1-Bromo-7-(2,6-difluoro-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid ethyl ester → 1-Cyano-7-(2,6-difluoro-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid ethyl ester

HRID 1480965Notes

Reaction equation

HRID 1480965 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8](Br)[C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][CH:12]=[C:11]([O:17][C:18]1[C:23]([F:24])=[CH:22][CH:21]=[CH:20][C:19]=1[F:25])[CH:10]=2)=[O:5])[CH3:2].[C:27]([Cu])#[N:28]>CN1C(=O)CCC1.C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([C:27]#[N:28])[C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][CH:12]=[C:11]([O:17][C:18]1[C:23]([F:24])=[CH:22][CH:21]=[CH:20][C:19]=1[F:25])[CH:10]=2)=[O:5])[CH3:2]

Participants

5

Reactant 2

HCID 898129771-Bromo-7-(2,6-difluoro-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid ethyl esterHCID 178418546HCID 178418546, compound

Product 1

HCID 898129111-Cyano-7-(2,6-difluoro-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid ethyl esterYield 73.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 1-bromo-7-(2,6-difluoro-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid ethyl ester (156 mg) and CuCN (66 mg) in NMP was stirred at 150° C. for 1 h; then cooled, diluted with DCM, filtered, then washed with water, dil. NaCl solution, dried over sodium sulphate, filtered, concentrated, the residue was column purified to give the desired product (100 mg). LC MS ESI: 371 (M+1)+.

Workup

  1. temperaturethen cooled
  2. filtrationfiltered
  3. washwashed with water, dil. NaCl solution
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified

Sources & evidence

ORD record
ord-f8a6de4514164ca9a412bf71e89e58a9
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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