Hydrochloric Acid → 4-(1-(7-(5,6-Dimethoxypyridin-2-ylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)benzoic acid

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Reaction Steps

To a stirred solution of methyl 4-(1-(7-(5,6-dimethoxypyridin-2-ylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)benzoate (350 mg, 0.65 mmol) in 20 mL of methanol and 40 mL of THF was added a solution of LiOH.H2O (274 mg, 6.5 mmol) in one portion at room temperature. Then the solution was stirred at room temperature for 24 hours. The solution was acidified with 1N HCl to pH=4. The solvent was evaporated and the residue was purified by preparative HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 ml/inj, flow rate: 20 ml/min; wavelength: 214 nm and 254 nm; the gradient conditions are: 30% acetonitrile/70% water (0.1% TFA V/V) initially, and then proceed to 55% acetonitrile/45% water (0.1% TFA V/V) in a linear fashion after just 9 min.) to give 4-(1-(7-(5,6-dimethoxypyridin-2-ylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)benzoic acid (70 mg, 20.5%) as a pale yellow solid. 1H NMR (300 MHz, DMSO): δ 8.87-8.18 (m, 2H), 8.67 (s, 1H), 8.03-7.96 (m, 5H), 7.44 (d, 1H, J=8.7 Hz), 4.66 (brs, 1H), 4.11 (brs, 2H), 3.90 (s, 3H), 3.78 (s, 3H), 3.68 (brs, 2H), 2.27 (brs, 1H), 2.08 (brs, 1H). LC-MS: 522 [M+H]+, tR=1.44 min. HPLC: 99.68% at 214 nm, 99.31% at 254 nm, tR=6.98 min.

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