Potassium Hydroxide → 1-Bromo-5-hydroxy-5-(5-(4-methyl-6-((4-(trifluoromethyl)pyridin-2-yl)amino)pyridin-2-yl)thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid

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Reaction Steps

To a solution of methyl 1-bromo-5-hydroxy-5-(5-(4-methyl-6-((4-(trifluoromethyl)pyridin-2-yl)amino)pyridin-2-yl)thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylate (50 mg, 0.081 mmol) in THF (1.6 mL) was added aqueous potassium hydroxide (172 μl, 1.61 mmol), and the mixture was stirred for 16 h at rt, after which time the reaction mixture was diluted with MeOH (2 mL), filtered, and purified by reverse phase HPLC using a C18 column and a mixture of MeCN and water modified with 0.1% TFA. The product-containing fractions were partitioned between pH 4 buffer (20 mL) and EtOAc (20 mL) and the layers were separated. The aqueous phase was extracted with EtOAc (1×20 mL)), then the combined organic phases were washed with brine (20 mL), dried, and concentrated to yield 1-bromo-5-hydroxy-5-(5-(4-methyl-6-((4-(trifluoromethyl)pyridin-2-yl)amino)pyridin-2-yl)thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid (25 mg, 52%) as a white solid. MS ESI calcd for C26H20BrF3N4O3S [M+H]+ 605, found 605. 1H NMR (600 MHz, dmso) δ 10.17 (s, 1H), 8.62 (s, 1H), 8.46 (d, J=5.0, 1H), 8.20 (s, 1H), 7.35-7.29 (m, 3H), 7.19 (s, 1H), 7.08 (s, 1H), 6.68 (s, 1H), 2.79 (s, 3H), 2.32-2.2.24 (m, 4H), 2.06 (br s, 1H), 1.96 (br s, 2H) ppm.

Provenance & Evidence