Dimethylformamide → N-(5-Chloropyridin-2-yl)-5-cyano-2-[(1-isopropylpiperidin-4-ylcarbonyl)amino]benzamide

HRID 988706Notes

Reaction equation

HRID 988706 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:29])[C:10]2[CH:15]=[C:14](I)[CH:13]=[CH:12][C:11]=2[NH:17][C:18]([CH:20]2[CH2:25][CH2:24][N:23]([CH:26]([CH3:28])[CH3:27])[CH2:22][CH2:21]2)=[O:19])=[N:6][CH:7]=1.[CH3:30][N:31](C)C=O>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:29])[C:10]2[CH:15]=[C:14]([C:30]#[N:31])[CH:13]=[CH:12][C:11]=2[NH:17][C:18]([CH:20]2[CH2:25][CH2:24][N:23]([CH:26]([CH3:28])[CH3:27])[CH2:22][CH2:21]2)=[O:19])=[N:6][CH:7]=1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 21906277N-(5-chloropyridin-2-yl)-5-iodo-2-[(1-isopropylpiperidin-4-ylcarbonyl)amino]benzamide

Product 1

HCID 21906481N-(5-Chloropyridin-2-yl)-5-cyano-2-[(1-isopropylpiperidin-4-ylcarbonyl)amino]benzamideYield 18%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
83 °C

Procedure

To a stirring solution of N-(5-chloropyridin-2-yl)-5-iodo-2-[(1-isopropylpiperidin-4-ylcarbonyl)amino]benzamide (0.50 g, 0.94 mmol) in N,N-dimethylformamide (6 mL) was added zinc cyanide (70 mg, 0.58 mmol) followed by tetrakis(triphenylphosphine)palladium(0) (49 mg, 0.04 mmol). The reaction mixture was stirred at 83° C. for 6 h and then at room temperature overnight. It was then partitioned between 3:1 chloroform:isopropanol and ammonium hydroxide and the layers separated. The organic phase was dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude product was suspended in methanol and filtered. The filtered solid was then slurried in diethyl ether and filtered to give 70 mg (18%) of the title compound as white solid. The methanolic filtrate was concentrated in vacuo and purified by chromatography over silica gel, eluting with 5-20% 2 M ammonia/methanol solution in dichloromethane. The chromatography product was slurried in methanol and filtered to give an additional 0.14 g (35%) of the title compound.

Workup

  1. customat room temperature
  2. customovernight
  3. customIt was then partitioned between 3:1 chloroform
  4. customisopropanol and ammonium hydroxide and the layers separated
  5. dry with materialThe organic phase was dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. filtrationfiltered
  9. filtrationfiltered

Sources & evidence

ORD record
ord-c6c0b2edc10a408981adccb9aaefe077
Source dataset
uspto-grants-2003_10
Patent number
US06635657B1

Reaction notes

Loading…