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

HRID 17861

反応式

HRID 17861 の反応式
Cl.[NH2:2][CH2:3][CH2:4][C:5]1[N:6]([CH3:24])[C:7](=[O:23])[C:8]2[C:13]([C:14]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[CH:12][C:11]([O:21][CH3:22])=[CH:10][CH:9]=2.C(N(CC)CC)C.Cl[CH2:33][CH2:34][CH2:35][C:36](Cl)=[O:37]>ClCCl>[CH3:22][O:21][C:11]1[CH:12]=[C:13]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:23])[N:6]([CH3:24])[C:5]([CH2:4][CH2:3][N:2]1[CH2:33][CH2:34][CH2:35][C:36]1=[O:37])=[C:14]2[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

参加物

5

反応物 3

HCID 8471TriethylamineHCID 783704-Chlorobutyryl chlorideHCID 684337913-(2-aminoethyl)-6-methoxy-2-methyl-4-phenylisoquinolin-1(2H)-one hydrochloride

生成物 1

HCID 111763416-Methoxy-2-methyl-3-[2-(2-oxopyrrolidin-1-yl)ethyl]-4-phenylisoquinolin-1(2H)-one

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

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]+.

後処理

  1. concentrationthe mixture was concentrated in vacuo
  2. additionTetrahydrofuran was added (15 mL)
  3. additionSodium hydride was added (58 mg, 60% dispersion in mineral oil, 1.45 mmol)
  4. waitat 50° C. for 2 hours
  5. customThe solution was partitioned between EtOAc and saturated NaHCO3 solution
  6. washthe organic layer was washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude residue was purified by preparative reversed phase HPLC

出典と根拠

ORDレコード
ord-6dcb4a31cdea4e57bf7d8219116a4bc5
出典データセット
uspto-grants-2010_06
特許番号
US07741322B2

関連ノート

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