Pyrazole → 2-Chloropyridine-4-carbonyl chloride

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Reaction Steps

Scheme III shows the synthesis of a pyrazole, compound 13, analogs of compound 5 in which the pyridine 10 ring bears a chlorine atom at position 2. 2-Chloropyridine-4-carboxylic acid, compound 9, is treated with thionyl chloride in a solvent such as toluene, and heated to reflux to give 2-chloropyridine-4-carboxylic acid chloride, compound 10, which is then converted to methyl 2-chloroisonicotinate, compound 11. Compound 11 is treated with a ketone 2 in the presence of a base such as sodium methoxide in a solvent such as tetrahydrofuran, at temperatures ranging from 25° C. up to reflux to provide a diketone, compound 12. Treatment of the diketone, compound 12, with an arylhydrazine derivative 4 in ethanol or other suitable solvent at a temperature ranging up to reflux, provides pyrazole compound 13. When R2 of ketone 2 is hydrido, then R2 of 13 is hydrido.

Provenance & Evidence