titled product. Proton NMR for the product was consistent with the titled compound. ESI+MS: 377.27 [M+H]+.

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