5-Phenyl-1,2,4-oxadiazole-3-carboxylic acid synthesis

Yield: 83%

Reaction Conditions:

with lithium hydroxide monohydrate in tetrahydrofuran;methanol;water at 20; for 3 h;

Steps:

111.c Synthesis of (S)-N-(1-(imidazo[1,2-a]pyrazin-8-yl)pyrrolidin-3-yl)-5-phenyl-1,2,4-oxadiazole-3-carboxamide
To a mixture of the above ester (900 mg, 4.1mmol), MeOH (5 mL), THF (5 mL) and DI H20 (5 mL) was added LiOH monohydrate (420 mg, 10 mmol). The resulting mixture was stirred at room temperature for 3 h. The mixture was then diluted with ice-water, pH adjusted to 3 with 1 N HCl, and mixture was then extracted with 10% MeOH in CH2C12. The organic layer was dried (Na2SO4), filtered and concentrated in vacuo give the desired compound as an offwhite solid (900 mg, 83% yield, which was used directly forthe next step). MS: (ES) m/z 219.1 (M+H⁺).

References:

ChemoCentryx, Inc.;Fan, Junfa;Krasinski, Antoni;Lange, Christopher W.;Lui, Rebecca M.;McMahon, Jeffrey P.;Powers, Jay P.;Zeng, Yibin;Zhang, Penglie US2014/154179, 2014, A1 Location in patent:Paragraph 0429; 0432