反应详情

A mixture of 1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(2-chloro-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea (1 equivalent), glycine ethyl ester hydrochloride (1-3 equivalents), potassium carbonate (2-6 equivalents), and sodium iodide (2-5 equivalents) in anhydrous DMF is stirred at selected temperatures between rt and 80° C. until the reaction is substantially complete as monitored by LCMS or TLC. The mixture is 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 extracts are washed with water or brine, then dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by 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 methyl ester.

1. customThe mixture is partitioned 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. washThe combined extracts are washed with water or brine
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe residue is purified by silica gel flash chromatography