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

HRID 2358157Notes

Reaction equation

HRID 2358157 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
100 °C

Procedure

0.5 g (2.10 mmol) of 2-amino-3-iodo-5-fluoropyridine obtained in step 12.1, 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 placed in a 25 ml sealed tube equipped with a magnetic stirrer and maintained under an argon sparge. After a few minutes, 0.05 g (0.22 mmol) of palladium acetate is added. The reaction mixture is stirred for 20 minutes while sparging with argon and is then rapidly sealed and maintained at 100° C. for 2 hours 30 minutes. The cooled solution is concentrated to dryness under reduced pressure. The residue is then taken up in ethyl acetate (100 ml) and water (75 ml). The organic phase is washed with water and then extracted with twice 50 ml of aqueous 2N sodium hydroxide solution. 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 sulfate 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. temperaturemaintained under an argon
  4. customsparge
  5. waitAfter a few minutes
  6. customwhile sparging with argon
  7. customis then rapidly sealed
  8. concentrationThe cooled solution is concentrated to dryness under reduced pressure
  9. washThe organic phase is washed with water
  10. extractionextracted with twice 50 ml of aqueous 2N sodium hydroxide solution
  11. temperaturecooled to 0° C.
  12. additionby adding hydrochloric acid (pH 3)
  13. extractionThe medium is extracted with ethyl acetate (4×50 ml)
  14. dry with materialthe combined organic phases are dried over sodium sulfate
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-31ce2b2074cf47bdbc021787947aeaa6
Source dataset
uspto-grants-2010_07
Patent number
US07763636B2

Reaction notes

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