Potassium Cyanide → HCID 11150337, compound

HRID 917773Notes

Reaction equation

HRID 917773 reaction equation
[F:1][C:2]1[CH:19]=[C:18](I)[CH:17]=[CH:16][C:3]=1[NH:4][C:5]1[C:6]([C:13]([NH2:15])=[O:14])=[CH:7][N:8]([CH3:12])[C:9](=[O:11])[CH:10]=1.[C-:21]#[N:22].[K+]>CN(C=O)C.[Cu]I.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>[C:21]([C:18]1[CH:17]=[CH:16][C:3]([NH:4][C:5]2[C:6]([C:13]([NH2:15])=[O:14])=[CH:7][N:8]([CH3:12])[C:9](=[O:11])[CH:10]=2)=[C:2]([F:1])[CH:19]=1)#[N:22]

Participants

6

Reactant 2

HCID 9032Potassium CyanideHCID 11338183HCID 11338183, compound

Product 1

HCID 11150337HCID 11150337, compoundYield 7%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

4-(2-Fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide (0.20 g, 0.5 mmol) was added to potassium cyanide (0.23 g, 3.5 mmol), copper(I)iodide (excess) and tetrakis(triphenylphosphine)palladium(0) (excess) in DMF (30 ml) and heated at 110° C. for 4 h. The reaction mixture was allowed to cool to RT and filtered through Celite® to remove any solid. The Celite® pad was washed well with 5% MeOH/EtOAc. The filtrate and washings were combined and concentrated under reduced pressure. The residue was dissolved in 5% MeOH/EtOAc, then washed with water, brine, dried (Na2SO4), concentrated and triturated with EtOAc giving an approximately 1:1 mixture of 4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide and 4-(4-cyano-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide. Further purification by preparative HPLC [90% (H2O/TFA)/(acetonitrile/TFA)—1% (H2O/TFA)/(acetonitrile/TFA) gradient elution 0.8 ml/min, pH 2.5-2.6] yielded 4-(4-cyano-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide (0.01 g, 7%); m.p. 261-266° C. 1H NMR [400 MHz, (CD3)2SO] δ 11.01 (s, 1H), 8.39 (s, 1H), 7.91 (dd and br s, J=11.2, 1.7 Hz, 2H), 7.72 (t, J=8.2 Hz, 1H), 7.66 (dd, J=8.6, 1.7 Hz, 1H), 7.52 (br s, 1H), 5.97 (s, 1H), 3.40 (s, 3H). HPLC 95.5% (254 nm). HRMS (FAB+) cald for C14H11FN4O2 286.0866 (M+), found 286.0864.

Workup

  1. temperatureto cool to RT
  2. filtrationfiltered through Celite®
  3. customto remove any solid
  4. washThe Celite® pad was washed well with 5% MeOH/EtOAc
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe residue was dissolved in 5% MeOH/EtOAc
  7. washwashed with water, brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customtriturated with EtOAc giving
  11. additionan approximately 1:1 mixture of 4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide and 4-(4-cyano-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide
  12. customFurther purification by preparative HPLC [90% (H2O/TFA)/(acetonitrile/TFA)—1% (
  13. washH2O/TFA)/(acetonitrile/TFA) gradient elution 0.8 ml/min, pH 2.5-2.6]

Sources & evidence

ORD record
ord-ec0f751db08b47dc8839874ff8342538
Source dataset
uspto-grants-2007_09
Patent number
US07273877B2

Reaction notes

Loading…