Dimethylformamide → 1h-Pyrazolo[4,3-b]pyridine-5,6-dicarboxylic acid,1-methyl-,5,6-dimethyl ester

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Reaction Conditions

Reaction Steps

Dimethylformamide (7.4 mL, 0.096 mol) is dissolved in 125 mL dichloroethane and the mixture cooled to -5° C. in an acetone/ice bath. Phosphorous oxychloride (8.9 mL, 0.095 mol) is added-in one portion and the clear colorless solution is allowed to warm slowly to room temperature, gradually turning yellow. The unpurified dimethyl [(1-methylpyrazol-4-yl)amino]butenedicarboxylate is dissolved in 75 mL of dichloroethane and added to the chilled Vilsmeier reagent dropwise keeping the reaction temperature below 5° C. The mixture is allowed to warm slowly to room temperature over four hours, and then is heated to reflux for one hour. The mixture is concentrated to a solid which is chromatographed using 3:1 hexanes/ethyl acetate. The fractions containing the desired product are combined and concentrated to give the product as a white solid (16.93 g, 71.4%), melting point 148°-149° C.

Provenance & Evidence