Sodium Hydroxide → 3-(7-(3-(2-Oxa-6-azaspiro[3.3]heptan-6-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acid

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Reaction Steps

To a stirred solution of methyl 3-(7-(3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoate (70 mg, 0.15 mmol) in 5 mL of THF and 5 mL of methanol was added a solution of 1N NaOH (2 mL) at room temperature. After the addition, the reaction was stirred at this temperature for 15 hours. The solvent was evaporated and the residue was diluted with water and adjusted to pH=2 by HCl (aq.). The precipitate was filtered, the cake 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: 40% acetonitrile/60% water (0.1% TFA V/V) initially, and then proceed to 70% acetonitrile/30% water (0.1% TFA V/V) in a linear fashion after just 9 min.) to give 3-(7-(3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acid (10 mg, 15%). 1H NMR (300 MHz, DMSO): δ 10.13 (s, 1H), 9.41 (s, 1H), 9.00 (s, 1H), 8.66 (d, 1H, J=8.1 Hz), 8.12-8.10 (m, 1H), 7.70 (t, 1H, J=7.9 Hz), 7.45 (s, 1H), 7.24-7.18 (m, 2H), 6.23 (d, 1H, J=7.5 Hz), 4.75 (s, 4H), 4.03 (s, 4H). LC-MS: 446 [M+H]+, tR=1.59 min. HPLC: 97.95% at 214 nm, 100% at 254 nm, tR=7.31 min.

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