Methanol → 5-[5-Bromo-4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-2-pyrimidinyl]-2-thiophenecarboxylic acid

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Reaction Conditions

Reaction Steps

A 100 mL round bottomed flask was charged with anhydrous methanol (50 mL). Then, SOCl2 (20 mL) was added dropwise with ice bath. After addition, the mixture was stirred for 1 h at 0° C. Then, the ice bath was removed and 5-(5-bromo-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)thiophene-2-carbonitrile (800 mg, 2.1 mmol, 1.0 equiv.) was added. The mixture was stirred overnight at rt and the solvent was removed. Then, methanol (10 mL) and 1 N HCl aqueous (5 mL) was added. The mixture was stirred for 1 h and the solvent was removed to give a residue, which was purified by silica gel column chromatography (PE/EA/MeOH=2:1:0.06 as eluant) to give a yellow solid. This solid and NaOH (6N, 3 mL) was dissolved in methanol/THF (10 mL/10 mL). The mixture was stirred for 2 h. The solvent was removed and water (10 mL) was added. Then, 1 N HCl was added until the pH of the solution reach 2-3. The mixture was filtered and the solid was collected as acid 5-(5-bromo-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)thiophene-2-carboxylic acid (332.5 mg, yield: 38.9%). LC-MS (m/z)=407.1 [M+H]+.

Provenance & Evidence