CN110407757A - A kind of synthetic method of 4,5,6- Triaminopyrimidine - Google Patents
A kind of synthetic method of 4,5,6- Triaminopyrimidine Download PDFInfo
- Publication number
- CN110407757A CN110407757A CN201910551344.4A CN201910551344A CN110407757A CN 110407757 A CN110407757 A CN 110407757A CN 201910551344 A CN201910551344 A CN 201910551344A CN 110407757 A CN110407757 A CN 110407757A
- Authority
- CN
- China
- Prior art keywords
- synthetic method
- pyrimidine
- nitro
- reaction
- triaminopyrimidines
- 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
- C07D239/50—Three nitrogen atoms
Abstract
The invention discloses one kind 4, 5, the synthetic method of 6- Triaminopyrimidine, pass through 5- nitro -4, 6- dihydroxy-pyrimidine, intermediate product 4 is made in phosphorus oxychloride and organic base, the chloro- 5- nitro-pyrimidine of 6- bis-, 4, ethyl alcohol is being added in product made from the chloro- 5- nitro-pyrimidine of 6- bis- and ammonium hydroxide, and hydrazine hydrate then, Raney's nickel is made 4, 5, the synthetic method of 6- Triaminopyrimidine, the present invention only needs 3 steps that object can be obtained, gross production rate is high, synthetic route is short, reaction is mild, time is short, safety easy to operate, 4 are used simultaneously, the chloro- 5- nitro-pyrimidine of 6- bis- is starting material, since the raw material has a large amount of commercial offers, it is cheap and easy to get, auxiliary material can be with recovery, it can obviously reduce cost, since the present invention has selected suitable raw material and auxiliary material, avoid noxious material pair in production process The pollution of environment, and pyrimidine yield and purity is high is made, there is good industrial applications prospect.
Description
Technical field
The invention belongs to medicine intermediate field, specially a kind of synthetic method of 4,5,6- Triaminopyrimidines.
Background technique
Pyrimidine ring is drug, one of most common heterocycle in natural products, and pyrimidine heterocyclic compounds are such as synthesizing
The intermediate of drug has important application in field of medicaments, is widely used in anticancer drug, the research and development of anti-AIDS drug etc.
Clinically, therefore, the preparation process for developing and optimizing such compound, has great significance, but in the prior art, doctor
The synthetic route of medicine intermediate is long, and yield is low, and toxicity is big, more serious to the damage ratio of environment.
It is mainly used for the medicine intermediate of 4,5,6- Triaminopyrimidine of synthesis in the present invention, 4,5,6- Triaminopyrimidines are one
The new medicine intermediate of kind, synthetic route is short, easy to operate, high income, and no pollution to the environment.
Summary of the invention
The purpose of the present invention is to provide a kind of synthetic methods of 4,5,6- Triaminopyrimidines, to solve above-mentioned background technique
The problem of synthetic route of middle proposition is long, and yield is low, and environmental pollution is serious.
To achieve the above object, the invention provides the following technical scheme: a kind of synthetic method of 4,5,6- Triaminopyrimidines,
The synthetic method of the 4,5,6- Triaminopyrimidine includes the following steps:
1) 5- nitro -4,6- dihydroxy-pyrimidine, phosphorus oxychloride and organic base mix by weight 1:5-10:3-7 and in 25-
Chlorination reaction is carried out at 100 DEG C, extra phosphorus oxychloride is removed after reaction, is extracted after adding water quenching to go out with organic solvent, and adjusting PH is
Neutrality is washed, dry, is concentrated to get intermediate product 4, the chloro- 5- nitro-pyrimidine of 6- bis-;
2) the obtained chloro- 5- nitro-pyrimidine of 4,6- bis- and ammonium hydroxide are mixed by weight 1:3-5 in step 1), are in temperature
Under the conditions of 30-100 DEG C, the substance after reaction is cooled to room temperature by heating heating reaction, product filtering washing, drying;
3) substance of step 2) reaction and ethyl alcohol are mixed by weight 1:5, then adds hydrazine hydrate, Raney's nickel,
The weight ratio of substance, hydrazine hydrate and Raney's nickel that middle step 2) is reacted is that 1:0.5-1:1-2 is mixed and carried out at 25-60 DEG C
Reduction reaction is filtered to remove Raney's nickel, is evaporated and recrystallizes to obtain 4,5,6- Triaminopyrimidine of product.
Further, it disperses 5- nitro -4,6- dihydroxy-pyrimidine in phosphorus oxychloride in step 1), is cooled to 5-10
DEG C, organic base is then added dropwise and is mixed.
Further, the chlorination reaction time in step 1) is 2-5 hours.
Further, the substance after reaction is cooled to after room temperature when removing phosphorus oxychloride in step 1) depressurize it is dense
Contracting.
Further, in step (1) plus water quenching is gone out to pour into 5 kilograms of trash ice and stirring 1 hour or so.
Further, it is extracted with ethyl acetate in step 1), it is neutral for adjusting PH with saturated sodium bicarbonate aqueous solution, then
It washed once with saturated sodium-chloride water solution, it is then dry with anhydrous sodium sulfate, it is washed with saturated sodium-chloride water solution and removes dechlorination
Change hydrogen.
Further, the heating heating reaction time is 5-8 hours in step 2).
Further, the substance generated step 2) in step 3) is added in ethyl alcohol, adds Raney's nickel, is in temperature
Hydrazine hydrate is added dropwise under conditions of 20-25 DEG C, probably needs be added dropwise within 1-2 hours, continues to be stirred to react half an hour, reduction reaction
Time is 1-2 hours.
Further, organic base is triethylamine, diisopropyl ethyl amine, triisopropylamine, n,N-Dimethylaniline, N, N-
Diethylaniline, N, N- dimethyl pyrazole piperidinyl amine, pyridine, 1,8- diaza-bicyclic (5,4,0) endecatylene -7, two ring
The mixing of one or more of [4.3.0] -1,5- phenodiazine -5- hendecene.
In the present invention, be cooled to room temperature, be cooled to temperature be 20-25 DEG C.
The reaction equation of above-mentioned technical proposal can indicate are as follows:
Compared with prior art, the beneficial effects of the present invention are: the present invention only needs 3 steps that object, gross production rate can be obtained
Height, synthetic route is short, and reaction is mild, and the time is short, safety easy to operate, while being starting using the chloro- 5- nitro-pyrimidine of 4,6- bis-
Raw material, cheap and easy to get since the raw material has a large amount of commercial offers, auxiliary material can obviously reduce cost with recovery, due to this
Suitable raw material and auxiliary material have been selected in invention, avoid pollution of the noxious material to environment in production process, and pyrimidine is made
Yield and purity is high, the relatively low problem of pyrimidine yield and purity compared to the prior art, produced by the present invention 4,5,6- tri- ammonia
Yl pyrimidines improve yield and purity, shorten the time, easy to operate, simplify postprocessing working procedures, also improve operating process
In safety, have good industrial applications prospect.
Specific embodiment
The technical scheme in the embodiments of the invention will be clearly and completely described below, it is clear that described implementation
Example is only a part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, this field is common
Technical staff's every other embodiment obtained without making creative work belongs to the model that the present invention protects
It encloses.
Embodiment 1:
The synthetic method of one kind 4,5,6- Triaminopyrimidine, the synthetic method of 4,5, the 6- Triaminopyrimidine includes as follows
Synthesis step:
1) it disperses 500 grams of 5- nitro -4,6- dihydroxy-pyrimidines in 2750 milliliters of phosphorus oxychloride, is cooled to 5 DEG C, drop
The triethylamine for adding 1500 milliliters, generates many white cigarettes and heating is obvious, is added dropwise to triethylamine, rises to reflux temperature 100
DEG C reaction 2.5 hours, it will be concentrated under reduced pressure after cooling 25 DEG C of mixture and remove extra phosphorus oxychloride, reactant is poured slowly into 5
Kilogram trash ice in stir 1 hour or so, extracted with 2000 milliliters of ethyl acetate, then adjust PH with saturated sodium bicarbonate aqueous solution
For neutrality, then washed once with saturated sodium-chloride water solution, it is then dry with anhydrous sodium sulfate, intermediate product 4,6- is obtained after concentration
Two 525 grams of chloro- 5- nitro-pyrimidines, purity are greater than 98%, yield 85%;
2) by 500 gram 4 in step 1), the chloro- 5- nitro-pyrimidine of 6- bis- is scattered in 2000 milliliters of concentrated ammonia liquor, heating heating
Reaction 5 hours, temperature are 60 DEG C, after reaction, are cooled to room temperature, after product filtering washing, 295 grams of product obtained by drying,
Purity is greater than 98%, and yield 74% can be directly used in next step;
3) 295 grams of substance made from step 2) are added in 1500 milliliters of ethyl alcohol, add 590 grams of Raney's nickel, room
The lower hydrazine hydrate for being added dropwise 300 milliliters of temperature, probably needs be added dropwise within 2 hours, continues to be stirred to react half an hour, be filtered to remove thunder Buddhist nun
Nickel, filtrate be evaporated product is faint yellow solid crude product, ethyl alcohol recrystallization obtains 210 grams of 4,5,6- Triaminopyrimidine of product, purity
98% or so, yield 88%.
Embodiment 2:
The synthetic method of one kind 4,5,6- Triaminopyrimidine, the synthetic method of 4,5, the 6- Triaminopyrimidine includes as follows
Synthesis step:
1) it disperses 500 grams of 5- nitro -4,6- dihydroxy-pyrimidines in 2000 milliliters of phosphorus oxychloride, is cooled to 6 DEG C, drop
The diisopropyl ethyl amine for adding 2000 milliliters, generates many white cigarettes and heating is obvious, is added dropwise to diisopropyl ethyl amine,
It rises to 100 DEG C of reflux temperature to react 5 hours, removes extra phosphorus oxychloride for being concentrated under reduced pressure after 25 DEG C of mixture cooling, it will be anti-
It answers object to be poured slowly into 5 kilograms of trash ice to stir 1 hour or so, be extracted with 2000 milliliters of ethyl acetate, then with unsaturated carbonate hydrogen
It is neutrality that sodium water solution, which adjusts PH, then is washed once with saturated sodium-chloride water solution, then dry with anhydrous sodium sulfate, after concentration
Intermediate product 4, bis- 600 grams of chloro- 5- nitro-pyrimidine of 6- are obtained, purity is greater than 98%, yield 97%;
2) by 600 gram 4 in step 1), the chloro- 5- nitro-pyrimidine of 6- bis- is scattered in 1800 milliliters of concentrated ammonia liquor, heating heating
Reaction 7 hours, temperature are 80 DEG C, after reaction, are cooled to room temperature (temperature is 25 DEG C), after product filtration washing, drying is
420 grams of product are obtained, purity is greater than 98%, and yield 87% can be directly used in next step;
3) 420 grams of substance made from step 2) are added in 2100 milliliters of ethyl alcohol, add 420 grams of Raney's nickel, room
400 milliliters of hydrazine hydrate is added dropwise under warm (25 DEG C), needs be added dropwise within 2 hours, continues to be stirred to react 1 hour, be filtered to remove thunder
Buddhist nun's nickel, filtrate be evaporated product be faint yellow solid crude product, recrystallize to obtain 304 grams of 4,5,6- Triaminopyrimidine of product, purity is big
In 98%, yield 90%.
Embodiment 3:
The synthetic method of one kind 4,5,6- Triaminopyrimidine, the synthetic method of 4,5, the 6- Triaminopyrimidine includes as follows
Synthesis step:
1) it disperses 500 grams of 5- nitro -4,6- dihydroxy-pyrimidines in 1500 milliliters of phosphorus oxychloride, is cooled to 7 DEG C, drop
The triisopropylamine for adding 2500 milliliters, generates many white cigarettes and heating is obvious, is added dropwise to triisopropylamine, rises to reflux
100 DEG C of temperature are reacted 4 hours, remove extra phosphorus oxychloride for being concentrated under reduced pressure after 25 DEG C of mixture cooling, and reactant is slow
It pours into 5 kilograms of trash ice and stirs 1 hour or so, extracted with 2000 milliliters of ethyl acetate, then use saturated sodium bicarbonate aqueous solution
Adjusting PH is neutrality, then is washed once with saturated sodium-chloride water solution, then dry with anhydrous sodium sulfate, and intermediate production is obtained after concentration
Object 4, bis- 580 grams of chloro- 5- nitro-pyrimidine of 6-, purity are greater than 98%, yield 94%;
2) by 500 gram 4 in step 1), the chloro- 5- nitro-pyrimidine of 6- bis- is scattered in 1500 milliliters of concentrated ammonia liquor, heating heating
Reaction 6 hours, temperature are 70 DEG C, after reaction, are cooled to room temperature (temperature is 25 DEG C), after product filtration washing, drying is
307 grams of product are obtained, purity is greater than 98%, and yield 76% can be directly used in next step;
3) will made from step 2) 300 grams of substance be added in 1600 milliliters of ethyl alcohol, add 480 grams of Raney's nickel, 25
250 milliliters of hydrazine hydrate is added dropwise at DEG C, probably needs be added dropwise within 1 hour, continues to be stirred to react 1 hour, be filtered to remove thunder Buddhist nun
Nickel, filtrate be evaporated product be faint yellow solid crude product, recrystallize to obtain 182 grams of 4,5,6- Triaminopyrimidine of product, purity is greater than
98%, yield 75%.
Embodiment 4:
The synthetic method of one kind 4,5,6- Triaminopyrimidine, the synthetic method of 4,5, the 6- Triaminopyrimidine includes as follows
Synthesis step:
1) it disperses 500 grams of 5- nitro -4,6- dihydroxy-pyrimidines in 4500 milliliters of phosphorus oxychloride, is cooled to 10 DEG C,
3000 milliliters of n,N-Dimethylaniline is added dropwise, generates many white cigarettes and heating is obvious, dripped to n,N-Dimethylaniline
Finish, rise to 100 DEG C of reflux temperature and react 3.5 hours, removes extra phosphorus oxychloride for being concentrated under reduced pressure after 25 DEG C of mixture cooling,
Reactant is poured slowly into 5 kilograms of trash ice and is stirred 1 hour or so, extracted with 2000 milliliters of ethyl acetate, then use saturated carbon
It is neutrality that sour hydrogen sodium water solution, which adjusts PH, then is washed once with saturated sodium-chloride water solution, then dry with anhydrous sodium sulfate, concentration
After obtain intermediate product 4, bis- 557 grams of chloro- 5- nitro-pyrimidine of 6-, purity is greater than 98%, yield 90%;
2) by 500 gram 4 in step 1), the chloro- 5- nitro-pyrimidine of 6- bis- is scattered in 2500 milliliters of concentrated ammonia liquor, heating heating
Reaction 7 hours, temperature are 65 DEG C, after reaction, are cooled to room temperature (temperature is 25 DEG C), after product filtration washing, drying is
320 grams of product are obtained, purity is greater than 98%, and yield 80% can be directly used in next step;
3) will made from step 2) 320 grams of substance be added in 2100 milliliters of ethyl alcohol, add 450 grams of Raney's nickel, 25
500 milliliters of hydrazine hydrate is added dropwise at DEG C, probably needs be added dropwise within 1 hour, continues to be stirred to react 1 hour, be filtered to remove thunder Buddhist nun
Nickel, filtrate be evaporated product be faint yellow solid crude product, recrystallize to obtain 240 grams of 4,5,6- Triaminopyrimidine of product, purity is greater than
98%, yield 93%.
When organic base is triethylamine, diisopropyl ethyl amine, triisopropylamine, N, accelerine, N, N- diethyl
Aniline, N, N- dimethyl pyrazole piperidinyl amine, pyridine, 1,8- diaza-bicyclic (5,4,0) endecatylene -7, two rings [4.3.0] -1
When with the mixing of one of 5- phenodiazine -5- hendecene or multi-solvents, can equally it be made according to the method for the embodiment of the present invention 1
It is standby to obtain the chloro- 5- pyrimidine t-butyl carboxamide of 2,4- bis-, and obtained by 4,5, the 6- Triaminopyrimidine and above-described embodiment 2 to 4
The performance of 4,5,6- Triaminopyrimidine is identical.
From embodiment 1 to 4 as can be seen that the present invention only needs 3 steps that object can be obtained, under different reaction conditions,
The purity and yield of medicine intermediate obtained are all different, from the result that measures of experiment it is found that obtained 4,5 in embodiment 1,
The purity of 6- Triaminopyrimidine and 98%, and embodiment 1-4 system are all larger than with purity obtained under embodiment 2-4 reaction condition
4,5, the 6- Triaminopyrimidine yields obtained are all larger than equal to 75%, and 4 yield of embodiment reaches 93%, production produced by the present invention
Object purity is high, and yield is also higher, and present invention process is easy to operate, and synthetic route is short, safety easy to operate, reaction temperature
With, and pyrimidine yield and purity is high, the relatively low problem of pyrimidine yield and purity compared to the prior art, system of the present invention is made
The 4,5,6- Triaminopyrimidine obtained can be used for being mass produced.
It should be noted that, in this document, relational terms such as first and second and the like are used merely to a reality
Body or operation are distinguished with another entity or operation, are deposited without necessarily requiring or implying between these entities or operation
In any actual relationship or order or sequence.Moreover, the terms "include", "comprise" or its any other variant are intended to
Non-exclusive inclusion, so that the process, method, article or equipment including a series of elements is not only wanted including those
Element, but also including other elements that are not explicitly listed, or further include for this process, method, article or equipment
Intrinsic element.
It although an embodiment of the present invention has been shown and described, for the ordinary skill in the art, can be with
A variety of variations, modification, replacement can be carried out to these embodiments without departing from the principles and spirit of the present invention by understanding
And modification, the scope of the present invention is defined by the appended.
Claims (9)
1. one kind 4,5, the synthetic method of 6- Triaminopyrimidine, it is characterised in that: the synthetic method of 4,5, the 6- Triaminopyrimidine
Include the following steps:
1) 5- nitro -4,6- dihydroxy-pyrimidine, phosphorus oxychloride and organic base mix by weight 1:5-10:3-7 and in 25-100
Chlorination reaction is carried out at DEG C, extra phosphorus oxychloride is removed after reaction, is extracted after adding water quenching to go out with organic solvent, is adjusted during PH is
Property, it washs, it is dry, it is concentrated to get intermediate product 4, the chloro- 5- nitro-pyrimidine of 6- bis-;
2) the obtained chloro- 5- nitro-pyrimidine of 4,6- bis- and ammonium hydroxide are mixed by weight 1:3-5 in step 1), are 30-100 in temperature
Under the conditions of DEG C, the substance after reaction is cooled to room temperature by heating heating reaction, product filtering washing, drying;
3) substance of step 2 reaction and ethyl alcohol are mixed by weight 1:5, hydrazine hydrate, Raney's nickel is then added, wherein walking
The substance, hydrazine hydrate of rapid 2) reaction and the weight ratio of Raney's nickel are that 1:0.5-1:1-2 is mixed and carried out restoring at 25-60 DEG C anti-
It answers, is filtered to remove Raney's nickel, be evaporated and recrystallize to obtain 4,5,6- Triaminopyrimidine of product.
2. according to claim 1 a kind of 4, the synthetic method of 5,6- Triaminopyrimidines, it is characterised in that: the step 1)
It is middle to disperse 5- nitro -4,6- dihydroxy-pyrimidine in phosphorus oxychloride, it is cooled to 5-10 DEG C, organic base is then added dropwise and is mixed
It closes.
3. according to claim 1 a kind of 4, the synthetic method of 5,6- Triaminopyrimidines, it is characterised in that: the step 1)
In the chlorination reaction time be 2-5 hours.
4. according to claim 1 a kind of 4, the synthetic method of 5,6- Triaminopyrimidines, it is characterised in that: the step 1)
It is concentrated under reduced pressure after the substance after reaction is cooled to room temperature when middle removing phosphorus oxychloride.
5. according to claim 1 a kind of 4, the synthetic method of 5,6- Triaminopyrimidines, it is characterised in that: the step
(1) in plus water quenching is gone out to pour into 5 kilograms of trash ice and stirring 1 hour.
6. according to claim 1 a kind of 4, the synthetic method of 5,6- Triaminopyrimidines, it is characterised in that: the step 1)
In be extracted with ethyl acetate, it is neutral for adjusting PH with saturated sodium bicarbonate aqueous solution, then washs one with saturated sodium-chloride water solution
It is secondary, it is then dry with anhydrous sodium sulfate.
7. according to claim 1 a kind of 4, the synthetic method of 5,6- Triaminopyrimidines, it is characterised in that: the step 2
The middle heating heating reaction time is 5-8 hours.
8. according to claim 1 a kind of 4, the synthetic method of 5,6- Triaminopyrimidines, it is characterised in that: the step 3)
The middle substance for generating step 2 is added in ethyl alcohol, adds Raney's nickel, and hydration is added dropwise under conditions of temperature is 20-25 DEG C
Hydrazine is added dropwise for 1-2 hours, continues to be stirred to react half an hour, the reduction reaction time is 1-2 hours.
9. according to claim 1 or 2 a kind of 4, the synthetic method of 5,6- Triaminopyrimidines, it is characterised in that: described to have
Machine alkali is triethylamine, diisopropyl ethyl amine, triisopropylamine, n,N-Dimethylaniline, N, N- diethylaniline, N, N- diformazan
Yl pyridines base amine, pyridine, 1,8- diaza-bicyclic (5,4,0) endecatylene -7, two ring [4.3.0] -1,5- phenodiazine -5- 11
The mixing of one or more of alkene.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910551344.4A CN110407757A (en) | 2019-06-24 | 2019-06-24 | A kind of synthetic method of 4,5,6- Triaminopyrimidine |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910551344.4A CN110407757A (en) | 2019-06-24 | 2019-06-24 | A kind of synthetic method of 4,5,6- Triaminopyrimidine |
Publications (1)
Publication Number | Publication Date |
---|---|
CN110407757A true CN110407757A (en) | 2019-11-05 |
Family
ID=68359696
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910551344.4A Pending CN110407757A (en) | 2019-06-24 | 2019-06-24 | A kind of synthetic method of 4,5,6- Triaminopyrimidine |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN110407757A (en) |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1989007599A2 (en) * | 1988-02-09 | 1989-08-24 | Georgia State University Foundation, Inc. | Novel diazines and their method of preparation |
CN102887899A (en) * | 2012-09-28 | 2013-01-23 | 扬州大学 | Novel chemical synthesis method for adenine |
CN106749253A (en) * | 2016-11-28 | 2017-05-31 | 台州市星明药业有限公司 | A kind of chemical synthesis process of adenine |
CN106749043A (en) * | 2016-11-28 | 2017-05-31 | 台州市星明药业有限公司 | A kind of adenine intermediate pyrimidine azo and preparation method thereof |
-
2019
- 2019-06-24 CN CN201910551344.4A patent/CN110407757A/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1989007599A2 (en) * | 1988-02-09 | 1989-08-24 | Georgia State University Foundation, Inc. | Novel diazines and their method of preparation |
CN102887899A (en) * | 2012-09-28 | 2013-01-23 | 扬州大学 | Novel chemical synthesis method for adenine |
CN106749253A (en) * | 2016-11-28 | 2017-05-31 | 台州市星明药业有限公司 | A kind of chemical synthesis process of adenine |
CN106749043A (en) * | 2016-11-28 | 2017-05-31 | 台州市星明药业有限公司 | A kind of adenine intermediate pyrimidine azo and preparation method thereof |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN105541845B (en) | Folic acid cleanly production technique | |
CN111423431B (en) | Preparation method of chlorantraniliprole and intermediate thereof | |
CN102558005A (en) | Environmentally-friendly method for synthesizing selenomethionine | |
CN102863359B (en) | Synthesis method of anti-flu medicine | |
CN104130198B (en) | 2-amino-4,6-dimethoxypyridin and preparation method thereof | |
CN102321086B (en) | Synthesizing method of adenine | |
CN108276414B (en) | A kind of preparation method of citric acid tropsch imatinib | |
CN110746365B (en) | Preparation method of 4-thiocyano-1, 4, 5-trisubstituted 1,2, 3-triazole | |
CN110407757A (en) | A kind of synthetic method of 4,5,6- Triaminopyrimidine | |
CN109824602B (en) | Synthesis method of 4-chloro-2-methylthiopyrimidine | |
CN102712593A (en) | Method for producing 2-amino-4-(trifluoromethyl)pyridine | |
CN110218192B (en) | Preparation method of 2-amino-4, 6-dimethoxypyrimidine | |
CN104447758A (en) | Synthesis process of pyrazolo[3,4-d]pyrimidine compounds | |
CN110452180A (en) | A method of the synthesis chloro- 5- amino -6- pyrimidinecarboxylic acid ethyl ester of 2- | |
CN104487445A (en) | Novel method for preparing 1-oxacephalosporin derivative | |
CN111303045A (en) | Production process of 2-ethoxy-4, 6-difluoropyrimidine | |
CN105294686A (en) | Preparation method of riociguat | |
CZ287703B6 (en) | Process for preparing 2-amino-4,6-dichloropyrimidine | |
CN110294715B (en) | Synthesis method of 2,4, 6-trichloro-5-methoxypyrimidine | |
CN114751909B (en) | Preparation method of rebaudinib intermediate | |
CN114230525B (en) | Preparation method of 2-amino-4, 6-dimethoxypyrimidine | |
CN113651751B (en) | Preparation method of N-methoxycarbonyl-3-trifluoromethylpyridine-2-sulfonamide | |
CN115677707B (en) | Method for preparing 2,4,6, 8-tetrahydroxypyrimido [5,4-d ] pyrimidine by diaminomaleonitrile method | |
CN110372605B (en) | Synthesis method of 2-methylthio-4, 6-dichloro-5-nitropyrimidine | |
CN105399688A (en) | Gefitinib preparation method |
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 |
Application publication date: 20191105 |
|
RJ01 | Rejection of invention patent application after publication |