7-(2-Chloro-5-fluoro-phenoxy)-4-hydroxy-1-iodo-isoquinoline-3-carboxylic acid ethyl ester → 7-(2-Chloro-5-fluoro-phenoxy)-1-cyano-4-hydroxy-isoquinoline-3-carboxylic acid ethyl ester

HRID 1480993Notes

Reaction equation

HRID 1480993 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8](I)[C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][CH:12]=[C:11]([O:17][C:18]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=1[Cl: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[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=1[Cl:25])[CH:10]=2)=[O:5])[CH3:2]

Participants

5

Reactant 2

HCID 898129217-(2-Chloro-5-fluoro-phenoxy)-4-hydroxy-1-iodo-isoquinoline-3-carboxylic acid ethyl esterHCID 178418546HCID 178418546, compound

Product 1

HCID 898130057-(2-Chloro-5-fluoro-phenoxy)-1-cyano-4-hydroxy-isoquinoline-3-carboxylic acid ethyl esterYield 84.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 7-(2-chloro-5-fluoro-phenoxy)-4-hydroxy-1-iodo-isoquinoline-3-carboxylic acid ethyl ester (180 mg) and CuCN (66 mg) in NMP (2 mL) was stirred at 130° 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 (120 mg). LC MS ESI: 387 (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-4c548f56067b47b4b4b1b23ec53ffc1e
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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