Hydrochloric Acid → 1-{2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]ethyl}-4-piperidinecarboxylic acid

Temperatur

50 °C

To a solution of ethyl 1-{2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]ethyl}-4-piperidinecarboxylate (D91) (30 mg) in THF (5 mL) was added aqueous NaOH (2 M, 1 mL). The reaction was stirred at 50° C. for 5 h. The mixture was cooled to room temperature and acidified with aqueous HCl (2 M) to pH 4-5, partitioned between ethyl acetate (50 mL) and water (50 mL). The organic phase was washed with water (50 mL) and brine (50 mL), dried over sodium sulphate and evaporated to give the crude product, which was purified by Mass Directed Auto Prep to afford 1-{2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]ethyl}-4-piperidinecarboxylic acid (E66) (1.8 mg, TFA salt). δH (DMSO-d6, 400 MHz): 1.36 (6H, d), 1.75 (2H, m), 1.91 (1H, m), 2.11 (2H, m), 3.11 (4H, m), 3.48 (4H, m), 3.65 (3H, s), 4.89 (1H, m), 7.23 (1H, t), 7.33 (1H, s), 7.47 (2H, m), 7.87 (1H, dd), 8.12 (1H, dd), 8.19 (1H, d), 9.24 (1H, br s), 12.56 (1H, br s). MS (ES): C28H31ClN4O4 requires 522; found 523.2 (M+H+).

1. temperatureThe mixture was cooled to room temperature
2. custompartitioned between ethyl acetate (50 mL) and water (50 mL)
3. washThe organic phase was washed with water (50 mL) and brine (50 mL)
4. dry with materialdried over sodium sulphate
5. customevaporated
6. customto give the crude product, which
7. customwas purified by Mass Directed Auto Prep

ORD-Eintrag

ord-a5828fc1d91345029d0f2a23782ff062

Quelldatensatz

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08217028B2