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

Temperature

107 °C

Route B: A mixture of 6-chloro-4-iodopyridin-3-ylamine (Preparation 106, 0.33 g, 1.30 mmol), pyruvic acid (0.27 mL, 3.89 mmol), DABCO (0.44 g, 3.89 mmol) and palladium acetate (0.015 g, 0.07 mmol) in dry DMF was stirred vigorously and degassed with argon for 15 min. The reaction mixture was heated to 107° C. for 5 h. The reaction mixture was allowed to cool to rt and stirred for 16 h. The volatiles were removed under reduced pressure and the residue partitioned between ethyl acetate (100 mL) and water (50 mL). The layers were separated and the aqueous extracted with ethyl acetate (2×50 mL). The combined organics were extracted with aqueous NaOH (2M, 3×70 mL). The combined aqueous extracts were acidified to pH 4 by careful addition of glacial acetic acid, then extracted with ethyl acetate (3×60 mL). The combined organics were washed with brine (50 mL), dried (MgSO4), filtered and concentrated in vacuo to give the title compound as a brown solid. RT=2.72 min, m/z (ES+)=197 [M+H]+

1. customdegassed with argon for 15 min
2. temperatureto cool to rt
3. stirringstirred for 16 h
4. customThe volatiles were removed under reduced pressure
5. customthe residue partitioned between ethyl acetate (100 mL) and water (50 mL)
6. customThe layers were separated
7. extractionthe aqueous extracted with ethyl acetate (2×50 mL)
8. extractionThe combined organics were extracted with aqueous NaOH (2M, 3×70 mL)
9. additionThe combined aqueous extracts were acidified to pH 4 by careful addition of glacial acetic acid
10. extractionextracted with ethyl acetate (3×60 mL)
11. washThe combined organics were washed with brine (50 mL)
12. dry with materialdried (MgSO4)
13. filtrationfiltered
14. concentrationconcentrated in vacuo

ORD record

ord-5a944648dfe044b7a50c053304f8c26a

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07405210B2