CN100390150C - Method for preparing imidazophenylurea hydrochloride - Google Patents
Method for preparing imidazophenylurea hydrochloride Download PDFInfo
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- CN100390150C CN100390150C CNB2006100831335A CN200610083133A CN100390150C CN 100390150 C CN100390150 C CN 100390150C CN B2006100831335 A CNB2006100831335 A CN B2006100831335A CN 200610083133 A CN200610083133 A CN 200610083133A CN 100390150 C CN100390150 C CN 100390150C
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- Prior art keywords
- imidazophenylurea
- hydrochloride
- preparation
- reaction
- triphosgene
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- POLOQMLJBKRUDG-UHFFFAOYSA-N Cl.N1C=NC2=C1C=CC=C2NC(=O)N Chemical compound Cl.N1C=NC2=C1C=CC=C2NC(=O)N POLOQMLJBKRUDG-UHFFFAOYSA-N 0.000 title claims description 26
- 238000000034 method Methods 0.000 title abstract description 5
- 238000002360 preparation method Methods 0.000 claims abstract description 25
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 18
- NJXPYZHXZZCTNI-UHFFFAOYSA-N 3-aminobenzonitrile Chemical compound NC1=CC=CC(C#N)=C1 NJXPYZHXZZCTNI-UHFFFAOYSA-N 0.000 claims abstract description 10
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 claims abstract description 9
- GWEHVDNNLFDJLR-UHFFFAOYSA-N 1,3-diphenylurea Chemical compound C=1C=CC=CC=1NC(=O)NC1=CC=CC=C1 GWEHVDNNLFDJLR-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 5
- 125000002636 imidazolinyl group Chemical group 0.000 claims abstract description 4
- 239000003054 catalyst Substances 0.000 claims abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 36
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 32
- 238000006243 chemical reaction Methods 0.000 claims description 23
- LUBJCRLGQSPQNN-UHFFFAOYSA-N 1-Phenylurea Chemical compound NC(=O)NC1=CC=CC=C1 LUBJCRLGQSPQNN-UHFFFAOYSA-N 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- HSLPBCRWOIMTGS-UHFFFAOYSA-N 1H-benzimidazol-4-ylurea Chemical compound N1=CNC2=C1C=CC=C2NC(=O)N HSLPBCRWOIMTGS-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
- 239000005864 Sulphur Substances 0.000 claims description 7
- 239000003960 organic solvent Substances 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- NSOXQYCFHDMMGV-UHFFFAOYSA-N Tetrakis(2-hydroxypropyl)ethylenediamine Chemical compound CC(O)CN(CC(C)O)CCN(CC(C)O)CC(C)O NSOXQYCFHDMMGV-UHFFFAOYSA-N 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 6
- 238000004809 thin layer chromatography Methods 0.000 claims description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 4
- 238000002425 crystallisation Methods 0.000 claims description 4
- 230000008025 crystallization Effects 0.000 claims description 4
- 239000012153 distilled water Substances 0.000 claims description 4
- 238000010992 reflux Methods 0.000 claims description 4
- PODWXQQNRWNDGD-UHFFFAOYSA-L sodium thiosulfate pentahydrate Chemical compound O.O.O.O.O.[Na+].[Na+].[O-]S([S-])(=O)=O PODWXQQNRWNDGD-UHFFFAOYSA-L 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 125000003944 tolyl group Chemical group 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 3
- 206010013786 Dry skin Diseases 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 238000009833 condensation Methods 0.000 claims description 2
- 230000005494 condensation Effects 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 239000012065 filter cake Substances 0.000 claims description 2
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 claims description 2
- 230000000630 rising effect Effects 0.000 claims description 2
- MLRXMTYSQKIKAK-UHFFFAOYSA-N 1,3-bis[3-(4,5-dihydro-1h-imidazol-2-yl)phenyl]urea;hydron;dichloride Chemical compound Cl.Cl.C=1C=CC(C=2NCCN=2)=CC=1NC(=O)NC(C=1)=CC=CC=1C1=NCCN1 MLRXMTYSQKIKAK-UHFFFAOYSA-N 0.000 abstract description 4
- 238000009776 industrial production Methods 0.000 abstract description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 abstract 1
- 239000002994 raw material Substances 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 3
- -1 open and stir Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000010792 warming Methods 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 2
- 235000010265 sodium sulphite Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 2
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- DPDMMXDBJGCCQC-UHFFFAOYSA-N [Na].[Cl] Chemical compound [Na].[Cl] DPDMMXDBJGCCQC-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000842 anti-protozoal effect Effects 0.000 description 1
- 239000003904 antiprotozoal agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- QUBBAXISAHIDNM-UHFFFAOYSA-N ethyldimethylbenzene Natural products CCC1=CC=CC(C)=C1C QUBBAXISAHIDNM-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- 238000000643 oven drying Methods 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical group [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a preparation method for imidocarb hydrochloride, which uses m-aminobenzonitrile as initial raw materials. Firstly, the m-aminobenzonitrile reacts with triphosgene to form the structure of diphenyl urea; then, an imidazoline structure is formed from the structure of diphenyl urea and ethylenediamine by cyclization reaction under the action of catalysts; finally, the imidazoline structure is condensed with concentrated hydrochloric acid to generate the imidocarb hydrochloride. The preparation method has the characteristics of simple process, high yield of the imidocarb hydrochloride, good quality, etc. and is suitable for industrial production.
Description
Technical field
The present invention relates to the preparation method of drug chemical, specifically, is a kind of preparation method of imidazophenylurea hydrochloride.
Background technology
Imidazophenylurea hydrochloride (Imidocarb Hydrochloride) is a kind of antiprotozoal chemicals of animal specific.Clinically usually by subcutaneous or intramuscular injection, in order to this insect infection of BABEI for the treatment of animals such as ox, sheep, dog etc.
U.S. Pat has been set forth the method for preparing imidazophenylurea hydrochloride (I) from 2-(3-aminophenyl) tetrahydroglyoxaline two hydrochloric acid for No. 3338917.Its basic way is in 2-(3-aminophenyl) tetrahydroglyoxaline two aqueous solution of hydrochloric acid, feeds phosgene, prepares imidazophenylurea hydrochloride through separation.
The defective of aforesaid method is: productive rate is lower, is not suitable for large-scale industrial production.
Summary of the invention
The preparation method who the purpose of this invention is to provide a kind of imidazophenylurea hydrochloride.This preparation method's technology is simple, yield is high, cost is low, has the good commercial prospect.
In order to achieve the above object, the present invention is by the following technical solutions:
M-aminophenyl formonitrile HCN and the structure that is dissolved in the triphosgene reaction formation sym-diphenylurea in the organic solvent; Then under catalyst action with quadrol generation ring-closure reaction, form imidazoline structure; Last and concentrated hydrochloric acid condensation generates imidazophenylurea hydrochloride.
Described catalyzer is Sodium Pyrosulfite, Sulfothiorine, sodium sulfate, sulphur, sodium sulphite, Sodium sulfhydrate, sodium-chlor, EDTA-2Na, sulphur trioxide or sulfurous gas.Preferably Sulfothiorine, sulphur or sodium sulphite particularly preferably are sulphur.
Described organic solvent is toluene, dimethylbenzene, tetrahydrofuran (THF), ethyl acetate, chloroform or methylene dichloride, or the mixture of above-mentioned organic solvent.Preferred solvent is ethyl acetate, dimethylbenzene or toluene, particularly preferably is toluene.
In the ring-closure reaction, be solvent, or be solvent with the mixture of above-mentioned solvent with primary isoamyl alcohol, propyl carbinol, Virahol, methyl alcohol, ethanol, normal hexane, dimethyl formamide or N,N-DIMETHYLACETAMIDE.Preferred solvent is methyl alcohol, ethanol or dimethyl formamide, particularly preferably is methyl alcohol.
The synthetic route of preparation imidazophenylurea hydrochloride of the present invention, as described below:
Generate being reflected at 0 ℃ to 70 ℃ of (IV) by m-aminophenyl formonitrile HCN and triphosgene (BTC) and finish, preferable reaction temperature is at 10 ℃ to 60 ℃, and particularly preferred temperature is at 30 ℃ to 50 ℃.
Imidazophenylurea (V) reacts with concentrated hydrochloric acid in suitable solvent such as distilled water, handles to obtain imidazophenylurea hydrochloride (I) through cooling.
The preparation method of imidazophenylurea hydrochloride of the present invention more specifically, comprises following steps:
(1) preparation of cyano group phenylurea
In the reaction vessel that agitator, thermometer and constant pressure funnel are housed, add m-aminophenyl formonitrile HCN, toluene, triethylamine, drip the toluene solution of triphosgene, in 1-2 hour, dropwise, use the terminal point of thin-layer chromatography following response in the reaction process; Filter, get off-white color or the Powdered crystallization of white cyano group phenylurea;
(2) preparation of imidazophenylurea hydrochloride
In the reaction vessel that agitator, thermometer and reflux exchanger are housed, add cyano group phenylurea, methyl alcohol, sulphur, add quadrol then, temperature rising reflux reacted 20 hours, used the terminal point of thin-layer chromatography following response in the reaction process; React and finish the back with the ice bath cooling, filter, the filter cake methanol wash gets faint yellow or off-white color imidazophenylurea powdery crystallization; Imidazophenylurea with the processing of distilled water suspendible, with concentrated hydrochloric acid acidifying, adding activated carbon decolorizing, is lowered the temperature and filtered then, and 65 ℃ of dryings get white or off-white color imidazophenylurea hydrochloride.
The imidazophenylurea hydrochloride that the present invention's reaction obtains, instrument detecting is consistent with the standard diagram of this material that document is put down in writing by analysis.The total recovery of this preparation method's imidazophenylurea hydrochloride is stable, usually above 50%.
The present invention has characteristics such as technology is simple, yield is high, quality is good, is particularly suitable for suitability for industrialized production.
Embodiment
Be embodiments of the invention below, described embodiment just is used for illustrating the present invention, and should not be considered to be limitation of the present invention.
Embodiment 1
The preparation of cyano group phenylurea
In the exsiccant reaction flask, drop into 50ml toluene, open and stir, drop into 5g m-aminophenyl formonitrile HCN and 2.0ml triethylamine then, be warming up to 50 ℃.Drip the triphosgene solution that is dissolved in the 2.2g in the 20ml toluene then, dropwise in 2 hours, continue reaction 2 hours.Reduce to room temperature, filter.With 10ml toluene and 10ml water washing, 65 ℃ of oven dryings, get 4.61g off-white color granular powder, fusing point is 192-195 ℃, yield is 84.10%.
Embodiment 2
The preparation of imidazophenylurea
In the exsiccant reaction flask, drop into 100ml methyl alcohol, stir, drop into 2g cyano group phenylurea, 2.0ml quadrol, 3g sulphur then, be warming up to 64.8 ℃, back flow reaction 20 hours, the terminal point of thin-layer chromatography following response.The ice bath cooling is filtered, and uses methanol wash, dries in 65 ℃ of baking ovens.Get off-white color product 2.50g, fusing point is 240-242 ℃, yield 92.60%.
Embodiment 3
The preparation of imidazophenylurea
In the exsiccant reaction flask, drop into 100ml methyl alcohol, stir, drop into 2g cyano group phenylurea, 2.0ml quadrol, 3g Sulfothiorine then, be warming up to 64.8 ℃, back flow reaction 20 hours, the terminal point of thin-layer chromatography following response.The ice bath cooling is filtered, and uses methanol wash, dries in 65 ℃ of baking ovens.Get off-white color product 2.48g, fusing point is 241-243 ℃, yield 91.85%.
Embodiment 4
The preparation of imidazophenylurea hydrochloride
In reaction flask, drop into the 0.5g imidazophenylurea, drop into 10ml distilled water then, stir.Transfer pH=3 with concentrated hydrochloric acid, add the 0.1g decolorizing with activated carbon then, stirred 1 hour, filter, the filtrate ice bath is cooled to 0 ℃, filters, and is dry in 65 ℃ of baking ovens.Get off-white color product 0.41g, fusing point＞350 ℃ (decomposition), yield is 68.33%.
More than the preparation method of imidazophenylurea hydrochloride provided by the present invention is described in detail, used specific case herein principle of the present invention and embodiment are set forth, the explanation of above embodiment just is used for helping to understand method of the present invention and core concept thereof; Simultaneously, for one of ordinary skill in the art, according to thought of the present invention, the part that all can change in specific embodiments and applications, in sum, this description should not be construed as limitation of the present invention.
Claims (6)
1. the preparation method of an imidazophenylurea hydrochloride is characterized in that, comprises following steps: m-aminophenyl formonitrile HCN and the structure that is dissolved in the triphosgene reaction formation sym-diphenylurea in the organic solvent; Then under catalyst action with quadrol generation ring-closure reaction, form imidazoline structure; Last and concentrated hydrochloric acid condensation generates imidazophenylurea hydrochloride; Described catalyzer is sulphur or Sulfothiorine; In the described ring-closure reaction, be solvent with methyl alcohol.
2. the preparation method of imidazophenylurea hydrochloride as claimed in claim 1 is characterized in that, the reaction that m-aminophenyl formonitrile HCN and triphosgene reaction form the sym-diphenylurea structure is to finish between 70 ℃ at 0 ℃.
3. the preparation method of imidazophenylurea hydrochloride as claimed in claim 1 or 2 is characterized in that, the reaction that m-aminophenyl formonitrile HCN and triphosgene reaction form the sym-diphenylurea structure is to finish between 50 ℃ at 30 ℃.
4. the preparation method of imidazophenylurea hydrochloride as claimed in claim 1 is characterized in that, described organic solvent is toluene, dimethylbenzene, tetrahydrofuran (THF), ethyl acetate, chloroform or methylene dichloride, or the mixture of above-mentioned organic solvent.
5. as the preparation method of claim 1 or 4 described imidazophenylurea hydrochlorides, it is characterized in that described organic solvent is a toluene.
6. the preparation method of imidazophenylurea hydrochloride as claimed in claim 1 is characterized in that, comprises following steps:
(1) preparation of cyano group phenylurea
In the reaction vessel that agitator, thermometer and constant pressure funnel are housed, add m-aminophenyl formonitrile HCN, toluene and triethylamine, drip the toluene solution of triphosgene, in 1-2 hour, dropwise, use the terminal point of thin-layer chromatography following response in the reaction process; Filter, get off-white color or the Powdered crystallization of white cyano group phenylurea;
(2) preparation of imidazophenylurea hydrochloride
In the reaction vessel that agitator, thermometer and reflux exchanger are housed, add cyano group phenylurea, methyl alcohol and sulphur, add quadrol then, temperature rising reflux reacted 20 hours, used the terminal point of thin-layer chromatography following response in the reaction process; React and finish the back with the ice bath cooling, filter, the filter cake methanol wash gets faint yellow or off-white color imidazophenylurea powdery crystallization; Imidazophenylurea is handled with the distilled water suspendible, used the concentrated hydrochloric acid acidifying then and add activated carbon decolorizing, cooling is filtered, and 65 ℃ of dryings get white or off-white color imidazophenylurea hydrochloride.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100831335A CN100390150C (en) | 2006-06-05 | 2006-06-05 | Method for preparing imidazophenylurea hydrochloride |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100831335A CN100390150C (en) | 2006-06-05 | 2006-06-05 | Method for preparing imidazophenylurea hydrochloride |
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| CN1850805A CN1850805A (en) | 2006-10-25 |
| CN100390150C true CN100390150C (en) | 2008-05-28 |
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| CN105949127B (en) * | 2016-05-12 | 2018-12-21 | 山东久隆恒信药业有限公司 | A kind of method of purification of imidazophenylurea |
| CN110256354A (en) * | 2019-07-26 | 2019-09-20 | 齐鲁动物保健品有限公司 | A kind of imidocard dipropionate impurity A and its impurity A preparation method |
| CN114671810B (en) * | 2022-03-21 | 2024-03-22 | 济南鸿湾生物技术有限公司 | Preparation method of imidazole phenylurea |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3338917A (en) * | 1960-10-14 | 1967-08-29 | Wander Ag Dr A | Diimidazolinylcarbanilide |
| US4623662A (en) * | 1985-05-23 | 1986-11-18 | American Cyanamid Company | Antiatherosclerotic ureas and thioureas |
| WO1996010559A1 (en) * | 1994-10-04 | 1996-04-11 | Fujisawa Pharmaceutical Co., Ltd. | Urea derivatives and their use as acat-inhibitors |
| CN1337395A (en) * | 2000-06-29 | 2002-02-27 | 阿迪尔公司 | Novel acardite compound, its preparation method and medicinal composition containing said compound |
-
2006
- 2006-06-05 CN CNB2006100831335A patent/CN100390150C/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3338917A (en) * | 1960-10-14 | 1967-08-29 | Wander Ag Dr A | Diimidazolinylcarbanilide |
| US4623662A (en) * | 1985-05-23 | 1986-11-18 | American Cyanamid Company | Antiatherosclerotic ureas and thioureas |
| WO1996010559A1 (en) * | 1994-10-04 | 1996-04-11 | Fujisawa Pharmaceutical Co., Ltd. | Urea derivatives and their use as acat-inhibitors |
| CN1337395A (en) * | 2000-06-29 | 2002-02-27 | 阿迪尔公司 | Novel acardite compound, its preparation method and medicinal composition containing said compound |
Non-Patent Citations (2)
| Title |
|---|
| 抗梨形虫新药咪唑苯脲合成与结构确证的研究. 戴国华等.兽医大学学报，第7卷第2期. 1987 |
| 抗梨形虫新药咪唑苯脲合成与结构确证的研究. 戴国华等.兽医大学学报，第7卷第2期. 1987 * |
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| CN1850805A (en) | 2006-10-25 |
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