反应详情

Alternatively, 1-[5-(1,1-dimethyl-2-oxo-ethyl)-isoxazol-3-yl]-3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea (I-4a) is prepared in the following manner. To a stirred mixture of dimethyl sulfoxide (1 equivalent) in anhydrous dichloromethane at −78° C. under an argon atmosphere is added dropwise oxalyl chloride (0.5 equivalents). After stirring for a further 20 to 40 min, compound 1-[5-(2-hydroxy-1,1-dimethyl-ethyl)-isoxazol-3-yl]-3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea (I-1) (0.3 equivalents) is added and the mixture is stirred at −78° C. Triethylamine (1-2 equivalents) is added, and the mixture is allowed to warm to rt, then the mixture is filtered through Celite and concentrated under reduced pressure. The residue is purified by silica gel flash chromatography to afford 1-[5-(1,1-dimethyl-2-oxo-ethyl)-isoxazol-3-yl]-3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea (I-4a).

1. customAlternatively, 1-[5-(1,1-dimethyl-2-oxo-ethyl)-isoxazol-3-yl]-3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea (I-4a) is prepared in the following manner
2. stirringthe mixture is stirred at −78° C
3. filtrationthe mixture is filtered through Celite
4. concentrationconcentrated under reduced pressure
5. customThe residue is purified by silica gel flash chromatography