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

HRID 17861

Reaction equation

HRID 17861 reaction equation
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

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-6dcb4a31cdea4e57bf7d8219116a4bc5
Source dataset
uspto-grants-2010_06
Patent number
US07741322B2

Linked notes

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