CN104496911A - Method for synthesizing 2,5-diamino-4,6-dihydroxypyrimidine hydrochloride - Google Patents

Method for synthesizing 2,5-diamino-4,6-dihydroxypyrimidine hydrochloride Download PDF

Info

Publication number
CN104496911A
CN104496911A CN201410735815.4A CN201410735815A CN104496911A CN 104496911 A CN104496911 A CN 104496911A CN 201410735815 A CN201410735815 A CN 201410735815A CN 104496911 A CN104496911 A CN 104496911A
Authority
CN
China
Prior art keywords
intermediate product
synthetic method
drip
acid
described step
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
Application number
CN201410735815.4A
Other languages
Chinese (zh)
Inventor
曾淼
余志强
徐剑锋
朱家可
卫海浩
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
SUZHOU KAIYUAN MINSHENG SCIENCE AND TECHNOLOGY Co Ltd
Original Assignee
SUZHOU KAIYUAN MINSHENG SCIENCE AND TECHNOLOGY Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by SUZHOU KAIYUAN MINSHENG SCIENCE AND TECHNOLOGY Co Ltd filed Critical SUZHOU KAIYUAN MINSHENG SCIENCE AND TECHNOLOGY Co Ltd
Priority to CN201410735815.4A priority Critical patent/CN104496911A/en
Publication of CN104496911A publication Critical patent/CN104496911A/en
Pending legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24Heterocyclic 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
    • C07D239/28Heterocyclic 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
    • C07D239/46Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52Two oxygen atoms
    • C07D239/54Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
    • C07D239/545Two 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention discloses a method for synthesizing 2,5-diamino-4,6-dihydroxypyrimidine hydrochloride. According to the method, dimethyl malonate and guanidine hydrochloride serving as raw materials are subjected to cyclization, nitrosation, reduction and salt-forming reactions to obtain a product, the total yield is 75 percent, and the product purity is 99.0 percent. The method can be used for simplifying operation, reducing cost, increasing reaction yield, reducing energy consumption and reducing emission of the 'three wastes', and is suitable for industrial production.

Description

A kind of synthetic method of 2,5-diamino-4,6-dihydroxy-pyrimidine hydrochloride
Technical field
The present invention relates to a kind of Abacavir intermediate synthetic method, be specifically related to the synthetic method of 2,5-diamino-4,6-dihydroxy-pyrimidine hydrochloride.
Background technology
Abacavir chemistry (1S by name, 4R)-cis-4-(2-amino-6-cyclopropyl amino-9-H-purine-9-base)-2-cyclopentenes-1-methyl alcohol, belong to efabirenz, the suppression copied HIV-1 is to stop copying of viral DNA double-strand by simulation nucleic acid, for virus, make their lack necessary chemical structure and the nucleic acid that can not connect below, clinical confirmation copies HIV has very strong restraining effect.Abacavir synthesizes primarily of 2 key intermediates: amino-4, the 6-bis-chloro-5-formamido group pyrimidines of 2-and (1S, 4R)-cis-4-acetylaminohydroxyphenylarsonic acid 2-cyclopentenes-1-methyl alcohol.
2-amino-4, the synthesis of 6-bis-chloro-5-formamido group pyrimidine is with 2,5-diamino-4,6-dihydroxy-pyrimidine hydrochloride is raw material, about 2,5-diamino-4, the synthesis report of 6-dihydroxy-pyrimidine hydrochloride mainly contains following two methods: (1) take diethyl malonate as starting raw material, is reacted into ring with Guanidinium hydrochloride, sodium methylate, then reacts with Sodium Nitrite, and then reduction reaction is carried out with vat powder, last and hydrochloric acid salify; (2) take diethyl malonate as starting raw material, be reacted into ring with Guanidinium hydrochloride, sodium methylate, then react with Sodium Nitrite, and then carry out hydrogenation reduction with palladium carbon catalyst, last and hydrochloric acid salify.Method (1) reaction times is longer, and aftertreatment is more loaded down with trivial details, has a large amount of waste water to produce, and vat powder exists certain security risk in production with transportation simultaneously, and cost is also higher; Method (2) uses palladium carbon catalyst, although reaction is thorough, product purity is high, wastewater flow rate is few, because catalyzer price is too high, the application in large production is subject to certain restrictions.
Summary of the invention
The object of the invention is to solve the problem, provide that a kind of cost is low, security is high and the synthetic method of energy consumption and three waste discharge can be reduced.
In order to achieve the above object, scheme of the present invention is:
A kind of synthetic method of 2,5-diamino-4,6-dihydroxy-pyrimidine hydrochloride, is characterized in that comprising the following steps:
1), by Guanidinium hydrochloride add in sodium methoxide solution, heat up and be stirred to 35 ~ 50 DEG C, then drip dimethyl malonate, rate of addition, to keep system homo(io)thermism for standard, drips 35 ~ 50 DEG C of insulation reaction 0.5 ~ 6h after terminating; Insulation terminate after successively through underpressure distillation, be dissolved in water, add acid for adjusting pH to 0 ~ 8, cooling, suction filtration, oven dry after obtain 2-diamino-4,6-dihydroxy-pyrimidine.The reaction equation of this step is:
2), in 2-diamino-4,6-dihydroxy-pyrimidine add sodium hydroxide solution and water, stir and be warming up to 30 ~ 80 DEG C, add Sodium Nitrite; Then drip salt acid for adjusting pH to 0 ~ 4, drip 30 ~ 80 DEG C of insulation reaction 0.5 ~ 3h after terminating, reaction terminates rear cooling, suction filtration, oven dry obtain 2-diamino-4,6-dihydroxyl-5-nitroso-group pyrimidine.The reaction equation of this step is:
3), to 2-diamino-4, water is added in 6-dihydroxyl-5-nitroso-group pyrimidine, stirring is warming up to 20 ~ 40 DEG C, then drip sodium hydrosulfide, during dropping, keep system temperature 20 ~ 40 DEG C, drip 20 ~ 50 DEG C of insulation reaction 0.5 ~ 4h after terminating, reaction end adds acid for adjusting pH to pH=0 ~ 9,2,5-diamino-4,6-dihydroxy-pyrimidine is obtained after cooling, suction filtration, oven dry.The reaction equation of this step is:
4), to 2,5-diamino-4, methyl alcohol is added in 6-dihydroxy-pyrimidine, stirring is warming up to 35 ~ 70 DEG C, then drips concentrated hydrochloric acid, and during dropping, system temperature remains on 35 ~ 70 DEG C, 50 ~ 80 DEG C of insulation reaction 0.5 ~ 4h after dropping terminates, 2,5-diamino-4,6-dihydroxy-pyrimidine hydrochloride (DADHP) is obtained after cooling, suction filtration, oven dry.The reaction equation of this step is:
Program Sodium sulfhydrate replaces vat powder reduction, and greatly reduce the consumption of reductive agent, reaction more fully and completely, significantly reduce production cost, the inorganic salt simultaneously produced due to reaction greatly reduce, and rinsing water also declines to a great extent, and the discharge of waste water also significantly reduces; In security, Sodium sulfhydrate is than vat powder safety and reliability; And the program reaction times is short, reaction conditions is gentle, and energy consumption also has and significantly declines; It is also more cheap that Sodium sulfhydrate compares palladium catalyst, is applicable to industrial production.
Preferably, described step 1) in the mol ratio of Guanidinium hydrochloride, dimethyl malonate and sodium methylate be 1:(1.0 ~ 1.5): (1.5 ~ 3.5).
Preferably, described step 2) in intermediate product I be 1:(1.1 ~ 1.5 with the mol ratio of Sodium Nitrite).
Preferably, described step 3) in intermediate product II be 1:(1.2 ~ 2.5 with the mol ratio of Sodium sulfhydrate).
Preferably, described step 4) in intermediate product III and the mol ratio of concentrated hydrochloric acid be 1:3.3.
Preferably, described step 1) in the scope of pH be pH=3 ~ 5.
Preferably, described step 2) in the scope of pH be pH=2 ~ 3.
Preferably, described step 3) in the scope of pH be pH=5 ~ 8.
Preferably, described step 1) and step 3) in when adding acid for adjusting pH acid used be the one in glacial acetic acid, concentrated hydrochloric acid, strong phosphoric acid.
Method Sodium sulfhydrate of the present invention replaces vat powder reduction, greatly reduces the consumption of reductive agent, and reaction more fully and completely, significantly reduce production cost, the inorganic salt simultaneously produced due to reaction greatly reduce, and rinsing water also declines to a great extent, and the discharge of waste water also significantly reduces; In security, Sodium sulfhydrate is than vat powder safety and reliability; And the program reaction times is short, reaction conditions is gentle, and energy consumption also has and significantly declines; And it is more cheap that Sodium sulfhydrate compares palladium catalyst, is applicable to suitability for industrialized production.The total recovery of the inventive method reaches 75%, and product purity reaches 99.0%; Method of the present invention can simplify the operation, and reduces costs, and improves the yield of reaction, more adapts to industrialization and produces.
Embodiment
Be described in detail the present invention below in conjunction with specific embodiment, to make those skilled in the art, the present invention may be better understood, thus make protection scope of the present invention and clearly limiting.
Below various raw-material title and manufacturer in embodiment.
Material name Manufacturer
Guanidinium hydrochloride Chinasun Specialty Products Co., Ltd
Dimethyl malonate Nanjing Ai Kang Chemical Co., Ltd.
Sodium Nitrite Hubei Ju Sheng Science and Technology Co., Ltd.
Concentrated hydrochloric acid Qidong Hong Lin Chemical Co., Ltd.
30% sodium hydroxide Qidong Hong Lin Chemical Co., Ltd.
Sodium sulfhydrate Henan Tian Zhishui Chemical Co., Ltd.
Methyl alcohol Shandong Zibo Linzhou City Dong Hui Chemical Co., Ltd.
Acetic acid Zhejiang Dong Yue Chemical Co., Ltd.
Strong phosphoric acid Qidong Hong Lin Chemical Co., Ltd.
Embodiment one
1), in four-hole bottle, drop into 28% sodium methoxide solution 298.7g, Guanidinium hydrochloride 76.4g, stir and be warming up to 50 DEG C, drip dimethyl malonate 114.4g, in dropping process, keep temperature to be 50 DEG C, drip and terminate rear 50 DEG C of insulation reaction 3 hours.Reaction terminates rear underpressure distillation and reclaims methyl alcohol, reclaims end and adds water 400g, then add concentrated hydrochloric acid and be adjusted to pH=3 ~ 4, share the sour 165g that desalts, and is down to room temperature, suction filtration, oven dry obtain intermediate product I98.2g.
2), intermediate product I98.2g and water 320g is added in reactor, add 30% aqueous sodium hydroxide solution 208g again, stirring is warming up to 40 DEG C, add Sodium Nitrite 63.5g, then start to drip concentrated hydrochloric acid and be adjusted to pH=2 ~ 3, within 1 hour, drip and terminate, 50 DEG C of insulated and stirred 2 hours, cooling, suction filtration, oven dry obtain intermediate product II 116.0g.
3), intermediate product II 116.0g and water 500g is added reactor, stirring is warming up to 40 DEG C, drip 15% Sodium sulfhydrate aqueous solution 336g, within 2 hours, drip and terminate, 40 ~ 45 DEG C of insulation reaction 2 hours, insulation terminates, and drips concentrated hydrochloric acid and is adjusted to pH=5 ~ 6, share and remove 200g, cooling, suction filtration, oven dry obtain intermediate product III99.5g.
4), intermediate product III99.5g and methyl alcohol 320g is added reactor, stirring is warming up to 55 ~ 60 DEG C, start to drip concentrated hydrochloric acid: 227g, within 1 hour, drip and terminate, 55 ~ 60 DEG C are incubated 1.5 hours, cooling, suction filtration, oven dry obtain product (DADHP) 102.5g, purity 98.5%, total recovery 70.7%.
Embodiment two
1), in four-hole bottle, drop into 28% sodium methoxide solution 373.3g, Guanidinium hydrochloride 76.4g, stir and be warming up to 40 DEG C, drip dimethyl malonate 124.8g, in dropping process, keep temperature to be 40 DEG C, drip and terminate rear 40 DEG C of insulation reaction 5 hours.Reaction terminates rear underpressure distillation and reclaims methyl alcohol, reclaims end and adds water 400g, then adds glacial acetic acid and regulate pH to pH=4 ~ 5, shares deicing acetic acid 125g, is down to room temperature, suction filtration, oven dry obtain intermediate product I98.8g.
2), intermediate product I98.8g and water 350g is added in reactor, add 30% aqueous sodium hydroxide solution 195g again, stirring is warming up to 50 DEG C, add Sodium Nitrite 66.2g, then start to drip concentrated hydrochloric acid and be adjusted to pH=2 ~ 3, within 1.5 hours, drip and terminate, 60 DEG C of insulated and stirred 1 hour, cooling, suction filtration, oven dry obtain intermediate product II 118.1g.
3), intermediate product II 118.1g and water 450g is added reactor, stirring is warming up to 35 DEG C, drip 15% Sodium sulfhydrate aqueous solution 426g, within 1.5 hours, drip and terminate, 35 ~ 40 DEG C of insulation reaction 3 hours, insulation terminates, and drips concentrated hydrochloric acid and regulates pH to pH=7 ~ 8, share and remove 165g, cooling, suction filtration, oven dry obtain intermediate product III103.7g.
4), intermediate product III103.7g and methyl alcohol 340g is added reactor, stirring is warming up to 50 ~ 55 DEG C, start to drip concentrated hydrochloric acid: 238g, within 0.5 hour, drip and terminate, 50 ~ 55 DEG C are incubated 2.5 hours, cooling, suction filtration, oven dry obtain product (DADHP) 104.5g, purity 98.8%, total recovery 72.3%.
Embodiment three
1), in four-hole bottle, drop into 28% sodium methoxide solution 448.0g, Guanidinium hydrochloride 76.4g, stir and be warming up to 45 DEG C, drip dimethyl malonate 135.2g, in dropping process, keep temperature to be 45 DEG C, drip and terminate rear 45 DEG C of insulation reaction 4 hours.Reaction terminates rear underpressure distillation and reclaims methyl alcohol, reclaims end and adds water 400g, then adds glacial acetic acid and regulate pH to pH=4 ~ 5, shares deicing acetic acid 126g, is down to room temperature, suction filtration, oven dry obtain intermediate product I99.3g.
2), intermediate product I99.3g and water 380g is added in reactor, add 30% aqueous sodium hydroxide solution 198g again, stirring is warming up to 50 DEG C, add Sodium Nitrite 69.0g, then start to drip concentrated hydrochloric acid and be adjusted to pH=2 ~ 3, within 1.5 hours, drip and terminate, 60 DEG C of insulated and stirred 1 hour, cooling, suction filtration, oven dry obtain intermediate product II 116.8g.
3), intermediate product II 116.8g and water 420g is added reactor, stirring is warming up to 30 DEG C, drip 15% Sodium sulfhydrate aqueous solution 561g, within 1 hour, drip and terminate, 45 ~ 50 DEG C of insulation reaction 1.5 hours, insulation terminates, and drips concentrated hydrochloric acid and regulates pH to pH=6 ~ 7, share and remove 185g, cooling, suction filtration, oven dry obtain intermediate product III103.7g.
4), intermediate product III103.7g and methyl alcohol 340g is added reactor, stirring is warming up to 60 ~ 65 DEG C, start to drip concentrated hydrochloric acid: 238g, within 1 hour, drip and terminate, 60 ~ 65 DEG C are incubated 1 hour, cooling, suction filtration, oven dry obtain product (DADHP) 108.5g, purity 99.0%, total recovery 75.2%.
Embodiment four
1), in four-hole bottle, drop into 28% sodium methoxide solution 477.8g, Guanidinium hydrochloride 76.4g, stir and be warming up to 35 DEG C, drip dimethyl malonate 140.4g, in dropping process, keep temperature to be 35 DEG C, drip and terminate rear 35 DEG C of insulation reaction 6 hours.Reaction terminates rear underpressure distillation and reclaims methyl alcohol, reclaims end and adds water 400g, then adds strong phosphoric acid and regulate pH to pH=3 ~ 4, shares and removes strong phosphoric acid 50g, be down to room temperature, suction filtration, oven dry obtain intermediate product I99.6g.
2), intermediate product I99.6g and water 400g is added in reactor, add 30% aqueous sodium hydroxide solution 210g again, stirring is warming up to 60 DEG C, add Sodium Nitrite 72.8g, then start to drip concentrated hydrochloric acid and be adjusted to pH=2 ~ 3, within 2 hours, drip and terminate, 60 DEG C of insulated and stirred 0.5 hour, cooling, suction filtration, oven dry obtain intermediate product II 120.2g.
3), intermediate product II 120.2g and water 400g is added reactor, stirring is warming up to 20 DEG C, drip 15% Sodium sulfhydrate aqueous solution 673g, within 1 hour, drip and terminate, 20 ~ 25 DEG C of insulation reaction 4 hours, insulation terminates, and drips strong phosphoric acid and regulates pH to pH=6 ~ 7, share and remove 70g, cooling, suction filtration, oven dry obtain intermediate product III106.6g.
4), intermediate product III106.6g and methyl alcohol 380g is added reactor, stirring is warming up to 40 ~ 45 DEG C, start to drip concentrated hydrochloric acid: 244g, within 0.5 hour, drip and terminate, 50 ~ 55 DEG C are incubated 3 hours, cooling, suction filtration, oven dry obtain product (DADHP) 106.5g, purity 99.0%, total recovery 73.8%.

Claims (9)

1. the synthetic method of diamino-4, a 6-dihydroxy-pyrimidine hydrochloride, is characterized in that comprising the following steps:
1), by Guanidinium hydrochloride add in sodium methoxide solution, heat up and be stirred to 35 ~ 50 DEG C, then drip dimethyl malonate, during dropping, keep system homo(io)thermism, drip 35 ~ 50 DEG C of insulation reaction 0.5 ~ 6h after terminating; Insulation terminate after successively through underpressure distillation, be dissolved in water, add acid for adjusting pH to 0 ~ 8, cooling, suction filtration, oven dry after obtain intermediate product I;
2), in intermediate product I add sodium hydroxide solution and water, stir and be warming up to 30 ~ 80 DEG C, add Sodium Nitrite; Then drip salt acid for adjusting pH to 0 ~ 4, drip 30 ~ 80 DEG C of insulation reaction 0.5 ~ 3h after terminating, reaction terminates rear cooling, suction filtration, oven dry obtain intermediate product II;
3), in intermediate product II, water is added, stirring is warming up to 20 ~ 40 DEG C, then sodium hydrosulfide is dripped, system temperature 20 ~ 40 DEG C is kept during dropping, 20 ~ 50 DEG C of insulation reaction 0.5 ~ 4h after dropping terminates, reaction end adds acid for adjusting pH to pH=0 ~ 9, obtains intermediate product III after cooling, suction filtration, oven dry;
4), in intermediate product II I, methyl alcohol is added, stirring is warming up to 35 ~ 70 DEG C, then concentrated hydrochloric acid is dripped, during dropping, system temperature remains on 35 ~ 70 DEG C, 50 ~ 80 DEG C of insulation reaction 0.5 ~ 4h after dropping terminates, 2,5-diamino-4,6-dihydroxy-pyrimidine hydrochloride is obtained after cooling, suction filtration, oven dry.
2. synthetic method according to claim 1, is characterized in that: described step 1) in the mol ratio of Guanidinium hydrochloride, dimethyl malonate and sodium methylate be 1:(1.0 ~ 1.5): (1.5 ~ 3.5).
3. synthetic method according to claim 1, is characterized in that: described step 2) in intermediate product I be 1:(1.1 ~ 1.5 with the mol ratio of Sodium Nitrite).
4. synthetic method according to claim 1, is characterized in that: described step 3) in intermediate product II be 1:(1.2 ~ 2.5 with the mol ratio of Sodium sulfhydrate).
5. synthetic method according to claim 1, is characterized in that: described step 4) in intermediate product III and the mol ratio of concentrated hydrochloric acid be 1:3.3.
6., according to the arbitrary described synthetic method of claim 1 to 5, it is characterized in that: described step 1) in the scope of pH be pH=3 ~ 5.
7., according to the arbitrary described synthetic method of claim 1 to 5, it is characterized in that: described step 2) in the scope of pH be pH=2 ~ 3.
8., according to the arbitrary described synthetic method of claim 1 to 5, it is characterized in that: described step 3) in the scope of pH be pH=5 ~ 8.
9., according to the arbitrary described synthetic method of claim 1 to 5, it is characterized in that: described step 1) and step 3) in when adding acid for adjusting pH acid used be the one in glacial acetic acid, concentrated hydrochloric acid, strong phosphoric acid.
CN201410735815.4A 2014-12-05 2014-12-05 Method for synthesizing 2,5-diamino-4,6-dihydroxypyrimidine hydrochloride Pending CN104496911A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201410735815.4A CN104496911A (en) 2014-12-05 2014-12-05 Method for synthesizing 2,5-diamino-4,6-dihydroxypyrimidine hydrochloride

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201410735815.4A CN104496911A (en) 2014-12-05 2014-12-05 Method for synthesizing 2,5-diamino-4,6-dihydroxypyrimidine hydrochloride

Publications (1)

Publication Number Publication Date
CN104496911A true CN104496911A (en) 2015-04-08

Family

ID=52938385

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201410735815.4A Pending CN104496911A (en) 2014-12-05 2014-12-05 Method for synthesizing 2,5-diamino-4,6-dihydroxypyrimidine hydrochloride

Country Status (1)

Country Link
CN (1) CN104496911A (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105801473A (en) * 2016-03-31 2016-07-27 常州大学 Synthetic method of 2,5-diamido-4,6-dihydroxypyridine
CN113173887A (en) * 2021-04-01 2021-07-27 河北利德检测技术有限公司 Synthetic method of triamterene intermediate

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101003511A (en) * 2007-01-19 2007-07-25 中国科学院上海有机化学研究所 Method for preparing 2 - amido - 4,6 - dichloro -formamido pyrimidines

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101003511A (en) * 2007-01-19 2007-07-25 中国科学院上海有机化学研究所 Method for preparing 2 - amido - 4,6 - dichloro -formamido pyrimidines

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
BY E. C. TAYLOJR.,等: "Hydrolysis of amino groups in certain 2,4,5,6-tetrasubstituted pyrimidines", 《JOURNAL OF THE AMERICAN CHEMICAL SOCIETY》 *
周惠良,等: "正交设计法催化氢化制备2,5-二氨基-4,6-二氰基嘧啶", 《石油化工应用》 *
孙昌俊,等: "《药物合成反应-理论与实践》", 31 May 2007, 化学工业出版社 *
王凯,等: "2,5 -二氨基-4,6-二羟基嘧啶盐酸盐的合成", 《武汉工程大学学报》 *
贾志涛,等: "2-氨基-4, 6-二氯-5-甲酰氨基嘧啶的合成", 《合成化学》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105801473A (en) * 2016-03-31 2016-07-27 常州大学 Synthetic method of 2,5-diamido-4,6-dihydroxypyridine
CN113173887A (en) * 2021-04-01 2021-07-27 河北利德检测技术有限公司 Synthetic method of triamterene intermediate

Similar Documents

Publication Publication Date Title
CN102898382B (en) Method for synthesizing 2-amino-4,6-dimethoxypyrimidine
CN109721545B (en) Preparation method of azoxystrobin intermediate
CN102050781A (en) Industrial preparation method of hydroxychloroquine sulfate
CN104496911A (en) Method for synthesizing 2,5-diamino-4,6-dihydroxypyrimidine hydrochloride
CN103130654B (en) 3,'3-dimethyl-4,4'-diaminodiphenyl methane (MDT) preparation method
CN103936681B (en) The preparation method of FADCP
CN104974098A (en) Synthetic method for 2,5-diamino-4,6-dihydroxypyrimidine hydrochloride
CN104119243B (en) A kind of energy-saving clean production method of iminodiethanoic acid
CN105399663A (en) 2, 3-dichloropyridine preparation method
CN103664812B (en) Preparation method of TTZ (thiotriazinone)
CN105566162A (en) Rilpivirine midbody preparing technology
CN101747284A (en) Method for preparing antioxidant
CN105085420B (en) A kind of method that compound phenazine is catalyzed and synthesized under the microwave radiation in aqueous phase
CN103896858A (en) Technology for preparing cytosine
CN102807536A (en) Preparation method of 1-(2,3-dichlorophenyl) piperazine hydrochloride
CN103980229B (en) A kind of preparation method of N-phenylpiperazine
CN104003905B (en) Single stage method cleaning procedure produces N-cyanoethyl aniline and the two cyanoethyl aniline of N, N-
CN104387328A (en) Method of preparing 2-chloropyrimidine
CN105348285A (en) Low-cost and high-yield adenine preparation method
CN104672146A (en) New high-yield preparation method of azoxystrobin
CN103755706B (en) A kind of environment-friendly preparation method synthesizing folic acid
CN105153041A (en) 5-fluctyosine preparation method suitable for industrial production
CN101940926B (en) Catalyst for reduction of aromatic nitro-compounds by hydrazine hydrate and preparation method thereof
CN101333199B (en) Method for synthesizing 4-(2-(N,N-dimethylamino)ethyl)morpholine
CN101830831B (en) Method for preparing ortho-diazanyl benzonitrile

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into 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: 20150408