1-Methylpyrrolidine → 1-Cyano-4-hydroxy-7-(4-methoxy-phenoxy)-isoquinoline-3-carboxylic acid butyl ester

HRID 409263Notes

Reaction equation

HRID 409263 reaction equation
[CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10](Br)[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[C:13]([O:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=1)[CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4].[Cu][C:30]#[N:31].CN1CCCC1>>[CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10]([C:30]#[N:31])[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[C:13]([O:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=1)[CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4]

Participants

4

Reactant 3

HCID 84541-MethylpyrrolidineHCID 866170761-Bromo-4-hydroxy-7-(4-methoxy-phenoxy)-isoquinoline-3-carboxylic acid butyl esterHCID 178418546HCID 178418546, compound

Product 1

HCID 671104471-Cyano-4-hydroxy-7-(4-methoxy-phenoxy)-isoquinoline-3-carboxylic acid butyl esterYield 76.5%

Conditions

Temperature
130 °C

Procedure

A mixture of 1-bromo-4-hydroxy-7-(4-methoxy-phenoxy)-isoquinoline-3-carboxylic acid butyl ester (190 mg, 0.43 mmol), copper(I) cyanide (76.3 mg, 0.85 mmol) and N-methyl-pyrrolidine (3 mL) was heated at 130° C. for 1 h. After cooled, reaction mixture was partitioned between ethyl acetate and water. Organic layer was washed with brine, dried over magnesium sulfate, filtered, and concentrated. Crude product was purified by silica gel chromatography (eluting with 2%-25% ethyl acetate in methylene chloride) to give the title compound (129 mg). MS-(+)-ion: M+1=392.80.

Workup

  1. temperatureAfter cooled
  2. customreaction mixture
  3. customwas partitioned between ethyl acetate and water
  4. washOrganic layer was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customCrude product was purified by silica gel chromatography (eluting with 2%-25% ethyl acetate in methylene chloride)

Sources & evidence

ORD record
ord-be0b590a065d4c1189cb4ed07f6828eb
Source dataset
uspto-grants-2014_06
Patent number
US08759373B2

Reaction notes

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