AU2018100847A4 - Anti-clavicular spirochete drugs ethyl imidazole synthesis method - Google Patents
Anti-clavicular spirochete drugs ethyl imidazole synthesis method Download PDFInfo
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- AU2018100847A4 AU2018100847A4 AU2018100847A AU2018100847A AU2018100847A4 AU 2018100847 A4 AU2018100847 A4 AU 2018100847A4 AU 2018100847 A AU2018100847 A AU 2018100847A AU 2018100847 A AU2018100847 A AU 2018100847A AU 2018100847 A4 AU2018100847 A4 AU 2018100847A4
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- solution
- clavicular
- spirochete
- ethyl imidazole
- drugs
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Anti-clavicular spirochete drugs ethyl imidazole synthesis method Abstract 5 The present invention discloses anti-clavicular spirochete drugs ethyl imidazole synthesis method, comprises the following steps: 2,5-dihydroxyimidazole-4-carboxylate, potassium sulfate solution were added to the reaction vessel, controlled the stirring speed, raised the temperature, continued the reaction; increased the temperature, added dicyclohexylamine solution, added the 10 octacarbonyl cobalt oxide powder in batches, continued to react, reduced the temperature, precipitated the solids, washed with sodium nitrate solution for several times, washed with cyclohexane solution for several times, recrystallized in the tripropylene glycol monomethyl ether solution, dehydrated with dehydration, got the finished product ethyl imidazole.
Description
The present invention discloses anti-clavicular spirochete drugs ethyl imidazole synthesis method, comprises the following steps:
2,5-dihydroxyimidazole-4-carboxylate, potassium sulfate solution were added to the reaction vessel, controlled the stirring speed, raised the temperature, continued the reaction; increased the temperature, added dicyclohexylamine solution, added the octacarbonyl cobalt oxide powder in batches, continued to react, reduced the temperature, precipitated the solids, washed with sodium nitrate solution for several times, washed with cyclohexane solution for several times, recrystallized in the tripropylene glycol mo no methyl ether solution, dehydrated with dehydration, got the finished product ethyl imidazole.
2018100847 21 Jun 2018
Anti-clavicular spirochete drugs ethyl imidazole synthesis method
FIELD OF THE INVENTION
The present invention relates to a method for preparing a pharmaceutical 5 intermediate which belongs to the field of organic synthesis, more particularly, relates to anti-clavicular spirochete drugs ethyl imidazole synthesis method.
GENERAL BACKGROUND
Ethyl imidazole has a significant anti-clavicular spirochete effect. Rapid absorpted by body after oral administration, it is widely distributed in the body, and through the blood-brain barrier into the central nervous system. Most of the existing synthesis methods are using the process that 2-mercaptoimidazole-4-carboxylate and nitric acid solution as the main reaction to generate ethyl imidazole. This synthesis method needs to use nitric acid solution as reactants, the ability of the equipment to resist corrosion is higher, the cost of production increases, the process is more complex, the final yield is not high, generally only about 80%. Therefore, it is necessary to propose a new synthesis method.
SUMMARY
Based on the technical problems of the background technology, the purpose of the present invention is to provide anti-clavicular spirochete drugs ethyl imidazole synthesis method, comprises the following steps:
A: 2,5-dihydroxyimidazole-4-carboxylate, potassium sulfate solution were added to the reaction vessel, controlled the stirring speed at 210-250 rpm, raised the temperature to 30-36 °C, continued the reaction 90-130 min;
B: increased the temperature to 40-45 °C, added dicyclohexylamine solution, added the octacarbonyl cobalt oxide powder in batches, continued to react for 2-3h, reduced the temperature to 10-15 °C, precipitated the solids, washed with sodium nitrate solution for several times, washed with cyclohexane solution for several times, recrystallized in the tripropylene glycol monomethyl ether solution, dehydrated with dehydration, got the finished product ethyl imidazole.
Preferably, the potassium sulfate solution has a mass fraction of 15-21%.
2018100847 21 Jun 2018
Preferably, the mass fraction of the dicyclohexylamine solution is 30-36%. Preferably, the sodium nitrate solution solution has a mass fraction of 10-17%. Preferably, the cyclohexane solution has a mass fraction of 40-45%.
Preferably, the mass fraction of tripropylene glycol monomethyl ether solution is
80-86%.
Throughout the reaction process can be the following reaction formula:
0H + C|2H2,N + Co2(CO)3
C2H5OOC'
Compared with the synthesis method disclosed in the background art, the invention provides anti-clavicular spirochete drugs ethyl imidazole synthesis method, it is unnecessary to use nitric acid solution as reactants, reducing the anti-corrosion capability of equipment, reducing intermediate links reaction, decreasing the reaction time and improving the reaction yield, at the same time, the present invention provides a new synthetic route which has laid a good foundation for further enhancing the yield of the reaction.
DESCRIPTION OF THE DRAWINGS
Figure 1 is the infrared analysis spectrum of finished product p-nitrobenzoic acid.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
The following examples with reference to specific embodiments of the present invention are further illustrated:
Embodiment 1
Anti-clavicular spirochete drugs ethyl imidazole synthesis method, comprises the following steps:
A: 2 mol 2,5-dihydroxyimidazole-4-carboxylate, 1.9L potassium sulfate solution with a mass fraction of 15% were added to the reaction vessel, controlled the stirring speed at 210 rpm, raised the temperature to 30 °C, continued the reaction 90 min;
2018100847 21 Jun 2018
B: increased the temperature to 40 °C, added 6mol dicyclohexylamine solution with a mass fraction of 30%, added 3 mol octacarbonyl cobalt oxide powder in 4 times, continued to react for 2h, reduced the temperature to 10 °C, precipitated the solids, washed with 1.2L sodium nitrate solution with a mass fraction of 10% for 5 times, washed with cyclohexane solution with a mass fraction of 40% for 3 times, recrystallized in the tripropylene glycol monomethyl ether solution with a mass fraction of 80%, dehydrated with anhydrous magnesium sulfate dehydration, got the finished product ethyl imidazole 240.8g, yield of 86%.
Embodiment 2
Anti-clavicular spirochete drugs ethyl imidazole synthesis method, comprises the following steps:
A: 2 mol 2,5-dihydroxyimidazole-4-carboxylate, 1.9L potassium sulfate solution with a mass fraction of 18% were added to the reaction vessel, controlled the stirring speed at 230 rpm, raised the temperature to 33 °C, continued the reaction 110 min;
B: increased the temperature to 42.5 °C, added 7mol dicyclohexylamine solution with a mass fraction of 33%, added 3.5 mol octacarbonyl cobalt oxide powder in 5 times, continued to react for 2.5h, reduced the temperature to 12.5 °C, precipitated the solids, washed with 1.2L sodium nitrate solution with a mass fraction of 13.5% for 6 times, washed with cyclohexane solution with a mass fraction of 42.5% for 4 times, recrystallized in the tripropylene glycol monomethyl ether solution with a mass fraction of 83%, dehydrated with activated alumina dehydration, got the finished product ethyl imidazole 254.8g, yield of 91%.
Embodiment 3
Anti-clavicular spirochete drugs ethyl imidazole synthesis method, comprises the following steps:
A: 2 mol 2,5-dihydroxyimidazole-4-carboxylate, 1.9L potassium sulfate solution with a mass fraction of 21% were added to the reaction vessel, controlled the stirring speed at 250 rpm, raised the temperature to 36 °C, continued the reaction 130 min;
B: increased the temperature to 45 °C, added 8mol dicyclohexylamine solution 30 with a mass fraction of 36%, added 4 mol octacarbonyl cobalt oxide powder in 6 times,
2018100847 21 Jun 2018 continued to react for 3h, reduced the temperature to 15 °C, precipitated the solids, washed with 1.2L sodium nitrate solution with a mass fraction of 17% for 7 times, washed with cyclohexane solution with a mass fraction of 45% for 5 times, recrystallized in the tripropylene glycol monomethyl ether solution with a mass fraction of 86%, dehydrated with anhydrous magnesium sulfate dehydration, got the finished product ethyl imidazole 263.2g, yield of 94%.
The embodiments of the present invention are merely preferred embodiments of the present invention, but the range of the present invention is not limited this, and any person who is familiar with those skilled in the arts, within the technical range of the present invention. It is intended that the technical solution and its inventive concept be replaced or modified equivalently with reference to the range of the invention.
2018100847 21 Jun 2018
Claims (4)
- Claims1. Anti-clavicular spirochete drugs ethyl imidazole synthesis method, comprises the following steps:5 A: 2,5-dihydroxyimidazole-4-carboxylate, potassium sulfate solution were added to the reaction vessel, controlled the stirring speed at 210-250 rpm, raised the temperature to 30-36 °C, continued the reaction 90-130 min;B: increased the temperature to 40-45 °C, added dicyclohexylamine solution, added the octacarbonyl cobalt oxide powder in batches, continued to react for 2-3h,10 reduced the temperature to 10-15 °C, precipitated the solids, washed with sodium nitrate solution for several times, washed with cyclohexane solution for several times, recrystallized in the tripropylene glycol monomethyl ether solution, dehydrated with dehydration, got the finished product ethyl imidazole.
- 2. Anti-clavicular spirochete drugs ethyl imidazole synthesis method according15 to claim 1 wherein the potassium sulfate solution has a mass fraction of 15-21%.
- 3. Anti-clavicular spirochete drugs ethyl imidazole synthesis method according to claim 1 wherein the mass fraction of the dicyclohexylamine solution is 30-36%.
- 4. Anti-clavicular spirochete drugs ethyl imidazole synthesis method according to claim 1 wherein the sodium nitrate solution solution has a mass fraction of 10-17%.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710715096.3A CN108239032A (en) | 2017-08-19 | 2017-08-19 | The anti-synthetic method for hooking Leptospiral drug imidazole carboxylate |
| CN2017107150963 | 2017-08-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2018100847A4 true AU2018100847A4 (en) | 2018-08-02 |
Family
ID=60037232
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2018100847A Ceased AU2018100847A4 (en) | 2017-08-19 | 2018-06-21 | Anti-clavicular spirochete drugs ethyl imidazole synthesis method |
Country Status (4)
| Country | Link |
|---|---|
| CN (1) | CN108239032A (en) |
| AU (1) | AU2018100847A4 (en) |
| GB (1) | GB201713880D0 (en) |
| IE (1) | IES20180200A2 (en) |
-
2017
- 2017-08-19 CN CN201710715096.3A patent/CN108239032A/en active Pending
- 2017-08-30 GB GBGB1713880.1A patent/GB201713880D0/en not_active Ceased
-
2018
- 2018-06-21 AU AU2018100847A patent/AU2018100847A4/en not_active Ceased
- 2018-06-26 IE IES20180200 patent/IES20180200A2/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| GB201713880D0 (en) | 2017-10-11 |
| IES20180200A2 (en) | 2019-11-13 |
| CN108239032A (en) | 2018-07-03 |
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| FGI | Letters patent sealed or granted (innovation patent) | ||
| MK22 | Patent ceased section 143a(d), or expired - non payment of renewal fee or expiry |