AU2018100846A4 - Anti-amoebic dysentery drug phenidone synthesis method - Google Patents
Anti-amoebic dysentery drug phenidone synthesis method Download PDFInfo
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- AU2018100846A4 AU2018100846A4 AU2018100846A AU2018100846A AU2018100846A4 AU 2018100846 A4 AU2018100846 A4 AU 2018100846A4 AU 2018100846 A AU2018100846 A AU 2018100846A AU 2018100846 A AU2018100846 A AU 2018100846A AU 2018100846 A4 AU2018100846 A4 AU 2018100846A4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- Nitrogen Condensed Heterocyclic Rings (AREA)
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Abstract
Anti-amoebic dysentery drug phenidone synthesis method Abstract 5 The present invention discloses anti-amoebic dysentery drug phenidone synthesis method, comprises the following steps: 5 -hydroxy-6-methoxy-4,7-diazepine and potassium chloride solution were added to the reaction vessel, raised the temperature of the solution and the stirring speed was controlled, reacted; added sodium sulfate solution, raised the temperature of the solution, and then added diethyl sebacate 10 solution, added ferrocene cobalt powder, then react, decreased the temperature, adjusted the pH, washed several times with benzyl chloride solution, 2,3-dimethylbutane solution many times, recrystallized in 2,4-dichlorotoluene solution, dehydrated with dehydration, got the finished product phenidone.
Description
The present invention discloses anti-amoebic dysentery drug phenidone synthesis method, comprises the following steps:5-hydroxy-6-methoxy-4,7-diazepine and potassium chloride solution were added to the reaction vessel, raised the temperature of the solution and the stirring speed was controlled, reacted; added sodium sulfate solution, raised the temperature of the solution, and then added diethyl sebacate solution, added ferrocene cobalt powder, then react, decreased the temperature, adjusted the pH, washed several times with benzyl chloride solution,
2,3-dimethylbutane solution many times, recrystallized in 2,4-dichlorotoluene solution, dehydrated with dehydration, got the finished product phenidone.
2018100846 21 Jun 2018
Anti-amoebic dysentery drug phenidone 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-amoebic dysentery drug phenidone synthesis method.
GENERAL BACKGROUND
Phenidone drugs are mainly used for anti-amoebic dysentery, dysentery drugs, the existing synthesis methods are mostly using the process that o-acetamid anisole generated 2,5-diamino anisole sulfate after nitration, reduction and hydrolysis, and then reacts with glycerol, concentrated sulfuric acid in the presence of iodine and potassium iodide, then 6-methoxy-4,7-diazepine after cyclization, and then gets the finished product after further oxidation. This synthesis method requires the use of nitric acid and concentrated sulfuric acid as reactants, due to the strong oxidation and corrosion of concentrated sulfuric acid, it is necessary that the equipmen requires high corrosion resistance ability, the production costs also increased, and the synthesis method is complicated and the final yield is not very high. 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-amoebic dysentery drug phenidone synthesis method, comprises the following steps:
A: 5-hydroxy-6-methoxy-4,7-diazepine and potassium chloride solution were added to the reaction vessel, raised the temperature of the solution to 30-40 °C and the stirring speed was controlled at 230-260 rpm, reacted for 2-3 h;
B: added sodium sulfate solution, raised the temperature of the solution to 50-60 °C, and then added diethyl sebacate solution, added ferrocene cobalt powder in
50-70 min, then react for 90-120 min, decreased the temperature to 10-17 °C, adjusted
2018100846 21 Jun 2018 the pH to 5.5-6, washed several times with benzyl chloride solution,
2,3-dimethylbutane solution many times, recrystallized in2,4-dichlorotoluene solution, dehydrated with dehydration, got the finished product phenidone.
Preferably, the potassium chloride solution has a mass fraction of 10-17%.
Preferably, the mass fraction of the sodium sulfate solution is 20-26%.
Preferably, the diethyl sebacate has a mass fraction of 35-41%.
Preferably, the benzyl chloride solution has a mass fraction of 40-46%.
Preferably, the 2,3-dimethylbutane solution has a mass fraction of 60-65%. Preferably, the mass fraction of 2,4-dichlorotoluene solution is 80-87%.
Throughout the reaction process can be the following reaction formula:
Compared with the synthesis method disclosed in the background art, the invention provides anti-amoebic dysentery drug phenidone synthesis method, it is unnecessary to use nitric acid and concentrated sulfuric acid as reactants, avoiding the strong oxidation and corrosion of nitric acid and concentrated sulfuric acid and reducing the production costs, 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 phenidone.
2018100846 21 Jun 2018
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
The following examples with reference to specific embodiments of the present invention are further illustrated:
Embodiment 1
Anti-amoebic dysentery drug phenidone synthesis method, comprises the following steps:
A: 3 mol 5-hydroxy-6-methoxy-4,7-diazepine and 1.6L potassium chloride solution with a mass fraction of 10% were added to the reaction vessel, raised the temperature of the solution to 30 °C and the stirring speed was controlled at 230rpm, reacted for 2 h;
B: added 900ml sodium sulfate solution with a mass fraction of 20%, raised the temperature of the solution to 50 °C, and then added 6 mol diethyl sebacate solution with a mass fraction of 35%, added 3 mol ferrocene cobalt powder in 3 times within 50 min, then reacted for 90 min, decreased the temperature to 10 °C, adjusted the pH to
5.5, washed 5 times with benzyl chloride solution with a mass fraction of 40%, washed times 2,3-dimethylbutane solution with a mass fraction of 60%, recrystallized in
2,4-dichlorotoluene solution with a mass fraction of 80%, dehydrated with anhydrous magnesium sulfate dehydration, got the finished product phenidone 548.lg, yield of 87%.
Embodiment 2
Anti-amoebic dysentery drug phenidone synthesis method, comprises the following steps:
A: 3 mol 5-hydroxy-6-methoxy-4,7-diazepine and 1.6L potassium chloride solution with a mass fraction of 13% were added to the reaction vessel, raised the temperature of the solution to 35 °C and the stirring speed was controlled at 250rpm, reacted for 2.5 h;
B: added 900ml sodium sulfate solution with a mass fraction of 23%, raised the temperature of the solution to 55 °C, and then added 7 mol diethyl sebacate solution with a mass fraction of 38%, added 3.5 mol ferrocene cobalt powder in 4 times within
60 min, then reacted for 110 min, decreased the temperature to 13 °C, adjusted the pH
2018100846 21 Jun2018 to 5.7, washed 5 times with benzyl chloride solution with a mass fraction of 43%, washed 6 times 2,3-dimethylbutane solution with a mass fraction of 62%, recrystallized in 2,4-dichlorotoluene solution with a mass fraction of 83%, dehydrated with activated alumina dehydration, got the finished product phenidone 573.3g, yield of 91%.
Embodiment 3
Anti-amoebic dysentery drug phenidone synthesis method, comprises the following steps:
A: 3 mol 5-hydroxy-6-methoxy-4,7-diazepine and 1.6L potassium chloride solution with a mass fraction of 17% were added to the reaction vessel, raised the temperature of the solution to 40 °C and the stirring speed was controlled at 260rpm, reacted for 3 h;
B: added 900ml sodium sulfate solution with a mass fraction of 26%, raised the temperature of the solution to 60 °C, and then added 8 mol diethyl sebacate solution with a mass fraction of 41%, added 4 mol ferrocene cobalt powder in 5 times within 70 min, then reacted for 120 min, decreased the temperature to 17 °C, adjusted the pH to 6, washed 7 times with benzyl chloride solution with a mass fraction of 46%, washed 8 times 2,3-dimethylbutane solution with a mass fraction of 65%, recrystallized in 2,4-dichlorotoluene solution with a mass fraction of 87%, dehydrated with anhydrous potassium carbonate dehydration, got the finished product phenidone 592.2g, 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.
2018100846 21 Jun 2018
Claims (4)
- Claims1. Anti-amoebic dysentery drug phenidone synthesis method, comprises the following steps:5 A: 5-hydroxy-6-methoxy-4,7-diazepine and potassium chloride solution were added to the reaction vessel, raised the temperature of the solution to 30-40 °C and the stirring speed was controlled at 230-260 rpm, reacted for 2-3 h;B: added sodium sulfate solution, raised the temperature of the solution to 50-60 °C, and then added diethyl sebacate solution, added ferrocene cobalt powder in10 50-70 min, then react for 90-120 min, decreased the temperature to 10-17 °C, adjusted the pH to 5.5-6, washed several times with benzyl chloride solution, 2,3-dimethylbutane solution many times, recrystallized in 2,4-dichlorotoluene solution, dehydrated with dehydration, got the finished product phenidone.
- 2. Anti-amoebic dysentery drug phenidone synthesis method according to claim15 1 wherein the potassium chloride solution has a mass fraction of 10-17%.
- 3. Anti-amoebic dysentery drug phenidone synthesis method according to claim 1 wherein the mass fraction of the sodium sulfate solution is 20-26%.
- 4. Anti-amoebic dysentery drug phenidone synthesis method according to claim 1 wherein the diethyl sebacate has a mass fraction of 35-41%.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710710185.9A CN108239088A (en) | 2017-08-19 | 2017-08-19 | The synthetic method of the luxuriant and rich with fragrance two pyridine ketone of anti-amoebic dysentery drug |
| CN2017107101859 | 2017-08-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2018100846A4 true AU2018100846A4 (en) | 2018-08-02 |
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| Application Number | Title | Priority Date | Filing Date |
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| AU2018100846A Ceased AU2018100846A4 (en) | 2017-08-19 | 2018-06-21 | Anti-amoebic dysentery drug phenidone synthesis method |
Country Status (3)
| Country | Link |
|---|---|
| CN (1) | CN108239088A (en) |
| AU (1) | AU2018100846A4 (en) |
| GB (1) | GB201713876D0 (en) |
-
2017
- 2017-08-19 CN CN201710710185.9A patent/CN108239088A/en active Pending
- 2017-08-30 GB GBGB1713876.9A patent/GB201713876D0/en not_active Ceased
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2018
- 2018-06-21 AU AU2018100846A patent/AU2018100846A4/en not_active Ceased
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| Publication number | Publication date |
|---|---|
| CN108239088A (en) | 2018-07-03 |
| GB201713876D0 (en) | 2017-10-11 |
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