35 results about "5-azacytosine" patented technology

A process of synthesizing a 5-azacytosine nucleoside, such as azacitidine and decitabine, comprises coupling a silylated 5-azacytosine with a protected D-ribofuranose of formula in the presence of a sulfonic acid catalyst.

The invention discloses a method for preparing improved decitabine (formula I), comprising: using 1-alpha-chlorine-3,5-two pairs of halo-benzoyl-2-deoxidation-D-ribose (formula II) as materials, concentrating with 2-4-bi-(trimethyl silicane)-5-azacytosine (formula III) to obtain I by de-protecting group. Materials used in the invention are easy to obtain at a low price. The invention also has the advantages of convenient operation and a high reaction yield, and is suitable for industrialized production.

The invention provides an industrialized production method for high-purity decitabine. The method comprises the following steps of: 1, performing silanization reaction of 5-azacytosine, bis(trimethylsilyl)amine and trimethyl chlorosilane, which serve as raw materials, to prepare 2,4-bis(trimethylsilyl)-5-azacytosine; 2, performing reaction of the product obtained by the step 1 and 1-chloro-3,5-bis-(4-chlorobenzoyl)-2-deoxy-D-ribofuranose, which serve as raw materials, to prepare a crude product of 1-(3,5-bis-(4-chlorobenzoyl)-2-deoxy-beta-D-ribofuranose)-5-azacytosine; 3, dissolving the product obtained by the step 2 in a C5 to C7 hydrocarbon, stirring, filtering and drying to obtain a refined product; and 4, producing the high-purity decitabine by using the product obtained by the step 3, methyl alcohol and sodium methoxide as raw materials. The method overcomes the disadvantages of need of column purification, low purity, difficult industrial production in the prior art, and has the advantages of simple and convenient operation, small solvent consumption, small influence on the environment, low labor intensity, short period, high product purity, single impurity and less than 0.1 percent total impurity content.

The invention relates to the field of pharmaceutical synthesis process and discloses a method for synthesizing azacitidine. The method comprises the following steps: performing silanization reaction on bis(trimethyl disilylamine) and 5-azacytosine by taking toluene as solvent under the catalysis of phase transfer catalyst of quaternary ammonium compounds under a moisture-isolated condition to generate a compound with structure of formula II; performing condensation reaction between the compound and ribose tetracetate to generate a compound with a structure of formula IV; and performing alcoholysis on the compound in an alkaline environment to generate the azacitidine. The synthesis method of the invention shortens the time of silanization reaction, reduces the waste amount of the bis(trimethyl disilylamine) and avoids influence of the moisture in methanol and ethanol in the purification stage on the purity of the finished product of azacitidine; moreover, the synthesis method has the advantages of cheap reagents, few reaction steps and mild reaction conditions and is favorable for industrial production.

The invention discloses a preparation method of 2'-deoxycytidine analogue decitabine (formula I) capable of effectively inhibiting growth of tumour cells. The method comprises the steps of using 1-methyl-2-deoxy-D-ribose (formula II) as initial raw material, subjecting the initial raw material and acetic anhydride to a reaction to obtain 1-methyl-3,5-diacetoxyl-2-deoxy-D-ribose (formula III); subjecting the compound of formula III and 2,4-bi-(trimethyl silicon)-5-azacytosine (formula IV) to a reaction to obtain 3',5'-diacetoxylgroup-5-aza-2'-deoxycytidine (formula V); hydrolysing the compound of formula V under the action of D315 macro-porous weakly basic anion exchange resin to obtain the decitabine (formula I). The raw materials of the invention are easily obtained, the reaction conditions are moderate and the operation is simple and convenient. The preparation method is suitable for commercial production.

A method for producing a β-enriched protected decitabine comprising:

• • a) coupling a protected 2-deoxy-ribofuranose with a protected 5-azacytosine in the presence of a catalyst to form a reaction mixture comprising the protected decitabine of formula I; and b) quenching the reaction mixture of step a) with a base. The β-enriched protected decitabine so made may be deprotected to produce a decitabine product in a high yield and purity.

The invention discloses a method for preparing decitabine. The method comprises the following steps of: using 2-deoxy-D-ribose as a raw material; protecting the raw material by a pivaloyl group, and then reacting the raw material with alkylated 5-azacytosine under the action of a proper amount of a catalyst namely trimethylsilyl trifluoromethanesulfonate; performing hydrolysis to prepare a crude product of the decitabine without purification by a chromatography column; and performing recrystallization to prepare pure decitabine under the condition of a proper solvent. The method for preparing the decitabine greatly improves the total yield, greatly reduces the product cost, and is more suitable for large-scale industrial production.

The present invention relates to a method for improving the soybean resistant cluster bud induction efficiency by using 5-azacytidine, and belongs to the technical field of transgene. The main technical scheme is as follows: sterilization, germination, preparation of agrobacterium liquid, soybean cotyledon node infection by agrobacterium, and resistant cluster bud induction. In an agrobacterium-mediated soybean cotyledon node genetic transformation system, the method uses a methylation inhibitor of the 5-azacytidine for the first time for carrying out demethylation treatment on the soybean cotyledon explants which induce resistant cluster buds, improves the induction efficiency of the resistant cluster buds of the soybean cotyledon explants, and may improve the transformation efficiency ofthe T0 generation.

The invention belongs to the field of pharmaceutical synthesis, and specifically relates to a preparation method of azacitidine, wherein the preparation method comprises the following steps: carryingout a reaction of 5-azacytosine with trimethylchlorosilane at the temperature of 70-80 DEG C for 2 h to obtain an azacitidine intermediate I; dissolving the azacitidine intermediate I with dichloromethane, under catalysis of boron trifluoride, carrying out condensation reaction with 1-chloro-2,3,5-tri-O-p-chlorobenzoyl-beta-D-ribose, after completion of the reaction, washing, drying, carrying outsuction filtration and carrying out reduced pressure distillation of the filtrate, to obtain an azacitidine intermediate II represented by the formula IV; and carrying out alcoholysis of the azacitidine intermediate II with ammonia gas, to obtain crude azacitidine, and purifying to obtain high-purity azacitidine. The preparation method has the advantages of mild reaction conditions, short reactiontime and high yield, and is suitable for industrial production.

The invention provides a preparation method of a beta-configuration decitabine precursor. The preparation method comprises the following step: under the action of a Lewis acid catalyst, directly performing a coupling reaction on acylated sugar adopting the structure of 1-alkenylmethoxy-2-deoxy-3, 5-di-O-acetyl-D-ribofuranose and a silicon ether compound of 5-azacytosine to obtain beta-configuration 1-(2-deoxy-3,5-di-O-acetyl-D-ribose)-4-amino-1,3,5-s-triazine-2-one. The beta-configuration decitabine precursor is high in selectivity, good in repeatability and very high in molar yield and purity.

The invention discloses a new synthesis method of 5-aza-cytosine, which includes the steps of: (1) adding dicyandiamide and formate into a sealed reaction device, performing a heating reaction and distilling out non-reacted formate and corresponding alcohol to obtain a white solid; (2) purifying the white solid with hydrochloric acid and ammonia water to obtain the 5-aza-cytosine. In the method, the 5-aza-cytosine is directly synthesized through a reaction on the dicyandiamide and formate in a high-pressure reaction kettle, wherein the formate serves as a reactant, a reaction solvent, and a dehydrator in a ring-closing reaction in the process, so that processes of hydrolysis of the formate, hydration of the dicyandiamide and dehydration of dicyandiamidine formate can be carried out simultaneously under a hydrothermal condition, thus simplifying the synthesis route, avoiding side reactions and increasing purity of product. The total reaction yield is higher than 70% on the basis of dicyandiamide, and product purity is higher than 98%.