Dimethylformamide → 6-Cyano-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester

HRID 2063970Notes

Reaction equation

HRID 2063970 reaction equation
[CH3:1][O:2][C:3](=[O:23])[C:4]1[CH:9]=[CH:8][C:7](Cl)=[N:6][C:5]=1[NH:11][C:12]1[CH:17]=[CH:16][C:15]([Si:18]([CH3:21])([CH3:20])[CH3:19])=[CH:14][C:13]=1[F:22].[CH3:24][N:25](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>[CH3:1][O:2][C:3](=[O:23])[C:4]1[CH:9]=[CH:8][C:7]([C:24]#[N:25])=[N:6][C:5]=1[NH:11][C:12]1[CH:17]=[CH:16][C:15]([Si:18]([CH3:21])([CH3:20])[CH3:19])=[CH:14][C:13]=1[F:22]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 591401556-Chloro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester

Product 1

HCID 591401856-Cyano-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester

Reagents, catalysts & solvents 2

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

Procedure

A degassed suspension of 6-chloro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester (4.8 g, 12.4 mmol), zinc cyanide (1.2 g, 10.2 mmol), and Pd(PPh3)4 (1.6 g, 1.36 mmol) in dimethylformamide (14 mL) was subjected to microwave irradiation at 190° C. for 20 minutes. This procedure was repeated seven times and all the reaction mixtures were combined and concentrated in vacuo. The resultant residue was dissolved in ethyl acetate and washed with a saturated aqueous solution of sodium hydrogen carbonate. The aqueous layer was separated and extracted with ethyl acetate three times. The combined organic extracts were washed with water and then brine, dried (Na2SO4), filtered and evaporated in vacuo. The resultant residue was subjected to flash chromatography (silica, gradient 0% to 100%, diethyl ether in pentane) to afford the title compound as a yellow solid (18.2 g). LCMS (method B): RT=4.74 min, M+H+=344.

Workup

  1. customirradiation at 190° C. for 20 minutes
  2. customthe reaction mixtures
  3. concentrationconcentrated in vacuo
  4. dissolutionThe resultant residue was dissolved in ethyl acetate
  5. washwashed with a saturated aqueous solution of sodium hydrogen carbonate
  6. customThe aqueous layer was separated
  7. extractionextracted with ethyl acetate three times
  8. washThe combined organic extracts were washed with water
  9. dry with materialbrine, dried (Na2SO4)
  10. filtrationfiltered
  11. customevaporated in vacuo

Sources & evidence

ORD record
ord-4ec28e01c4784ab0b4c0ff59d3d95944
Source dataset
uspto-grants-2012_10
Patent number
US08288408B2

Reaction notes

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