Dimethylformamide → HCID 69200517, compound

HRID 1745813Notes

Reaction equation

HRID 1745813 reaction equation
[CH3:1][O:2][C:3](=[O:16])[CH2:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12](Br)[CH:13]=2)[CH:8]=[N:7][CH:6]=1.[CH3:17][N:18](C=O)C>C(Cl)(Cl)Cl.[C-]#N.[C-]#N.[Zn+2].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:1][O:2][C:3](=[O:16])[CH2:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C:17]#[N:18])[CH:13]=2)[CH:8]=[N:7][CH:6]=1

Participants

7

Reactant 2

HCID 6228DimethylformamideHCID 69199203HCID 69199203, compound

Product 1

HCID 69200517HCID 69200517, compound

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6212ChloroformSolvent

Conditions

Temperature
120 °C

Procedure

A solution of (6-bromo-isoquinolin-4-yl)-acetic acid methyl ester (52 mg, 0.19 mmol), prepared as described as an intermediate for Intermediate 31, in DMF (3 ml) is added to zinc dicyanide (26 mg, 0.22 mmol) under a nitrogen atmosphere. To the resulting mixture is added 1,1′-bis(diphenylphosphino)ferrocene (15 mg) and tris(dibenzylideneacetone)dipalladium(0) (8 mg) and the resulting mixture stirred at 120° C. for 22 h. The solution is cooled and diluted with chloroform (30 ml) and washed with water (2×20 ml) followed by brine (20 ml). Further chloroform is added (40 ml) and the solution dried over MgSO4, filtered and concentrated. Repetitive flash silica column chromatography (eluants 40:1 CH2Cl2:methanol, then 50:1 CH2Cl2:methanol) gives (6-cyano-isoquinolin-4-yl)-acetic acid methyl ester [MH]+ 227. This intermediate is saponified by treatment with LiOH in 3:1 THF/water. The resulting mixture is partially evaporated to remove the THF, diluted to 10 ml with water then washed with ethyl acetate. The aqeous phase is then neutralised with 1M hydrochloric acid (to pH 4-5) and exhaustively extracted with ethylacetate. The organic phase is dried over MgSO4, filtered and concentrated to give (6-cyano-isoquinolin-4-yl)-acetic acid M+ 212.

Workup

  1. temperatureThe solution is cooled
  2. washwashed with water (2×20 ml)
  3. additionFurther chloroform is added (40 ml)
  4. dry with materialthe solution dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-11e8dfcf1dc24573b4abe43cf9988c98
Source dataset
uspto-grants-2006_03
Patent number
US07019136B2

Reaction notes

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