Tetrahydrofuran → HCID 58456383, compound

Participants

Reaction Steps

Methyl 2,2-dimethyl-3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propanoate (278 mg, 0.617 mmol) was taken up in MeOH (4 mL)/THF (4 mL), and 1 M KOH (648 μL, 0.648 mmol) was added. The reaction was stirred at room temperature overnight. LC/MS analysis showed only ˜40% conversion, so additional 1 M KOH (123 μL, 0.123 mmol) was added, and the reaction was stirred at 50° C. overnight. The reaction was subsequently evaporated to dryness, providing 2,2-dimethyl-3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propanoic acid (potassium salt) as a yellow solid that was used without purification in subsequent reactions (337 mg, 87% pure, 100% yield). A small portion (40 mg) was purified by reverse phase HPLC (50-100% MeCN/water w/0.025% TFA). Product fractions were combined and evaporated to provide a clean sample of 2,2-dimethyl-3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}-phenyl)-1,3-thiazol-2-yl]propanoic acid (TFA salt) as an off-white foam (28 mg). MS ESI: [M+H]+ m/z 437.0. 1H NMR (600 MHz, DMSO-d6) δ 12.41 (s, 1H), 10.23 (s, 1H), 8.80 (d, J=4.9, 1H), 7.98-7.86 (m, 2H), 7.44 (s, 1H), 7.26 (d, J=4.9, 1H), 7.11 (s, 1H), 3.16 (s, 2H), 2.29 (s, 3H), 1.16 (s, 6H). rhSYK activity=+++

Provenance & Evidence