Dimethylamine, hydrochloride → 3-(2-(4-Dimethylaminomethyl-benzyl)-4-methyl-1-oxo-1,2-dihydro-isoquinolin-6-yl)-4-methyl-benzoic acid, methyl ester

HRID 907324Notes

Reaction equation

HRID 907324 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[C:18](=[O:22])[NH:17][CH:16]=[C:15]2[CH3:23].[H-].[Na+].Cl[CH2:27][C:28]1[CH:33]=[CH:32][C:31]([CH2:34]Cl)=[CH:30][CH:29]=1.Cl.[CH3:37][NH:38][CH3:39]>CN(C=O)C.C(OCC)(=O)C.C(N(CC)CC)C>[CH3:37][N:38]([CH2:27][C:28]1[CH:33]=[CH:32][C:31]([CH2:34][N:17]2[CH:16]=[C:15]([CH3:23])[C:14]3[C:19](=[CH:20][CH:21]=[C:12]([C:3]4[CH:4]=[C:5]([CH:10]=[CH:11][C:2]=4[CH3:1])[C:6]([O:8][CH3:9])=[O:7])[CH:13]=3)[C:18]2=[O:22])=[CH:30][CH:29]=1)[CH3:39]

Participants

8

Reactant 4

HCID 10473Dimethylamine, hydrochlorideHCID 12171alpha,alpha'-Dichloro-p-xyleneHCID 24758Sodium hydrideHCID 575517644-Methyl-3-(4-methyl-1-oxo-1,2-dihydro-isoquinolin-6-yl)-benzoic acid, methyl ester

Product 1

HCID 575517203-(2-(4-Dimethylaminomethyl-benzyl)-4-methyl-1-oxo-1,2-dihydro-isoquinolin-6-yl)-4-methyl-benzoic acid, methyl ester

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of the product of Example 93 step ii) in DMF (10 mL) was treated with 60% sodium hydride in mineral oil (0.12 g) and the mixture was stirred at room temperature under a nitrogen atmosphere for 20 mins before the addition of 1,4-di(chloromethyl)benzene (0.74 g). After stirring for a further 20 mins the reaction was treated with dimethylamine hydrochloride (0.98 g), followed by triethylamine (5 mL). Stirring was continued for 16 hours before being diluted with ethyl acetate (150 mL) and washing with water (150 mL). The organic layer was dried with anhydrous sodium sulphate and concentrated in vacuo to give a brown oil, which was purified (SiO2, eluting with ethyl acetate containing 2.5% MeOH and 0.25% triethylamine) to give the sub-titled compound (0.25 g).

Workup

  1. stirringStirring
  2. waitwas continued for 16 hours
  3. washwashing with water (150 mL)
  4. dry with materialThe organic layer was dried with anhydrous sodium sulphate
  5. concentrationconcentrated in vacuo
  6. customto give a brown oil, which
  7. customwas purified
  8. wash(SiO2, eluting with ethyl acetate containing 2.5% MeOH and 0.25% triethylamine)

Sources & evidence

ORD record
ord-74a987fc88af4bc29388dac8012e1f38
Source dataset
uspto-grants-2011_09
Patent number
US08012979B2

Reaction notes

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