Water → [3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic Acid 2-dimethylamino-ethyl Ester-Hydrochloride Salt

HRID 1072527Notes

Reaction equation

HRID 1072527 reaction equation
Cl.[N+](C1C=C[C:8]([O:11][C:12](=[O:33])[NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([CH:20]3[C:29]4[C:24](=[C:25]([Cl:31])[CH:26]=[C:27]([Cl:30])[CH:28]=4)[CH2:23][N:22]([CH3:32])[CH2:21]3)[CH:15]=2)=[CH:7]C=1)([O-])=O.[CH3:34][N:35](C)[CH2:36]CO.O.C(=O)([O-])[O-].[K+].[K+]>ClCCl>[ClH:30].[CH3:34][N:35]([CH3:36])[CH2:7][CH2:8][O:11][C:12](=[O:33])[NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH:20]2[C:29]3[C:24](=[C:25]([Cl:31])[CH:26]=[C:27]([Cl:30])[CH:28]=3)[CH2:23][N:22]([CH3:32])[CH2:21]2)[CH:15]=1

Participants

6

Reactant 4

HCID 962WaterHCID 79022-(Dimethylamino)ethanolHCID 11430Potassium CarbonateHCID 223868924-Nitrophenyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl]carbamate hydrochloride2×

Product 1

HCID 69802468[3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic Acid 2-dimethylamino-ethyl Ester-Hydrochloride SaltYield 73.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

Under stirring and argon atmosphere [3(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid 4-nitro-phenyl ester—hydrochloride salt (15 mg, example 151, intermediate 1) was suspended in dichloromethane (1.5 ml) and 2-dimethylamino-ethanol (3 mg) dissolved in dichloromethane (0.5 ml) was added. After stirring for 6 h and standing over night dichloromethane, water and saturated potassium carbonate solution were added. The organic layer was separated, washed three times with saturated potassium carbonate solution, dried over magnesium sulphate, filtered and concentrated in vacuo. The crude material was purified by preparative HPLC. The product containing fractions were combined and the acetonitrile was removed in vaccuo. After addition of sodium bicarbonate the aqueous phase was extracted with ethyl acetate. The organic layer was separated, dried (magnesium sulphate), filtered and concentrated in vaccuo. The residue was dissolved in water/2N hydrochloric acid and freeze dried to give 5 mg of the title compound.

Workup

  1. additionwas added
  2. stirringAfter stirring for 6 h
  3. waitstanding over night
  4. customThe organic layer was separated
  5. washwashed three times with saturated potassium carbonate solution
  6. dry with materialdried over magnesium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude material was purified by preparative HPLC
  10. additionThe product containing fractions
  11. customthe acetonitrile was removed in vaccuo
  12. additionAfter addition of sodium bicarbonate the aqueous phase
  13. extractionwas extracted with ethyl acetate
  14. customThe organic layer was separated
  15. dry with materialdried (magnesium sulphate)
  16. filtrationfiltered
  17. concentrationconcentrated in vaccuo
  18. dissolutionThe residue was dissolved in water/2N hydrochloric acid
  19. customfreeze dried

Sources & evidence

ORD record
ord-c40e2415e62c4f788c7b8a7f5b759091
Source dataset
uspto-grants-2005_06
Patent number
US06911453B2

Reaction notes

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