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

Temperature

100 °C

0.5 g (2.10 mmol) of 2-amino-3-iodo-5-fluoropyridine obtained in Stage 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 bubbled with argon. After some minutes, 0.05 g (0.22 mmol) of palladium acetate is added. The reaction mixture is stirred and bubbled with argon for 20 minutes, then it is quickly sealed and heated to 100° C. for 2.5 h. The cooled solution is concentrated at reduced pressure. The residue is then taken up in ethyl acetate (100 mL) and water (75 mL). The organic phase is washed with water then extracted with 2×50 mL of aqueous solution of 2N sodium hydroxide. The basic aqueous phases are combined, cooled to 0° C. then acidified by adding hydrochloric acid (pH 3). The mixture is extracted with ethyl acetate (4×50 mL), the combined organic phases are dried over sodium sulfate and then concentrated at reduced pressure. We obtain 0.158 g (0.88 mmol) of the expected product in the form of a yellow powder.

1. customsealed tube
2. customequipped with a magnetic stirrer
3. custombubbled with argon
4. waitAfter some minutes
5. custombubbled with argon for 20 minutes
6. customit is quickly sealed
7. concentrationThe cooled solution is concentrated at reduced pressure
8. washThe organic phase is washed with water
9. extractionthen extracted with 2×50 mL of aqueous solution of 2N sodium hydroxide
10. temperaturecooled to 0° C.
11. additionby adding hydrochloric acid (pH 3)
12. extractionThe mixture is extracted with ethyl acetate (4×50 mL)
13. dry with materialthe combined organic phases are dried over sodium sulfate
14. concentrationconcentrated at reduced pressure

ORD record

ord-cbb6d12789914f0a9b56bbb3ad3d9444

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08716272B2