- Method for preparing temsirolimus
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The invention discloses a method for preparing temsirolimus. The method comprises the following steps: (1) preparing 2,2,5-trimethyl-5-carboxy-1,3-dioxane; (2) cooling the 2,2,5-trimethyl-5-carboxy-1,3-dioxane and dichloromethane to 0-5 DEG C under the protection of nitrogen, performing stirring for dissolving, adding DIPEA and 2,4,6-trichlorobenzoyl chloride, and carrying out a reaction to obtainan acid anhydride product; (3) adding the acid anhydride product to dichloromethane containing rapamycin and 4-(N,N-dimethylamino)pyridine, and carrying out a reaction; and (4) mixing a product obtained in step (3) with tetrahydrofuran containing p-toluenesulfonic acid, dropwise adding ethylene glycol at 0-5 DEG C, adding water after the reaction is finished, performing extraction by using ethylacetate, and washing and drying the extracted product to prepare the temsirolimus. The method has the advantages of simple preparation process, high yield, high purity and low cost, and is suitable for industrialized production.
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- Intermediate of temsirolimus and preparation method thereof
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The invention provides an intermediate of temsirolimus. The intermediate has better selectivity and higher yield when used for preparation of the temsirolimus. The intermediate provided by the invention has a structural formula which is described in the specification.
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Paragraph 0051-0053; 0055; 0059; 0060; 0062; 0063; 0067
(2019/01/06)
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- Preparation method for temsirolimus
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The invention provides a preparation method for temsirolimus. The preparation method comprises the following steps: step 1, dissolving 2,2,5-trimethyl-1,3-dioxane-5-carboxylic acid in a solvent underan alkaline condition, dropwise adding a solution of 2,4,6-trichlorobenzoyl chloride under stirring at a normal temperature, after a reaction is completed, carrying out cooling, adding a rapamycin double-protection compound, then dropwise adding an alkaline solution, and carrying out a reaction so as to obtain a coupled intermediate; and step 2, dissolving the coupled intermediate into a solvent,carrying out cooling, dropwise adding an inorganic acid solution, and carrying out deprotection so as to obtain the temsirolimus. The preparation method provided by the invention has the advantages ofsimple process, easy operation, high reaction yield, few by-products and applicability to industrial production.
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Page/Page column 8-12
(2019/01/08)
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- Synthesis process for temsirolimus
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The invention discloses a synthesis process for temsirolimus. The synthesis process comprises the following steps: step 1, preparing 2,2,5-trimethyl-5-carboxyl-1, 3-dioxane; step 2, preparing anhydride; step 3, carrying out esterification reaction; step 4, carrying out hydrolysis reaction and finally obtaining the target product, temsirolimus. According to the synthesis process disclosed by the invention, in the reaction of the step 2, DIPEA (diisopropanolamine) is selected as alkali and methylene chloride is selected as a solvent so that anhydride reaction liquid can be directly used in the reaction in the step 3, and technological operation is reduced; the selectivity of the direct esterification reaction is achieved by lowering the temperature and controlling the usage amount of DMAP (dimethylaminopyridine) and the usage amount of anhydride, and the by-products of 31-esterification are reduced; the esterification selectivity is improved greatly, and the reaction route is simplified; and by selecting an ethylene glycol, para-toluenesulfonic acid and tetrahydrofuran deprotection system, the reaction time is reduced greatly, and the yield is improved.
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Paragraph 0009; 0010
(2016/12/26)
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- PROCESS FOR THE PREPARATION OF RAPAMYCIN DERIVATIVES
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The invention relates to processes for the preparation of compound of CCI-779 having the Formula (I), which is useful as an antineoplastic agent. The invention further relates to certain novel intermediates useful in the preparation of compound of CCI-779 and processes for their preparation. The invention also relates to pharmaceutical compositions that include the compound of CCI-779, prepared according to the processes disclosed herein.
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- 39-DESMETHOXY-39-METHYL DERIVATIVES OF RAPAMYCIN.
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The present invention relates to novel 39-desmethoxy-39- methylrapamycin derivatives, methods for their production, and uses thereof. In a further aspect the present invention provides for the use of these 39-desmethoxy- 39-methylrapamycin derivatives in the treatment of cancer and/or B-cell malignancies, the induction or maintenance of immunosuppression, the treatment of transplantation rejection, graft vs. host disease, autoimmune disorders, diseases of inflammation, vascular disease and fibrotic diseases, the stimulation of neuronal regeneration or the treatment of fungal infections.
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- 39-DESMETHOXY DERIVATIVES OF RAPAMYCIN
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The present invention relates to novel 39-desmethoxyrapamycin derivatives, methods for their production, and uses thereof. In a further aspect the present invention provides for the use of these 39-desmethoxyrapamycin derivatives in the treatment of cancer and / or B-cell malignancies, the induction or maintenance of immunosuppression, the treatment of transplantation rejection, graft vs. host disease, autoimmune disorders, diseases of inflammation, vascular disease and fibrotic diseases, the stimulation of neuronal regeneration or the treatment of fungal infections.
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Page/Page column 35
(2008/06/13)
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