Hydrochloric Acid → 1-{2-[3-(5-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-(methyloxy)phenyl]ethyl}-4-piperidinecarboxylic acid

To a solution of ethyl 1-{2-[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-(methyloxy)phenyl]ethyl}-4-piperidinecarboxylate (D104) (38.7 mg, 0.071 mmol) in Tetrahydrofuran (THF) (10 mL), Ethanol (2 mL) and Water (1 mL) was added sodium hydroxide (56.9 mg, 1.423 mmol). The reaction mixture was stirred at room temperature overnight (16 h). Sodium hydroxide (56.9 mg, 1.423 mmol) was added again. The reaction mixture was stirred at room temperature for 4 hours. The reaction mixture was acidified with 2N HCl solution till pH ˜6.0. The organic solvent was removed. Then the mixture was extracted with EA/THF. The combined organic layers were concentrated. The residue was re-dissolved in THF/water and then purified by Mass Directed AutoPrep to afford 1-{2-[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-(methyloxy)phenyl]ethyl}-4-piperidinecarboxylic acid (E73) (10 mg) as a TFA salt. δH (DMSO-d6, 400 MHz): 1.35 (6H, d), 1.78 (2H, m), 1.94 (1H, m), 2.12 (2H, d), 2.55 (1H, m), 3.08 (4H, m), 3.29 (3H, m), 3.49 (3H, m), 3.66 (2H, d), 4.87 (1H, dt), 7.29 (1H, t), 7.40 (1H, d), 7.49 (1H, m), 7.93 (1H, m), 8.04 (1H, dd), 8.16 (1H, d), 9.51 (1H, br. s.), 12.59 (1H, br. s.). δF (DMSO-d6, 376 MHz): −73.5. MS (ES): C28H34ClN3O3S requires 515.2. found 516.2 (M+H+).

1. stirringThe reaction mixture was stirred at room temperature for 4 hours
2. customThe organic solvent was removed
3. extractionThen the mixture was extracted with EA/THF
4. concentrationThe combined organic layers were concentrated
5. dissolutionThe residue was re-dissolved in THF/water
6. custompurified by Mass Directed AutoPrep

ORD record

ord-9f99957349ef4f8eb6481dcaf9daf5fc

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08389508B2