反应详情

To a solution of ethyl 1-{2-[3-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylate (D112) (200 mg, 0.368 mmol) in Isopropanol (8 mL) and Water (8.00 mL) was added NaOH (3.68 mL, 1.841 mmol). The reaction was stirred at 90° C. for 2 hr before the isopropanol was removed in vacuo. The residue was acidified with aq HCl (2 M) until pH ˜2. The aqueous layer was extracted with ethyl acetate and the organic phases were dried and concentrated, purified by Mass Directed AutoPrep to afford 1-{2-[3-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylic acid (E75) (93 mg) as a TFA salt. δH (DMSO-d6, 400 MHz): 1.06 (3H, t), 1.28 (6H, d), 1.68 (2H, m), 2.05 (2H, m), 2.51 (1H, m), 2.73 (2H, m), 3.07 (4H, m), 3.23 (2H, m), 3.48 (1H, m), 3.64 (1H, m), 5.37 (1H, m), 7.30 (2H, m), 7.68 (1H, d), 8.47 (1H, d), 8.81 (1H, d), 9.54 (1H, s br). δF (DMSO-d6, 376 MHz): −73.6. MS (ES): C26H31ClN4O3S requires 514.2. found 515.0 (M+H+).

1. customwas removed in vacuo
2. extractionThe aqueous layer was extracted with ethyl acetate
3. customthe organic phases were dried
4. concentrationconcentrated
5. custompurified by Mass Directed AutoPrep