反应详情

Alternatively, [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 is prepared in the following manner. To a stirred 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) and potassium carbonate (2-6 equivalents) in anhydrous acetone is added tetrabutylammonium iodide (0.1-1 equivalent) and the mixture is stirred and heated under reflux 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. customAlternatively, [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 is prepared in the following manner
2. temperatureheated
3. temperatureunder reflux until the reaction
4. customThe mixture is partitioned between water
5. additioneither dichloromethane or a mixture of isopropanol and dichloromethane
6. customThe organic layer is separated
7. extractionthe aqueous layer is further extracted with dichloromethane
8. additiona mixture of isopropanol and dichloromethane
9. washThe combined extracts are washed with water or brine
10. dry with materialdried over magnesium sulfate
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. customThe residue is purified by silica gel flash chromatography