CN104387327A - Synthetic method of 3, 4-dihydropyrimidinone medicine intermediates - Google Patents
Synthetic method of 3, 4-dihydropyrimidinone medicine intermediates Download PDFInfo
- Publication number
- CN104387327A CN104387327A CN201410707282.9A CN201410707282A CN104387327A CN 104387327 A CN104387327 A CN 104387327A CN 201410707282 A CN201410707282 A CN 201410707282A CN 104387327 A CN104387327 A CN 104387327A
- Authority
- CN
- China
- Prior art keywords
- synthetic method
- dihydropyrimidinone
- reaction
- otf
- medicine intermediates
- 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
- C07D239/20—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D239/22—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to ring carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a synthetic method of 3, 4-dihydropyrimidinone medicine intermediates. The synthetic method comprises the following steps: under the condition without a solvent at the temperature of 80 DEG C, with Sr(OTf)2/H2O2 as a catalyst system and benzyl halide, beta-carboxyl carboxylic ester and urea as reaction raw materials, synthesizing 3, 4-dihydropyrimidinone medicine intermediates. According to the synthetic method disclosed by the invention, by using the Sr(OTf)2/H2O2 catalytic condition, Biginelli condensation reaction is carried out on the benzyl halide, the beta-carboxyl carboxylic ester and the urea; the 3, 4-dihydropyrimidinone medicine intermediates are efficiently obtained by virtue of a one-pot method; the reaction has the advantages of wide application range, mild reaction condition, high product yield, environmental protection, recoverable catalyst without weakening activity and the like, and the yield reaches 95 percent.
Description
Technical field
The invention belongs to chemical field, relate to the synthetic method of 3,4-dihydro-pyrimidin ketone pharmaceutical intermediate.
Background technology
1893, Biginelli phenylacetic aldehyde, methyl aceto acetate and urea are raw material, and in ethanol is rained in concentrated hydrochloric acid catalysis, backflow obtains 3,4-dihydro-pyrimidin ketone pharmaceutical intermediate for 18 hours, the classical Biginelli reaction being used for synthesis 3,4-dihydro-pyrimidin ketone pharmaceutical intermediate that Here it is.Due to its biological and pharmacological action widely, gas synthetic method obtains great concern, and the synthetic method of many improvement, for the preparation of this class pharmaceutical intermediate, mainly can be divided into catalysis synthesis process, microwave promoted synthesis method, solid-phase synthesis etc.There is more technical problem in existing method, as used expensive reagent, long reaction time, epidemic prevention condition is harsh, and productive rate ground, catalyzer can not reclaim use, and environmental pollution is large.
Summary of the invention
Given this, it is high that the object of the invention is to provide a kind of productive rate, the synthetic method of simple 3, the 4-dihydro-pyrimidin ketone pharmaceutical intermediates of method.
For solving above technical problem, technical scheme provided by the invention is, provides a kind of synthetic method of 3,4-dihydro-pyrimidin ketone pharmaceutical intermediate, under 80 DEG C of condition of no solvent, with Sr (OTf)
2/ H
2o
2for catalyst system, with halogenation benzyl, β-alkylcarboxylic ester and urea for reaction principle synthesizes 3,4-dihydro-pyrimidin ketone pharmaceutical intermediate, reaction equation is as follows:
Further, described H
2o
2equivalent be 1.2.
Further, described Sr (OTf)
2usage quantity be 1mol%.
Compared with prior art, a technical scheme tool in technique scheme has the following advantages:
Present invention uses Sr (OTf)
2/ H
2o
2under catalytic condition, there is Biginelli condensation reaction in halogenation benzyl, β-oxo carboxylic acid's ester and urea." one kettle way " obtains 3,4-dihydro-pyrimidin ketone pharmaceutical intermediate efficiently.This reaction have applied widely, reaction conditions is gentle, product yield is high, environmental friendliness, catalyzer is recyclable to be used and the advantages such as non-inactivation again, and productive rate reaches 95%.
Embodiment
Embodiment 1
In 25ml two mouthfuls of round-bottomed flasks, add the Benzyl Chloride of 1mmol, then add 1.2mmolH
2o
2, reacting by heating 0.5h, adds 1,3-dicarboxyl propane and the 1.5mmol urea of 1, mmol, adds 0.01mmol Sr (OTf) simultaneously
2, be heated to 80 DEG C, stirring reaction.Follow the tracks of with TLC in reaction process, wait after reacting completely, cooling, adds a small amount of water and ethanol, and filter and obtain solid, solid uses 5ml water and washing with alcohol again, and recrystallization obtains straight product in ethanol.Productive rate is 95.1%.
After reaction terminates, add 5ml water, stir 3 minutes.Solid particulate natural filtration, and water and 5ml washing with alcohol, obtaining target product with ethyl alcohol recrystallization.Aqueous phase concentrating under reduced pressure, obtain the trifluoromethanesulfonic acid strontium solid of white, then dry 4h under 5mmHg, 180 DEG C of high temperature, the rate of recovery is 90%.
Below be only the preferred embodiment of the present invention, it should be pointed out that above-mentioned preferred implementation should not be considered as limitation of the present invention, protection scope of the present invention should be as the criterion with claim limited range.For those skilled in the art, without departing from the spirit and scope of the present invention, can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.
Claims (3)
1. the synthetic method of a dihydro-pyrimidin ketone pharmaceutical intermediate, is characterized in that, under 80 DEG C of condition of no solvent, with Sr (OTf)
2/ H
2o
2for catalyst system, with halogenation benzyl, β-alkylcarboxylic ester and urea for reaction principle synthesizes 3,4-dihydro-pyrimidin ketone pharmaceutical intermediate, reaction equation is as follows:
2. the synthetic method of 3,4-dihydro-pyrimidin ketone pharmaceutical intermediates according to claim 1, is characterized in that, described H
2o
2equivalent be 1.2.
3. the synthetic method of 3,4-dihydro-pyrimidin ketone pharmaceutical intermediates according to claim 1, is characterized in that, described Sr (OTf)
2usage quantity be 1mol%.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410707282.9A CN104387327A (en) | 2014-11-27 | 2014-11-27 | Synthetic method of 3, 4-dihydropyrimidinone medicine intermediates |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410707282.9A CN104387327A (en) | 2014-11-27 | 2014-11-27 | Synthetic method of 3, 4-dihydropyrimidinone medicine intermediates |
Publications (1)
Publication Number | Publication Date |
---|---|
CN104387327A true CN104387327A (en) | 2015-03-04 |
Family
ID=52605304
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201410707282.9A Pending CN104387327A (en) | 2014-11-27 | 2014-11-27 | Synthetic method of 3, 4-dihydropyrimidinone medicine intermediates |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN104387327A (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104496809A (en) * | 2014-11-27 | 2015-04-08 | 苏州乔纳森新材料科技有限公司 | Synthesis method of drug intermediate phenyl acetate |
CN105801491A (en) * | 2016-04-13 | 2016-07-27 | 江苏科技大学 | Synthesizing method for 3,4-dihydropyrimidinone derivative |
-
2014
- 2014-11-27 CN CN201410707282.9A patent/CN104387327A/en active Pending
Non-Patent Citations (1)
Title |
---|
唐文渊等: "Sr(OTf)2/H2O2催化的3,4-二氢嘧啶酮类药物中间体的合成", 《科学技术与工程》 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104496809A (en) * | 2014-11-27 | 2015-04-08 | 苏州乔纳森新材料科技有限公司 | Synthesis method of drug intermediate phenyl acetate |
CN105801491A (en) * | 2016-04-13 | 2016-07-27 | 江苏科技大学 | Synthesizing method for 3,4-dihydropyrimidinone derivative |
CN105801491B (en) * | 2016-04-13 | 2018-04-17 | 江苏科技大学 | The synthetic method of 3,4 dihydro-pyrimidin ketones derivants |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Rafiee et al. | Cs2. 5H0. 5PW12O40 catalyzed diastereoselective synthesis of β-amino ketones via three component Mannich-type reaction in water | |
CN106632073B (en) | The synthetic method of ionic liquid constant temperature catalyzing 3,4- dihydropyrimidine-2-keto class compound | |
CN111269115A (en) | Preparation method of cinnamate in eutectic solvent | |
CN105968075A (en) | Method for preparing DFF (2,5-diformylfurane) by photocatalytically oxidizing HMF (5-hydroxymethylfurfural) | |
CN109761851A (en) | A kind of preparation method of isophthalodinitrile | |
CN104387327A (en) | Synthetic method of 3, 4-dihydropyrimidinone medicine intermediates | |
CN103030614A (en) | Extracting method of synthetic peach aldehyde | |
CN102351777B (en) | Preparation method for chiral 3-hydroxyl-3-methylene nitro indole-2-ketone derivative | |
CN107721936A (en) | The method of the ketone compounds of 3,4 dihydro-pyrimidin of synthesis in water 2 | |
An et al. | An Efficient and Solvent‐Free Reaction for Synthesis of Bis (indol‐3‐yl) methanes Catalyzed by Sulfamic Acid | |
CN103497123A (en) | Preparation method for ketoxime | |
CN109180497A (en) | A kind of preparation method of N- alkylate | |
CN109081817A (en) | CuI/ ionic liquid normal temperature and pressure catalysis converts CO2The method for synthesizing 1,3- oxazolidine -2- ketone compounds | |
CN105327703B (en) | The preparation method of gold nano catalyst and the catalyst prod obtained and application | |
CN107721935A (en) | A kind of synthetic method of 3,4 dihydro-pyrimidin ketone pharmaceutical intermediates | |
CN104130181A (en) | Continuous synthesis method of 2,2,6,6-tetramethyl-4-piperidone | |
CN107556230A (en) | A kind of method that 1,4 dihydropyridine compounds are prepared using micro-reaction device | |
CN111116339B (en) | Method for artificially synthesizing curcumin and derivatives thereof | |
US20210347750A1 (en) | Rapid synthesis method for biomass-based amine | |
CN103360341B (en) | Chiral amine compound that one class Terleu is derivative and its preparation method and application | |
CN103965042B (en) | A kind of synthetic method of ethoxy ethyl acrylate | |
CN106187792B (en) | The synthesis of difunctional ionic liquid-catalyzed Beta-aminoketones compound | |
CN106475141A (en) | (S) the unilateral Fe Anderson type heteropolyacid catalyst modified of 1 (3 hydroxyl 1 phenylpropyl) thiourea, preparation method and applications | |
CN105348285A (en) | Low-cost and high-yield adenine preparation method | |
CN106748705B (en) | Method for artificially synthesizing curcumin and derivatives thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20150304 |