反应详情

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).

1. custompartitioned between water
2. additioneither dichloromethane or a mixture of isopropanol and dichloromethane
3. customThe organic layer is separated
4. extractionthe aqueous layer is further extracted with dichloromethane
5. additiona mixture of isopropanol and dichloromethane
6. dry with materialThe combined organic layers are dried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe residue is purified by preparative reverse-phase HPLC or silica gel flash chromatography