CN106632080A - Flucytosine manufacturing process - Google Patents
Flucytosine manufacturing process Download PDFInfo
- Publication number
- CN106632080A CN106632080A CN201610720494.XA CN201610720494A CN106632080A CN 106632080 A CN106632080 A CN 106632080A CN 201610720494 A CN201610720494 A CN 201610720494A CN 106632080 A CN106632080 A CN 106632080A
- Authority
- CN
- China
- Prior art keywords
- kettle
- water
- reaction
- temperature
- flucytosine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- 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
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a flucytosine manufacturing process. The flucytosine manufacturing process comprises the following steps of condensation, cyclization, acidification, chlorination, amination and acidolysis. The flucytosine manufacturing process has the advantages of simplicity in operation procedure, safety in manufacturing operation, few technological process, low investment cost and suitability for mass production.
Description
Technical field
The present invention relates to pharmaceutical chemistry synthesis technical field, and in particular to a kind of production technology of Flucytosine.
Background technology
Flucytosine, for treating cryptococcus and candida albicans etc. caused by fungal infection, such as mycotic septicemia, the internal membrane of heart
Scorching, meningitis and lung and urethral infection antifungal.Be mainly used in skin and mucosa candidiasis, candida albicans endocarditis,
Candida arthritis, crypotococcal and chromoblastomycosis.Blood picture should be made regular check on during medication.Liver and kidney function not whole blood
Liquid patient and pregnant woman use with caution；Serious potential renal insufficiency patient disabling.The product contain abroad as treatment serious systemic white
Pearl bacterium and the choice drug of Cryptococcus infections, for fungoid meningitis, fungoid respiratory tract infection and black fungi disease are controlled
Treat.
But the production process of existing production chlorine cytimidine is more complicated and the Flucytosine purity produced and
Yield is relatively low, improve input cost.
The content of the invention
The present invention is the above-mentioned deficiency of solution, there is provided a kind of production technology of Flucytosine, is allowed to yield and significantly improves, produces
Safety, technical process are few, input cost is low.
The technical solution of the present invention：
A kind of production technology of Flucytosine, the production process of the Flucytosine is comprised the following steps：
Condensation, cyclization workshop section
To condensation（Cyclization）Kettle（Condensation, ring-closure reaction are carried out in same kettle）It is middle to add the solvent toluene for measuring and consolidate
Body sodium methoxide, chuck leads to hot water, under certain condition, Ethyl formate and methylfluoracetate is added dropwise, and drop finishes, insulation reaction 5 hours,
Obtain intermediate fluoric acid ester alcohol sodium stand-by；
Quantitative dimethyl suflfate and urea is added in reactor, at room temperature to obtain Methyl Isourea Sulfate stand-by for reaction；
Condensation reaction terminate after in cyclization（Condensation）The quantitative Methyl Isourea Sulfate of addition and 30% methanolic sodium methoxide are molten in kettle
Liquid, ring-closure reaction 5 hours under room temperature generate intermediate fluorouracil；After reaction terminates, material is proceeded to into layering kettle, added water quiet
Layering is put, the organic phase containing toluene carries out precipitation into toluene recovery kettle, the toluene of recovery is applied mechanically；Water mutually goes acidifying kettle further
Process；
(2) acidification of acidification section
The water of layering kettle is mutually proceeded to into acidifying kettle, 30% appropriate hydrochloric acid is added, chuck is logical to be steam heated to 50 DEG C, pressure-
In the case of 0.1Mpa, the NaOH in the hydrochloric acid of addition and in water phase surveys PH to 7 or so, and acidifying terminates；Acidifying kettle gas phase Jing
Condensation obtains methyl alcohol, alcohol mixture, and by-product methyl alcohol, ethanol are obtained after rectification and purification；Leftover materials go to press filtration in acidifying kettle
Machine press filtration, the solid barrelling for obtaining is standby；
Check that water is boiled to add water in kettle backward kettle without exception, then open manhole and put into packaged press filtration solid material, open chuck steaming
Vapour, is heated to uniform temperature, and insulation is lowered the temperature after 1 hour, centrifugation, the cyclocomplex fluorouracil solid for obtaining Jing after airflow drying,
Part as selling outside by-product, partly for the next step, press filtration and centrifuge waste water decontamination water treatment station；
(3) chlorination workshop section
Toluene, N, N dimethyl aniline, the metered chlorination tank of cyclocomplex fluorouracil, chuck are led to into steam, control temperature is one
Determine POCl3 is added dropwise in scope, fluorouracil occurs chlorination reaction with POCl3, generate the chloro- 5- fluorine of 2- methoxyl group -4- phonetic
Pyridine；
Check that hydrolysis kettle is without exception to add water into kettle, chuck leads to chilled brine, chloride is instilled in kettle, and temperature in the kettle keeps
25-45 DEG C, there is hydrolysis, production hydrogen chloride and phosphoric acid in the complete POCl3 of unreacted and dichloro phosphoric acid, and in N, N- bis-
Methylaniline forms hydrochloride and is dissolved in water；Material after hydrolysis stands, layering, and oil phase enters precipitation kettle, carries out precipitation, precipitation kettle
Last remaining material is the chloro- 5-FUs of chloride 2- methoxyl group -4- and goes the toluene recovery of amination operation, abjection to apply mechanically；
Water mutually enters neutralization kettle, and is neutralized DMA hydrochloride in water phase with the ammoniacal liquor and liquid caustic soda that reclaim, is allowed to shape
Into DMA, it is layered again afterwards, water layer enters sewage plant, containing N, N dimethyl aniline layer distillation dehydration rear enclosure is used；
(4) amination workshop section
The chloro- 5-FUs of chloride 2- methoxyl group -4- are proceeded to into amination kettle, 28% ammoniacal liquor is added, jacket steam intensification is opened, one
Aminating reaction is carried out under fixed condition；After aminating reaction terminates, cooling proceeds to filter press carries out press filtration, and the water layer containing ammoniacal liquor goes chlorination
In post and kettle；With being centrifuged after alcohol beating washing, mother liquor precipitation recovered alcohol, aminate filter cake removes hydrolysis procedure to filter cake；
(5) acidolysis workshop section
Add suitable quantity of water in acidolysis kettle, the concentrated sulfuric acid is added dropwise, add the aminate 2- methoxyl groups -4- amidos -5-FU after centrifugation
Filter cake, is incubated at 80 DEG C -90 DEG C, and be hydrolyzed reaction；After sampling confirms that acidolysis reaction terminates, cooling proceeds to neutralization kettle, temperature
At 30 DEG C -50 DEG C, with decrease temperature crystalline in liquid caustic soda and after remaining sulfuric acid, refining kettle is entered after centrifugation, add appropriate activity
Charcoal and water, are press-filtered out waste active carbon after intensification, then are centrifuged after lowering the temperature, and centrifuge waste water is back to acidolysis workshop section, and centrifugal solids Jing are double
Flucytosine product is obtained after cone vacuum drying.
As the further optimization of this programme, the step（1）Middle certain condition is under 50 DEG C -60 DEG C, condition of normal pressure.
As the further optimization of this programme, the step（2）In be heated to uniform temperature between 70 DEG C -80 DEG C.
As the further optimization of this programme, the step（3）Middle control temperature adds within the specific limits POCl3,
The temperature control is between 40 DEG C -50 DEG C.
As the further optimization of this programme, the step（4）In be under certain condition 80 DEG C -90 of controlling reaction temperature
DEG C, in kettle under pressure 0.5MPa-0.8MPa.
Beneficial effects of the present invention：
1. the present invention is by with methylfluoracetate, Ethyl formate, sodium methoxide, POCl3, ammonia etc. as primary raw material, Jing condensations,
The reaction of the operations such as cyclization, acidifying, chlorination, amination, acidolysis obtains product, and operational sequence is simple, production operation is safe, be adapted to scale
Metaplasia is produced；2. this project condenses recycling design using three-level chilled brine, and toluene, methyl alcohol, the condensation efficiency of ethanol are respectively
99%th, 96%, 97%, the recycling of solvent is improved, reduction is passed through cost.
Specific embodiment
All features disclosed in this specification, or disclosed all methods or during the step of, except mutually exclusive
Feature and/or step beyond, can combine by any way.
This specification（Including any accessory claim, summary）Disclosed in any feature, unless specifically stated otherwise,
Equivalent by other or with similar purpose alternative features are replaced.I.e., unless specifically stated otherwise, each feature is a series of
An example in equivalent or similar characteristics.
Embodiment：
A kind of production technology of Flucytosine, the production process of the Flucytosine is comprised the following steps：
Condensation, cyclization workshop section
To condensation（Cyclization）Kettle（Condensation, ring-closure reaction are carried out in same kettle）It is middle to add the solvent toluene for measuring and consolidate
Body sodium methoxide, chuck leads to hot water, under certain condition, Ethyl formate and methylfluoracetate is added dropwise, and drop finishes, insulation reaction 5 hours,
Obtain intermediate fluoric acid ester alcohol sodium stand-by；
Quantitative dimethyl suflfate and urea is added in reactor, at room temperature to obtain Methyl Isourea Sulfate stand-by for reaction；
Condensation reaction terminate after in cyclization（Condensation）The quantitative Methyl Isourea Sulfate of addition and 30% methanolic sodium methoxide are molten in kettle
Liquid, ring-closure reaction 5 hours under room temperature generate intermediate fluorouracil；After reaction terminates, material is proceeded to into layering kettle, added water quiet
Layering is put, the organic phase containing toluene carries out precipitation into toluene recovery kettle, the toluene of recovery is applied mechanically；Water mutually goes acidifying kettle further
Process；
(2) acidification of acidification section
The water of layering kettle is mutually proceeded to into acidifying kettle, 30% appropriate hydrochloric acid is added, chuck is logical to be steam heated to 50 DEG C, pressure-
In the case of 0.1Mpa, the NaOH in the hydrochloric acid of addition and in water phase surveys PH to 7 or so, and acidifying terminates；Acidifying kettle gas phase Jing
Condensation obtains methyl alcohol, alcohol mixture, and by-product methyl alcohol, ethanol are obtained after rectification and purification；Leftover materials go to press filtration in acidifying kettle
Machine press filtration, the solid barrelling for obtaining is standby；
Check that water is boiled to add water in kettle backward kettle without exception, then open manhole and put into packaged press filtration solid material, open chuck steaming
Vapour, is heated to uniform temperature, and insulation is lowered the temperature after 1 hour, centrifugation, the cyclocomplex fluorouracil solid for obtaining Jing after airflow drying,
Part as selling outside by-product, partly for the next step, press filtration and centrifuge waste water decontamination water treatment station；
(3) chlorination workshop section
Toluene, N, N dimethyl aniline, the metered chlorination tank of cyclocomplex fluorouracil, chuck are led to into steam, control temperature is one
Determine POCl3 is added dropwise in scope, fluorouracil occurs chlorination reaction with POCl3, generate the chloro- 5- fluorine of 2- methoxyl group -4- phonetic
Pyridine；
Check that hydrolysis kettle is without exception to add water into kettle, chuck leads to chilled brine, chloride is instilled in kettle, and temperature in the kettle keeps
25-45 DEG C, there is hydrolysis, production hydrogen chloride and phosphoric acid in the complete POCl3 of unreacted and dichloro phosphoric acid, and in N, N- bis-
Methylaniline forms hydrochloride and is dissolved in water；Material after hydrolysis stands, layering, and oil phase enters precipitation kettle, carries out precipitation, precipitation kettle
Last remaining material is the chloro- 5-FUs of chloride 2- methoxyl group -4- and goes the toluene recovery of amination operation, abjection to apply mechanically；
Water mutually enters neutralization kettle, and is neutralized DMA hydrochloride in water phase with the ammoniacal liquor and liquid caustic soda that reclaim, is allowed to shape
Into DMA, it is layered again afterwards, water layer enters sewage plant, containing N, N dimethyl aniline layer distillation dehydration rear enclosure is used；
(4) amination workshop section
The chloro- 5-FUs of chloride 2- methoxyl group -4- are proceeded to into amination kettle, 28% ammoniacal liquor is added, jacket steam intensification is opened, one
Aminating reaction is carried out under fixed condition；After aminating reaction terminates, cooling proceeds to filter press carries out press filtration, and the water layer containing ammoniacal liquor goes chlorination
In post and kettle；With being centrifuged after alcohol beating washing, mother liquor precipitation recovered alcohol, aminate filter cake removes hydrolysis procedure to filter cake；
(5) acidolysis workshop section
Add suitable quantity of water in acidolysis kettle, the concentrated sulfuric acid is added dropwise, add the aminate 2- methoxyl groups -4- amidos -5-FU after centrifugation
Filter cake, is incubated at 80 DEG C -90 DEG C, and be hydrolyzed reaction；After sampling confirms that acidolysis reaction terminates, cooling proceeds to neutralization kettle, temperature
At 30 DEG C -50 DEG C, with decrease temperature crystalline in liquid caustic soda and after remaining sulfuric acid, refining kettle is entered after centrifugation, add appropriate activity
Charcoal and water, are press-filtered out waste active carbon after intensification, then are centrifuged after lowering the temperature, and centrifuge waste water is back to acidolysis workshop section, and centrifugal solids Jing are double
Flucytosine product is obtained after cone vacuum drying.
As the further optimization of this programme, the step（1）Middle certain condition is under 50 DEG C -60 DEG C, condition of normal pressure.
As the further optimization of this programme, the step（2）In be heated to uniform temperature between 70 DEG C -80 DEG C.
As the further optimization of this programme, the step（3）Middle control temperature adds within the specific limits POCl3,
The temperature control is between 40 DEG C -50 DEG C.
As the further optimization of this programme, the step（4）In be under certain condition 80 DEG C -90 of controlling reaction temperature
DEG C, in kettle under pressure 0.5MPa-0.8MPa.
The present invention is produced by condensation, cyclization workshop section, acidification of acidification section, chlorination workshop section, amination workshop section, acidolysis workshop section process
The yield of Flucytosine is 79%, operational sequence is simple, production operation is safe, be adapted to large-scale production；This project adopts three-level
Chilled brine condenses recycling design, and toluene, methyl alcohol, the condensation efficiency of ethanol are respectively 99%, 96%, 97%, improve the recovery of solvent
Utilize, reduction is passed through cost.
The basic teaching of the present invention is illustrated, for the people with the usual technical ability in this area, many extensions and change
Change will be aobvious and the person of being apparent from.Because the present invention that specification is disclosed can be in other spies without departing from spirit of the invention or general characteristics
Setting formula is implementing, and some forms of these particular forms have been noted, so, specification embodiments of the disclosure should be regarded as
Illustrate rather than restriction.The scope of the present invention is defined by appended claim, rather than by described above institute circle
It is fixed, for all changes of the impartial meaning and scope that fall into claim still will be contained within the scope of it.
Claims (5)
1. a kind of production technology of Flucytosine, it is characterised in that the production process of the Flucytosine includes following step
Suddenly：
Condensation, cyclization workshop section
To condensation（Cyclization）Kettle（Condensation, ring-closure reaction are carried out in same kettle）It is middle to add the solvent toluene for measuring and consolidate
Body sodium methoxide, chuck leads to hot water, under certain condition, Ethyl formate and methylfluoracetate is added dropwise, and drop finishes, insulation reaction 5 hours,
Obtain intermediate fluoric acid ester alcohol sodium stand-by；
Quantitative dimethyl suflfate and urea is added in reactor, at room temperature to obtain Methyl Isourea Sulfate stand-by for reaction；
Condensation reaction terminate after in cyclization（Condensation）The quantitative Methyl Isourea Sulfate of addition and 30% methanolic sodium methoxide are molten in kettle
Liquid, ring-closure reaction 5 hours under room temperature generate intermediate fluorouracil；After reaction terminates, material is proceeded to into layering kettle, added water quiet
Layering is put, the organic phase containing toluene carries out precipitation into toluene recovery kettle, the toluene of recovery is applied mechanically；Water mutually goes acidifying kettle further
Process；
(2) acidification of acidification section
The water of layering kettle is mutually proceeded to into acidifying kettle, 30% appropriate hydrochloric acid is added, chuck is logical to be steam heated to 50 DEG C, pressure-
In the case of 0.1Mpa, the NaOH in the hydrochloric acid of addition and in water phase surveys PH to 7 or so, and acidifying terminates；Acidifying kettle gas phase Jing
Condensation obtains methyl alcohol, alcohol mixture, and by-product methyl alcohol, ethanol are obtained after rectification and purification；Leftover materials go to press filtration in acidifying kettle
Machine press filtration, the solid barrelling for obtaining is standby；
Check that water is boiled to add water in kettle backward kettle without exception, then open manhole and put into packaged press filtration solid material, open chuck steaming
Vapour, is heated to uniform temperature, and insulation is lowered the temperature after 1 hour, centrifugation, the cyclocomplex fluorouracil solid for obtaining Jing after airflow drying,
Part as selling outside by-product, partly for the next step, press filtration and centrifuge waste water decontamination water treatment station；
(3) chlorination workshop section
Toluene, N, N dimethyl aniline, the metered chlorination tank of cyclocomplex fluorouracil, chuck are led to into steam, control temperature is one
Determine POCl3 is added dropwise in scope, fluorouracil occurs chlorination reaction with POCl3, generate the chloro- 5- fluorine of 2- methoxyl group -4- phonetic
Pyridine；
Check that hydrolysis kettle is without exception to add water into kettle, chuck leads to chilled brine, chloride is instilled in kettle, and temperature in the kettle keeps
25-45 DEG C, there is hydrolysis, production hydrogen chloride and phosphoric acid in the complete POCl3 of unreacted and dichloro phosphoric acid, and in N, N- bis-
Methylaniline forms hydrochloride and is dissolved in water；Material after hydrolysis stands, layering, and oil phase enters precipitation kettle, carries out precipitation, precipitation kettle
Last remaining material is the chloro- 5-FUs of chloride 2- methoxyl group -4- and goes the toluene recovery of amination operation, abjection to apply mechanically；
Water mutually enters neutralization kettle, and is neutralized DMA hydrochloride in water phase with the ammoniacal liquor and liquid caustic soda that reclaim, is allowed to shape
Into DMA, it is layered again afterwards, water layer enters sewage plant, containing N, N dimethyl aniline layer distillation dehydration rear enclosure is used；
(4) amination workshop section
The chloro- 5-FUs of chloride 2- methoxyl group -4- are proceeded to into amination kettle, 28% ammoniacal liquor is added, jacket steam intensification is opened, one
Aminating reaction is carried out under fixed condition；After aminating reaction terminates, cooling proceeds to filter press carries out press filtration, and the water layer containing ammoniacal liquor goes chlorination
In post and kettle；With being centrifuged after alcohol beating washing, mother liquor precipitation recovered alcohol, aminate filter cake removes hydrolysis procedure to filter cake；
(5) acidolysis workshop section
Add suitable quantity of water in acidolysis kettle, the concentrated sulfuric acid is added dropwise, add the aminate 2- methoxyl groups -4- amidos -5-FU after centrifugation
Filter cake, is incubated at 80 DEG C -90 DEG C, and be hydrolyzed reaction；After sampling confirms that acidolysis reaction terminates, cooling proceeds to neutralization kettle, temperature
At 30 DEG C -50 DEG C, with decrease temperature crystalline in liquid caustic soda and after remaining sulfuric acid, refining kettle is entered after centrifugation, add appropriate activity
Charcoal and water, are press-filtered out waste active carbon after intensification, then are centrifuged after lowering the temperature, and centrifuge waste water is back to acidolysis workshop section, and centrifugal solids Jing are double
Flucytosine product is obtained after cone vacuum drying.
2. a kind of production technology of Flucytosine according to claim 1, it is characterised in that the step（1）In it is certain
Condition is under 50 DEG C -60 DEG C, condition of normal pressure.
3. a kind of production technology of Flucytosine according to claim 1, it is characterised in that the step（2）Middle heating
To uniform temperature between 70 DEG C -80 DEG C.
4. a kind of production technology of Flucytosine according to claim 1, it is characterised in that the step（3）Middle control
Temperature adds within the specific limits POCl3, and the temperature control is between 40 DEG C -50 DEG C.
5. a kind of production technology of Flucytosine according to claim 1, it is characterised in that the step（4）In one
Be 80 DEG C -90 DEG C of controlling reaction temperature under fixed condition, in kettle under pressure 0.5MPa-0.8MPa.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610720494.XA CN106632080A (en) | 2016-08-25 | 2016-08-25 | Flucytosine manufacturing process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610720494.XA CN106632080A (en) | 2016-08-25 | 2016-08-25 | Flucytosine manufacturing process |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106632080A true CN106632080A (en) | 2017-05-10 |
Family
ID=58852328
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610720494.XA Pending CN106632080A (en) | 2016-08-25 | 2016-08-25 | Flucytosine manufacturing process |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106632080A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107963994A (en) * | 2018-01-22 | 2018-04-27 | 精华制药集团南通有限公司 | A kind of green method for preparing 5 FU 5 fluorouracil |
| CN108033917A (en) * | 2017-12-15 | 2018-05-15 | 浙江先锋科技股份有限公司 | A kind of preparation method of 5-flurocytosine |
| CN108047094A (en) * | 2017-12-19 | 2018-05-18 | 湖北远大富驰医药化工股份有限公司 | A kind of O- methyl-isoureas Methylsulfate novel preparation method |
| CN108586268A (en) * | 2018-01-22 | 2018-09-28 | 精华制药集团南通有限公司 | N, the method for accelerine recycling are recycled in a kind of Flucytosine chlorinated effluent |
| CN108585260A (en) * | 2018-01-22 | 2018-09-28 | 精华制药集团南通有限公司 | A kind of method that Flucytosine chlorinated effluent recycles |
| CN110105290A (en) * | 2019-05-14 | 2019-08-09 | 浙江伟锋药业有限公司 | A kind of preparation method of 5-flurocytosine |
| CN111303045A (en) * | 2019-11-25 | 2020-06-19 | 温州大学 | Production process of 2-ethoxy-4, 6-difluoropyrimidine |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB806584A (en) * | 1956-05-08 | 1958-12-31 | Hoffmann La Roche | Novel pyrimidine derivatives and a process for the manufacture thereof |
| US2945038A (en) * | 1956-09-26 | 1960-07-12 | Hoffmann La Roche | 5-fluorocytosine and preparation thereof |
| US3040026A (en) * | 1959-06-03 | 1962-06-19 | Hoffmann La Roche | Processes and intermediates for deoxyfluorocytidine |
| CN103435557A (en) * | 2013-08-08 | 2013-12-11 | 爱斯特（成都）生物制药有限公司 | 5-fluorocytosine preparation method |
| CN103601686A (en) * | 2013-11-08 | 2014-02-26 | 大连九信生物化工科技有限公司 | Method for synthesizing fluorine-containing pyrimidine compounds by virtue of one-pot method |
| CN103923019A (en) * | 2014-03-20 | 2014-07-16 | 蚌埠中实化学技术有限公司 | Preparation method of 2-hydroxy-4-amino-5-fluoropyrimidine |
| CN104356071A (en) * | 2014-11-21 | 2015-02-18 | 山东金城医药化工股份有限公司 | Preparation method for 5-fluorocytosine |
| CN105153041A (en) * | 2015-10-20 | 2015-12-16 | 浙江先锋科技股份有限公司 | 5-fluctyosine preparation method suitable for industrial production |
| CN105272922A (en) * | 2014-06-06 | 2016-01-27 | 上海迪赛诺化学制药有限公司 | Method for 5-fluorocytosine |
| CN106349169A (en) * | 2016-08-25 | 2017-01-25 | 宿迁市万和泰化工有限公司 | Flucytosine preparation method applicable to industrial production |
-
2016
- 2016-08-25 CN CN201610720494.XA patent/CN106632080A/en active Pending
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB806584A (en) * | 1956-05-08 | 1958-12-31 | Hoffmann La Roche | Novel pyrimidine derivatives and a process for the manufacture thereof |
| US2945038A (en) * | 1956-09-26 | 1960-07-12 | Hoffmann La Roche | 5-fluorocytosine and preparation thereof |
| US3040026A (en) * | 1959-06-03 | 1962-06-19 | Hoffmann La Roche | Processes and intermediates for deoxyfluorocytidine |
| CN103435557A (en) * | 2013-08-08 | 2013-12-11 | 爱斯特（成都）生物制药有限公司 | 5-fluorocytosine preparation method |
| CN103601686A (en) * | 2013-11-08 | 2014-02-26 | 大连九信生物化工科技有限公司 | Method for synthesizing fluorine-containing pyrimidine compounds by virtue of one-pot method |
| CN103923019A (en) * | 2014-03-20 | 2014-07-16 | 蚌埠中实化学技术有限公司 | Preparation method of 2-hydroxy-4-amino-5-fluoropyrimidine |
| CN105272922A (en) * | 2014-06-06 | 2016-01-27 | 上海迪赛诺化学制药有限公司 | Method for 5-fluorocytosine |
| CN104356071A (en) * | 2014-11-21 | 2015-02-18 | 山东金城医药化工股份有限公司 | Preparation method for 5-fluorocytosine |
| CN105153041A (en) * | 2015-10-20 | 2015-12-16 | 浙江先锋科技股份有限公司 | 5-fluctyosine preparation method suitable for industrial production |
| CN106349169A (en) * | 2016-08-25 | 2017-01-25 | 宿迁市万和泰化工有限公司 | Flucytosine preparation method applicable to industrial production |
Non-Patent Citations (4)
| Title |
|---|
| 卢玉华等: "《药物合成手册》", 30 September 1989 * |
| 张奕华等: "氟胞嘧啶合成工艺的改造", 《中国药科大学学报》 * |
| 李年平等: "5-氟胞嘧啶的合成", 《医药工业》 * |
| 韩长日等: "《精细有机化工产品生产技术手册 下》", 30 June 2010 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108033917A (en) * | 2017-12-15 | 2018-05-15 | 浙江先锋科技股份有限公司 | A kind of preparation method of 5-flurocytosine |
| CN108033917B (en) * | 2017-12-15 | 2019-12-10 | 浙江先锋科技股份有限公司 | Preparation method of 5-fluorocytosine |
| CN108047094A (en) * | 2017-12-19 | 2018-05-18 | 湖北远大富驰医药化工股份有限公司 | A kind of O- methyl-isoureas Methylsulfate novel preparation method |
| CN108047094B (en) * | 2017-12-19 | 2020-08-21 | 湖北远大富驰医药化工股份有限公司 | Novel preparation method of O-methyl isourea methyl sulfate |
| CN107963994A (en) * | 2018-01-22 | 2018-04-27 | 精华制药集团南通有限公司 | A kind of green method for preparing 5 FU 5 fluorouracil |
| CN108586268A (en) * | 2018-01-22 | 2018-09-28 | 精华制药集团南通有限公司 | N, the method for accelerine recycling are recycled in a kind of Flucytosine chlorinated effluent |
| CN108585260A (en) * | 2018-01-22 | 2018-09-28 | 精华制药集团南通有限公司 | A kind of method that Flucytosine chlorinated effluent recycles |
| CN110105290A (en) * | 2019-05-14 | 2019-08-09 | 浙江伟锋药业有限公司 | A kind of preparation method of 5-flurocytosine |
| CN110105290B (en) * | 2019-05-14 | 2020-06-23 | 浙江伟锋药业有限公司 | Preparation method of 5-fluorocytosine |
| CN111303045A (en) * | 2019-11-25 | 2020-06-19 | 温州大学 | Production process of 2-ethoxy-4, 6-difluoropyrimidine |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106632080A (en) | Flucytosine manufacturing process | |
| CN103724261B (en) | A kind of industrialized process for preparing of hydroxychloroquine sulfate quinoline | |
| CN103420881B (en) | A kind of preparation method of medicinal racemization hydroxyl Methionine calcium salt newly | |
| CN104140420A (en) | Synthesis process of thiothiamine | |
| CN109437245A (en) | The method of organic solvent Isolating chlorinated sodium and sodium bromide | |
| CN104059023A (en) | Environment-friendly preparation method for key intermediate 2-methyl-4-amino-5-aminomethyl pyrimidine of vitamin B1 | |
| WO2021047490A1 (en) | Method for preparing dexibuprofen | |
| CN100395230C (en) | Method for preparing high-purity gahapentin | |
| CN102617595A (en) | Preparation method of fluoroquinolone antibacterial medicament marbofloxacin | |
| CN105218390A (en) | A kind of Propacetamol Hydrochloride preparation technology of improvement | |
| CN112457270A (en) | Preparation method of dichloro pentachloromethyl thiazole | |
| CN117447427A (en) | Preparation method of furosemide | |
| CN102993028A (en) | Purifying method of dimethyl diallyl ammonium chloride monomer | |
| CN104496825B (en) | The preparation method of 2-fluorine ethylamine hydrochloride | |
| CN101781264A (en) | Production method of 1-methyl-5-mercapto-1,2,3,4-tetrazole | |
| CN106316956A (en) | Industrial production method for pyrazole | |
| CN105330545A (en) | Method for recycling oxalic acid from triazine ring cyclization mother liquor dreg with tin chloride as catalyst | |
| CN109912531A (en) | The preparation method of high-purity Febustat | |
| CN106892873B (en) | A kind of preparation method of 5- trifluoromethyl uracil | |
| CN105348285B (en) | Low-cost and high-yield adenine preparation method | |
| CN106336366A (en) | Method for synthesizing 4-(2-aminoethyl)benzsulfamide | |
| CN106749098A (en) | A kind of friendly process for preparing dioxopromethazine hydrochloride as oxidant with oxygen | |
| CN112438272A (en) | Evodiamine analog and application thereof in preventing and treating plant pathogenic fungi | |
| CN110862429A (en) | Preparation method of sodium aescinate | |
| CN106496075B (en) | The preparation method and L-citrulline prepared therefrom of a kind of L-citrulline crude product |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170510 |