Carbon Dioxide → 7-(2-chloro-4,6-dimethylphenyl)-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridine-3-carboxylic acid

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Reaction Conditions

Reaction Steps

3-Bromo-7-(2-chloro-4,6-dimethylphenyl)-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridine (1-1; 1.46 g) and a few crystals of 1,10 phenanthroline were dissolved in 25 mL of dry tetrahydrofuran and chilled to −78° C. under an argon atmosphere. A 2.0 M solution of n-butyllithium in cyclohexane was added dropwise until the dark color of the phenanthroline/organolithium complex persisted. An additional 2.05 mL of the n-butyllithium solution was added. After 10 minutes, carbon dioxide, generated from dry ice, was bubbled through the reaction mixture for 5 minutes. After the reaction mixture had been stirred at −78° C. for 5 minutes, the cooling bath was removed and the mixture was allowed to warm for 5 minutes before being quenched by the addition of water. The mixture was partitioned between ethyl acetate and water, acidified with dilute hydrochloric acid. The ethyl acetate was dried with magnesium sulfate and concentrated. The residue was flash chromatographed on silica gel eluting with an acetone/hexane gradient to provide 1.11 g of 5-1: mp 247.8-248.3° C.

Provenance & Evidence