Hydrochloric Acid → [2-(2-{4-[3-(5-Tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yloxy)-ethylamino]-acetic acid

Participants

Reaction Steps

A mixture of [2-(2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yloxy)-ethylamino]-acetic acid methyl ester (1 equivalent) and lithium hydroxide monohydrate (3-6 equivalents) in 50% aq THF is stirred at selected temperatures between rt and 60° C. until the reaction is substantially complete as monitored by LCMS or TLC. The reaction mixture is neutralized with aq hydrochloric acid and partitioned between water and either dichloromethane or a mixture of isopropanol and dichloromethane. The organic layer is separated and the aqueous layer is further extracted with dichloromethane or a mixture of isopropanol and dichloromethane. The combined organic layers are dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by preparative reverse-phase HPLC or silica gel flash chromatography to afford [2-(2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yloxy)-ethylamino]-acetic acid (I-3).

Provenance & Evidence