CN108929390A - A kind of method that microwave reaction synthesizes the more glucose sodium that relaxes - Google Patents
A kind of method that microwave reaction synthesizes the more glucose sodium that relaxes Download PDFInfo
- Publication number
- CN108929390A CN108929390A CN201710367011.7A CN201710367011A CN108929390A CN 108929390 A CN108929390 A CN 108929390A CN 201710367011 A CN201710367011 A CN 201710367011A CN 108929390 A CN108929390 A CN 108929390A
- Authority
- CN
- China
- Prior art keywords
- relaxes
- sodium
- glucose sodium
- glucose
- synthesizes
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
- C08B37/0012—Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof
Abstract
The invention belongs to pharmaceutical fields, in particular to the method that a kind of microwave reaction synthesizes the more glucose sodium that relaxes, present invention firstly provides the more glucose sodium that relaxes is prepared in Aquo System, using the combination of water or water and organic solvent as reaction dissolvent, all or part of N used instead of conventional method, the organic solvents such as dinethylformamide, it avoids causing recycling difficult using a large amount of high boiling organic solvents, pollution is big, environmental protection disadvantage at high cost, the present invention is under the conditions of microwave radiation, with 3- mercaptopropionic acid, alkali, 6- deoxidation -6- perhalogeno-gamma-cyclodextrin is the easypro more glucose sodium of raw material rapid synthesis；The easypro more glucose sodium crude product that reaction generates only needs simply to recrystallize the easypro more glucose sodium that high-purity once can be obtained；Method provided by the invention, which has, to be swift in response, and impurity generates less, and subsequent purification is simple, the high advantage of product purity；This method has good economy, and energy consumption is greatly reduced, high production efficiency, is suitable for industrialized production.
Description
Technical field
The invention belongs to pharmaceutical field, in particular to a kind of method of the easypro more glucose sodium of microwave reaction synthesis.
Background technique
Relax the more entitled 6A of glucose Sodium chemistry, 6B, 6C, 6D, 6E, 7F, 6G, eight-S- of 6H- (2- carboxyethyl) -6A, 6B, 6C,
Eight thio-y-cvclodextrin of 6D, 6E, 7F, 6G, 6H-, eight sodium salts, structural formula are：
The more glucose sodium that relaxes is a kind of novel muscle relaxant reversal agent researched and developed by Dutch Organon company, clinically conduct
Rocuronium or the effect of vecuronium neuromuscular blockade are reversed, there is good curative effect, and have fabulous safety；From 2008
Year July European Union ratify its listing since, listed in states such as Japan, South Korea, the U.S., and just declare production in China and list.
Report at present both at home and abroad about more glucose sodium preparation process of relaxing is less, and basic purification process is dependent on film dialysis
Or column chromatography is purified, and is obtained that high purity product difficulty is big, is unfavorable for the progress of large-scale industrial production.
J.Med.Chem.2002,45,1806-1816PP propose that in n,N-Dimethylformamide system, triphenyl phosphorus is urged
Under change, bromine reacts to obtain 6- deoxidation -6- perbromo--gamma-cyclodextrin with gamma-cyclodextrin.The product and 3- mercapto-propionate
Under the catalysis of Carbon Dioxide caesium, reaction obtains the easypro more glucose methyl esters of product, then through sodium hydroxide hydrolysis, obtains the more glucose that relaxes
Sodium.Yield 60%.Method obtains the more glucose sodium crude product that relaxes according to this, and purity is lower, does not there is the report being further purified.
J.2011,6,2390, gamma-cyclodextrin iodo -2399 is first obtained 6- deoxidation -6- periodo-γ-by Chem.Asian
Cyclodextrin crude product, the crude product and acetic anhydride are purified by silica gel column chromatography at ester, then sodium methoxide hydrolysis, and it is higher to obtain purity
6- deoxidation -6- periodo-gamma-cyclodextrin highly finished product.Finally target product is obtained at ether in 3- mercaptopropionic acid.Among the reaction
Body purity is high, impurity is few, and the post-processing purifying of product is relatively simple.But iodo cyclodextrin is prepared using column chromatography technique, is increased
Reaction step, takes a long time.And when preparing easypro more glucose sodium as raw material using iodo cyclodextrin made from this method, not
Qualified product can be directly obtained, the purification difficult problem for the more glucose sodium product that relaxes can be still faced.
WO0140316PP uses iodine to react under triphenyl phosphorus catalysis with gamma-cyclodextrin as halide reagent, and it is de- to generate 6-
Oxygen -6- periodo-gamma-cyclodextrin.The intermediate obtains target production again with 3- mercaptopropionic acid at thioether after film dialysis purification
Object.This method route is simple and reliable, and reactivity is higher, but the purifying of product obtains high-purity and relax only with film dialysis purification
The difficulty of more glucose sodium is higher.
CN105348412 discloses a kind of purification process of more glucose sodium crude product that relaxes, by easypro more glucose sodium crude product in acidity
Under the conditions of hydrolyze, obtain free acid solid, the mashing washing purifying of free acid solid water；Free acid is reacted with organic amine again, is made
Standby easypro more glucammonium salts, obtained ammonium salt recrystallization purifying；It is free that free acid, free acid solid water are beaten under acid condition
Plasm scouring purifying, obtained free acid are reacted with sodium hydroxide, prepare the more glucose sodium pure product that relaxes.Column chromatography is not used in this method,
The methods of dialysis, but complex steps, need the multiple conversions between free acid and salt, inconvenient.In addition, due to the more glucose that relaxes
The unstability of self structure, during in acid condition free, self structure has the risk of dissociation, is formed acid broken
Bad impurity increases the difficulty of refined product.
CN106565858 discloses a kind of purification process of more glucose sodium that relaxes, and the more glucose sodium crude product that relaxes is in amberlite
Under the processing of rouge, be converted to relax more sugar lime, through recrystallization purifying, then by ion exchange resin be converted to relax more glucose sodium.The party
The product purity that method obtains is preferable, mild condition.But treatment process is relatively complicated, needs to handle ion exchange resin, increases
The difficulty of industrial applications.
Summary of the invention
In view of the deficiencies of the prior art, the present invention provides a kind of microwave reactions to synthesize the new method for the more glucose sodium that relaxes.
In order to achieve the above object, the technical solution adopted by the present invention is as follows：
A kind of method that microwave reaction synthesizes the more glucose sodium that relaxes：3- mercaptopropionic acid, alkali, 6- deoxidation -6- perhalogeno-γ-ring
Dextrin reacts under microwave radiation in Aquo System, generates the more glucose sodium crude product that relaxes.
Preferably, the reaction carries out under atmosphere of inert gases, and byproduct of reaction is less, and yield is higher, product purity
It is higher.
Preferably, the 6- deoxidation -6- perhalogeno-the ratio between gamma-cyclodextrin and the amount of substance of 3- mercaptopropionic acid is：1:8
~20；6- deoxidation -6- the perhalogeno-the ratio between gamma-cyclodextrin and the amount of substance of alkali be：1:8~32.
Preferably, acid binding agent of the alkali as reaction is neutralized with the halogen acids generated in reaction process, is hydroxide
Any one or more combinations in sodium, sodium carbonate, sodium bicarbonate, sodium acetate and sodium phosphate.
Preferably, the Aquo System is water or water and methanol, ethyl alcohol, tetrahydrofuran, n,N-Dimethylformamide, two
One or more combinations in first sulfoxide, 1,4- dioxane；The N, N- bis- completely or partially used instead of conventional method with water
The organic solvents such as methylformamide avoid causing recycling difficult using a large amount of high boiling organic solvents, and pollution is big, and environmental protection is at high cost
The shortcomings that.
Preferably, under atmosphere of inert gases, the more glucose sodium crude product that relaxes is recrystallized, further increases and relaxes more
The purity of glucose sodium.
Preferably, the solvent of the recrystallization is water, methanol, ethyl alcohol, acetonitrile, acetone, n,N-Dimethylformamide, Isosorbide-5-Nitrae-
The combination of any one or more in dioxane；Recrystallization temperature is 40 DEG C -100 DEG C；Relax more glucose sodium crude product and recrystallization
The mass ratio of solvent is：1:3~15.
Preferably, the inert gas is nitrogen, argon gas, helium, combination any one or more in carbon dioxide.
Compared with the existing technology, advantages of the present invention is as follows,
The method that microwave reaction of the invention synthesizes the more glucose sodium that relaxes, is put forward for the first time in Aquo System and prepares the more glucose that relaxes
Sodium, using the combination of water or water and organic solvent as reaction dissolvent, all or part of N, N- used instead of conventional method
The organic solvents such as dimethylformamide avoid causing recycling difficult using a large amount of high boiling organic solvents, and pollution is big, environmentally friendly cost
High disadvantage, the present invention are original with 3- mercaptopropionic acid, alkali, 6- deoxidation -6- perhalogeno-gamma-cyclodextrin under the conditions of microwave radiation
Expect the easypro more glucose sodium of rapid synthesis；The easypro more glucose sodium crude product that reaction generates, which only needs simply to recrystallize, once can be obtained high-purity
Easypro more glucose sodium；Compared with prior art, method provided by the invention has and is swift in response, and impurity generates few, subsequent purification
Simply, the high advantage of product purity；This method has good economy, and energy consumption is greatly reduced, high production efficiency, is suitable for work
Industry metaplasia produces.
Detailed description of the invention
Fig. 1 is the commercially available more glucose sodium injection HPLC figure that relaxes；
Fig. 2 is the commercially available more glucose sodium injection HPLC integral result figure that relaxes；
Fig. 3 is the more glucose sodium crude product HPLC figure prepared by the present invention that relaxes；
Fig. 4 is the more glucose sodium crude product HPLC integral result figure prepared by the present invention that relaxes；
Fig. 5 is the more glucose sodium highly finished product HPLC figure prepared by the present invention that relaxes；
Fig. 6 is the more glucose sodium highly finished product HPLC integral result figure prepared by the present invention that relaxes.
Specific embodiment
Embodiment 1：
The synthesis of easypro more glucose sodium crude product
Sodium hydroxide (23.5g, 588mmol) is put into reaction flask, it is complete that the dissolution of 150ml water is added；To flask under stirring
6- deoxidation -6- periodo-γ-is added in middle dropwise addition 3- mercaptopropionic acid aqueous solution (39.0g, 368mmol are dissolved in 80ml water)
Cyclodextrin (40g, 18.4mmol), finishes, and is placed in microwave reactor, reacts 30 minutes under 500w microwave radiation；End of reaction,
Be cooled to room temperature, be added with stirring 700mLDMF crystallization, filter, collect solid, be dried in vacuo off-white powder 45g, purity are
98.33% (see attached drawing 3-4).
Embodiment 2：
The purifying of easypro more glucose sodium
Under nitrogen protection, the more glucose sodium crude product 40g that relaxes is taken, is dissolved in 100ml water, in the mixed solution of 600ml ethyl alcohol, stirred
It mixes and is warming up to 40 DEG C, be down to room temperature, there is white solid precipitation, filter, obtain white solid 35g.The solid is detected through HPLC, purity
99.82%, meet the requirement for the more glucose sodium raw materials medicine that relaxes (see attached drawing 5-6).
Embodiment 3：
The synthesis of easypro more glucose sodium crude product
Sodium carbonate (15.9g, 150mmol) is put into reaction flask, 75ml water and 115ml n,N-Dimethylformamide is added；
3- mercaptopropionic acid aqueous solution (19.5g, 184mmol are dissolved in 80ml water) is added dropwise into flask under stirring, 6- deoxidation-is added
6- periodo-gamma-cyclodextrin (40g, 18.4mmol), finishes, and is placed in microwave reactor, and 60 points are reacted under 300w microwave radiation
Clock；End of reaction is cooled to room temperature, is added with stirring 400mLDMF crystallization, and solid is collected in filtering, be dried in vacuo off-white color is solid
Body 40g, purity 98.26%
Embodiment 4：
The purifying of easypro more glucose sodium
Under argon gas protection, the more glucose sodium crude product 40g that relaxes is taken, is dissolved in 40ml water, in the mixed solution of 120mlDMF, stirring
100 DEG C are warming up to, room temperature is down to, there is white solid precipitation, filters, obtains white solid 32g.The solid is detected through HPLC, purity
99.87%, meet the requirement for the more glucose sodium raw materials medicine that relaxes.
Embodiment 5：
The synthesis of easypro more glucose sodium crude product
Under argon gas protection, sodium carbonate (15.9g, 150mmol) is put into reaction flask, 75ml water and 115ml N, N- bis- is added
Methylformamide；3- mercaptopropionic acid aqueous solution (15.6g, 147mmol are dissolved in 80ml water) is added dropwise into flask under stirring,
6- deoxidation -6- perbromo--gamma-cyclodextrin (33g, 18.4mmol) is added, finishes, is placed in microwave reactor, 300w microwave spoke
Penetrate lower reaction 60 minutes；End of reaction is cooled to room temperature, is added with stirring 400mLDMF crystallization, filtering, collects solid, and vacuum is dry
It is dry to obtain off-white powder 46g, purity 98.45%
Embodiment 6：
The purifying of easypro more glucose sodium
Under argon gas protection, the more glucose sodium crude product 40g that relaxes is taken, is dissolved in 40ml water, in the mixed solution of 120mlDMF, stirring
100 DEG C are warming up to, room temperature is down to, there is white solid precipitation, filters, obtains white solid 34g.The solid is detected through HPLC, purity
99.89%, meet the requirement for the more glucose sodium raw materials medicine that relaxes.
In above-described embodiment, it is as follows to be all made of the measurement of HPLC method easypro more glucose sodium content, method：
Sample is taken, is set in 25ml volumetric flask, first plus on a small quantity water shaking makes to dissolve, then solubilizer is diluted to scale, shakes up, and makees
For test solution；Precision measures solution 1ml and sets in 100ml volumetric flask, and solubilizer is diluted to scale, shakes up, as control
Solution.It (is flowing with phosphate buffer using octadecylsilane chemically bonded silica as filler according to chromatographic condition under content determination item
Phase A, acetonitrile are Mobile phase B, carry out linear gradient elution, Detection wavelength 200nm).20 μ l of contrast solution is taken to inject liquid phase color
Spectrometer adjusts detector sensitivity, makes the 10~25% of the peak height full scale of principal component chromatographic peak.It is accurate again to measure test sample
Solution and each 20 μ l of contrast solution, are injected separately into liquid chromatograph, and 3 times of record chromatogram to principal component peak retention time.
It relaxes in more glucose sodium, according to the description of Yuan Yan producer, medicinal active ingredient is 6- eight-(2- carboxy ethyl) sulphur
Generation-gamma-cyclodextrin sodium salt and 6- seven-(2- carboxy ethyl) thio-y-cvclodextrin sodium salt.Therefore, following as described in the examples
Purity is 6- eight-(2- carboxy ethyl) thio-y-cvclodextrin sodium salt and 6- seven-(2- carboxy ethyl) thio-γ-ring in product
The sum of the amount of dextrin sodium salt accounts for the percentage of product quality.
It should be noted that above-described embodiment is only presently preferred embodiments of the present invention, there is no for the purpose of limiting the invention
Protection scope, the equivalent substitution or substitution made on the basis of the above all belong to the scope of protection of the present invention.
Claims (8)
1. a kind of method that microwave reaction synthesizes the more glucose sodium that relaxes, which is characterized in that 3- mercaptopropionic acid, alkali, 6- deoxidation -6- perhalogeno
Generation-gamma-cyclodextrin reacts under microwave radiation in Aquo System, generates the more glucose sodium crude product that relaxes.
2. easypro more glucose sodium preparation method as described in claim 1, which is characterized in that the reaction is under atmosphere of inert gases
It carries out.
3. the method that microwave reaction as described in claim 1 synthesizes the more glucose sodium that relaxes, the 6- deoxidation -6- perhalogeno-γ-ring
The ratio between dextrin and the amount of substance of 3- mercaptopropionic acid are：1:8~20；6- deoxidation -6- perhalogeno-the gamma-cyclodextrin and alkali
The ratio between amount of substance is：1:8~32.
4. the method that microwave reaction as described in any one of claims 1-3 synthesizes the more glucose sodium that relaxes, which is characterized in that the alkali
For any one or more combinations in sodium hydroxide, sodium carbonate, sodium bicarbonate, sodium acetate and sodium phosphate.
5. the method that microwave reaction as described in claim 1 synthesizes the more glucose sodium that relaxes, which is characterized in that the Aquo System
It is water or water and methanol, ethyl alcohol, tetrahydrofuran, N,N-dimethylformamide, dimethyl sulfoxide, a kind of or more in 1,4- dioxane
Kind combination.
6. the method that microwave reaction as described in claim 1 synthesizes the more glucose sodium that relaxes, which is characterized in that in atmosphere of inert gases
Under, the more glucose sodium crude product that relaxes is recrystallized.
7. the method that microwave reaction as claimed in claim 6 synthesizes the more glucose sodium that relaxes, which is characterized in that the recrystallization it is molten
Agent be water, methanol, ethyl alcohol, acetonitrile, acetone, N,N-dimethylformamide, any one or more in 1,4- dioxane group
It closes；Recrystallization temperature is 40 DEG C -100 DEG C；Relax the more mass ratio of glucose sodium crude product and recrystallization solvent be：1:3~15.
8. the method that the microwave reaction as described in claim 2 or 6 synthesizes the more glucose sodium that relaxes, which is characterized in that the indifferent gas
Body is nitrogen, argon gas, helium, combination any one or more in carbon dioxide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710367011.7A CN108929390A (en) | 2017-05-23 | 2017-05-23 | A kind of method that microwave reaction synthesizes the more glucose sodium that relaxes |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710367011.7A CN108929390A (en) | 2017-05-23 | 2017-05-23 | A kind of method that microwave reaction synthesizes the more glucose sodium that relaxes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108929390A true CN108929390A (en) | 2018-12-04 |
Family
ID=64450270
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710367011.7A Pending CN108929390A (en) | 2017-05-23 | 2017-05-23 | A kind of method that microwave reaction synthesizes the more glucose sodium that relaxes |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108929390A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109593143A (en) * | 2018-12-29 | 2019-04-09 | 博瑞生物医药（苏州）股份有限公司 | A kind of more glucose sodium that relaxes prepares the purification process of intermediate |
| CN112538123A (en) * | 2019-09-20 | 2021-03-23 | 鲁南制药集团股份有限公司 | Crystal form M of sugammadex sodium |
| CN112538124A (en) * | 2019-09-20 | 2021-03-23 | 鲁南制药集团股份有限公司 | Crystal form of sugammadex sodium |
| CN112574330A (en) * | 2019-09-28 | 2021-03-30 | 鲁南制药集团股份有限公司 | Crystal form of sugammadex sodium |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014125501A1 (en) * | 2013-02-14 | 2014-08-21 | Neuland Laboratories Limited | An improved process for preparation of sugammadex sodium |
| EP2609120B1 (en) * | 2010-08-25 | 2015-07-29 | Davuluri, Ramamohan Rao | Improved process for preparation of sugammadex |
| CN104844732A (en) * | 2015-03-27 | 2015-08-19 | 山东滨州智源生物科技有限公司 | Preparation method for sugammadex sodium |
| CN105348412A (en) * | 2014-08-22 | 2016-02-24 | 江苏恩华药业股份有限公司 | Method for purifying sugammadex sodium |
| WO2016194001A1 (en) * | 2015-05-29 | 2016-12-08 | Alaparthi Lakshmi Prasad | Processes for preparation of sugammadex and intermediates thereof |
| CN106565858A (en) * | 2016-10-13 | 2017-04-19 | 王炳永 | Purification method for sugammadex sodium |
-
2017
- 2017-05-23 CN CN201710367011.7A patent/CN108929390A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2609120B1 (en) * | 2010-08-25 | 2015-07-29 | Davuluri, Ramamohan Rao | Improved process for preparation of sugammadex |
| WO2014125501A1 (en) * | 2013-02-14 | 2014-08-21 | Neuland Laboratories Limited | An improved process for preparation of sugammadex sodium |
| US20160009827A1 (en) * | 2013-02-14 | 2016-01-14 | Ponnaiah Ravi | An Improved Process for Preparation of Sugammadex Sodium |
| CN105348412A (en) * | 2014-08-22 | 2016-02-24 | 江苏恩华药业股份有限公司 | Method for purifying sugammadex sodium |
| CN104844732A (en) * | 2015-03-27 | 2015-08-19 | 山东滨州智源生物科技有限公司 | Preparation method for sugammadex sodium |
| WO2016194001A1 (en) * | 2015-05-29 | 2016-12-08 | Alaparthi Lakshmi Prasad | Processes for preparation of sugammadex and intermediates thereof |
| CN106565858A (en) * | 2016-10-13 | 2017-04-19 | 王炳永 | Purification method for sugammadex sodium |
Non-Patent Citations (3)
| Title |
|---|
| 刘晓瀛: "《医用化学实验实训》", 31 January 2013, 东北大学出版社 * |
| 国家电力需求侧管理指导中心编著: "《电力需求侧管理实用技术》", 31 July 2005, 中国电力出版社 * |
| 杨光富: "《有机合成》", 31 August 2016, 华东理工大学出版社 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109593143A (en) * | 2018-12-29 | 2019-04-09 | 博瑞生物医药（苏州）股份有限公司 | A kind of more glucose sodium that relaxes prepares the purification process of intermediate |
| CN109593143B (en) * | 2018-12-29 | 2021-02-09 | 博瑞生物医药（苏州）股份有限公司 | Purification method for preparing intermediate from sugammadex sodium |
| CN112538123A (en) * | 2019-09-20 | 2021-03-23 | 鲁南制药集团股份有限公司 | Crystal form M of sugammadex sodium |
| CN112538124A (en) * | 2019-09-20 | 2021-03-23 | 鲁南制药集团股份有限公司 | Crystal form of sugammadex sodium |
| CN112574330A (en) * | 2019-09-28 | 2021-03-30 | 鲁南制药集团股份有限公司 | Crystal form of sugammadex sodium |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108929389A (en) | A kind of environmentally protective easypro more glucose sodium preparation method | |
| CN106565858B (en) | A kind of purification process for the more glucose sodium that relaxes | |
| CN108929390A (en) | A kind of method that microwave reaction synthesizes the more glucose sodium that relaxes | |
| Coenen et al. | Preparation of nca [17‐18F]‐fluoroheptadecanoic acid in high yields via aminopolyether supported, nucleophilic fluorination | |
| CN100374453C (en) | 2-18F-2-deoxidized-D-glucose synthesis process | |
| CN107778383A (en) | A kind of process for purification for the more glucose sodium that relaxes | |
| CN104447443A (en) | Preparation method for apremilast and intermediate of apremilast | |
| CN104262073B (en) | Small modules formula multifunction automatic18f labelling PET pharmaceutical synthesis instrument | |
| JP7261269B2 (en) | Precursor for radiofluorination | |
| CN114736112A (en) | Preparation method and application of PET imaging agent for myocardial metabolism | |
| CN107522673B (en) | 1,2,4, 5-tetrazine compound for bioorthogonal reaction and preparation method and application thereof | |
| CN101863948A (en) | High-purity (2 beta, 3 alpha, 5 alpha, 16 beta, 17 beta)-2-(4-morpholinyl)-16-(1-pyrrolidinyl)-androstane-3,17-diol or composition thereof and preparation method thereof | |
| CN103880945A (en) | Method for preparing high-purity thymalfasin | |
| CN108047148A (en) | A kind of preparation method of the western Nader's impurity of thunder | |
| CN107311877B (en) | A kind of positron medicine [18F] FDOPA novel processing step and its intermediate | |
| Manikowski et al. | An alternative route for fondaparinux sodium synthesis via selective hydrogenations and sulfation of appropriate pentasaccharides | |
| CN113105432B (en) | Carbon-11 (C)11C) Radiopharmaceutical, preparation method and application thereof | |
| CN102010345B (en) | Method for preparing D-phenylalanine through dynamic kinetic resolution | |
| CN108239089A (en) | A kind of synthetic method of AVM hereinafter Batan sodium | |
| CN104961787A (en) | Synthetic method for cordycepin | |
| CN103951665A (en) | Method for preparing novel tropenol amino acid anionic chiral ionic liquid, immobilization method thereof and method for resolving DL-phenylalanine and DL-tryptophan by using same | |
| CN100460416C (en) | Method for preparing adenosine | |
| CN109320500B (en) | A kind of18F-labeled benzimidazole compound and preparation method and application thereof | |
| CN113527162A (en) | Radioactive fluorine labeled phenylsulfone compound, preparation method and application thereof | |
| CN111100042B (en) | Preparation method of 2-methoxy-5-sulfonamide benzoic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20181204 |
|
| RJ01 | Rejection of invention patent application after publication |