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

Temperature

107 °C

Route A: To a solution of 5-chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid ethyl ester (Preparation 17, 1.78 g, 7.9 mmol) in ethanol (70 mL) was added sodium hydroxide solution (5.2 mL, 2M, 10.3 mmol) and the mixture heated under reflux for 2 h. The solvent was removed in vacuo and the solid dissolved in water (150 mL) and acidified to pH 4 with acetic acid to give the title compound as a brown solid that was isolated by filtration. δH (CD3OD): 7.13 (1H, s), 7.68 (1H, s), 8.58 (1H, s); m/z (ES+)=197 [M+H]+. 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. customwas isolated by filtration
2. customdegassed with argon for 15 min
3. temperatureto cool to rt
4. stirringstirred for 16 h
5. customThe volatiles were removed under reduced pressure
6. customthe residue partitioned between ethyl acetate (100 mL) and water (50 mL)
7. customThe layers were separated
8. extractionthe aqueous extracted with ethyl acetate (2×50 mL)
9. extractionThe combined organics were extracted with aqueous NaOH (2M, 3×70 mL)
10. additionThe combined aqueous extracts were acidified to pH 4 by careful addition of glacial acetic acid
11. extractionextracted with ethyl acetate (3×60 mL)
12. washThe combined organics were washed with brine (50 mL)
13. dry with materialdried (MgSO4)
14. filtrationfiltered
15. concentrationconcentrated in vacuo

ORD record

ord-6008ad75ea1b4fa9adf8a32519f69c36

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08158622B2