Pyruvic Acid → 5-Fluoro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid

HRID 1097262Notes

Reaction equation

HRID 1097262 reaction equation
[NH2:1][C:2]1[C:7](I)=[CH:6][C:5]([F:9])=[CH:4][N:3]=1.[C:10]([OH:15])(=[O:14])[C:11]([CH3:13])=O.N12CCN(CC1)CC2>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C)C=O>[F:9][C:5]1[CH:6]=[C:7]2[CH:13]=[C:11]([C:10]([OH:15])=[O:14])[NH:1][C:2]2=[N:3][CH:4]=1

Participants

6

Reactant 3

HCID 1060Pyruvic AcidHCID 9237DabcoHCID 184559742-Amino-5-fluoro-3-iodopyridine

Product 1

HCID 454802985-Fluoro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acidYield 41.9%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

0.5 g (2.10 mmol) of 2-amino-3-iodo-5-fluoropyridine obtained in step 5.1, 0.55 g (6.3 mmol) of pyruvic acid, 0.71 g (6.3 mmol) of 1,4-diazabicyclo[2.2.2]octane (DABCO) and 15 ml of anhydrous dimethylformamide are introduced into a 25 ml sealed tube equipped with a magnetic stirrer and subjected to sparging with argon. After a few minutes, 0.05 g (0.22 mmol) of palladium acetate is added. The reaction mixture is kept stirring and subjected to sparging with argon for 20 minutes and then rapidly sealed and brought to 100° C. for 2 h 30. The cooled solution is concentrated under reduced pressure. The residue is subsequently taken up with ethyl acetate (100 ml) and water (75 ml). The organic phase is washed with water and then extracted with twice 50 ml of a 2N aqueous solution of sodium hydroxide. The basic aqueous phases are combined, cooled to 0° C. and then acidified by adding hydrochloric acid (pH 3). The medium is extracted with ethyl acetate (4×50 ml), and the combined organic phases are dried over sodium sulphate and then concentrated under reduced pressure. 0.158 g (0.88 mmol) of the expected product is obtained in the form of a yellow powder.

Workup

  1. customsealed tube
  2. customequipped with a magnetic stirrer
  3. customto sparging with argon
  4. waitAfter a few minutes
  5. customto sparging with argon for 20 minutes
  6. customrapidly sealed
  7. concentrationThe cooled solution is concentrated under reduced pressure
  8. washThe organic phase is washed with water
  9. extractionextracted with twice 50 ml of a 2N aqueous solution of sodium hydroxide
  10. additionby adding hydrochloric acid (pH 3)
  11. extractionThe medium is extracted with ethyl acetate (4×50 ml)
  12. dry with materialthe combined organic phases are dried over sodium sulphate
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0865a0be9e2a4023984d1058ab5667b4
Source dataset
uspto-grants-2012_03
Patent number
US08143248B2

Reaction notes

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