CN108101855A - A kind of Preparation method and use of the amino acid esters compound of -6- of piperidyl containing 4- methylpyrimidine heterocycles - Google Patents
A kind of Preparation method and use of the amino acid esters compound of -6- of piperidyl containing 4- methylpyrimidine heterocycles Download PDFInfo
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- CN108101855A CN108101855A CN201711366887.6A CN201711366887A CN108101855A CN 108101855 A CN108101855 A CN 108101855A CN 201711366887 A CN201711366887 A CN 201711366887A CN 108101855 A CN108101855 A CN 108101855A
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- C07—ORGANIC CHEMISTRY
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- 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
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Abstract
The invention discloses a kind of preparation methods and bioactivity of the amino acid esters compound for the compound 6 methylpyrimidine heterocycle Han 4 piperidyl for preventing cucumber mosaic virus, are compounds represented by general formula (I) and preparation method thereof.Invention describes using 2 amino, 4 piperidyl, 6 methylpyrimidine, substitution aldehyde, malonate as raw material, paraxylene is solvent, the amino acid esters compound of microwave one pot process 6 methylpyrimidine heterocycle Han 4 piperidyl.The compounds of this invention I2Good inhibiting effect is respectively provided with to cucumber mosaic virus and tobacco ralstonia solanacearum.
Description
Technical field
The present invention relates to technical field of chemistry, relate in particular to a kind of ammonia of -6- of piperidyl containing 4- methylpyrimidine heterocycles
Base acid esters compound, the compound preparation method and have to Cucumber Mosaic Virus and tobacco ralstonia solanacearum and inhibit to make
Purposes.
Background technology
Cucumber mosaic virus (Cucumber Mosaic Virus, CMV) belongs to Bromoviridae member, is distribution
Most wide, harm is most heavy, most one of virus of Economic Importance.Left and right tobacco and vegetables flake have the disease in world wide
After the distribution and harm of poison, tobacco and vegetables infection yield and quality is caused to decline or even have no harvest, brought seriously to agricultural production
(Shen little Ying, Song Shuan, Luo Jing, Zhang Xin, the anti-tobacco cucumber mosaic virus polysaccharide of peace moral honor screen and its tobacco are prevented economic loss
Influence [J] microorganism journals of imperial enzymatic activity, 2013,53 (08):882-888.).Effective at present and satisfactory anti-plant
The practical kind of viral agent is not much, and the therapeutic medicament of especially special efficacy is less, the medicament reported field practical application its
Preventive effect is mostly below 60%.For this purpose, it is extremely urgent to formulate out efficient, new anti cucumber mosaic virus medicament.
Tobacco is important industrial crops, the tobacco as caused by Ralstonia solanacearum (Ralstonia solanacearum)
Bacterial wilt harm is huge.The disease is typical vascular bundle diseases, and each position of Tobacco Root, stem, leaf can be infected, and diseased plant root becomes
It is black to rot, tobacco is caused destructive to endanger that (Liu Wei, Liu Peng, Shen little Ying, peace are bestowed by heaven, and into giant dragon, peace moral honor tobacco green grass or young crops is withered
Screening, identification and its Bacteriostatic Activities [J] Journal of Northwest Sci Tech University of Agriculture and Forestry (natural sciences of sick antagonistic Bacillus
Version), 2014,42 (02):123-130.).Mainly producing cigarette provinces and regions in China at present has generation.Currently for tobacco ralstonia solanacearum
Preferable disease-resistant variety is there is no, develops the attention of the effective chemical prevention medicament person that has been received by studies in China.
Nineteen ninety-five, Chengdu Inst. of Biology, Chinese Academy of Sciences to (Xiang Guxi, Hu Houzhi, Chen Jiaren, Chen Wei such as Gu Xi
Newly, a kind of new farm antibiotics of the gloomy of Wu Lin --- Ningnanmycin [J] microorganism journals, 1995,35 (5): 368-374.)
Cystosine nucleocide type antibiotic Ningnanmycin is extracted from the zymotic fluid of Strepcomces noursei var. xichangensis
(ningnanmycin).Multiple spot controlling experiment is carried out to it in Sichuan Province and Yunnan Province of China, demonstration result shows：Ningnan enzyme element
Control effect to tobacco mosaic disease is 69.4%~95.4%, and average effect of increasing production is 26.1%, is superior to ZhiBingLing(SIC), bacterium
The cleer and peaceful NC-83 of poison, and can significantly improve the inherent quality of tobacco leaf.In greenhouse after the 3-10d of dispenser interval, manually it is inoculated with respectively
CMV, TMV and PVY, experiment show that Ningnan enzyme element is up to 90.9% to the control effect of the tobacco mosaic disease caused by CMV and TMV
With 92.9%, 53.8% is up to the control effect of tobacco mosaic disease caused by PVY.
Jasmine acid esters (jasmonates, Jas) is a kind of newfound plant endogenous hormones, and it is jasmonic to represent object
(jasmonic acid, JA) and methyl jasmonate (methyl jasmonate, MJ).(the Creelmna R A such as Creelmna；
Mellut J E.Biosynthesis and action of jasmonates in plnat[J]. Annual Review
ofPlant Physiology and Plant Molecular Biology,1997,48:355-381)
Research find JAs plant it is disease-resistant in work, be one of carrier of resistance signal, join in plant disease-resistant
With local and system resistance.
To formulate new and effective anti cucumber mosaic virus agent, the present invention utilizes active group on the basis of previous work
Group's splicing principle, pyrimidine heterocyclic is introduced into amino-acid ester structure, and design has synthesized the serial -6- methylpyrimidines of piperidyl containing 4-
The amino acid esters compound of heterocycle it is expected to filter out the drug of the anti cucumber mosaic virus of high activity and tobacco ralstonia solanacearum.
The content of the invention
Present invention aims at provide a kind of piperidines containing 4- with anti cucumber mosaic virus and tobacco ralstonia solanacearum activity
Amino acid esters compound of base -6- methylpyrimidine heterocycles and preparation method thereof.
The bright another object of this law is the purposes for preventing Cucumber Mosaic Virus (CMV) and tobacco ralstonia solanacearum.
A kind of amino acid esters compound of -6- of piperidyl containing 4- methylpyrimidine heterocycles of the present invention, general formula are following formula
(I)：
Wherein：R1For phenyl, monosubstituted phenyl, the monosubstituted methoxyphenyl of contraposition, the monosubstituted aminomethyl phenyl of contraposition, hexamethylene
Base or furfuryl；R2Methyl or ethyl.
The amino acid esters compound of the present invention -6- methylpyrimidine heterocycles of piperidyl containing 4-, having synthesized compound is：
Compound I1：
Diethyl -2- (((4- (- 1 base of methyl -6- piperidines) pyrimidine -2-base) amino) (benzyl) malonic acid；
Compound I2：
Diethyl -2- ((4- (methoxyphenyl) ((- 1 base of 4- methyl -6- piperidines) pyrimidine -2-base) amino) (methyl) third
Diacid；
Compound I3：
Diethyl -2- ((4- chlorphenyls) (4- (- 1 base of methyl -6- piperidines) pyrimidine -2-base) amino) (methyl) malonic acid；
Compound I4：
Diethyl -2- (cyclohexyl) ((4- (- 1 base of methyl -6- piperidines) pyrimidine -2-base) amino) (methyl) malonic acid；
Compound I5：
Dimethyl -2- (((4- (- 1 base of methyl -6- piperidines) pyrimidine -2-base) amino) (benzyl) malonic acid；
Compound I6：
Dimethyl -2- (((4- (- 1 base of methyl -6- piperidines) pyrimidine -2-base) amino) (benzyl) malonic acid；
Compound I7：
Diethyl -2- (furans -2- bases) ((4- (- 1 base of methyl -6- piperidines) pyrimidine -2-base) amino) (methyl) malonic acid；
Compound I8：
Diethyl -2- (cyclohexyl) ((4- (- 1 base of methyl -6- piperidines) pyrimidine -2-base) amino) (methyl) malonic acid；
The preparation method of the amino acid esters compound of the present invention -6- methylpyrimidine heterocycles of piperidyl containing 4-, is with 2- ammonia
Base -4- piperidyl -6- methylpyrimidines, substitution aldehyde, malonate are raw material, and paraxylene is solvent, and microwave one pot process contains
The amino acid esters compound of 4- piperidyl -6- methylpyrimidine heterocycles, synthetic route are：
Which part compound (I1-I2) following structural features：
A kind of preparation of the amino acid esters compound of -6- of piperidyl containing 4- methylpyrimidine heterocycles described in present invention
Method is synthesized through the following steps：
By 2- amino -4- piperidyl -6- methylpyrimidines, substitution aldehyde, malonate input single port bottle, paraxylene is added in,
To 100 DEG C, reaction terminates for 50 minutes, paraxylene is recovered under reduced pressure, by pillar layer separation (petroleum ether for microwave heating：Acetic acid second
Ester=4:1V/V) obtain target product I1-I8,
The purposes of the amino acid esters compound of the present invention -6- methylpyrimidine heterocycles of piperidyl containing 4- refers to cucumber mosaic
Virosis and tobacco ralstonia solanacearum are respectively provided with the drug or medicament of inhibitory action.
Beneficial effects of the present invention：The present invention has been synthesized is respectively provided with inhibition to Cucumber Mosaic Virus and tobacco ralstonia solanacearum
The amino acid esters compound of the 4- piperidyl -6- methylpyrimidine heterocycles of effect.It can be used to prevent simultaneously without such compound at present
The report in terms of Cucumber Mosaic Virus and tobacco ralstonia solanacearum is controlled, synthetic route of the present invention is reasonable, and synthesis material is easy to get, operation
Simply, reaction yield is higher.And the compound I in the present invention2Cucumber Mosaic Virus and tobacco ralstonia solanacearum are respectively provided with
Inhibitory action.And I2In terms of cucumber mosaic virus is prevented, activity is either treated, protected or be passivated, is superior to compare
Medicament Ningnanmycin.Compound I2It is 100% and commodity to the inhibiting rate of tobacco Ralstonia solanacearum under 200 and 100ug/mL concentration
It is suitable to change comparison medicament Thiodiazole-copper.In addition, compound I of the invention, also optimal to bioactivity2Preparation method carried out depth
The research entered, and finally determine the optimal compound I of activity in the present invention2Continuous production preparation method.
Description of the drawings
Fig. 1 is continuously to prepare I2 schematic diagrames using MCT microreactors.
Specific embodiment
Embodiment 1：Compound I1Synthesis：
In 100mL single port bottles, 2- amino -4- piperidyl -6- methylpyrimidines (0.001mol), benzaldehyde are added in
(0.001mol), diethyl malonate (0.0015mol) adds in paraxylene (30mL) as solvent, at 100 DEG C of microwave, 50 points
Reaction was completed after clock, and paraxylene is recovered under reduced pressure, by pillar layer separation (petroleum ether：Ethyl acetate=4:1V/V) obtain target
Product.
Embodiment 2：Compound I2Synthesis：
In 100mL single port bottles, 2- amino -4- piperidyl -6- methylpyrimidines (0.001mol), 4- methoxybenzene first are added in
Aldehyde (0.001mol), diethyl malonate (0.0015mol) add in paraxylene (30mL) as solvent, at 100 DEG C of microwave, 50
Reaction was completed after minute, paraxylene is recovered under reduced pressure, by pillar layer separation (petroleum ether：Ethyl acetate=4:1V/V) obtain mesh
Mark product.
Embodiment 3：Compound I3Synthesis：
In 100mL single port bottles, 2- amino -4- piperidyl -6- methylpyrimidines (0.001mol), 4- chlorobenzaldehydes are added in
(0.001mol), diethyl malonate (0.0015mol) adds in paraxylene (30mL) as solvent, at 100 DEG C of microwave, 50 points
Reaction was completed after clock, and paraxylene is recovered under reduced pressure, by pillar layer separation (petroleum ether：Ethyl acetate=4:1V/V) obtain target
Product.
Embodiment 4：Compound I4Synthesis：
In 100mL single port bottles, 2- amino -4- piperidyl -6- methylpyrimidines (0.001mol), hexahydrobenzaldehyde are added in
(0.001mol), diethyl malonate (0.0015mol) adds in paraxylene (30mL) as solvent, at 100 DEG C of microwave, 50 points
Reaction was completed after clock, and paraxylene is recovered under reduced pressure, by pillar layer separation (petroleum ether：Ethyl acetate=4:1V/V) obtain target
Product.
Embodiment 5：Compound I5Synthesis：
In 100mL single port bottles, 2- amino -4- piperidyl -6- methylpyrimidines (0.001mol), benzaldehyde are added in
(0.001mol), dimethyl malenate (0.0015mol) adds in paraxylene (30mL) as solvent, at 100 DEG C of microwave, 50 points
Reaction was completed after clock, and paraxylene is recovered under reduced pressure, by pillar layer separation (petroleum ether：Ethyl acetate=4:1V/V) obtain target
Product.
Embodiment 6：Compound I6Synthesis：
In 100mL single port bottles, 2- amino -4- piperidyl -6- methylpyrimidines (0.001mol), p-tolyl aldehyde are added in
(0.001mol), dimethyl malenate (0.0015mol) adds in paraxylene (30mL) as solvent, at 100 DEG C of microwave, 50 points
Reaction was completed after clock, and paraxylene is recovered under reduced pressure, by pillar layer separation (petroleum ether：Ethyl acetate=4:1V/V) obtain target
Product.
Embodiment 7：Compound I7Synthesis：
In 100mL single port bottles, 2- amino -4- piperidyl -6- methylpyrimidines (0.001mol), furfural are added in
(0.001mol), dimethyl malenate (0.0015mol) adds in paraxylene (30mL) as solvent, at 100 DEG C of microwave, 50 points
Reaction was completed after clock, and paraxylene is recovered under reduced pressure, by pillar layer separation (petroleum ether：Ethyl acetate=4:1V/V) obtain target
Product.
Embodiment 8：Compound I8Synthesis：
In 100mL single port bottles, 2- amino -4- piperidyl -6- methylpyrimidines (0.001mol), hexahydrobenzaldehyde are added in
(0.001mol), dimethyl malenate (0.0015mol) adds in paraxylene (30mL) as solvent, at 100 DEG C of microwave, 50 points
Reaction was completed after clock, and paraxylene is recovered under reduced pressure, by pillar layer separation (petroleum ether：Ethyl acetate=4:1V/V) obtain target
Product.
To the receipts of the amino acid esters compound of -6- methylpyrimidine heterocycles of piperidyl containing 4- of above-described embodiment 1-8 synthesis
Rate, physical aspect and elemental analysis are as shown in table 1, nuclear magnetic resonance spectroscopy (1H NMR) data as shown in table 2, nuclear magnetic resonance carbon
Spectrum (13C NMR) data are as shown in table 3, and for infrared spectrum (IR) data as shown in table 4, mass spectrum (MS) data are as shown in table 5：
The physicochemical property of 1 target compound of table and elemental analysis
2 target compound of table1H NMR datas
3 target compound of table13C NMR datas
The infrared data of 4 target compound of table
| Compound | IR(KBr)(cm-1) |
| I1 | 3378,2973,1736,1553,1431,1237,1172,826,791 |
| I2 | 3481,2962,1738,1571,1446,1243,1163,858,790 |
| I3 | 3411,2927,1742,1567,1465,1258,1169,920,762 |
| I4 | 3379,2980,1733,1578,1454,1243,1190,852,788 |
| I5 | 3391,2969,1727,1570,1437,1247,1173,858,779 |
| I6 | 3490,2961,1741,1569,1448,1251,1171,864,790 |
| I7 | 3400,2926,1728,1579,1451,1243,1172,927,778 |
| I8 | 3388,2991,1730,1577,1454,1240,1165,881,792 |
The mass spectrum of 5 target compound of table
| Compound | MS(ESI):m/z |
| I1 | 441([M+H]+),463([M+Na]+),479([M+K]+). |
| I2 | 471([M+H]+),493([M+Na]+),509([M+K]+). |
| I3 | 475([M+H]+),497([M+Na]+),513([M+K]+). |
| I4 | 447([M+H]+),469([M+Na]+),485([M+K]+). |
| I5 | 413([M+H]+),435([M+Na]+),451([M+K]+). |
| I6 | 427([M+H]+),449([M+Na]+),465([M+K]+). |
| I7 | 403([M+H]+),425([M+Na]+),441([M+K]+). |
| I8 | 419([M+H]+),441([M+Na]+),457([M+K]+). |
Embodiment 9, the treatment of target compound anti cucumber mosaic virus, passivation and protection activity
(1) test method
A. Virus purification
Using week snow quadratic method (Zhou, X.P.；Xu,Z.X.；Xu,J.；Li,D.B.J.South Chin.Agric.
Univ.1995,16,74-79), choose and be inoculated with 3 weeks or more, on CMV systemic infection host Nicotiana tabacum.L plant
Portion's blade, is homogenized in phosphate buffer, and double gauze filtering, 8000g centrifugations are handled by 2 polyethylene glycol, then centrifuged,
Precipitation is suspended with phosphate buffer to get to CMV refining liquid bodies.Entire experiment carries out at 4 DEG C, is surveyed with ultraviolet specrophotometer
Determine the absorbance of 260nm wavelength, virus concentration is calculated according to formula.
Virus concentration (mg/mL)=(A260× extension rate)/E0.1% 1cm 260nm
Wherein E represents extinction coefficient, i.e. during wavelength 260nm, concentration is the suspension of 0.1% (1mg/mL), is l in light path
Centimetre when light absorption (optical density) value.The E of CMV0.1% 1cm 260nmIt is 5.0.
B, medicament acts on the active treatment that CMV infects：The 5-6 leaf phases Jian Seli toppings of growing way always are selected, are spread to full leaf
Even diamond dust dips viral juice (6 × 10 with spread pen-3Mg/mL) full leaf virus inoculation is rinsed with clear water after naturally dry.Treat leaf
After piece is done, medicament is gently spread in left half leaf with writing brush, right half leaf spreads the concentration of corresponding solvent as control, 6-7 days postscripts
Withered spot number is recorded, inhibiting rate is calculated by following equation.
C, the live body protective effect that medicament infects CMV
Medicament is protected the live body that CMV infects and is rented：The 5-6 leaf phases Jian Seli toppings of growing way always are selected, with writing brush on a left side
Half leaf gently spreads medicament, and the solvent that right half leaf spreads corresponding concentration compares, and 24 small backward full leafs sprinkle evenly diamond dust, use spread pen
Dip viral juice (6 × 10-3Mg/mL) full leaf virus inoculation is rinsed with clear water, and withered spot number is recorded after 6-7 days, by following equation
Calculate inhibiting rate.
D, the live body passivation that medicament infects CMV
The live body passivation that medicament infects CMV:The 5-6 leaf phases Jian Seli toppings of growing way always are selected, are sprinkled evenly to full leaf
Diamond dust, with phosphate buffer by CMV；Viral dilution is to 6 × 10-3Mg/mL mixes compound with isometric viral juice
Passivation 30 minutes, with the artificial frictional inoculation of spread pen in of the right age half industry of bamboo water pipe color Li Zuo sprinkled with diamond dust, the solvent of matched doses with
Viral juice combined inoculation records withered spot number, based on following equation in of the right age bamboo water pipe color multitude right half leaf sprinkled with diamond dust after 6-7 days
Calculate inhibiting rate.
X%=(CK-T)/CK × 100
X:Relative inhibition (%)；
CK:It is not coated with the average withered spot number of half leaf of dispenser agent；
T:Spread the average withered spot number of half leaf of medicament；
Wherein, the average that CK and T is repeated three times using each group.
(2) biological test result
6 target compound of table is to the treatment of cucumber mosaic virus, protection, passivation activity
| Compound | Concentration (μ g/mL) | Therapeutic effect (%) | Protecting effect (%) | Passivation effect (%) |
| I1 | 500 | 42.9±2.8 | 47.8±1.3 | 64.2±1.5 |
| I2 | 500 | 54.5±2.2 | 67.2±1.6 | 93.1±3.4 |
| I3 | 500 | 33.1±3.1 | 53.4±2.1 | 63.2±2.5 |
| I4 | 500 | 23.3±2.1 | 33.5±2.6 | 52.3±2.8 |
| I5 | 500 | 22.3±3.1 | 38.2±2.3 | 51.1±1.2 |
| I6 | 500 | 42.3±0.9 | 48.3±1.0 | 58.8±0.9 |
| I7 | 500 | 24.5±1.1 | 37.2±1.3 | 44.1±1.2 |
| I8 | 500 | 46.3±2.1 | 59.9±3.7 | 82.3±1.8 |
| Ningnanmycin | 500 | 50.0±2.2 | 64.6±2.8 | 92.3±2.7 |
Using half leaf withered spot method, concentration 500mg/L tests the anti-of target compound by comparison medicament of Ningnanmycin
CMV activity, the amino acid esters of -6- methylpyrimidine heterocycles of piperidyl containing 4- are can be seen that from 6 biological activity determination result of table
It closes during object is respectively provided with CMV when outstanding inhibitory activity, wherein I2In terms for the treatment of, protection, passivation, comparison medicament is superior to
Ningnanmycin.
In order to further study the anti-CMV activity of the amino acid esters compound of -6- methylpyrimidine heterocycles of piperidyl containing 4-,
We determine I in such compound2Treatment EC50Value, the results are shown in Table 7.
7 partial target compound of table is to the EC of the therapeutic activity of CMV50Value
| Compound | EC50(μg/mL) |
| I2 | 213.2±1.9 |
| Ningnanmycin | 298.5±2.7 |
As a result as can be seen that I2To the EC of CMV protection activities50For 213.2 μ g/mL, better than comparison medicament Ningnanmycin
298.5μg/mL。
Embodiment 10, the test method of tobacco bacterial wilt：
The concentration of tested compound is respectively 100 and 200ug/mL, and DMSO dissolvings are used as blank control in the medium,
Thiodiazole-copper is comparison medicament, and tobacco bacterial wilt opportunistic pathogen is carried out line culture on NA solid mediums, is placed on 30 DEG C of constant temperature
It is cultivated in incubator, until growing single bacterium colony.The more single bacterium colony of center pink, white edge is chosen with collarium is connect, is put into NB liquid
In body culture medium, shaken cultivation is spare to exponential phase in 30 DEG C, 180rpm constant-temperature tables.By compound and comparison medicament
The toxic NB fluid nutrient mediums 5mL for being each configured to concentration 100 and 200ug/mL is added in test tube, is added in 40uL and is contained tobacco
In the NB fluid nutrient mediums of bacterial wilt opportunistic pathogen, the shaken cultivation 48h in 30 DEG C, 180rpm constant-temperature tables, by the bacterium of each concentration
Liquid measures OD on spectrophotometer595Value, and in addition measure the toxic sterile NB fluid nutrient mediums OD of corresponding concentration595Value.
Correct the OD values=values of OD containing bacterium culture medium-aseptic culture medium OD values
Inhibiting rate %=[(control medium bacterium solution OD values after correction-correct toxic culture medium OD values)/compare training after correcting
Support base bacterium solution OD values] X 100%.
As can be seen from the above table：At the concentration tested, target compound has certain suppression to tobacco bacterial wilt pathogen
System activity, wherein compound I2, it is 100% and commercialization to the inhibiting rate of tobacco Ralstonia solanacearum under 200 and 100ug/mL concentration
Comparison medicament Thiodiazole-copper is suitable.
Embodiment 10 continuously prepares I using MCT microreactors2。
The toluene solution of the 2- amino -4- piperidyl -6- methylpyrimidines of the 0.1mol/L of 500mL is taken to be placed in A bottles (to be designated as
A bottles), the concentration for taking 500mL is that the P-methoxybenzal-dehyde of 0.1mol/L and the mixed toluene solution of diethyl malonate are put
In B bottles；With in MPK2005 constant flow pump is pressed to be promoted with the flow velocity of 10mL/min respectively by A bottles and B bottles, into MCT microreactors
(MCT microreactors set 90 DEG C of reaction temperature) stops reaction after 50 minutes, be recovered under reduced pressure in collection of products bottle to diformazan
Benzene, product is through pillar layer separation (petroleum ether：Ethyl acetate=4:1V/V) obtain 34.5g target products I2, yield：90.0%.Profit
A gram grade target product I can be continuously produced in high yield with MCT microreactors2。
The embodiment of the present invention, which is aided with, illustrates technical scheme.Effect of the present invention be synthetic route is simple, yield compared with
Height obtains new, efficient prevention Cucumber Mosaic Virus and the new medicament of tobacco ralstonia solanacearum sum.
Claims (6)
1. a kind of amino acid esters compound of -6- of piperidyl containing 4- methylpyrimidine heterocycles, it is characterised in that：Its general formula is following formula
(I)：
Wherein：R1For phenyl, monosubstituted phenyl, the monosubstituted methoxyphenyl of contraposition, the monosubstituted aminomethyl phenyl of contraposition, cyclohexyl or
Furfuryl；R2Methyl or ethyl.
2. a kind of amino acid esters chemical combination of -6- of piperidyl containing 4- methylpyrimidine heterocycles according to claim 1
Object, it is characterised in that：Partially synthetic compound is as follows：
Compound I1：
Diethyl -2- (((4- (- 1 base of methyl -6- piperidines) pyrimidine -2-base) amino) (benzyl) malonic acid；
Compound I2：
Diethyl -2- ((4- (methoxyphenyl) ((- 1 base of 4- methyl -6- piperidines) pyrimidine -2-base) amino) (methyl) malonic acid；
Compound I3：
Diethyl -2- ((4- chlorphenyls) (4- (- 1 base of methyl -6- piperidines) pyrimidine -2-base) amino) (methyl) malonic acid；
Compound I4：
Diethyl -2- (cyclohexyl) ((4- (- 1 base of methyl -6- piperidines) pyrimidine -2-base) amino) (methyl) malonic acid；
Compound I5：
Dimethyl -2- (((4- (- 1 base of methyl -6- piperidines) pyrimidine -2-base) amino) (benzyl) malonic acid；
Compound I6：
Dimethyl -2- (((4- (- 1 base of methyl -6- piperidines) pyrimidine -2-base) amino) (benzyl) malonic acid；
Compound I7：
Diethyl -2- (furans -2- bases) ((4- (- 1 base of methyl -6- piperidines) pyrimidine -2-base) amino) (methyl) malonic acid；
Compound I8：
Diethyl -2- (cyclohexyl) ((4- (- 1 base of methyl -6- piperidines) pyrimidine -2-base) amino) (methyl) malonic acid.
3. a kind of conjunction of the amino acid esters compound of -6- of piperidyl containing 4- methylpyrimidine heterocycles as claimed in claim 1 or 2
Into method, it is characterised in that：Using 2- amino -4- piperidyl -6- methylpyrimidines, substitution aldehyde, malonate as raw material, paraxylene
For solvent, the amino acid esters compound of the microwave one pot process -6- methylpyrimidine heterocycles of piperidyl containing 4-, synthetic route
For：
4. a kind of system of the amino acid esters compound of -6- of piperidyl containing 4- methylpyrimidine heterocycles according to claim 3
Preparation Method, it is characterised in that：100 DEG C of the microwave heating is reacted 50 minutes, paraxylene is recovered under reduced pressure, by column chromatography point
From obtaining target product.
5. a kind of system of the amino acid esters compound of -6- of piperidyl containing 4- methylpyrimidine heterocycles according to claim 4
Preparation Method, it is characterised in that：The pillar layer separation condition is petroleum ether：Ethyl acetate=4:1V/V.
6. a kind of amino acid esters compound of -6- of piperidyl containing 4- methylpyrimidine heterocycles as claimed in claim 1 or 2 is being made
Application in the drug and medicament of standby prevention cucumber mosaic virus and tobacco ralstonia solanacearum.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN115677606A (en) * | 2022-08-26 | 2023-02-03 | 贵州理工学院 | Chiral malonate type compound, preparation and application thereof |
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| CN101817803A (en) * | 2010-04-29 | 2010-09-01 | 贵州大学 | Beta-amino acid esters having optical activity and containing benzothiazole groups and synthetic method and application thereof |
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| CN101817803A (en) * | 2010-04-29 | 2010-09-01 | 贵州大学 | Beta-amino acid esters having optical activity and containing benzothiazole groups and synthetic method and application thereof |
| CN103980225A (en) * | 2014-04-30 | 2014-08-13 | 淮海工学院 | Synthetic method of beta-amino acid with thiazole ring connected to nitrogen |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115677606A (en) * | 2022-08-26 | 2023-02-03 | 贵州理工学院 | Chiral malonate type compound, preparation and application thereof |
| CN115677606B (en) * | 2022-08-26 | 2023-08-29 | 贵州理工学院 | Chiral malonate compound, preparation and application thereof |
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