Hydrochloric Acid → 4-(6-Chloropyrazolo[1,5-a]pyrimidin-3-yl)-2-thiophenecarboxylic acid

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Reaction Steps

To a sealed tube containing DMF (3 mL) and water (1 mL) was added 3-bromo-6-chloropyrazolo[1,5-a]pyrimidine (150 mg, 0.645 mmol), methyl-4-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolan-2-yl)-thiophene-2-carboxylate (216 mg, 0.807 mmol), Biotage polymer-bound triphenylphosphine-Pd(0), and sodium carbonate (85 mg, 0.807 mmol). The reaction flask was backfilled with nitrogen gas three times and irradiated in the microwave at 110° C. for 1 h. The solution was allowed to cool to room temperature, and a 1:1 solution of dichloromethane: methanol was added. The solution was filtered and the resulting filtrate concentrated under reduced pressure and water was added. The precipitate was filtered and washed with water once to afford crude methyl 4-(6-chloropyrazolo[1,5-a]-pyrimindin-3-yl)-thiophene-2-carboxylate. The crude methyl ester was taken up in THF (3 mL) and MeOH (3 mL) and 1N KOH in MeOH (2 mL, 3.10 mmol) was added. The solution was heated at 60° C. for 3 h. After hydrolysis, the solution was acidified with 1N HCl and the precipitate collected by filtration to afford the title compound (0.125 g, 0.447 mmol). LRMS (APCI) calc'd for (C11H6ClN3O2S) [M+H]+, 280.0; found 280.0.

Provenance & Evidence