Sodium hydride → 3,5-dimethyl-1-pyrazin-2-yl-1H-pyrazole-4-carboxylic acid ethyl ester

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Reaction Conditions

Reaction Steps

step 1—To a solution of 3,5-dimethyl-1H-pyrazole-4-carboxylic acid ethyl ester (1 g, 5.95 mmol) in DMF (20 mL) cooled to 0° C. was added portionwise NaH (60% in mineral oil, 171 mg, 7.13 mmol). After hydrogen evolution ceased, 2-chloro-pyrazine (0.64 mL, 7.13 mmol) was added and the reaction was stirred at 50° C. for 24 h. The reaction mixture was cooled to RT, partitioned between EtOAc and saturated NH4Cl. The aqueous layer was extracted twice with EtOAc. The combined organic layers were dried (Na2SO4), filtered and evaporated. The residue was purified via SiO2 chromatography eluting with hexane/EtOAc to afford 0.64 g (44%) of 3,5-dimethyl-1-pyrazin-2-yl-1H-pyrazole-4-carboxylic acid ethyl ester (124a). The ethyl ester was hydrolyzed to the corresponding acid with KOH in aqueous EtOH as described in step 2 of example 31.

Provenance & Evidence