Hydrochloric Acid → HCID 135719057, compound

HRID 1251229Notes

Reaction equation

HRID 1251229 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]=[C:23]([F:25])[C:22]([O:26]CC4C=CC=CC=4)=[C:21]([F:34])[CH:20]=3)[N:10]=2)[CH2:5][CH2:4]1)[CH3:2].Cl>CO.[Pd]>[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]=[C:23]([F:25])[C:22]([OH:26])=[C:21]([F:34])[CH:20]=3)[N:10]=2)[CH2:5][CH2:4]1)[CH3:2]

Participants

5

Reactant 2

HCID 313Hydrochloric Acid2×HCID 22503215HCID 22503215, compound

Product 1

HCID 135719057HCID 135719057, compoundYield 64.9%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

The resulting 1-(4-ethylpiperazin-1-yl)-3-(4-benzyloxy-3,5-difluorophenyl)isoquinoline (6.44 g) was converted into a hydrochloride in a conventional manner. The hydrochloride was dissolved in methanol (200 ml), followed by the addition of 10% palladium/carbon catalyst (0.48 g), and then the catalytic reduction was conducted at atmospheric pressure overnight. The catalyst was filtered off, while the solvent was evaporated. Water was added to the resulting residue, followed by the addition of an aqueous solution of saturated sodium bicarbonate, and the mixture was extracted with chloroform. The extract was washed with brine, dried over magnesium sulfate, and the solvent was evaporated, to give obtain 1-(4-ethylpiperazin-1-yl)-3-(3,5-difluoro-4-hydroxyphenyl)isoquinoline (3.36 g) as a pale brown amorphous. Sodium hydride (0.04 g) was washed with n-hexane, suspended in N,N-dimethylformamide (2 ml) and stirred under ice-cooling. The above-described 1-(4-ethylpiperazin-1-yl)-3-(3,5-difluoro-4-hydroxyphenyl)isoquinoline (0.30 g) dissolved in N,N-dimethylformamide (2 ml) was added thereto, and the mixture was stirred at room temperature for 50 min. The mixture was again ice-cooled, followed by the addition of 2-methoxyethyl bromide (115 ml), and the mixture was stirred in nitrogen atmosphere at 50° C. overnight. Water was added to the reaction solution, and then it was extracted with ethyl acetate. The extract was washed with water and brine, and dried over magnesium sulfate. The solvent was evaporated, and the resulting residue was purified by silica gel column chromatography (chloroform/methanol system), to give 0.26 g of the free compound of the title compound as a brown viscous oil.

Workup

  1. customwas conducted at atmospheric pressure overnight
  2. filtrationThe catalyst was filtered off, while the solvent
  3. customwas evaporated
  4. additionWater was added to the resulting residue
  5. additionfollowed by the addition of an aqueous solution of saturated sodium bicarbonate
  6. extractionthe mixture was extracted with chloroform
  7. washThe extract was washed with brine
  8. dry with materialdried over magnesium sulfate
  9. customthe solvent was evaporated
  10. customto give

Sources & evidence

ORD record
ord-cd16c6d81e9841a39872c31e48abe203
Source dataset
uspto-grants-2002_01
Patent number
US06340759B1

Reaction notes

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