CN107325053A - A kind of refined and discoloration method of Orazamide - Google Patents
A kind of refined and discoloration method of Orazamide Download PDFInfo
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- CN107325053A CN107325053A CN201710694983.7A CN201710694983A CN107325053A CN 107325053 A CN107325053 A CN 107325053A CN 201710694983 A CN201710694983 A CN 201710694983A CN 107325053 A CN107325053 A CN 107325053A
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- Prior art keywords
- orazamide
- refined
- crude product
- discoloration method
- activated carbon
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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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
- C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
- C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/557—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms, e.g. orotic acid
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of refined and discoloration method of Orazamide, comprise the following steps：(A) by the Orazamide crude product containing pigment impurity, add solvent and dissolve by heating；(B) input activated carbon and sodium hydrosulfite, are stirred at reflux at a temperature of controlling；(C) filtering cooling crystallization, obtains the Orazamide of white, and yield is 80%~90%.The method mild condition of the present invention, the operation cycle is short, and decolorizing efficiency is good, environment-friendly, and decolorising agent is economical and easily available, is adapted to industrialized production.
Description
Technical field
The present invention relates to organic medicinal chemistry field, a kind of refined and discoloration method of Orazamide is more particularly related to.
Background technology
Orazamide is the Orotate of 4- amino -5- Imidazole carboxamides, is mainly used in acute, chronic hepatitis, fatty liver, liver
Hardening, the treatment of icteric hepatitis, can additionally alleviate the symptom of alcoholic hepatitis.Orazamide outward appearance is white, still
The crude product obtained in building-up process is mostly light grey to lark, and its pigment impurity is more difficult in refined to be removed.It is right at present
Method that the pigment impurity is removed is temporarily without document report, in order to remove the color in medicine, generally by add activated carbon,
The decolorising agents such as diatomite are decolourized, but this method, which needs repeatedly to refine, could remove pigment impurity, greatly reduce product
Yield.
The content of the invention
It is an object of the invention to provide a kind of discoloration method of Orazamide, needed for above-mentioned conventional decolouring technology many
The technological deficiency of secondary refinery decolorization, the present inventor has carried out a large amount of exploration discoveries to the discoloration method of Orazamide：By one
The method for determining to add joint decolorising agent at temperature, it is only necessary to which primary purification can just make it that the outward appearance of product is qualified.This method operation letter
It is single, without repeatedly refined, greatly improve product yield.
The refined and discoloration method of the Orazamide of the present invention, comprises the following steps：
(A) by the Orazamide crude product containing pigment impurity, solvent dissolving is added；
(B) input activated carbon and sodium hydrosulfite, are stirred at reflux at a temperature of controlling；
(C) filtering cooling crystallization, obtains the Orazamide of white, and yield is 80%~90%.
It is preferred that the refined and discoloration method of the Orazamide of the present invention, comprises the following steps：
(A) by the Orazamide crude product containing pigment impurity, solvent is added in 20~90 DEG C of dissolvings；
(B) input activated carbon and sodium hydrosulfite in the case where temperature is 20~90 DEG C, are stirred at reflux；
(C) filtering cooling crystallization, obtains the Orazamide of white, and yield is 80%~90%.
It is an option that the refined and discoloration method of the Orazamide of the present invention, comprises the following steps：
(A) by the Orazamide crude product containing pigment impurity, solvent is added in 60~80 DEG C of heating for dissolving；
(B) input activated carbon and sodium hydrosulfite in the case where temperature is 60~80 DEG C, continue temperature rising reflux and stir 10~30min；
(C) filtering cooling crystallization, temperature is 5~20 DEG C, obtains the Orazamide of white, and yield is 83%~90%.
In the refined and discoloration method of the Orazamide of the present invention, described solvent is selected from water, methanol, ethanol or isopropyl
Alcohol, is used alone a kind of or is used in mixed way, when being used in mixed way two kinds of solvents, the mixing ratio of two kinds of solvents is 1-2：3-1；Compared with
Good, when being used in mixed way water and ethanol, the mixing ratio of two kinds of solvents is 1-2：2-1, the usage amount of solvent is Orazamide
30~60 times of crude product weight, preferred solvent is absolute ethyl alcohol.
In the refined and discoloration method of the Orazamide of the present invention, the usage amount of activated carbon is Orazamide crude product weight
10~30%, it is preferred that the usage amount of activated carbon be Orazamide crude product weight 20~30%.
In the refined and discoloration method of the Orazamide of the present invention, the usage amount of sodium hydrosulfite is Orazamide crude product weight
5~20%, it is preferred that the usage amount of sodium hydrosulfite be Orazamide crude product weight 10~15%.
The refined and discoloration method of the Orazamide of the present invention, comprises the following steps：
(A) by the Orazamide crude product containing pigment impurity, solvent is added in 60~80 DEG C of heating for dissolving, described solvent
For water and ethanol, the use ratio of water and ethanol is 1:1, the use ratio of solvent and Orazamide crude product is 50:1；
(B) input activated carbon and sodium hydrosulfite in the case where temperature is 60~80 DEG C, continue temperature rising reflux and stir 10~20min, living
Property charcoal usage amount be the 20~30% of Orazamide crude product, the usage amount of sodium hydrosulfite is the 10~15% of Orazamide crude product；
(C) filter while hot, filtrate continues to be cooled to 10~20 DEG C, and a large amount of white solids are separated out, and continues to be incubated 0.5h, mistake
Filter, obtains white Orazamide solid, then 50 DEG C of forced air drying 2h, and yield is 80%~90%.
The present invention is compared to the other decoloration process of Orazamide and had the advantage that：
(1) use and use joint decolorising agent to add sodium hydrosulfite reduction de- for activated carbon decolorizing in the method and step (B) of the present invention
Color, the decolorising agent is cheap and easy to get, and decolorizing effect will be far better than other decolorising agents；
(2) primary purification is only needed to add decolouring using the method for the present invention, yield is needed not move through many between 80%~90%
Secondary refined plus decolouring, substantially increases product yield；
In summary, raw material of the present invention is easy to get, high income, effect are good, steady quality, it is adaptable to industrialized production there is provided
One more economical, more easily the discoloration method of Orazamide.
In the present invention, refer in particular to as non-, all amount, percentage are mass unit, are using Orazamide crude product as base
Plinth.All raw material, equipment can be bought from market.
Embodiment
Below by embodiment, the present invention will be further described, and preparating example of the present invention and implementation are merely illustrative this
Invention, rather than the limitation to invention.
Embodiment 1：
Lurid Orazamide crude product 20g is put into 50 times of volume absolute ethyl alcohols under normal temperature, temperature 70 C is warming up to,
The disposable Orazamide crude product that adds weighs 20% activated carbon and 10% sodium hydrosulfite, continues temperature rising reflux stirring 15min, rotating speed
300rpm.Filter while hot, continue to be cooled to 10~20 DEG C in filtrate 1h, a large amount of white solids are separated out, continue to be incubated 0.5h, mistake
Filter, obtains white solid, in 50 DEG C of forced air drying 2h, weigh 17.4g, yield 87%.
Embodiment 2：
Light yellow Orazamide crude product 20g is put into 50 times of volume absolute ethyl alcohols and water (volume ratio ethanol under normal temperature：Water=
1:1) in, 80 DEG C of temperature is warming up to, disposable addition Orazamide crude product weighs 25% activated carbon and Orazamide crude product weighs 15%
Sodium hydrosulfite, continues temperature rising reflux stirring 15min, rotating speed 300rpm.Filter while hot, continue to be cooled to 10~20 DEG C in filtrate 1h,
A large amount of white solids are separated out, and continue to be incubated 0.5h, filtering obtains white solid, in 50 DEG C of forced air drying 2h, is weighed as 16.9g,
Yield 84.5%.
Embodiment 3：
Light grey Orazamide crude product 20g is put into 50 times of volume of water under normal temperature, 80 DEG C of temperature is warming up to, it is disposable to add
Enter Orazamide crude product and weigh 25% activated carbon and 10% sodium hydrosulfite, continue temperature rising reflux stirring 15min, rotating speed 300rpm.
Filter while hot, continue to be cooled to 10~20 DEG C in filtrate 1h, a large amount of white solids are separated out, continue to be incubated 0.5h, filtering obtains white
Color solid, in 50 DEG C of forced air drying 2h, is weighed as 17.7g, yield 88.5%.
Embodiment 4：
Light grey Orazamide crude product 20g is put into 50 times of volume of water under normal temperature, temperature 70 C is warming up to, it is disposable to add
Enter activated carbon and 15% sodium hydrosulfite that Orazamide crude product weighs 15%, continue temperature rising reflux stirring 15min, rotating speed 150rpm.Take advantage of
Continue to be cooled to 5~15 DEG C in heat filtering, filtrate 50min, a large amount of white solids are separated out, continue to be incubated 0.5h, filtering obtains white
Color solid, in 50 DEG C of forced air drying 2h, is weighed as 16.5g, yield 82.5%.
Comparative example 1：
Light grey Orazamide crude product 20g is put into 50 times of volume of water under normal temperature, Orazamide crude product is added and weighs 10%
Activated carbon and temperature rising reflux stirring 15min, rotating speed 500rpm.Filter while hot, continue to be cooled to 10~30 DEG C in filtrate 1h, greatly
Measure solid to separate out, continue to be incubated 0.5h, filtering obtains dark gray solid, in 50 DEG C of forced air drying 2h, is weighed as 17.9g, repeats
Add same ratio water and activated carbon carry out decolorization 2 times after obtain white solid, in 50 DEG C of forced air drying 2h, weigh
For 13.5g, yield 67.5%.
Comparative example 2：
Light grey Orazamide crude product 20g is put into 50 times of volume of water under normal temperature, Orazamide crude product is added and weighs 30%
Activated carbon and temperature rising reflux stirring 15min, rotating speed 500rpm.Filter while hot, continue to be cooled to 10~30 DEG C in filtrate 1h, greatly
Measure solid to separate out, continue to be incubated 0.5h, filtering obtains dark gray solid, in 50 DEG C of forced air drying 2h, is weighed as 17.9g, obtains
White solid, in 50 DEG C of forced air drying 2h, is weighed as 13.5g, yield 77.5%.
Comparative example 3：
Light grey Orazamide crude product 20g is put into 50 times of volume of water under normal temperature, 80 DEG C of temperature is warming up to, it is disposable to add
Enter the sodium hydrosulfite that Orazamide crude product weighs 30%, continue temperature rising reflux stirring 15min, rotating speed 300rpm.Filter while hot, filtrate 1h
Inside continue to be cooled to 10~20 DEG C, a large amount of white solids are separated out, continue to be incubated 0.5h, filtering obtains white solid, in 50 DEG C of drums
Dry 2h is air-dried, 17.7g, yield 68.5% is weighed as.
The Orazamide that we are obtained by embodiment 1-4, is compared to comparative example and needs not move through multiple refine
Plus decolourize, you can white Orazamide is obtained, and color is substantially white in comparative example.
Claims (10)
1. the refined and discoloration method of a kind of Orazamide, it is characterised in that comprise the following steps：
(A) by the Orazamide crude product containing pigment impurity, solvent dissolving is added；
(B) input activated carbon and sodium hydrosulfite, are stirred at reflux at a temperature of controlling；
(C) filtering cooling crystallization, obtains the Orazamide of white.
2. the refined and discoloration method of Orazamide according to claim 1, it is characterised in that comprise the following steps：
(A) by the Orazamide crude product containing pigment impurity, solvent is added in 20~90 DEG C of dissolvings；
(B) input activated carbon and sodium hydrosulfite in the case where temperature is 20~90 DEG C, are stirred at reflux；
(C) filtering cooling crystallization, obtains the Orazamide of white, and yield is 80%~90%.
3. the refined and discoloration method of Orazamide according to claim 1, it is characterised in that comprise the following steps：
(A) by the Orazamide crude product containing pigment impurity, solvent is added in 60~80 DEG C of heating for dissolving；
(B) input activated carbon and sodium hydrosulfite in the case where temperature is 60~80 DEG C, continue temperature rising reflux and stir 10~30min；
(C) filtering cooling crystallization, temperature is 5~20 DEG C, obtains the Orazamide of white, and yield is 83%~90%.
4. the refined and discoloration method of the Orazamide according to one of claim 1-3, it is characterised in that described solvent
Selected from water, methanol, ethanol or isopropanol, it is used alone a kind of or is used in mixed way.
5. the refined and discoloration method of Orazamide according to claim 4, it is characterised in that molten when being used in mixed way two kinds
During agent, the mixing ratio of two kinds of solvents is 1-2：3-1.
6. the refined and discoloration method of Orazamide according to claim 5, it is characterised in that when being used in mixed way water and second
During alcohol, the mixing ratio of two kinds of solvents is 1-2：2-1.
7. the refined and discoloration method of the Orazamide according to one of claim 1-3, it is characterised in that the use of solvent
Measure as 30~60 times of Orazamide crude product weight.
8. the refined and discoloration method of Orazamide according to one of claim 1-3, it is characterised in that activated carbon makes
Consumption is the 10~30% of Orazamide crude product weight.
9. the refined and discoloration method of Orazamide according to one of claim 1-3, it is characterised in that sodium hydrosulfite makes
Consumption is the 5~20% of Orazamide weight.
10. the refined and discoloration method of a kind of Orazamide, it is characterised in that comprise the following steps：
(A) by the Orazamide crude product containing pigment impurity, solvent is added in 60~80 DEG C of heating for dissolving, described solvent is water
And ethanol, the use ratio of water and ethanol is 1:1, the use ratio of solvent and Orazamide crude product is 50:1；
(B) input activated carbon and sodium hydrosulfite in the case where temperature is 60~80 DEG C, continue temperature rising reflux and stir 10~20min, activated carbon
Usage amount be the 20~30% of Orazamide crude product, the usage amount of sodium hydrosulfite is the 10~15% of Orazamide crude product；
(C) filter while hot, filtrate continues to be cooled to 10~20 DEG C, and a large amount of white solids are separated out, continue to be incubated 0.5h, filtering is obtained
To white Orazamide solid, then 50 DEG C of forced air drying 2h, yield is 80%~90%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710694983.7A CN107325053A (en) | 2017-08-15 | 2017-08-15 | A kind of refined and discoloration method of Orazamide |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710694983.7A CN107325053A (en) | 2017-08-15 | 2017-08-15 | A kind of refined and discoloration method of Orazamide |
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| CN107325053A true CN107325053A (en) | 2017-11-07 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201710694983.7A Pending CN107325053A (en) | 2017-08-15 | 2017-08-15 | A kind of refined and discoloration method of Orazamide |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3271398A (en) * | 1962-03-05 | 1966-09-06 | Fujisawa Pharmaceutical Co | Orotic acid salt of 4-amino-5-imidazolecarboxamide |
| JPS5163173A (en) * | 1974-11-28 | 1976-06-01 | Nippon Soda Co | 5 *4 * aminoimidazooru 4 * 5 * karubokishiamidono seiseiho |
-
2017
- 2017-08-15 CN CN201710694983.7A patent/CN107325053A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3271398A (en) * | 1962-03-05 | 1966-09-06 | Fujisawa Pharmaceutical Co | Orotic acid salt of 4-amino-5-imidazolecarboxamide |
| JPS5163173A (en) * | 1974-11-28 | 1976-06-01 | Nippon Soda Co | 5 *4 * aminoimidazooru 4 * 5 * karubokishiamidono seiseiho |
Non-Patent Citations (1)
| Title |
|---|
| 湖南医药工业研究所三室310组: "抗肝炎药阿卡明的合成", 《医药工业》 * |
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Application publication date: 20171107 |