159351-68-5

Upstream product

• 18162-48-6 tert-butyldimethylsilyl chloride 
• 102229-10-7 2-(tert-butyldimethylsilyloxy)ethanol 
• 53123-88-9 sirolimus 
• 159351-69-6 everolimus 
• 75-21-8 oxirane 
• 69739-34-0 t-butyldimethylsiyl triflate 
• 164162-36-1 2-(t-Butyldimethylsilyloxy)ethyl trifluoromethanesulfonate 

Downstream Products

• 159351-69-6 everolimus 

Relevant academic research and scientific papers

Purification method of everolimus

The invention provides a purification method of everolimus. According to the method, derivatization, separation and hydrolysis are carried out on everolimus, the treated everolimus has greatly reducedimpurity rapamycin content, and further by means of one-time preparation of liquid phase for purification, a high purity product with high yield can be obtained, thereby reducing the industrial costof the purification steps. The invention also further provides a preparation method of everolimus. The method has the advantages of high yield and simple operation, and is suitable for industrial production.

RAPAMYCIN ANALOGS AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same.

Preparation method of everolimus

The invention discloses a preparation method of everolimus. The preparation method comprises the following step of performing deprotection reaction on an everolimus intermediate C. The preparation method of everolimus adopts a manner of regioselective protection of rapamycin 28-hydroxyl, so that the selectivity of a 40-hydroxyl alkylation reaction is improved; side reactions are reduced; a total yield of everolimus calculated from rapamycin can reach above 70%; compared with yields reported in available literatures, the yield is greatly increased; a technical operation procedure is simplified;the product quality is ensured; and the preparation method has better industrial application and popularization prospects.

Method used for purifying everolimus intermediate, and method used for preparing everolimus

The invention belongs to the field of pharmacy engineering, and more specifically relates to a method used for purifying an everolimus intermediate, and a method used for preparing everolimus. The method used for purifying the everolimus intermediate comp

PROCESS FOR THE SYNTHESIS OF EVEROLIMUS AND INTERMEDIATES THEREOF

The present invention relates to a novel process for the synthesis of everolimus of formula (I) and intermediates thereof.

METHOD FOR THE SYNTHESIS OF RAPAMYCIN DERIVATIVES

The present invention relates to a method for the production of a rapamycin derivative of formula (I), the method comprising the preparation of a 2-(tri-substituted silyl)oxyethyl triflate by reacting ethylene oxide and a tri-substituted silyl triflate, reaction of the resulting 2-(tri-substituted silyl)oxyethyl triflate with rapamycin in the presence of a molar excess of organic base, and deprotection to obtain the rapamycin derivative of compound (I).

Process for preparing not takes charge of according to Uygur

The invention provides a preparation technology for everolimus. The preparation method comprises the two steps of: 1) reacting sirolimus with 2-(tert-butyldiMethylsilyloxy) ethyl trifluoromethane sulfonate in the presence of proper solvent and organic base, to obtain an intermediate A; 2) reacting the intermediate A with inorganic acid in an organic solvent to obtain everolimus, wherein the organic base used in the step 1) is selected from large-steric hindrance or non-nucleophilic bases such as triethylamine, N,N-diisopropylethylamine, 1,8-diazabicycloundec-7-ene or N-methylmorpholine, acid used in the step 2) is hydrochloric acid, sulfuric acid or phosphoric acid. According to the technology, the total yield in the two steps and the purity of a final product are greatly improved as compared with those reported by the existing literature, the process route is short, the reaction conditions are mild, and the reaction result is also stable and reliable.

ALKYLATION WITH AN ALKYL FLUOROALKYL SULFONATE

The present invention discloses a process for preparing a chemical compound comprising reacting a nucleophile with an alkyl fluoroalkyi sulfonate in the presence of a base of formula NR1 R2R3, wherein R1 and R2 are independently 2-methylpropyl or isopropyl and R3 is - CH(R4)(R5), wherein R4 and R5 are identical or different alkyls that are optionally connected to form a ring. The invention also relates to a process for preparing an alkyl fluoroalkyi sulfonate. The invention further relates to a use of the base in a chemical reaction comprising an alkyl fluoroalkyi sulfonate. The process and uses are suitable for preparing chemical compounds, reactants or intermediates thereof, and in particular for preparing API or reactants, like for example everolimus or reactants for its preparation.

PROCESS FOR MAKING EVEROLIMUS

An improved process of making the compound everolimus is disclosed. The process is based on a reaction of rapamycin with 2-(t-hexyldimethylsilyloxy)ethyl triflate of formula (3C) in an inert solvent in the presence of a base, to form 40-O-2-(t-hexyldimethylsilyloxy)ethylrapamycin which is deprotected by an acid to form everolimus.