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), ethanolamine (1-3 equivalents), potassium carbonate (2-5 equivalents) and sodium iodide (2-5 equivalents) in anhydrous DMF is stirred at 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 separated aqueous layer is further extracted with dichloromethane or a mixture of isopropanol and dichloromethane, and the combined organic layers are washed with water or brine, then 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 1-(5-tert-butyl-isoxazol-3-yl)-3-(4-{7-[2-(2-hydroxy-ethylamino)-ethoxy]-benzo[d]imidazo[2,1-b]thiazol-2-yl}-phenyl)-urea (I-2).

1. customThe mixture is partitioned between water
2. additioneither dichloromethane or a mixture of isopropanol and dichloromethane
3. extractionThe separated aqueous layer is further extracted with dichloromethane
4. additiona mixture of isopropanol and dichloromethane
5. washthe combined organic layers are washed with water or brine
6. dry with materialdried 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