- METHODS FOR IMPROVING PURITY OF TENOFOVIR DISOPROXIL FUMARATE, AND COMPOSITIONS THEREOF
-
Methods for producing tenofovir disoproxil fumarate with improved purity are provided. In particular, methods for producing tenofovir disoproxil fumarate with reduced levels of chloromethyl isopropyl carbonate are described. Also described are compositions containing tenofovir disoproxil fumarate with improved purity, and an analysis method that can be used to determine the purity of such compositions with improved accuracy and sensitivity.
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Paragraph 0189; 0197; 0199; 0201; 0203; 0205;0207
(2020/07/16)
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- Method for preparing tenofovir disoproxil
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The invention provides a novel method for preparing tenofovir disoproxil fumarate by a solvent-free method. The method comprises the following steps: adding an acid-binding agent and tetrabutylammonium bromide into excessive POC (chloromethyl isopropyl carbonate); adding PMPA (tenofovir) at room temperature; after material charge is completed, raising the temperature to 40-70 DEG C and performinga reaction for 2-5 hours; after the reaction is completed, transferring the reaction system into ice water for water precipitation; separating out a material; performing filtering to obtain a tenofovir disoproxil crude product; standing a water layer for layering; separating out POC; performing washing with water; performing rectifying and recycling for later use; dissolving the tenofovir disoproxil crude product with dichloromethane; performing dehydrating, concentrating and drying; adding isopropanol for dissolving; and adding fumaric acid for salifying to obtain tenofovir disoproxil. The method provided by the invention has the advantages of high conversion rate, high yield, recoverable POC, less wastewater and the like, is suitable for industrial production, and has great application value.
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Paragraph 0024-0028
(2020/01/03)
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- A method for preparing for [...] (by machine translation)
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The invention relates to a method for preparing for [...]. Specifically, the invention relates to an industrial production level of preparation for fuwei two pyrrole fufu ester of the method, the method can improve the reaction yield, reducing the impurity, is simple and easy to control, is conducive to industrial expansion of production. (by machine translation)
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Paragraph 0039-0041; 0058-0061
(2019/03/28)
-
- Preparation method of tenofovir disoproxil fumarate
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The invention belongs to the technical field of medicines and particularly relates to a preparation method of tenofovir disoproxil fumarate. The preparation method of tenofovir disoproxil fumarate comprises the following steps: taking tenofovir and chloromethyl isopropyl carbonate (CMIC) as raw materials, and carrying out a reaction in the presence of a solvent and a catalyst; filtering the mixedsolution after the reaction, and carrying out washing, extracting, concentrating, and crystallizing to obtain a tenofovir disoproxil wet product; and adding the obtained tenofovir disoproxil wet product and fumaric acid into a solvent, carrying out a reaction after dissolution, and then carrying out filtering, crystallizing and drying to obtain the tenofovir disoproxil fumarate. The preparation method provided by the invention has the advantages of high yield and low cost; the crystal form of the product prepared by the process is good; 99.8% of the product can pass through a 65-mesh screen; solid-liquid separation is easily realized; a residual solvent can easily reach the standard; the product has fluidity; the bulk density is 0.4g/ml or above; and the absorption of oral solid preparations is facilitated.
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Paragraph 0006; 0019; 0047-0071
(2018/08/28)
-
- Preparation method of high-purity tenofovir disoproxil fumarate
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The invention discloses a preparation method of high-purity tenofovir disoproxil fumarate. The preparation method comprises: (1) performing esterification reaction on tenofovir and chloromethyl isopropyl carbonate in a certain molar ratio in a N-methylpyrrolidone solvent under the catalyzing action of triethylamine and tetrabutylammonium bromide to obtain an esterification reaction solution; (2) adding esterification reaction solution into mixed crystallization liquid in a certain ratio, stirring at low temperature to achieve crystallization, filtering, and drying filter cakes to obtain high-purity tenofovirester, wherein the mixed crystallization liquid is a mixture of a water-insoluble solvent and icewater; and (3) dissolving the high-purity tenofovirester, and salifying to obtain tenofovir disoproxil fumarate. In the preparation method, the esterification reaction conversion rate is high, the quantity of by-products is small, the post-processing operation is easy, multiple extraction is avoided, the direct crystallization is adopted to obtain the high-purity tenofovir disoproxil fumarate, and finally the tenofovir disoproxil fumarate with the purity of more than or equal to 99.5% is obtained by salifying. The preparation method is low in cost, high in yield, economical, feasible, and suitable for industrial production.
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Paragraph 0020
(2018/12/02)
-
- Preparation method of tenofovir disoproxil fumarate
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The invention provides a preparation method of tenofovir disoproxil fumarate. The preparation method comprises the following steps: performing an etherification reaction, performing a hydrolysis reaction, performing a condensation reaction, and performing refining and performing a salt forming reaction to obtain the tenofovir disoproxil fumarate. According to the method provided by the invention,the tenofovir disoproxil fumarate prepared by the method has a high yield, and is easy to purify and suitable for industrialized mass production.
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Paragraph 7-21
(2018/10/11)
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- Synthesis Method For Improved Tenofovir Disoproxil Fumarate Using Ion-Exchange Resin And Method For Preparing Oral Dissolving Film Form Using The Same
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The present invention relates to a synthesis method of preventing the formation of impurities and byproducts in the synthesis of tenofovir disoproxil fumarate (Teno-DF) used as a medicine for hepatitis B and HIV treatment due to its function to promote bioactivities. In the synthesis method of the present invention, an ion-exchange resin (Dowex 50W hydrogen form, sulfonic acidic cation exchange resin) is used to enhance the yield and purity of the compound. The present invention also relates to a method of preparing an oral dissolving film dosage form in the manufacture of a medicine using the tenofovir compound with high purity obtained by the synthesis method of the present invention as an effective ingredient.
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Paragraph 0129-0132
(2018/01/14)
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- Method for synthesizing high-purity Tenofovir disoproxil fumarate
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The invention discloses a method for synthesizing high-purity Tenofovir disoproxil fumarate. The method comprises the following steps: (1) carrying out a dual-esterification reaction; (2) carrying out extractive separation; (3) carrying out a salt forming reaction; (4) preparing crude Tenofovir disoproxil fumarate; (5) carrying out recrystallization. According to the method for synthesizing the high-purity Tenofovir disoproxil fumarate, disclosed by the invention, the processing steps are simple, the reaction conditions are mild, the yield is relatively high, and the obtained product is relatively high in purity, is adaptable to industrial production and application and has a broad market prospect.
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Paragraph 0018
(2018/03/01)
-
- Efficient preparation method of Tenofovir
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The present invention relates to an effective manufacturing method for tenofovir. According to the present invention, (R)-9-[2-(hydroxy)propyl] adenine (HPA) and diethyl p-toluene sulfonyl oxymethylphosphonate (DESMP) are reacted with each other by a magnesium catalyst, and the (R)-9-[2-(hydroxy)propyl] adenine (HPA) is synthesized. The synthesized (R)-9-[2-(hydroxy)propyl] adenine (HPA) is dealkylated. Therefore, the affective manufacturing method for tenofovir can manufacture the tenofovir (PMPA) of high yield and high purity.COPYRIGHT KIPO 2017
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Paragraph 0146; 0147; 0152-0156
(2017/07/14)
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- Preparation method for tenofovir disoproxil fumarate (TDF)
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The invention provides a novel preparation method for tenofovir disoproxil fumarate (TDF). The TDF is obtained by conducting esterifying and salifying refining on TDF-SM which is used as a raw material. The preparation method for the TDF has the characteristics that the reaction condition is mild, production cost is low, quality is good, and industrialized production is convenient.
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Paragraph 0015; 0019; 0023; 0027
(2017/06/02)
-
- PREPARATION METHOD FOR (R)-9-[2-(PHOSPHONOMETHOXY)PROPYL]ADENINE WITH HIGH PURITY
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The present invention relates to a method for preparing (R)-9-[2-(phosphonomethoxy)propyl]adenine (PMPA) with high purity. The method includes easy processing steps and uses, as an intermediate, (diethoxyphosphoryl)methyl naphthalen-2-sulfonate or (diethoxyphosphoryl)methyl naphthalen-2-sulfonate generating little impurities to provide high purity. Thus, it is possible to obtain PMPA with high purity. Particularly, (diethoxyphosphoryl) methyl naphthalen-1-sulfonate is a solid material, is handled with ease during the use for preparation of PMPA, is suitable for mass production, allows production with uniform and constant quality, and thus can be introduced in a precise equivalent amount during the reaction. In addition, the method uses no reagent sensitive to contact with moisture and air, and thus is safe, shows high reproducibility, and is suitable for mass production. Further, PMPA obtained by the method according to the present invention has significantly high purity. Thus, when such PMPA is used, it is possible to obtain tenofovir disoproxil and acid addition salts thereof with high purity, thereby facilitating production of high-quality material medicine.COPYRIGHT KIPO 2016
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Paragraph 0121; 0122; 0123; 0124
(2016/10/17)
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- A fast dissolving film-formulation for oral dosage of tenofovir disoproxil fumarate and the manufacturing method thereof
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The present invention relates to an oral dissolving film dosage form using tenofovir disoproxil fumarate (Teno-DF), which is used as a therapeutic agent for hepatitis B or AIDS due to physiological activity promoting function thereof, and to a preparing method therefor. The method for preparing tenofovir disoproxil fumarate of the present invention can increase the yield and purity in the synthesis of the compound by using an ion exchange resin (Dowex 50W hydrogen form, sulfonic acidic cation exchange resin), and furthermore, unlike a dosage form obtained by coating a film on a tablet as the conventional art, the oral dissolving film dosage form provided in the present invention is convenient for a patient to take.
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Paragraph 0113; 0114; 0115; 0116; 0118; 0119
(2017/05/12)
-
- For [...] a method for preparing and its fumarate (by machine translation)
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For [...] a method for preparing and its fumarate, which belongs to the field of preparation of compound, the method comprising the following steps: tynofovir anhydrous or tynofovir hydrate with methyl isopropyl carbonate reaction occur condensation reaction, the condensation reaction from the reaction solution obtained is poured into the supersaturated salt solution, mixing, filtration, washing, drying, obtain crude [...] ; crude [...] will be to add a certain amount of low boiling point non-polar organic solvent, heating to reflux temperature for the beating reflux, the gradient temperature after mixing, filtering, with a low boiling point non-polar organic solvent washing, drying, obtain powder [...] ; in the presence of isopropanol, powdery [...][...] with fumaric acid reaction. The method comprises after treatment is simple, high yield, high purity of the obtained product, low impurity content, and the like. (by machine translation)
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Paragraph 0052-0053; 0062-0063; 0067-0068; 0072-0073
(2017/10/27)
-
- Method for the preparation of high purity Tenofovir Disoproxil Fumarate
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The present invention relates to a preparation method of tenofovir disoproxil fumarate and, more particularly, to a preparation method of tenofovir disoproxil fumarate having less than 0.04% of tenofovir mono-isoproxil fumarate by making a reaction between tenofovir disoproxil and fumaric acid in presence of water or a mixed solvent of water and an organic solvent. Different from the conventional method of forming salt in an organic solvent, the preparation method of the present invention forms salt in an aqueous solution, and thus is remarkably environment-friendly. In addition, the preparation method in the present invention can manufacture tenofovir disoproxil fumarate which hardly has a residual solvent, and thus is very useful for industrial purposes.COPYRIGHT KIPO 2016
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Paragraph 0052; 0053
(2017/03/17)
-
- Synthetic method of tenofovir disoproxil fumarate
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The invention provides a synthetic method of tenofovir disoproxil fumarate. The method has the advantages of mild reaction conditions, low production cost, high yield and good quality of the product, and convenience for industrial production.
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Paragraph 0020
(2016/10/10)
-
- New method for synthesizing tenofovir disoproxil fumarate
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The invention provides a new method for synthesizing tenofovir disoproxil fumarate. The reaction conditions are mild, the production cost is low, the product yield is high, the quality is high, and the method is convenient for industrial production.
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Paragraph 0019; 0021
(2016/10/27)
-
- Preparation method for tenofovir disoproxil fumarate
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The invention provides a preparation method for tenofovir disoproxil fumarate. The reaction conditions are mild, the production cost is low, the product yield is high, the quality is high, and the preparation method is convenient for industrial production.
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Paragraph 0018; 0020
(2016/10/27)
-
- Method for synthesizing tenofovir disoproxil fumarate
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The invention provides a method for synthesizing tenofovir disoproxil fumarate and belongs to the technical field of synthesis of organic compounds. According to the method, tenofovir is taken as a starting material and subjected to esterification and salt formation refining, and tenofovir disoproxil fumarate is prepared. The method for synthesizing tenofovir disoproxil fumarate has the advantages of mild reaction conditions, low production cost, high product yield and good quality and facilitates industrial production.
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Paragraph 0018; 0020
(2016/11/07)
-
- New method for preparing tenofovir disoproxil fumarate
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The invention provides a new method for preparing tenofovir disoproxil fumarate. Reaction conditions are mild, production cost is low, product yield is high, quality is good, and industrial production can be conveniently realized.
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Paragraph 0020
(2016/11/09)
-
- Method for preparing tenofovir disoproxil fumarate through two-step method
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The invention provides a method for preparing tenofovir disoproxil fumarate through a two-step method. The reaction conditions are mild, the production cost is low, the product yield is high, the quality is good, and the method is convenient for industrial production.
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Paragraph 0018; 0020
(2016/11/17)
-
- Method for synthesizing tenofovir fumarate by two-step process
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The invention provides a method for synthesizing tenofovir fumarate by a two-step process, belonging to the technical field of organic compound synthesis. By using tenofovir as an initial raw material, esterification and salification refinement are performed to obtain the tenofovir fumarate. The method provided by the invention has the advantages of mild reaction conditions, low production cost, high product yield and good quality, and is convenient for industrial production.
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Paragraph 0016; 0020
(2016/12/01)
-
- A process for the preparation of antiviral drugs
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The invention discloses a preparation method of anantiviral medicine tenofovirdisoproxil fumarate. The preparation method disclosed by the invention comprises the following steps of: performing addition reaction on adenine serving as raw material and (R)-epoxypropane in the presence of alkali; then, performing substitution reaction with (diethyoxyl phosphoracyl) methyl-4-methyl benzenesulfonate; then, hydrolyzing by using a hydrobromic acid solution; crystallizing to obtain tenofovir monohydrate; and reacting the product tenofovir monohydrate with chloromethyl isopropyl carbonate and fumaric acid to obtain tenofovirdisoproxil fumarate. The selected initial raw material is low in cost and easily available, and the synthetic line is simplified and the utilization ratio of the raw material and the total yield are improved. The intermediate obtained in the reaction is purified by the recrystallization method, so that the yield is high, less three-wastes are generated in the reaction process, and the cost is low; therefore, the preparation method is favorable for industrial production.
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Paragraph 0062; 0063
(2017/02/09)
-
- Method for synthesizing tenofovir disoproxil fumarate conveniently
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The invention provides a method for synthesizing tenofovir disoproxil fumarate conveniently and belongs to the technical field of synthesis of organic compounds. Tenofovir is taken as a starting material and subjected to esterification and salifying refining, and the tenofovir disoproxil fumarate is obtained. The method for synthesizing the tenofovir disoproxil fumarate conveniently has the advantages of mild reaction conditions, low production cost, high product yield, good quality and facilitation of industrial production.
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Paragraph 0028; 0020
(2016/10/31)
-
- Method for preparing tenofovir disoproxil fumarate
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The invention provides a method for preparing tenofovir disoproxil fumarate, and belongs to the technical field of organic compound synthesis. According to the method, tenofovir is taken as a starting material, and tenofovir disoproxil fumarate is obtained through esterification, salt formation and refining. The method provided by the invention is mild in reaction condition, low in production cost, and high in product yield and quality, and facilitates industrialized production.
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Paragraph 0018; 0020
(2016/11/14)
-
- A [...] can be industrialized mass production method for the preparation of (by machine translation)
-
The invention relates to a can be industrialized mass production method for preparing [...], comprising the following steps : (R) - 9 - [2 - (b b oxygen phosphine acid radical methoxy ) propyl] adenine preparation, tenofovir synthetic, refining and dewatering, and [...][...] for the synthesis. The technical scheme of the invention the operation is simple, the selected reagent are relatively cheaper, less side reaction, high yield, less wastes of generated during the reaction process, the protection of the environment, and is suitable for industrial mass production. (by machine translation)
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Paragraph 0015
(2016/12/07)
-
- A method for preparing [...]
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The invention discloses a preparation method of tenofovir disoproxil fumarate, belonging to the technical field of synthesis of tenofovir disoproxil fumarate. The preparation method comprises the following steps: preparing tenofovir disoproxil, preparing a tenofovir disoproxil fumarate crude product and refining the tenofovir disoproxil fumarate, wherein in the step of refining the tenofovir disoproxil fumarate, by virtue of a 65% ethanol solution which is used as a tenofovir disoproxil fumarate recrystallizing solvent, the tenofovir disoproxil fumarate is kept in an environment at 5-10 DEG C for 3-6h until the tenofovir disoproxil fumarate is naturally separated out and crystallized. The preparation method disclosed by the invention can be used for solving the problems of high contents of organic residue and side reactant in the process of preparing the tenofovir disoproxil fumarate, and the total yield can reach more than 40%; in addition, the tenofovir disoproxil fumarate occupies a high content in a final product, and the preparation method is simple and convenient to operate in the recrystallizing process, low in cost, and free from toxic and harmful side reactions or products.
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Paragraph 0040-0044
(2017/04/03)
-
- Improved Method for Preparing (R)-9-[2-(phosphonomethoxy)propyl]adenine
-
The present invention relates to a method for preparing high purity (R)-9-[2-(phosphonomethoxy)propyl]adenine (PMPA), According to the present invention, the method uses dialkyl methylsulfonyl-oxymethyl phosphonate, which generates only a small amount of impurities in a reaction and has high purity, as an intermediate to prepare the high purity PMPA with a small amount of impurities. The present invention does not use a reagent sensitive to air and moisture contact to enhance safety and allow reproducible production and is easily handled to enable mass production. The high purity PMPA prepared by using the method can be used to prepare tenofovir disoproxil and acidic salt thereof in order to give a very favorable advantage for the production of high quality drug ingredient.COPYRIGHT KIPO 2016
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Paragraph 0083; 0084
(2021/06/15)
-
- NUCLEOTIDE ANALOGS
-
PROBLEM TO BE SOLVED: To provide, e.g., intermediates for phosphonomethoxy nucleotide analogs, in particular, intermediates suitable for use in efficient oral delivery of such analogs. SOLUTION: Novel compounds are provided that comprise esters of antiviral phosphonomethoxy nucleotide analogs with carbonates and/or carbamates having the structure -OC(R2)2OC(O)X(R)a, The compounds are useful as intermediates for the preparation of antiviral compounds or oligonucleotides, or are useful for administration directly to patients for antiviral therapy or prophylaxis (R2 is as described in the specifications ). COPYRIGHT: (C)2015,JPOandINPIT
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Paragraph 0166; 0167; 0181
(2018/11/22)
-
- NOVEL TENOFOVIR DISOPROXIL OROTATE AND METHOD FOR PREPARING SAME
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The present invention relates to a tenofovir disoproxil orotate which is a novel salt, a manufacturing method thereof, a pharmaceutical composition including the tenofovir disoproxil orotate as an active ingredient for treating hepatitis B disease or acquired immunodeficiency syndrome (AIDS) wherein the tenofovir disoproxil orotate has an outstanding heat stability and is obtained with high purity when manufactured. In addition, patients with hepatitis B disease or AIDS can take the tenofovir disoproxil orotate safely for a long time because the purity of the tenofovir disoproxil orotate rather increases, in other word, each content of dimer impurities and s-isomer impurities maintains 0.1% at most, even though the tenofovir disoproxil orotate is exposed to high temperature for a long time when turned into formulation, delivered, or stored.COPYRIGHT KIPO 2015
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Paragraph 0056; 0057
(2016/12/07)
-
- AN IMPROVED PROCESS FOR THE PREPARATION OF TENOFOVIR DISOPROXIL AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
-
An improved process for the preparation of Tenofovir disoproxil and pharmaceutically acceptable salts thereof, comprising following steps: a) alkylation of adenine with (R)-4-methyl-1,3-dioxolan-2-one and isolation of (R)-1-(6-amino-9H-purin-9-yI)propan-2-ol; b) alkylation of (R)-1-(6-amino-9H-purin-9-yl) propan-2-ol with a dialkyl p-toluenesulphonyloxymethylphosphonate or dialkyl halomethylphosphonate to give dialkylester of (R)-9-[2-(phosphonomethoxy)propyl]adenine; c) preparation of (R)-9-[2-(phosphonomethoxy)propyl]adenine ((R)-PMPA; Tenofovir) by dealkylation of the phosphonate moiety with a mineral acid under microwave irradiation; d) preparation of Tenofovir disoproxil; e) preparation of the fumarate salt or other pharmaceutically acceptable salt of Tenofovir disoproxil.
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Page/Page column 6; 24
(2015/04/28)
-
- PROCESS FOR THE PREPARATION OF TENOFOVIR
-
The present invention provides a process for preparation of tenofovir by dealkylation of its phosphonate ester using Ionic complexes. The present invention also provides a process for preparation of tenofovir disoproxil or a salt thereof using the tenofovir of the present invention.
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Paragraph 0092; 0093; 0094; 0095; 0096
(2014/10/16)
-
- PROCESS FOR THE PREPARATION OF TENOFOVIR DISOPROXIL FUMARATE
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The present invention relates to an improved process for the preparation of Tenofovir Disoproxil and its pharmaceutically acceptable salts comprising the steps of: a) esterifying Tenofovir with chloromethyl isopropyl carbonate in presence of a base, phase transfer catalyst and optionally dehydrating agent, in a suitable solvent; b) optionally purifying Tenofovir Disoproxil; and c) converting of Tenofovir Disoproxil into its pharmaceutically acceptable salts. The present invention further relates to a process for the preparation of Tenofovir by reacting 1-(6-amino-purin-9-yl)-propan-2-ol with toluene-4-sulfonic acid diethoxy phosphoryl methyl ester in presence of a base in a non-polar solvent medium followed by hydrolysis.
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Page/Page column 4
(2013/02/28)
-
- PROCESS FOR THE PREPARATION OF TENOFOVIR
-
The present invention provides a process for preparation of tenofovir by dealkylation of its phosphonate ester using Ionic complexes. The present invention also provides a process for preparation of tenofovir disoproxil or a salt thereof using the tenofovir of the present invention.
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Page/Page column 15; 16
(2013/06/05)
-
- PROCESS FOR THE PREPARATION OF TENOFOVIR
-
The present invention provides a process for the preparation of tenofovir. The present invention also provides a process for the preparation of tenofovir disoproxil or a salt thereof and its pharmaceutical composition using the tenofovir of the present invention.
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Paragraph 0126; 0127; 0128; 0129; 0130; 0131; 0132
(2013/07/05)
-
- Process for the preparation of tenofovir
-
The present invention provides a process for the preparation of tenofovir. The present invention also provides a process for the preparation of tenofovir disoproxil or a salt thereof and a pharmaceutical composition containing the tenofovir of the present invention.
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Page/Page column 13-14
(2012/06/18)
-
- PROCESS FOR THE PREPARATION OF TENOFOVIR
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The present invention provides a process for the preparation of tenofovir. The present invention also provides a process for the preparation of tenofovir disoproxil or a salt thereof and its pharmaceutical composition using the tenofovir of the present invention.
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Page/Page column 19-20
(2012/06/30)
-
- AN IMPROVED PROCESS FOR THE PREPARATION OF TENOFOVIR DISOPROXIL FUMARATE
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The present invention relates to an improved process for the preparation of Tenofovir Disoproxil and its pharmaceutically acceptable salts comprising the steps of: a) esterifying Tenofovir with chloromethyl isopropyl carbonate in presence of a base, phase transfer catalyst and optionally dehydrating agent, in a suitable solvent; b) optionally purifying Tenofovir Disoproxil; and c) converting of Tenofovir Disoproxil into its pharmaceutically acceptable salts. The present invention further relates to a process for the preparation of Tenofovir by reacting l-(6-amino-purin-9-yl)-propan- 2-ol with toluene-4-sulfonic acid diethoxy phosphoryl methyl ester in presence of a base in a non-polar solvent medium followed by hydrolysis.
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-
-
- Process improvements for the manufacture of tenofovir disoproxil fumarate at commercial scale
-
The three-step manufacturing process used in the synthesis of tenofovir disoproxil fumarate (1) was studied and optimized, leading to a more productive and robust process. The yield was improved from about 13% overall to 24%. Key process improvements identified included implementation of a telescoped process for the second stage that obviated the need for an extraction and solvent exchange, and significant optimization of the final reaction, including the beneficial effect of adding a quaternary ammonium salt to the alkylation reaction and development of a nonaqueous process for removal of NMP and triethylamine from the product mixture to decrease the level of decomposition of product during the isolation.
- Ripin, David H. Brown,Teager, David S.,Fortunak, Joseph,Basha, Shaik Mahaboob,Bivins, Nylea,Boddy, Christopher N.,Byrn, Stephen,Catlin, Kelly K.,Houghton, Stephen R.,Jagadeesh, S. Tirumala,Kumar, K. Anesh,Melton, Jack,Muneer, Shaik,Rao, L. Nagaprasada,Rao, R. Venkateswara,Ray, Puma Chandra,Reddy, Nardla Gopal,Reddy, Ravi Mallikarjuna,Shekar, K. Chandra,Silverton, Tricia,Smith, Daniel T.,Stringham, Rodger W.,Subbaraju, Gottumukkala V.,Talley, Frajovon,Williams, Adrian
-
experimental part
p. 1194 - 1201
(2011/04/26)
-
- CRYSTALLINE FORM OF TENOFOVIR DISOPROXIL AND A PROCESS FOR ITS PREPARATION
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Crystalline Form C of tenofovir disoproxil, salts thereof and a process for its preparation. The process involves adding a solution comprising tenofovir disoproxil and an organic solvent to salt-saturated water, whereby the crystalline Form C of tenofovir disoproxil precipitates. The crystalline Form C of tenofovir disoproxil may be converted to a salt thereof. There is also provided a process for purifying a crude product comprising tenofovir monoisoproxil and tenofovir disoproxil.
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Page/Page column 12
(2009/12/05)
-
- NOVEL PROCESS FOR ACYCLIC PHOSPHONATE NUCLEOTIDE ANALOGS
-
The present invention provides a novel process for the preparation of acyclic phosphonate nucleotide analogs using novel intermediates. Thus, for example, (R)-9-(2-phosphonomethoxypropyl)adenine is reacted with dimethylformamide dimethylacetal to give N4-dimethylaminomethyledino-9-(2-phosphonomethoxy ethyl) adenine, which is then reacted with chloromethyl-2-propyl carbonate in presence of triethylamine to give (R)—N4-Dimethylaminomethyledino-9-(2-phosphono methoxypropyl) adenine disoproxil, followed by deprotection with acetic acid to get tenofovir disoproxil. Tenofovir disoproxil is then treated with fumaric acid to give tenofovir disoproxil fumarate.
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Page/Page column 4
(2009/01/24)
-
- NOVEL PROCESS FOR ACYCLIC PHOSPHONATE NUCLEOTIDE ANALOGS
-
The present invention provides a novel process for the preparation of acyclic phosphonate nucleotide analogs using novel intermediates. Thus, for example, (R)-9-(2-phosphonomethoxypropyl)adenine is reacted with dimethylformamide dimethylacetal to give N4-dimethylaminomethyledino-9-(2-phosphonomethoxy ethyl) adenine, which is then reacted with chloromethyl-2-propyl carbonate in presence of triethylamine to give (R)-N4-Dimethylaminomethyledino-9-(2-phosphono methoxypropyl) adenine disoproxil, followed by deprotection with acetic acid to get tenofovir disoproxil. Tenofovir disoproxil is then treated with fumaric acid to give tenofovir disoproxil fumarate.
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Page/Page column 9-10
(2008/06/13)
-
- Nucleotide analog composition and synthesis method
-
The invention relates to a composition comprising a solution of 9-[2-(phosphono-methoxy)propyl]adenine (PMPA) at a pH of about 2.7 ― 3.5 wherein the solution has less than about 0.1 g/ml (R, S)-PMPA and wherein about 90 ― 94 % of the PMPA is in the (R) configuration.
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