CN104774223A - Method for producing tildipirosin by using tylosin alkali - Google Patents
Method for producing tildipirosin by using tylosin alkali Download PDFInfo
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- CN104774223A CN104774223A CN201510135381.9A CN201510135381A CN104774223A CN 104774223 A CN104774223 A CN 104774223A CN 201510135381 A CN201510135381 A CN 201510135381A CN 104774223 A CN104774223 A CN 104774223A
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Abstract
The present invention relates to a method for producing tildipirosin by using tylosin alkali, wherein the process steps comprise that tylosin alkali is subjected to a series treatments such as dissolving, hydrolysis, extraction and synthesis to produce the tildipirosin. The present invention provides the tildipirosin production process, wherein the product yield is more than or equal to 80%, and the domestic and foreign market competitiveness of the products are easily enhanced.
Description
Technical field
The invention belongs to microbiotic synthesis technical field, particularly relate to a kind of method utilizing tylosin alkali to produce safe ground Luo Xin.
Background technology
The Macrolide semisynthetic antibiotics of the up-to-date animal specific of safe Di Luoxinshi offshore company Intervet-Schering Plough company exploitation is the derivative of tylosin.On March 8th, 2011, the veterinary medicine council of European Union (CVMP)) permit the market license application of the aseptic parenteral solution (commodity are called Zuprevo) that Intervet company is main component with safe ground Luo Xin, will in succession ratify listing in European Union member countries subsequently.No. CAS of safe ground Luo Xin is 328898-40-4, and molecular formula is C
41h
71n
3o
8, molecular weight 734.02, fusing point is 192 DEG C, is dissolved in polar organic solvent (as methyl alcohol, acetone etc.), slightly soluble in water.
Safe ground Luo Xin is broad spectrum antibiotic, all there is anti-microbial activity to some Gram-positives and gram negative bacterium, to cause pig, ox respiratory system disease pathogenic bacteria especially responsive, as actinobacillus pleuropneumoniae, pasteurella multocida, bordetella branchiseptica, haemophilus parasuis and hemolytic mannheim bacterium, sleep Histophilus etc.
Luo Xin is identical with the mechanism of action of other Macrocyclolactone lactone kind medicines on safe ground, can be combined, the synthesis of peptide chain and prolongation are obstructed, affect the synthesis of bacterioprotein with the ribosome 50s subunit of sensitive organism.In China, it is tylosin and tilmicosin comparatively widely that current Macrocyclolactone lactone kind medicine uses, although the use of these two kinds of medicines all achieves good effect, but along with the prolongation of duration of service, there is resistance in various degree in a lot of area, and these two kinds of medicines adopt spice or drinking water administration mode usually, generally need repeatedly repeat administration competence exertion drug effect.The respiratory tract disease of safe ground Luo Xin to ox, pig has fairly obvious result for the treatment of, drug effect is better than tylosin, tilmicosin, and possess that animal specific, consumption are few, the high and low many merits such as residual of the elimination transformation period of single administration whole-course treatment, overlength, bioavailability, its application will be further expanded, therefore, good development and application values is had.
At present, the production technique about safe ground Luo Xin there is no open, and domestic and international imitation medicine is all in research and development and predevelopment phase; China's Some Enterprises has carried out sieve new synthesis process research of safe ground, is also only in development, and domestic there are no bibliographical information.
Summary of the invention
Object of the present invention is just to provide a kind of method utilizing tylosin alkali to produce safe ground Luo Xin.
Technical scheme taked for achieving the above object is:
Utilize tylosin alkali to produce a method of safe ground Luo Xin, it is characterized in that its processing step is:
1) tylosin alkali is dissolved in organic solvent, obtains tylosin solution;
2) in above-mentioned tylosin solution, add piperidines, stir and adopt after being warming up to 50 ~ 70 DEG C stream addition to add formic acid and react, obtain product A solution;
3) in above-mentioned product A solution, add purified water, be hydrolyzed under pH3 ~ 5, temperature 30 ~ 50 DEG C of conditions, leave standstill afterwards, Liquid liquid Separation, obtain the aqueous solution of product B;
4) in the aqueous solution of product B, add Hydrogen bromide, react under pH2 ~ 4, temperature 60 ~ 80 DEG C of conditions, obtain product C solution;
5) product C solution is adjusted to pH9 ~ 10, solid-liquid separation after leaving standstill, and the wet solid product C purified water washing obtained, drying, obtain the solid product C that moisture content is less than 2%;
6) solid product C is dissolved in pyridine, adds triphenyl phosphorus successively and iodine reacts, after the reaction times terminates, add quencher purified water, sherwood oil successively again, abundant stirring, Liquid liquid Separation after leaving standstill, obtain the organic solution containing product D, vacuum-drying obtains solid product D;
7) solid product D is dissolved in piperidines, then adds triethylamine and formic acid reacts, final vacuum drying obtains solid product safe ground Luo Xin.
Process 1) in, described organic solvent is methylene dichloride or N-BUTYL ACETATE or ethyl acetate, its consumption for: the organic solvent dissolved needed for 1mol tylosin is 1.2 ~ 1.5L.
Process 2) and process 7) in, the usage ratio of described piperidines is: the piperidines adding 1.1 ~ 1.2mol in 1mol tylosin.
Process 2) consumption of described formic acid is: the formic acid adding 0.02 ~ 0.06mol in 1mol tylosin, reaction times 60 ~ 80min.
Process 3) in, the add-on of described purified water is product A liquor capacity 50 ~ 90%, hydrolysis time 30 ~ 60min.
Process 4) in, described hydrobromic add-on is 50 ~ 60% of the aqueous solution volume of product B, reaction times 20 ~ 40min.
Process 6) in, the consumption of described pyridine is: the pyridine adding 1.05 ~ 1.15mol in 1mol tylosin.
Process 6) in, described triphenylphosphine consumption is: the triphenylphosphine adding 1.10 ~ 1.20mol in 1mol tylosin, and described iodine consumption is: the iodine adding 0.52 ~ 0.62mol in 1mol tylosin, reaction times 30 ~ 60min.
Process 6) in, the consumption of described quencher purified water is 2 ~ 6 times of tylosin molal quantity; Described sherwood oil usage ratio is: the sherwood oil adding 1.5 ~ 2.0L in 1mol tylosin.
Process 7) in, described triethylamine consumption is: the triethylamine adding 0.03 ~ 0.06mol in 1mol tylosin; Described formic acid consumption is: the formic acid adding 0.2 ~ 0.6mol in 1mol tylosin.
Described pH acid solution or alkaline solution adjustment, wherein acid solution is sulfuric acid or hydrochloric acid, and concentration controls 30 ~ 50%, and alkaline solution is sodium hydroxide or sodium bicarbonate, and concentration controls 30 ~ 40%.
Process 5) in, described purified water washing institute water consumption is 3 ~ 7 times of tylosin molal quantity.
Process 6) and process 7) in, vacuum-drying controling parameters is: vacuum degree control is at-0.02 ~-0.1MPa, and temperature controls at 60 ~ 80 DEG C, and time of drying is 30 ~ 60min.
Technical superiority of the present invention:
1 the invention provides a kind of effective novel method of producing safe ground Luo Xin.
2 synthesis total recoverys, more than 80%, are conducive to the domestic and international market competitive power strengthening product.
specific implementation method
Be explained the present invention with example below, it should be understood that example is for illustration of the present invention instead of limitation of the present invention.Scope of the present invention and core content are determined according to claims.
Tylosin alkali source in following embodiment:
First adopt the tylosin broth of streptomyces fradiae fermentative production as starting raw material, obtain tylosin solution through extraction, reextraction and refinery decolorization technique, after alkalization, solid-liquid separation obtains tylosin alkali.
Embodiment 1
The tylosin alkali of 10mol is dissolved in methylene dichloride, obtains tylosin solution 20L.
Add 11mol piperidines in tylosin solution, stir 20min, be warming up to 50 DEG C, adopt feeding method to add formic acid 0.2mol, mixing speed controls at 60r/min, and time controling, at 60min, obtains product A solution.
Product A solution adds purified water 10L, and regulate pH to 5 with sour 30% hydrochloric acid soln, temperature controls at 30 DEG C, and mixing speed controls at 60r/min, and hydrolysis time controls at 30min, obtains product B solution.After hydrolysis reaction terminates, leave standstill 20min, then Liquid liquid Separation, obtain the aqueous solution of product B.
Product B solution adds 50% Hydrogen bromide, and regulate pH to 4, temperature controls at 60 DEG C, and mixing speed controls at 50r/min, and time controling, at 20min, obtains product C solution.
The product C solution sodium hydroxide of 30% is adjusted to pH9, and solid-liquid separation after standing 20min, obtain wet solid product C purified water and wash 1 time, consumption is 30L.Washing terminates, and carry out drying treatment, temperature controls at 60 DEG C, and dry end, the moisture content in solid product C is 1.9%.
Solid product C is dissolved in the pyridine of 10.5mol, and temperature controls at 40 DEG C, and mixing speed controls at 60r/min.First add 11mol triphenyl phosphorus, next adds 5.2mol iodine, and time controling is at 30min.Reaction times terminates, and adds quencher purified water 20L, stirs 10min.Add sherwood oil 15mol, continue to stir 20min, stir and terminate, leave standstill 30min.Leave standstill and terminate, carry out Liquid liquid Separation, obtain the organic solution containing product D.Adopt vacuum drying method, vacuum degree control is at-0.02MPa, and temperature controls at 70 DEG C, and time of drying is 30min.Vacuum-drying terminates, and obtains solid product D.
Solid product D is dissolved in 11mol piperidines, and temperature controls at 40 DEG C, and mixing speed controls at 50r/min, and add 0.3mol triethylamine and 0.2mol formic acid respectively, time controling is at 120min.Reaction terminates, and carry out vacuum-drying, vacuum degree control is at-0.02MPa, and temperature controls at 60 DEG C, and time of drying is 30min.Dry end, obtain solid product safe ground Luo Xin 8.13mol, mole total recovery is 81.3%.
Embodiment 2
The tylosin alkali of 10mol is dissolved in N-BUTYL ACETATE, obtains tylosin solution 30L.
Add 11.2mol piperidines in tylosin solution, stir 25min, be warming up to 55 DEG C, adopt feeding method to add formic acid 0.3mol, mixing speed controls at 65r/min, and time controling, at 65min, obtains product A solution.
Product A solution adds purified water 18L, and regulate pH to 4.5 with 35% sulphuric acid soln, temperature controls at 35 DEG C, and mixing speed controls at 65r/min, and hydrolysis time controls at 40min, obtains product B solution.After hydrolysis reaction terminates, leave standstill 30min, then Liquid liquid Separation, obtain the aqueous solution of product B.
Product B solution adds 52% Hydrogen bromide, and regulate pH to 3.5, temperature controls at 65 DEG C, and mixing speed controls at 55r/min, and time controling, at 25min, obtains product C solution.
The product C solution sodium carbonate of 33% is adjusted to pH9.2, and solid-liquid separation after standing 22min, obtain wet solid product C purified water and wash 1 time, consumption is 40L.Washing terminates, and carry out drying treatment, temperature controls at 65 DEG C, and dry end, the moisture content in solid product C is 1.8%.
Solid product C is dissolved in the pyridine of 10.8mol, and temperature controls at 45 DEG C, and mixing speed controls at 65r/min.First add 11.2mol triphenyl phosphorus, next adds 5.5mol iodine, and time controling is at 38min.Reaction times terminates, and adds quencher purified water 30L, stirs 12min.Add sherwood oil 16mol, continue to stir 25min, stir and terminate, leave standstill 37min.Leave standstill and terminate, carry out Liquid liquid Separation, obtain the organic solution containing product D.Adopt vacuum drying method, vacuum degree control is at-0.03MPa, and temperature controls at 70 DEG C, and time of drying is 40min.Vacuum-drying terminates, and obtains solid product D.
Solid product D is dissolved in 11.2mol piperidines, and temperature controls at 45 DEG C, and mixing speed controls at 55r/min, and add 0.4mol triethylamine and 0.3mol formic acid respectively, time controling is at 130min.Reaction terminates, and carry out vacuum-drying, vacuum degree control is at-0.03MPa, and temperature controls at 65 DEG C, and time of drying is 35min.Dry end, obtain solid product safe ground Luo Xin 8.27mol, mole total recovery is 82.7%.
Embodiment 3
The tylosin alkali of 10mol is dissolved in N-BUTYL ACETATE, obtains tylosin solution 40L.
Add 11.5mol piperidines in tylosin solution, stir 30min, be warming up to 60 DEG C, adopt feeding method to add formic acid 0.4mol, mixing speed controls at 70r/min, and time controling, at 70min, obtains product A solution.
Product A solution adds purified water 28L, and regulate pH to 4 with 40% hydrochloric acid soln, temperature controls at 40 DEG C, and mixing speed controls at 70r/min, and hydrolysis time controls at 45min, obtains product B solution.After hydrolysis reaction terminates, leave standstill 40min, then Liquid liquid Separation, obtain the aqueous solution of product B.
Product B solution adds 55% Hydrogen bromide, and regulate pH to 3, temperature controls at 70 DEG C, and mixing speed controls at 60r/min, and time controling, at 30min, obtains product C solution.
The product C solution sodium hydroxide of 35% is adjusted to pH9.5, and solid-liquid separation after standing 25min, obtain wet solid product C purified water and wash 1 time, consumption is 50L.Washing terminates, and carry out drying treatment, temperature controls at 70 DEG C, and dry end, the moisture content in solid product C is 1.6%.
Solid product C is dissolved in the pyridine of 11.1mol, and temperature controls at 50 DEG C, and mixing speed controls at 70r/min.First add 11.5mol triphenyl phosphorus, next adds 5.7mol iodine, and time controling is at 45min.Reaction times terminates, and adds quencher purified water 50L, stirs 15min.Add sherwood oil 17mol, continue to stir 30min, stir and terminate, leave standstill 45min.Leave standstill and terminate, carry out Liquid liquid Separation, obtain the organic solution containing product D.Adopt vacuum drying method, vacuum degree control is at-0.04MPa, and temperature controls at 75 DEG C, and time of drying is 45min.Vacuum-drying terminates, and obtains solid product D.
Solid product D is dissolved in 11.5mol piperidines, and temperature controls at 50 DEG C, and mixing speed controls at 60r/min, and add 0.45mol triethylamine and 0.4mol formic acid respectively, time controling is at 140min.Reaction terminates, and carry out vacuum-drying, vacuum degree control is at-0.05MPa, and temperature controls at 70 DEG C, and time of drying is 45min.Dry end, obtain solid product safe ground Luo Xin 8.36mol, mole total recovery is 83.6%.
Embodiment 4
The tylosin alkali of 10mol is dissolved in N-BUTYL ACETATE, obtains tylosin solution 50L.
Add 11.7mol piperidines in tylosin solution, stir 35min, be warming up to 65 DEG C, adopt feeding method to add formic acid 0.5mol, mixing speed controls at 75r/min, and time controling, at 75min, obtains product A solution.
Product A solution adds purified water 40L, and regulate pH to 3.5 with 45% sulphuric acid soln, temperature controls at 45 DEG C, and mixing speed controls at 75r/min, and hydrolysis time controls at 55min, obtains product B solution.After hydrolysis reaction terminates, leave standstill 50min, then Liquid liquid Separation, obtain the aqueous solution of product B.
Product B solution adds 58% Hydrogen bromide, and regulate pH to 2.5, temperature controls at 75 DEG C, and mixing speed controls at 65r/min, and time controling, at 35min, obtains product C solution.
The product C solution sodium hydroxide of 37% is adjusted to pH9.7, and solid-liquid separation after standing 28min, obtain wet solid product C purified water and wash 1 time, consumption is 60L.Washing terminates, and carry out drying treatment, temperature controls at 78 DEG C, and dry end, the moisture content in solid product C is 1.4%.
Solid product C is dissolved in the pyridine of 11.4mol, and temperature controls at 55 DEG C, and mixing speed controls at 75r/min.First add 11.7mol triphenyl phosphorus, next adds 5.9mol iodine, and time controling is at 55min.Reaction times terminates, and adds quencher purified water 50L, stirs 18min.Add sherwood oil 19mol, continue to stir 35min, stir and terminate, leave standstill 55min.Leave standstill and terminate, carry out Liquid liquid Separation, obtain the organic solution containing product D.Adopt vacuum drying method, vacuum degree control is at-0.07MPa, and temperature controls at 78 DEG C, and time of drying is 55min.Vacuum-drying terminates, and obtains solid product D.
Solid product D is dissolved in 11.7mol piperidines, and temperature controls at 55 DEG C, and mixing speed controls at 65r/min, and add 0.53mol triethylamine and 0.5mol formic acid respectively, time controling is at 150min.Reaction terminates, and carry out vacuum-drying, vacuum degree control is at-0.07MPa, and temperature controls at 75 DEG C, and time of drying is 55min.Dry end, obtain solid product safe ground Luo Xin 8.35mol, mole total recovery is 83.5%.
Embodiment 5
The tylosin alkali of 10mol is dissolved in N-BUTYL ACETATE, obtains tylosin solution 60L.
Add 12mol piperidines in tylosin solution, stir 40min, be warming up to 70 DEG C, adopt feeding method to add formic acid 0.6mol, mixing speed controls at 80r/min, and time controling, at 80min, obtains product A solution.
Product A solution adds purified water 54L, and regulate pH to 3 with 50% hydrochloric acid soln, temperature controls at 50 DEG C, and mixing speed controls at 80r/min, and hydrolysis time controls at 60min, obtains product B solution.After hydrolysis reaction terminates, leave standstill 60min, then Liquid liquid Separation, obtain the aqueous solution of product B.
Product B solution adds 60% Hydrogen bromide, and regulate pH to 2, temperature controls at 80 DEG C, and mixing speed controls at 70r/min, and time controling, at 40min, obtains product C solution.
The product C solution sodium carbonate of 40% is adjusted to pH10, and solid-liquid separation after standing 30min, obtain wet solid product C purified water and wash 1 time, consumption is 70L.Washing terminates, and carry out drying treatment, temperature controls at 80 DEG C, and dry end, the moisture content in solid product C is 1.2%.
Solid product C is dissolved in the pyridine of 11.5mol, and temperature controls at 60 DEG C, and mixing speed controls at 80r/min.First add 12mol triphenyl phosphorus, next adds 6.2mol iodine, and time controling is at 60min.Reaction times terminates, and adds quencher purified water 60L, stirs 20min.Add sherwood oil 20mol, continue to stir 40min, stir and terminate, leave standstill 60min.Leave standstill and terminate, carry out Liquid liquid Separation, obtain the organic solution containing product D.Adopt vacuum drying method, vacuum degree control is at-0.1MPa, and temperature controls at 80 DEG C, and time of drying is 60min.Vacuum-drying terminates, and obtains solid product D.
Solid product D is dissolved in 12mol piperidines, and temperature controls at 60 DEG C, and mixing speed controls at 70r/min, and add 0.6mol triethylamine and 0.6mol formic acid respectively, time controling is at 160min.Reaction terminates, and carry out vacuum-drying, vacuum degree control is at-0.1MPa, and temperature controls at 80 DEG C, and time of drying is 60min.Dry end, obtain solid product safe ground Luo Xin 8.29mol, mole total recovery is 82.9%.
Claims (13)
1. utilize tylosin alkali to produce a method of safe ground Luo Xin, it is characterized in that its processing step is:
1) tylosin alkali is dissolved in organic solvent, obtains tylosin solution;
2) in above-mentioned tylosin solution, add piperidines, stir and adopt after being warming up to 50 ~ 70 DEG C stream addition to add formic acid and react, obtain product A solution;
3) in above-mentioned product A solution, add purified water, be hydrolyzed under pH3 ~ 5, temperature 30 ~ 50 DEG C of conditions, leave standstill afterwards, Liquid liquid Separation, obtain the aqueous solution of product B;
4) in the aqueous solution of product B, add Hydrogen bromide, react under pH2 ~ 4, temperature 60 ~ 80 DEG C of conditions, obtain product C solution;
5) product C solution is adjusted to pH9 ~ 10, solid-liquid separation after leaving standstill, and the wet solid product C purified water washing obtained, drying, obtain the solid product C that moisture content is less than 2%;
6) solid product C is dissolved in pyridine, adds triphenyl phosphorus successively and iodine reacts, after the reaction times terminates, add quencher purified water, sherwood oil successively again, abundant stirring, Liquid liquid Separation after leaving standstill, obtain the organic solution containing product D, vacuum-drying obtains solid product D;
7) solid product D is dissolved in piperidines, then adds triethylamine and formic acid reacts, final vacuum drying obtains solid product safe ground Luo Xin.
2. according to the method utilizing tylosin alkali to produce safe ground Luo Xin according to claim 1, it is characterized in that process 1) in, described organic solvent is methylene dichloride or N-BUTYL ACETATE or ethyl acetate, its consumption for: the organic solvent dissolved needed for 1mol tylosin is 1.2 ~ 1.5L.
3., according to the method utilizing tylosin alkali to produce safe ground Luo Xin according to claim 1, it is characterized in that process 2) and process 7) in, the usage ratio of described piperidines is: the piperidines adding 1.1 ~ 1.2mol in 1mol tylosin.
4., according to the method utilizing tylosin alkali to produce safe ground Luo Xin according to claim 1, it is characterized in that process 2) consumption of described formic acid is: the formic acid adding 0.02 ~ 0.06mol in 1mol tylosin, reaction times 60 ~ 80min.
5., according to the method utilizing tylosin alkali to produce safe ground Luo Xin according to claim 1, it is characterized in that process 3) in, the add-on of described purified water is product A liquor capacity 50 ~ 90%, hydrolysis time 30 ~ 60min.
6., according to the method utilizing tylosin alkali to produce safe ground Luo Xin according to claim 1, it is characterized in that process 4) in, described hydrobromic add-on is 50 ~ 60% of the aqueous solution volume of product B, reaction times 20 ~ 40min.
7., according to the method utilizing tylosin alkali to produce safe ground Luo Xin according to claim 1, it is characterized in that process 6) in, the consumption of described pyridine is: the pyridine adding 1.05 ~ 1.15mol in 1mol tylosin.
8. according to the method utilizing tylosin alkali to produce safe ground Luo Xin according to claim 1, it is characterized in that process 6) in, described triphenylphosphine consumption is: the triphenylphosphine adding 1.10 ~ 1.20mol in 1mol tylosin, described iodine consumption is: the iodine adding 0.52 ~ 0.62mol in 1mol tylosin, reaction times 30 ~ 60min.
9., according to the method utilizing tylosin alkali to produce safe ground Luo Xin according to claim 1, it is characterized in that process 6) in, the consumption of described quencher purified water is 2 ~ 6 times of tylosin molal quantity; Described sherwood oil usage ratio is: the sherwood oil adding 1.5 ~ 2.0L in 1mol tylosin.
10., according to the method utilizing tylosin alkali to produce safe ground Luo Xin according to claim 1, it is characterized in that process 7) in, described triethylamine consumption is: the triethylamine adding 0.03 ~ 0.06mol in 1mol tylosin; Described formic acid consumption is the formic acid adding 0.2 ~ 0. 6mol in 1mol tylosin.
11. according to the method utilizing tylosin alkali to produce safe ground Luo Xin according to claim 1, it is characterized in that described pH acid solution or alkaline solution adjustment, wherein acid solution is sulfuric acid or hydrochloric acid, concentration controls 30 ~ 50%, alkaline solution is sodium hydroxide or sodium bicarbonate, and concentration controls 30 ~ 40%.
12., according to the method utilizing tylosin alkali to produce safe ground Luo Xin according to claim 1, is characterized in that process 5) in, described purified water washing institute water consumption is 3 ~ 7 times of tylosin molal quantity.
13. according to the method utilizing tylosin alkali to produce safe ground Luo Xin according to claim 1, it is characterized in that process 6) and process 7) in, vacuum-drying controling parameters is: vacuum degree control is at-0.02 ~-0.1MPa, and temperature controls at 60 ~ 80 DEG C, and time of drying is 30 ~ 60min.
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Cited By (6)
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| CN105254693A (en) * | 2015-11-13 | 2016-01-20 | 周金华 | Synthetic method for tildipirosin |
| CN105440093A (en) * | 2015-11-17 | 2016-03-30 | 宁夏泰瑞制药股份有限公司 | Synthetic method of tildipirosin |
| CN106046086A (en) * | 2016-06-02 | 2016-10-26 | 天津大学 | Method for preparing amorphous tildipirosin |
| CN108033988A (en) * | 2017-12-28 | 2018-05-15 | 山东鲁抗舍里乐药业有限公司 | A kind of preparation method of tylonolide |
| CN113121625A (en) * | 2019-12-31 | 2021-07-16 | 湖北龙翔药业科技股份有限公司 | Preparation method of tildipirosin |
| CN114920789A (en) * | 2022-07-07 | 2022-08-19 | 京山瑞生制药有限公司 | Preparation method of tildipirosin key intermediate |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105254693A (en) * | 2015-11-13 | 2016-01-20 | 周金华 | Synthetic method for tildipirosin |
| CN105254693B (en) * | 2015-11-13 | 2017-12-22 | 周金华 | A kind of synthetic method of tylonolide |
| CN105440093A (en) * | 2015-11-17 | 2016-03-30 | 宁夏泰瑞制药股份有限公司 | Synthetic method of tildipirosin |
| CN106046086A (en) * | 2016-06-02 | 2016-10-26 | 天津大学 | Method for preparing amorphous tildipirosin |
| CN106046086B (en) * | 2016-06-02 | 2019-07-19 | 天津大学 | It is a kind of to prepare the unformed method of tylonolide |
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| CN113121625A (en) * | 2019-12-31 | 2021-07-16 | 湖北龙翔药业科技股份有限公司 | Preparation method of tildipirosin |
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| CN114920789A (en) * | 2022-07-07 | 2022-08-19 | 京山瑞生制药有限公司 | Preparation method of tildipirosin key intermediate |
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