343261-52-9

Upstream product

• 1246021-94-2 C₆₅H₁₀₅NO₁₆Si 
• 865860-80-6 2,2,5-trimethyl-[1,3]dioxane-5-carboxylic acid vinyl ester 
• 866026-99-5 3-hydroxy-2-hydroxymethyl-2-methyl-propionic acid vinyl ester 
• 162635-03-2 rapamycin 42-ester with 2,2,5-trimethyl[1,3]dioxane-5-carboxylic acid 

Relevant academic research and scientific papers

Temsirolimus intermediate compound

The invention belongs to the field of pharmaceutical chemicals, and particularly relates to a temsirolimus intermediate compound. The preparation method of the temsirolimus intermediate compound comprises the following steps: inert gas protection, addition of a compound VI and a compound VII into an organic solvent A, addition of organic alkali, temperature control reaction, TLC detection, addition of a solvent B for dilution after the reaction is finished, drying with anhydrous sodium sulfate, and vacuum concentration, thereby obtaining a compound I. The invention provides the novel temsirolimus intermediate compound I. When the compound is used for preparing temsirolimus, generation of by-products can be effectively avoided, and the synthesized intermediate does not generate new impurities; and the reaction is faster, economic and environment-friendly, yield is higher, and the method is suitable for industrial production.

Preparation method of tansemmus

The present invention belongs to the field of pharmaceutical synthesis technology, specifically relates to a method of preparation of tansimos, the present invention preparation of tansimmus method comprising: compound VIII added to the organic solvent A, slowly adding acid, temperature control reaction, TLC detection, reaction completed, adding organic solvent B dilution, adding purified water, extraction, organic layer with anhydrous magnesium sulfate drying, filtration, reduced pressure concentration of the target compound I; provides a new method of synthesizing tansemmus, the entire synthesis method is simple to operate, high reaction yield, The resulting product is of high purity; the new intermediate compound VI provided by the present invention can effectively improve the regional selectivity of the rapamycin esterification reaction due to the large steric block during the reaction, effectively avoiding the generation of 31-esterification and 31,42-diesterification by-products.

Method for separating and purifying temsirolimus

The invention discloses a method for separating and purifying temsirolimus. The method comprises the following steps: (1) synthesis of a crude product; and (2) separation and purification. The specific separation and purification method has the advantages of great improvement of the purity and the yield of temsirolimus, reduction of the cost, and broad market application prospect.

Preparation method for temsirolimus

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.

Intermediate of temsirolimus and preparation method thereof

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.

Method for preparing temsirolimus

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.

PROCESS FOR PREPARING TORISEL

A process for preparing Torisel, which is a derivative of Rapamycin, is provided. The process comprises the following steps: acetalating 2,2-dihydroxymethylpropionic acid with substituted or unsubstituted aromatic aldehyde in the presence of p-toluenesulfonic acid as catalyst to form the intermediate II; reacting the obtained intermediate with 2,4,6-trichlorobenzoyl chloride; then esterifying the obtained chloride with Rapamycin and finally deprotecting the diol to provide the product Torisel with yield over 35.6%. The aromatic aldehyde is one selected from benzaldehyde, p-methoxybenzaldehyde, p-chlorobenzaldehyde and p-trifluoromethyl benzaldehyde.

PROCESS FOR SYNTHESIS OF TORISEL

A process for synthesis of torisel comprises the following steps: firstly, the intermediate compound II is obtained by protecting 2,2-bis(hydroxymethyl) propionic acid with substituted boracic acid, then reacted with acylation reagent 2,4,6-trichlorobenzoyl chloride, and then condensed with rapamycin, last deprotected with diol to obtain torisel. The whole yield is 54.8%.

PROCESS FOR THE PREPARATION OF RAPAMYCIN DERIVATIVES

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.

REGIOSELECTIVE ACYLATION OF RAPAMYCIN AT THE C-42 POSITION

The invention refers to the selective acylation of Rapamycin at the 42-position (I) with an acylating agent of the formula (II) wherein R4 and R5 are the same or different, individually the rest of an acetal, especially tetrahydropyran, or of a carbonate or the rest of a silyl ether or taken together are the rest of a boronate, an acetal or ketal.