Sodium hydride → 5-chloro-6,7-bis((4-methoxybenzyl)oxy)-2-(2-(pyrrolidin-1-yl)ethyl)-3,4-dihydroisoquinolin-1(2H)-one

HRID 525848Notes

Reaction equation

HRID 525848 reaction equation
[Cl:1][C:2]1[C:11]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)=[C:10]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)[CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][NH:6][C:7]2=[O:32].[H-].[Na+].Cl[CH2:36][CH2:37][N:38]1[CH2:42][CH2:41][CH2:40][CH2:39]1.CC[NH+](CC)CC.CC[NH+](CC)CC.C([O-])([O-])=O>CN(C)C=O.ClCCl>[Cl:1][C:2]1[C:11]([O:12][CH2:13][C:14]2[CH:15]=[CH:16][C:17]([O:20][CH3:21])=[CH:18][CH:19]=2)=[C:10]([O:22][CH2:23][C:24]2[CH:25]=[CH:26][C:27]([O:30][CH3:31])=[CH:28][CH:29]=2)[CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]([CH2:36][CH2:37][N:38]1[CH2:42][CH2:41][CH2:40][CH2:39]1)[C:7]2=[O:32]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 816691-(2-Chloroethyl)pyrrolidineHCID 15264167Carbonic acid--N,N-diethylethanamine (1/2)HCID 867327155-chloro-6,7-bis((4-methoxybenzyl)oxy)-3,4-dihydroisoquinolin-1(2H)-one

Product 1

HCID 867327165-chloro-6,7-bis((4-methoxybenzyl)oxy)-2-(2-(pyrrolidin-1-yl)ethyl)-3,4-dihydroisoquinolin-1(2H)-oneYield 34%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To the solution of 5-chloro-6,7-bis((4-methoxybenzyl)oxy)-3,4-dihydroisoquinolin-1(2H)-one (1.017 g, 2.241 mmol) in N,N-dimethylformamide (DMF) (10 ml) was added sodium hydride (0.179 g, 4.48 mmol). Stirred at rt for 10 min. 1-(2-Chloroethyl)pyrrolidine (0.329 g, 2.465 mmol) (first freed as free base with MP-carbonate resin) was added and the mixture was heated at 40° C. for 12 h. Mixture extracted with EtOAc, washed with water, NaCl, dried over magnesium sulfate. Chromotagraphed eluting with 0-10% methanol:dichloromethane to give 5-chloro-6,7-bis((4-methoxybenzyl)oxy)-2-(2-(pyrrolidin-1-yl)ethyl)-3,4-dihydroisoquinolin-1(2H)-one (420 mg, 0.762 mmol, 34.0% yield). LCMS (M+H)+: 551.0

Workup

  1. additionwas added
  2. temperaturethe mixture was heated at 40° C. for 12 h
  3. extractionMixture extracted with EtOAc
  4. washwashed with water, NaCl
  5. dry with materialdried over magnesium sulfate
  6. washChromotagraphed eluting with 0-10% methanol

Sources & evidence

ORD record
ord-71feb879378444cf82a989cab3e2cd2c
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

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