07-11-2013 дата публикации
Номер: US20130296550A1
Принадлежит:
A method for synthesizing temsirolimus, the method including: using a substituted boric acid to protect 2,2-dimethylol propionic acid to produce intermediate II; carrying out a reaction between the intermediate II and 2,4,6-trichlorobenzoyl chloride; carrying out condensation reaction between a resulting product and rapamycin to produce intermediate III; and finally using a diol to remove a protecting group from the intermediate III to yield temsirolimus. 2. The method of claim 1 , whereinthe substituted boric acid is selected from the group consisting of ethylboronic acid, propylboronic acid, cyclohexylboronic acid, and benzylboronic acid; anda molar ratio between 2,2-dimethylol propionic acid and the substituted boric acid is 1:1.3. The method of claim 1 , wherein in step 2) claim 1 ,a molar ratio between rapamicin, the intermediate II, and 2,4,6-trichlorobenzoyl chloride is 1:1-1.5:1-1.4;the first organic solvent is selected from the group consisting of toluene, benzene, xylene, ether, methyl tert-butyl ether, tetrahydrofuran, dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, and ethyl acetate;the alkali is selected from the group consisting of triethylamine, N,N-diisopropylethylamine, and N,N-dimethylaniline; andthe acid binding agent is selected from the group consisting of pyridine, 4-dimethylaminopyridine (DMAP), 4-pyrrolidinopyridine, and N-methylimidazole.4. The method of claim 1 , wherein in step 3) claim 1 ,{'sub': 1', '6, 'the diol is selected from the group consisting of 1,2-, 1,3-, 1,4-, 1,5-diol, and a C-Calkyl substituted diol;'}a molar ratio between the intermediate III and the diol is 1:1-10; andthe second organic solvent is selected from the group consisting of toluene, benzene, xylene, ether, methyl tert-butyl ether, tetrahydrofuran, dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, ethyl acetate, and acetone. This application is a continuation-in-part of International Patent Application No. PCT/CN2011/ ...
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