CN105924402A - Preparation method of 2-amido methylpyrimidine hydrochloride - Google Patents
Preparation method of 2-amido methylpyrimidine hydrochloride Download PDFInfo
- Publication number
- CN105924402A CN105924402A CN201610304245.2A CN201610304245A CN105924402A CN 105924402 A CN105924402 A CN 105924402A CN 201610304245 A CN201610304245 A CN 201610304245A CN 105924402 A CN105924402 A CN 105924402A
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- CN
- China
- Prior art keywords
- preparation
- amido
- feldalat
- aminomethyl pyrimidine
- hydrochloride
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- 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.)
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Classifications
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- 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
- C07D239/26—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
Abstract
The invention discloses a preparation method of 2-amido methylpyrimidine hydrochloride, and relates to the technical field of organic synthesis. The preparation method comprises the steps that 2-amido methylpyrimidine mesylate is taken as a raw material, sodium methylate is added at certain temperature, suction filtration is conducted after reacting is finished, the temperature of filtrate is decreased to certain temperature, an enough amount of hydrochloric acid gas is introduced, and stirring and filtering are conducted to obtain the product 2-amido methylpyrimidine hydrochloride. The 2-amido methylpyrimidine hydrochloride is simple in preparation technology, low in cost and simple in aftertreatment; in addition, the product purity reaches 99.5% or above, the yield reaches 85% or above, and the preparation method is suitable for industrialized production.
Description
Technical field:
The present invention relates to technical field of organic synthesis, be specifically related to the system of a kind of 2-aminomethyl pyrimidine hydrochloride
Preparation Method.
Background technology:
2-aminomethyl pyrimidine hydrochloride, CAS 372118-67-7, is the raw material of medicine avanaphil,
Avanaphil, No. CAS: 330784-47-9, Chinese another name: 4-[(3-chloro-4-methoxy benzyl) ammonia
Base]-2-[2-(methylol)-1-pyrrolidinyl]-N-(2-Pyrimidylmethyl)-5-pyrimidine Methanesulfomide is a kind of phosphoric acid
Diesterase 5 (PDE5) inhibitor, is used for treating male erectile dysfunction (ED).
WO2005/113553 2-cyanopyrimidine is raw material, under conditions of methanol, water, hydrogen chloride, uses
The method of palladium carbon catalytic hydrogenation, prepares 2-aminomethyl pyrimidine hydrochloride;US2004/142930 2-cyano group
Pyrimidine is raw material, under conditions of ethanol, hydrogen chloride, by the method for nickel catalytic hydrogenation, prepares 2-amido first
Yl pyrimidines hydrochlorate.There is the shortcoming that preparation cost is high, product purity is low in both approaches, is not suitable for work
Industry large-scale production.
Summary of the invention:
The technical problem to be solved is the 2-amido providing a kind of low cost, yield and purity high
The preparation method of methylpyrimidine hydrochlorate.
The technical problem to be solved uses following technical scheme to realize:
The preparation method of a kind of 2-aminomethyl pyrimidine hydrochloride, is former with 2-aminomethyl pyrimidine mesylate
Material, adds Feldalat NM at a certain temperature, and reaction terminates rear sucking filtration, gained filtrate is down to uniform temperature,
It is passed through enough HCl gas again, stirring, filter, obtain product 2-aminomethyl pyrimidine hydrochloride.
The addition temperature of described Feldalat NM is-10~10 DEG C.
Described Feldalat NM is solid or Feldalat NM/methanol solution.
The temperature that is passed through of described HCl gas is-10~10 DEG C.
The invention has the beneficial effects as follows: the present invention is with 2-aminomethyl pyrimidine mesylate as raw material, with methanol
After sodium reaction again with hydrochloric acid reaction, i.e. prepare 2-aminomethyl pyrimidine hydrochloride, preparation technology is simple, cost
Low, post processing is simple, and product purity reaches more than 99.5%, and yield reaches more than 85%, is suitable for industry
Metaplasia is produced.
Detailed description of the invention:
For the technological means making the present invention realize, creation characteristic, reach purpose and effect and be readily apparent from
Solve, below in conjunction with specific embodiment, the present invention is expanded on further.
Embodiment 1
Reaction bulb adds 2-aminomethyl pyrimidine mesylate, is cooled to-10 DEG C, is dividedly in some parts Feldalat NM
Solid, stirs 1h, and sucking filtration, filtrate again puts in reaction bulb, is cooled to-10 DEG C, is passed through enough salt
Acid gas, reacts 2h, sucking filtration, is dried, obtains 2-aminomethyl pyrimidine hydrochloride, and purity is more than 99.5%,
Yield 89%.
Embodiment 2
Reaction bulb adds 2-aminomethyl pyrimidine mesylate, is cooled to-10 DEG C, drip Feldalat NM/methanol
Liquid, stirs 1h, and sucking filtration, filtrate again puts in reaction bulb, is cooled to-10 DEG C, is passed through enough salt
Acid gas, reacts 2h, sucking filtration, is dried, obtains 2-aminomethyl pyrimidine hydrochloride, and purity is more than 99.5%,
Yield 86%.
Embodiment 3
Reaction bulb adds 2-aminomethyl pyrimidine mesylate, is cooled to 0 DEG C, be dividedly in some parts Feldalat NM solid
Body, stirs 1h, and sucking filtration, filtrate puts in reaction bulb again, is cooled to 0 DEG C, is passed through enough hydrogen chloride gas
Body, reacts 2h, sucking filtration, is dried, obtains 2-aminomethyl pyrimidine hydrochloride, and purity is more than 99.5%, receives
Rate 88.5%.
Embodiment 4
Reaction bulb adds 2-aminomethyl pyrimidine mesylate, is cooled to 0 DEG C, drip Feldalat NM/methanol solution
Body, stirs 1h, and sucking filtration, filtrate again puts in reaction bulb, is cooled to 0-5 DEG C, is passed through enough hydrochloric acid
Gas, reacts 2h, sucking filtration, is dried, obtains 2-aminomethyl pyrimidine hydrochloride, and purity is more than 99.5%,
Yield 86.5%.
The ultimate principle of the present invention and principal character and advantages of the present invention have more than been shown and described.One's own profession
Skilled person will appreciate that of industry, the present invention is not restricted to the described embodiments, above-described embodiment and explanation
The principle that the present invention is simply described described in book, without departing from the spirit and scope of the present invention,
The present invention also has various changes and modifications, and these changes and improvements both fall within claimed invention model
In enclosing.Claimed scope is defined by appending claims and equivalent thereof.
Claims (4)
1. the preparation method of a 2-aminomethyl pyrimidine hydrochloride, it is characterised in that: with 2-aminomethyl
Pyrimidine mesylate is raw material, adds Feldalat NM at a certain temperature, and reaction terminates rear sucking filtration, by gained
Filtrate is down to uniform temperature, then is passed through enough HCl gas, stirring, filters, obtains product 2-amido first
Yl pyrimidines hydrochlorate.
The preparation method of 2-aminomethyl pyrimidine hydrochloride the most according to claim 1, it is characterised in that:
The addition temperature of described Feldalat NM is-10~10 DEG C.
The preparation method of 2-aminomethyl pyrimidine hydrochloride the most according to claim 1, it is characterised in that:
Described Feldalat NM is solid or Feldalat NM/methanol solution.
The preparation method of 2-aminomethyl pyrimidine hydrochloride the most according to claim 1, it is characterised in that:
The temperature that is passed through of described HCl gas is-10~10 DEG C.
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CN201610304245.2A CN105924402A (en) | 2016-05-06 | 2016-05-06 | Preparation method of 2-amido methylpyrimidine hydrochloride |
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CN201610304245.2A CN105924402A (en) | 2016-05-06 | 2016-05-06 | Preparation method of 2-amido methylpyrimidine hydrochloride |
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CN201610304245.2A Pending CN105924402A (en) | 2016-05-06 | 2016-05-06 | Preparation method of 2-amido methylpyrimidine hydrochloride |
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004083495A (en) * | 2002-08-27 | 2004-03-18 | Koei Chem Co Ltd | Method for preparing 2-aminomethylpyrimidine and its salt |
CN102584799A (en) * | 1999-09-16 | 2012-07-18 | 田边三菱制药株式会社 | Aromatic nitrogenous six-membered ring compounds |
CN103254180A (en) * | 2013-05-23 | 2013-08-21 | 苏州明锐医药科技有限公司 | Preparation method of Avanafil |
WO2015001567A1 (en) * | 2013-07-01 | 2015-01-08 | Msn Laboratories Private Limited | Process for the preparation of (s)-4-[(3-chloro-4-methoxybenzyl)amino]-2-[2- (hydroxymethyl)-1-pyrrolidinyl]-n-(2-pyrimidinyl methyl-5-pyrimidine carboxamide |
WO2015177807A1 (en) * | 2014-05-22 | 2015-11-26 | Wanbury Ltd. | A process for the preparation of avanafil and its novel intermediates |
CN105229010A (en) * | 2013-01-29 | 2016-01-06 | 阿普廷伊克斯股份有限公司 | Spiral shell-lactan nmda receptor conditioning agent and uses thereof |
-
2016
- 2016-05-06 CN CN201610304245.2A patent/CN105924402A/en active Pending
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102584799A (en) * | 1999-09-16 | 2012-07-18 | 田边三菱制药株式会社 | Aromatic nitrogenous six-membered ring compounds |
JP2004083495A (en) * | 2002-08-27 | 2004-03-18 | Koei Chem Co Ltd | Method for preparing 2-aminomethylpyrimidine and its salt |
CN105229010A (en) * | 2013-01-29 | 2016-01-06 | 阿普廷伊克斯股份有限公司 | Spiral shell-lactan nmda receptor conditioning agent and uses thereof |
CN103254180A (en) * | 2013-05-23 | 2013-08-21 | 苏州明锐医药科技有限公司 | Preparation method of Avanafil |
WO2015001567A1 (en) * | 2013-07-01 | 2015-01-08 | Msn Laboratories Private Limited | Process for the preparation of (s)-4-[(3-chloro-4-methoxybenzyl)amino]-2-[2- (hydroxymethyl)-1-pyrrolidinyl]-n-(2-pyrimidinyl methyl-5-pyrimidine carboxamide |
WO2015177807A1 (en) * | 2014-05-22 | 2015-11-26 | Wanbury Ltd. | A process for the preparation of avanafil and its novel intermediates |
Non-Patent Citations (3)
Title |
---|
四川医学院: "《药物化学》", 31 January 1981 * |
田红潮,等: "阿伐那非的合成研究进展", 《山东化工》 * |
胡惟笑,等: "《有机化合物制备手册》", 31 March 1995 * |
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Application publication date: 20160907 |