Tetrahydrofuran → 3-[4-(3-Cyanopropoxy)phenyl]-1-(4-ethylpiperazin-1-yl)isoquinoline hydrochloride

HRID 1814455Notes

Reaction equation

HRID 1814455 reaction equation
[CH2:1]([N:3]1[CH2:8][CH2:7][N:6]([C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH:12]=[C:11]([C:19]3[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=3)[N:10]=2)[CH2:5][CH2:4]1)[CH3:2].[H-].[Na+].[H][H].Br[CH:31]([CH3:34])[C:32]#[N:33].[Cl-:35].[NH4+].O1CCC[CH2:38]1>C(OCC)(=O)C>[ClH:35].[C:32]([CH2:31][CH2:34][CH2:38][O:25][C:22]1[CH:21]=[CH:20][C:19]([C:11]2[N:10]=[C:9]([N:6]3[CH2:5][CH2:4][N:3]([CH2:1][CH3:2])[CH2:8][CH2:7]3)[C:18]3[C:13]([CH:12]=2)=[CH:14][CH:15]=[CH:16][CH:17]=3)=[CH:24][CH:23]=1)#[N:33]

Participants

8

Reactant 6

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 1405382-BromopropionitrileHCID 1357190421-(1-Ethylpiperazin-4-yl)-3-(4-hydroxyphenyl)isoquinolineHCID 178418361HCID 178418361, compound

Product 1

HCID 225030853-[4-(3-Cyanopropoxy)phenyl]-1-(4-ethylpiperazin-1-yl)isoquinoline hydrochloride

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-(4-ethylpiperazin-1-yl)-3-(4-hydroxyphenyl)isoquinoline (0.30 g) obtained in Example 7 in tetrahydrofuran (15 ml) was added 60% sodium hydride (36 mg) at room temperature. After the evolution of hydrogen was ceased, bromopropionitrile (0.14 g) was added thereto, and the resulting mixture was reacted at room temperature for 12 hr. Ethyl acetate and an aqueous solution of ammonium chloride were added to the reaction solution, and the resulting organic layer was then separated, washed with water, dried and concentrated. To the resulting residue were added ethanol and a 2N aqueous solution of hydrochloric acid, and the resulting mixture was reacted at 50° C. for 30 min, followed by the evaporation. The resulting residue was partitioned between ethyl acetate and water. The resulting organic layer was washed with water and brine, and dried. The solvent was removed, and the resulting residue was purified by NH-silica gel column chromatography (ethyl acetate/hexane system), to give the title compound as a pale yellow oil. The oil was converted into a hydrochloride in a conventional manner, to give 0.12 g of the title compound as a yellow powder.

Workup

  1. customthe resulting mixture was reacted at room temperature for 12 hr
  2. customthe resulting organic layer was then separated
  3. washwashed with water
  4. customdried
  5. concentrationconcentrated
  6. additionTo the resulting residue were added ethanol
  7. customa 2N aqueous solution of hydrochloric acid, and the resulting mixture was reacted at 50° C. for 30 min
  8. customfollowed by the evaporation
  9. customThe resulting residue was partitioned between ethyl acetate and water
  10. washThe resulting organic layer was washed with water and brine
  11. customdried
  12. customThe solvent was removed
  13. customthe resulting residue was purified by NH-silica gel column chromatography (ethyl acetate/hexane system)

Sources & evidence

ORD record
ord-18c7e9678e304726b735eb7e935548a2
Source dataset
uspto-grants-2005_04
Patent number
US06875761B2

Reaction notes

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