CN85106722A - 1, the preparation of 3-dihydro-4-pyridine acyl-2H-imidazole-2-ketone compound - Google Patents
1, the preparation of 3-dihydro-4-pyridine acyl-2H-imidazole-2-ketone compound Download PDFInfo
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Abstract
1,3-dihydro-4-pyridine acyl-2H-imidazoles-2-ketone prepared by following three steps:
A) reduction 1-pyridyl-1,3-diketone-2-oximido alkane obtains 1-pyridyl-1-hydroxyl-2-amino-3-ketone alkane; B) hydroxyl amino ketone and the cyanic acid ion reaction that obtains obtained 1,3-dihydro-4-hydroxyl (pyridyl)-methyl-2H-imidazoles-2-ketone;
C) the resulting hydroxy-methyl compound of oxidation obtains 1 at last, 3-dihydro-4-pyridine acyl-2H-imidazoles-2-ketone.
Description
The present invention relates to produce 1 of formula I formula, the method for 3-dihydro-4-pyridine acyl-2H-imidazole-2-ketone compound.
R in the formula
1Be the alkyl of a hydrogen or 1-4 carbon atom, Ar is a 2-, 3-or 4-pyridyl and medicinal salts thereof.These compounds, particularly 4-ethyl-1,3-dihydro-5-(4-pyridine acyl)-2H-imidazoles-2-ketone has significant cardiotonic, is the beneficial agents of treatment cardiac failure.
Have the method for several these compounds of preparation in the prior art.One of them is, at the lewis' acid catalyzer particularly in the presence of aluminum chloride, imidazoles-2-ketone and pyridine acyl chlorides or pyridine acylbromide or pyridine carboxylic acid or pyridine acid anhydride reactant.There are some serious problems in this method, comprises being the devil when mixing with the solid aluminium complex compound, and causes productive rate very low mainly due to reaction product is difficult to separate from the solid of retort.
The other method of prior art, shown in reaction signal formula I, structure is that two ketoximes of II are reduced into the amino diketone that structure is an III, and then obtains chemical compounds I with the cyanate reaction.
When using this method, some difficulties have also been run into.Particularly, because active to hydrogenization near the ketone group of pyridine ring in compound ii, so it and oximido be reduced simultaneously, obtains hydroxyl amino ketone IV.
This pair reaction causes removing the compound IV of generation from hydrogenation mixture, cause the overall yield of the chemical compounds I of wanting to reduce.
The applicant finds, by the reaction path of following signal formula II, can improve the productive rate of required product I.
Reaction signal formula II
This improved reaction process need not to remove and pays the hydroxyl amino ketone IV that reaction is generated in the signal formula.Hydroxyl amino ketone and cyanic acid ion reaction generate cyclisation product in reaction signal formula II, and the productive rate of above-mentioned amino diketone III of its productivity ratio and cyanic acid ion reaction generation cyclisation product is much higher.
The applicant is surprised to find that; the reaction that a step does not have in signal formula I although the method for signal formula II is many; promptly needing bar structure is pyridine acyl imidazoles-2-ketone that the alcohol of V is oxidized to needs; but when using signal formula II, compound ii changes into pyridine acyl imidazoles-2-ketone I with much higher overall yield.
React the illustrated principle of signal formula II according to the present invention, pyridine acyl imidazole-2-ketone compound I can be made through three-step reaction by two oxime compound II.Method more particularly of the present invention comprises with suitable reductive agent two ketoxime II is reduced into hydroxyl amino ketone IV, to be reoxidised into needed pyridine acyl imidazoles-2-ketone I after the cyanate cyclisation.
The applicant has found to pass through reduction in succession with two ketoxime II, and cyclisation and three steps of oxidation prepare the method for pyridine acyl imidazoles-2-ketone I.Because productive rate is higher than other currently known methods, so method of the present invention is more suitable for the production in enormous quantities in chemical compounds I.
Said in the literary composition " alkyl of 1-4 carbon atom ", be meant methyl, ethyl, propyl group, sec.-propyl, just-butyl, or isobutyl-.
Raw material two ketoxime II make with any known proper method easily, for example, and with the nitrosification of corresponding diketone VI, wherein R
1Be the alkyl of hydrogen or 1-4 carbon atom, Ar is 2-, 3-, or 4-pyridyl.
Suitable nitrosation reaction can be referring to O.Tousler in " Organic Reaction " V. the method that VII is chatted in P.327-337.
Two ketoxime II are reduced into hydroxyl amino ketone IV, can adopt currently known methods to reach by using suitable reductive agent.The reductive agent that the applicant uses is, a) hydrogen use acetate, follows the 10% palladium carbon handled with diluted acid as catalyzer, perhaps b) metallic zinc and formic acid or acetate.Obviously also have other suitable reductive agent of countless versions two ketoxime II can be changed into alkyl keto-amine IV.Because when separating as free alkali, hydroxyl amino ketone instability is more proper so the compound IV is separated with the additive salt form of acid.The mineral acid that can generate suitable salt has hydrochloric acid, Hydrogen bromide, sulfuric acid and phosphoric acid, and some acid metal-salts, for example ortho-phosphoric acid-hydrogen sodium and sal enixum.The organic acid that can generate suitable salt has monocarboxylic acid, di-carboxylic acid, tribasic carboxylic acid.For example acetate, oxyacetic acid, lactic acid, pyruvic acid, propanedioic acid, Succinic Acid, pentanedioic acid, FUMARIC ACID TECH GRADE, oxysuccinic acid, tartrate, citric acid, xitix, maleic acid, hydroxy-maleic acid, phenylformic acid, hydroxy-benzoic acid, toluylic acid, styracin, Whitfield's ointment, 2-phenoxy benzoic acid and sulfonic compound are as methylsulfonic acid and 2-ethylenehydrinsulfonic acid.A hydrochlorate that generates or diacid salt can hydrated form or in fact anhydrous form existence.In general, the acid salt of these compounds is crystal, in the water-soluble and various hydrophilic organic solvent, compares with its free alkali form, and is in fact more stable.
The proper method of two ketoxime II of reducing comprises uses metal hydride reduction, as with lithium aluminum hydride or sodium borohydride; Use hydrogen and metal catalyst, as Raney nickel, platinum, palladium, rhodium, ruthenium and platinum oxide catalytic reduction; Use lithium, sodium, potassium, calcium, zinc, magnesium, tin or iron in liquefied ammonia or lower molecular weight aliphatic amide or sodium, aluminium or zinc amalgam, zinc, tin or iron in hydroxylic solvent or the dissolution of metals method in the presence of aqueous inorganic acid or organic acid such as formic acid, acetate or hydrochloric acid reduce.
The applicant has prepared hydroxyl amino ketone compound IV by the method that adds zinc powder in formic acid with the reduction of two ketoxime II.Wanting reductive two ketoximes to be dissolved in the suitable non-active solvent, as ethanol, Virahol, propyl carbinol, primary isoamyl alcohol, water, inorganic acid aqueous solution, example hydrochloric acid, sulfuric acid or organic acid are as acetate, methylsulfonic acid, formic acid preferably.Add acid then, example hydrochloric acid or methylsulfonic acid preferably add methylsulfonic acid in lysed reactant.The solution of gained slowly is added in metallic reducing thing (preferably zinc powder) and the formic acid blended oar, stirs, generally need with 5 minutes to 10 hours preferably 1-2 hour until reacting completely.Reaction times depends primarily on reactant, solvent and temperature.Temperature can be from 0 ℃ to 150 ℃, preferably 25 ℃-80 ℃.Product can separate from reaction mixture by free alkali form, but preferably with prior art method commonly used, with the isolated in form of acid salt.For example, add contain 10% methyl alcohol Virahol in dense residue, hydroxyl amino ketone just is settled out from solution, then filtering separation.
In addition, the applicant utilizes hydrogen and palladium-carbon catalyst, and 10% palladium-carbon catalyst preferably reduces two ketoxime II, has prepared hydroxyl amino ketone compounds IV.Two ketoximes that are reduced are dissolved in the appropriate solvent, add little amount of catalyst, be preferably less than and be reduced 10% of compound weight, reaction is performed until and consumes 3 normal hydrogen.Reaction times is depended on the compound that is reduced, the pressure of hydrogen, solvent and temperature.Hydrogen pressure can be a 1-10 normal atmosphere, preferably a normal atmosphere.Temperature can be 0 ℃-50 ℃, preferably about 25 ℃.The suitable solvent comprises any non-active solvent, as ethyl acetate, ethanol, water, acetate preferably.After reacting completely, hydrochloric acid or other suitable mineral acid are added in the reaction mixture, then, the filtering solid catalyst.Hydroxyl amino ketone or its acid salt can reclaim by proper method.For example, simple solvent is removed method.
Common staff just can be cyclized into hydroxymethyl imidazoles-2-ketone V with hydroxyl amino ketone IV and cyanic acid ion effect by any appropriate means.Hydroxyl amino ketone and 1-5 gram equivalent, the cyanate reaction of preferably about two gram equivalents 5 minutes to about 24 hours.The length in reaction times depends on reactant, solvent and temperature.Temperature can be from-78 ℃ to 100 ℃ about, be preferably in about 0 ℃-50 ℃.The suitable solvent of this reaction is any non-active solvent, water for example, or solvent that can be water-soluble, and as acetate (organic acid), methyl alcohol or ethanol (alcohol), perhaps ether, tetrahydrofuran (THF), 1, ethers such as 4-dioxane.Preferably arbitrary water blended non-aqueous solvent.The most desirable solvent is a water.Any cyanic acid root may be used in this cyclization.What the applicant used is potassium cyanate, still, the cyanate of any simple basic metal or alkaline-earth metal such as lithium, sodium or calcium, the cyanate of magnesium-yttrium-transition metal also can be used.
The product of this reaction or its acid salt can separate by currently known methods.For example, change into corresponding sodium salts or sylvite, make it redeposition with carbonic acid gas or mineral acid such as dilute hydrochloric acid then.The final step of reaction signal formula II is that hydroxyl imidazoles-2-ketone V is oxidized to required pyridine acyl imidazoles-2-ketone I.This can finish by the appropriate method known to the people who is familiar with this technical field.The suitable oxygenant that is used for this method has Manganse Dioxide, the acid chromic acid aqueous solution in acetate or acetone; Sodium dichromate 99 in acetate; The chromium trioxide pyridine complex is as Sarrett reagent or Collins reagent; Potassium permanganate and sulfuric acid and acetic acid aqueous solution; 40% peracetic acid; Between-the chlorine peroxybenzoic acid; Tetrachlorobenzoquinone, 2,3-two chloro-5,6-dicyano-1,4-benzoquinones and N-fontanel are for imide, preferably the N-chlorosuccinimide.
The applicant selects for use with following N-fontanel and comes oxidation hydroxymethyl imidazoles-2-ketone V for imide reaction: 1, and 3-two bromo-5,5-T10,1,3 dichloro 5,5 dimethyl hydantoin, the N-chloro-acetamide, N-bromo-succinimide, preferably N-chlorosuccinimide.Oxidation can be undertaken by following steps.Oxidized compound is dissolved in the appropriate solvent, and the N-fontanel that adds 1-5 gram equivalent is for imide, preferably about 1 gram equivalent.Approximately from-78 to 80 ℃ of temperature of reaction, reacting completely needs 1/2 hour to 48 hours approximately, but this depends on used reactant, solvent and other reaction conditions.The suitable solvent comprises any non-active solvent, for example, and N,N-DIMETHYLACETAMIDE, methyl alcohol, dimethyl formamide, preferably dimethyl formamide-methanol co-solvent.The products therefrom I can be separated by the proper method of knowing usually, for example, and the method for first post precipitation recrystallization.
The applicant reacts hydroxymethyl imidazoles-2-ketone V oxidation by Manganse Dioxide.Oxidized compound is dissolved in the appropriate solvent, adds 1 gram equivalent or more more Manganse Dioxide, preferably 2 or 3 gram equivalents.Reacted 15 minutes to 10 hours, preferably about 1-2 hour, this depended primarily on reactant, solvent and temperature.Temperature can be 0 ℃-150 ℃,, preferably about 25 ℃-80 ℃.The suitable solvent has pentane, chloroform, methylene dichloride, benzene, acetone, preferably acetate.Pyridine acyl imidazoles-2-the ketone that obtains can separate from reaction mixture with the method for knowing usually.For example, the applicant comes separated product by filtering and remove the method for desolvating.
Some following object lessons further clearly illustrate the method described in the present invention and state the preferred plan that the contriver imagines in order to implement its invention.Yet, be not to be used for explaining claim scope of the present invention.
Example 1
The 1-(4-pyridyl)-preparation of 1-hydroxyl-2-amino-3-ketone pentane
In 1000ml acetate, dissolve 23.0g(0.11mol) the 1-(4-pyridyl)-1,3-diketone-2-oximido pentane.Add 1.0g10% palladium carbon, feed hydrogen, until consuming 3 gram equivalent hydrogen.With this mixture of 18.5ml 12N hcl acidifying, filter, steam solvent, obtain the 1-(4-pyridyl)-dihydrochloride of 1-hydroxyl-2-amino-3-ketone pentane; M.p.225 ℃.
With the method for top example 1, but the 1-(4-pyridyl)-1,3-diketone-2-oximido pentane replaces with following compound:
The 1-(2-pyridyl)-1,3-diketone-2-oximido pentane;
The 1-(4-pyridyl)-1,3-diketone-2-oximido butane;
The 1-(3-pyridyl)-1,3-diketone-2-oximido propane;
The 1-(4-pyridyl)-1,3-diketone-4-methyl-2-oximido pentane; Or
The 1-(2-pyridyl)-1,3-diketone-2-oximido heptane,
Then obtain respectively:
The 1-(2-pyridyl)-1-hydroxyl-2-amino-3-ketone pentane;
The 1-(4-pyridyl)-1-hydroxyl-2-amino-3-ketone butane;
The 1-(3-pyridyl)-1-hydroxyl-2-amino-3-ketone propane;
The 1-(4-pyridyl)-1-hydroxyl-2-amino-4-methyl-3-ketone pentane; Or
The 1-(2-pyridyl)-1-hydroxyl-2-amino-3-ketone heptane.
Example 2
The 1-(4-pyridyl)-preparation of 1-hydroxyl-2-amino-3-ketone pentane
Heating (50 ℃) dissolving 1.0g 1-(4-pyridyl in 20ml acetate)-1,3-diketone-2-oximido pentane.With the acidifying of dry hydrogen chloride gas, slowly add zinc powder, stirred cooling 1 hour.Add dry ether, 1-(4-pyridyl)-1-hydroxyl-2-amino-3-ketone pentane then separates out from solution, thick solid product, can in next step, use, and need not to purify.
Use aforesaid method, but replace the 1-(4-pyridyl with following compound)-1,3-diketone-2-oximido pentane:
The 1-(3-pyridyl)-1,3-diketone-4-methyl-2-oximido hexane;
The 1-(4-pyridyl)-1,3-diketone-2-oximido heptane;
The 1-(3-pyridyl)-1,3-diketone-4-methyl-2-oximido pentane,
Then obtain respectively:
The 1-(3-pyridyl)-1-hydroxyl-2-amino-4-methyl-3-ketone hexane;
The 1-(4-pyridyl)-1-hydroxyl-2-amino-3-ketone pentane;
The 1-(3-pyridyl)-1-hydroxyl-2-amino-4-methyl-3-ketone pentane.
Example 3
The 1-(4-pyridyl)-preparation of 1-hydroxyl-2-amino-3-ketone pentane
Dissolving 7.5kg(91% purity in 37.8kg 88% formic acid, 36.37mol) 1-(4-pyridyl)-1,3-diketone-2-oximido pentane and 7.0kg methylsulfonic acid.The solution that obtains slowly is added in the mixed pulp of 8.3kg zinc powder and 35.7kg formic acid.By suitable cooling and control adding speed, temperature of reaction is remained on about 60 ℃.This mixture then, is cooled to 20 ℃, elimination solid formic acid zinc in 55 ℃ of stirrings 2 hours.In formic acid filtrate, add the 3.6kg methylsulfonic acid.70 ℃ of decompressions (40mmHg) remove formic acid removal.The mixing solutions that adds 5.9kg methyl alcohol and 53.3kg Virahol in the resistates, 20 ℃ were stirred 4 hours down.Collect solid matter with centrifugal method, the aqueous isopropanol washing so that 12.5kg contains 10% methyl alcohol after the drying, obtains 11.0kg 1-(4-pyridyl)-dimethanesulfonate of 1-hydroxyl-2-amino-3-ketone pentane, productive rate is 87%.
Example 4
4-ethyl-1,3-dihydro-5-[hydroxyl (4-pyridyl)-methyl]-preparation of 2H-imidazoles-2-ketone
In 100ml water, dissolve 29.0g(0.11mol) the 1-(4-pyridyl)-1-hydroxyl-2-amino-3-ketone pentane dihydrochloride and 17.9g(0.22mol) potassium cyanate.This solution in 50 ℃ warm 10 minutes, room temperature was placed 10 hours then, the solid of separating out is collected in cooling, obtains 4-ethyl-1,3-dihydro-5-[hydroxyl (4-pyridyl)-methyl]-2H-imidazoles-2-ketone.m.p.234-36℃
According to top example 4 described methods, but the 1-(4-pyridyl)-1-hydroxyl-2-amino-3-ketone pentane replaces with following compound:
The 1-(2-pyridyl)-1-hydroxyl-2-amino-3-ketone pentane;
The 1-(4-pyridyl)-1-hydroxyl-2-amino-3-ketone butane;
The 1-(3-pyridyl)-1-hydroxyl-2-amino-3-ketone propane;
The 1-(4-pyridyl)-1-hydroxyl-2-amino-4-methyl-3-ketone pentane;
The 1-(2-pyridyl)-1-hydroxyl-2-amino-3-ketone heptane.
The 1-(3-pyridyl)-1-hydroxyl-2-amino-4-methyl-3-ketone hexane;
The 1-(4-pyridyl)-1-hydroxyl-2-amino-3-ketone heptane.
The 1-(3-pyridyl)-1-hydroxyl-2-amino-4-methyl-3-ketone pentane,
Obtain respectively:
1,3-dihydro-4-ethyl-5-[hydroxyl (2-pyridyl) methyl]-2H-imidazoles-2-ketone;
1,3-dihydro-4-[hydroxyl (4-pyridyl) methyl]-5-methyl-2H-imidazoles-2-ketone;
1,3-dihydro-4-[hydroxyl (3-pyridyl) methyl]-2H-imidazoles-2-ketone;
1,3-dihydro-4-[hydroxyl (4-pyridyl) methyl]-the 5-(1-methyl) ethyl-2H-imidazoles-2-ketone;
4-butyl-1,3-dihydro-5-[hydroxyl (2-pyridine) methyl]-2H-imidazoles-2-ketone;
1,3-dihydro-4-[hydroxyl (3-pyridyl) methyl]-the 5-(1-methyl)-propyl group-2H-imidazoles-2-ketone;
4-butyl-1,3-dihydro-5-[hydroxyl (4-pyridyl) methyl]-2H-imidazoles-2-ketone;
1,3-dihydro-4-[hydroxyl-(3-pyridyl) methyl]-the 5-(1-methyl)-ethyl-2H-imidazoles-2-ketone.
Example 5
1,3-dihydro-4-ethyl-5-(4-pyridine acyl)-preparation of 2H-imidazoles-2-ketone
In 25ml acetate, dissolve 2.15g(0.009mol) chemical compounds I, and be heated to 50 ℃.Slowly adding 0.55g(0.006mol) Manganse Dioxide continued heated and stirred 30 minutes.Filter, boil off solvent.Resistates is dissolved in rare (10%) hydrochloric acid, is adjusted to PH4 with sodium bicarbonate.Separate out solid 1, the 4-pyridine acyl of 3-dihydro-4-ethyl-5-))-2H-imidazoles-2-ketone, product is purified with the ethyl alcohol recrystallization method, m.p.264 ℃.
Use the method for above-mentioned example 4, but 1,3-dihydro-4-ethyl-5-[hydroxyl (4-pyridyl) methyl]-2H-imidazoles-2-ketone, replace with following compound:
1,3-dihydro-4-ethyl-5-[hydroxyl (2-pyridyl) methyl]-2H-imidazoles-2-ketone;
1,3-dihydro-4-[hydroxyl (4-pyridyl) methyl]-5-methyl-2H-imidazoles-2-ketone;
1,3-dihydro-4-[hydroxyl (3-pyridyl) methyl]-2H-imidazoles-2-ketone;
1,3-dihydro-4-[hydroxyl (4-pyridyl) methyl]-the 5-(1-methyl) ethyl-2H-imidazoles-2-ketone;
4-butyl-1,3-dihydro-5-[hydroxyl (2-pyridyl) methyl]-2H-imidazoles-2-ketone;
1,3-dihydro-4-[hydroxyl (3-pyridyl) methyl]-the 5-(1-methyl)-propyl group-2H-imidazoles-2-ketone;
4-butyl-1,3-dihydro-5-[hydroxyl (4-pyridyl) methyl]-2H-imidazoles-2-ketone;
1,3-dihydro-4-[hydroxyl (3-pyridyl) methyl]-the 5-(1-methyl)-ethyl-2H-imidazoles-2-ketone,
Obtain respectively:
1,3-dihydro-4-ethyl-5-(2-pyridine acyl)-2H-imidazoles-2-ketone;
1,3-dihydro-4-methyl-5-(4-pyridine acyl)-2H-imidazoles-2-ketone;
1,3-dihydro-4-(3-pyridine acyl)-2H-imidazoles-2-ketone;
1,3-dihydro-4-(1-methyl) ethyl-5-(4-pyridine acyl)-2H-imidazoles-2-ketone;
4-butyl-1,3-dihydro-5-(2-pyridine acyl)-2H-imidazoles-2-ketone;
1,3-dihydro-4-(1-methyl) propyl group-5-(3-pyridine acyl)-2H-imidazoles-2-ketone;
4-butyl-1,3-dihydro-5-(4-pyridine acyl)-2H-imidazoles-2-ketone;
1,3-dihydro-4-(1-methyl) ethyl-5-(3-pyridine acyl)-2H-imidazoles-2-ketone.
Example 6
1,3-dihydro-4-ethyl-5-(4-pyridine acyl)-preparation of 2H-imidazoles-2-ketone.
With 2.8kg N-chlorosuccinimide and 17.0kg dimethyl formamide wiring solution-forming, in 0 ℃, with the time more than 2 hours, be added to ethyl-1,3-dihydro-5-[hydroxyl (4-pyridyl) methyl by 4.6kg 4-]-soup compound that 2H-imidazoles-2-ketone and 2.9kg methyl alcohol and 14.0kg dimethyl formamide are formed in.The mixture that obtains is in 0 ℃ of stirring 5 hours, then, warm 3 hours in 60 ℃.The solution that adds the 1.7kg sodium acetate and be made into by 0.39kg sodium metabisulfite and 5.5kg water in reaction mixture stirred 4 hours in 25 ℃.The 21kg solvent is removed in vacuum distilling (80 ℃, 24mm Hg).Stir adding 17.5kg water in strong solution down, in-4 ℃ of coolings 12 hours.Centrifugal, collect solid product, after the drying, obtain 3.3kg 1,3-dihydro-4-ethyl-5-(4-pyridine acyl)-2H-imidazoles-2-ketone (productive rate 72%, purity 99%).
Claims (20)
1, a kind of preparation general formula is
The method of hydroxyl amino ketone, comprise that the reduction general formula is
Two ketoximes and to reclaim two ones of products be content.Ar in two general formulas is 2-, 3-or 4-pyridyl, R
1Be the alkyl of a hydrogen or 1-4 carbon atom.
2, in the method for claim 1 regulation, two ketoximes reduce with hydrogen and metal catalyst.
3, in the method for claim 1 regulation, two ketoximes reduce with hydrogen and palladium-carbon catalyst.
4, in the method for claim 2 regulation, Ar is the 4-pyridyl, R
1Alkyl for 1-4 carbon atom.
5, in the method for claim 4 regulation, R
1Be ethyl.
6, in the method for claim 1 regulation, two ketoximes reduce with the dissolution of metals method.
7, in the method for claim 1 regulation, the mixture that two ketoximes are formed with metallic zinc, formic acid and methylsulfonic acid reduces.
8, in the method for claim 6 regulation, Ar is the 4-pyridyl, R
1Alkyl for 1-4 carbon atom.
9, in the method for claim 8 regulation, R
1It is ethyl.
10, a kind of preparation general formula is
The method of hydroxymethyl-imidazoles-2-ketone, comprised that general formula is
The hydroxyl amino ketone and the reaction of basic metal or alkaline-earth metal cyanate and reclaim product two portions content.Ar in two general formulas is 2-, 3-or 4-pyridyl, R
1Be the alkyl of a hydrogen or 1-4 carbon atom.
11, in the method for claim 10 regulation, basic metal or alkaline-earth metal cyanate are potassium cyanates.
12, in the method for claim 10 regulation, Ar is the 4-pyridyl, R
1It is the alkyl of 1-4 carbon atom.
13, in the method for claim 12 regulation, R
1It is ethyl.
14, a kind of preparation general formula is
The method of pyridine acyl imidazoles-2-ketone, comprised being with general formula
Hydroxymethyl imidazoles-2-oxidation of ketones and reclaim product two portions content.Ar is 2-in two general formulas, 3-or 4-pyridyl, R
1Be the alkyl of a hydrogen or 1-4 carbon atom.
15, in the method for claim 14 regulation, hydroxymethyl imidazoles-2-ketone is with the oxidation of N-chlorosuccinimide.
16, in the method for claim 14 regulation, hydroxymethyl imidazoles-2-ketone is to use the Manganse Dioxide oxidation.
17, in the method for claim 14 regulation, Ar is the 4-imidazolyl, R
1It is the alkyl of a hydrogen or 1-4 carbon atom.
18, in the method for claim 16 regulation, R
1It is ethyl.
19, a kind of preparation general formula
The method of pyridine acyl imidazoles-2-ketone comprise
A) reduction general formula
Two ketoximes obtain general formula
Hydroxyl amino ketone, in the above-mentioned general formula, Ar is 2-, 3-or 4-pyridyl, R
1Alkyl for hydrogen or 1-4 carbon atom;
B) with cyanic acid ion reaction, make the cyclisation of resulting hydroxyl amino ketone, obtain general formula and be
Hydroxymethyl imidazoles-2-ketone, Ar in this general formula and R
1The same;
C) hydroxymethyl of oxidation gained imidazoles-2-ketone obtains needed pyridine acyl imidazoles-2-ketone, and separated product.
20, in the method for claim 19 regulation, two ketoximes are by metallic zinc, the mixture reduction that formic acid and methylsulfonic acid are formed, the N-chlorosuccinimide oxidation of hydroxymethyl imidazoles-2-ketone.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 91103557 CN1055737A (en) | 1985-09-06 | 1985-09-06 | The preparation of 1-3-dihydro-4-pyridine acyl-2H-imidazole-2-ketone compound |
| CN 85106722 CN1019197B (en) | 1984-07-30 | 1985-09-06 | Preparation of 1,3-dihydro-4-pyridoyl-2h-imidazol-2-ones |
| CN 91103558 CN1031264C (en) | 1985-09-06 | 1985-09-06 | Preparation of 1,3-dihydro-4-pyridoyl-2H-imidazol-2-ones |
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|---|---|---|---|
| US63585284A | 1984-07-30 | 1984-07-30 | |
| CN 85106722 CN1019197B (en) | 1984-07-30 | 1985-09-06 | Preparation of 1,3-dihydro-4-pyridoyl-2h-imidazol-2-ones |
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| CN 91103558 Division CN1031264C (en) | 1985-09-06 | 1985-09-06 | Preparation of 1,3-dihydro-4-pyridoyl-2H-imidazol-2-ones |
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| CN1019197B CN1019197B (en) | 1992-11-25 |
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| CN114082442A (en) * | 2021-11-18 | 2022-02-25 | 河南大学 | Succinimidyl ionic liquid and method for catalytically synthesizing quinazoline-2, 4(1H,3H) -diketone by using same |
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| CN114082442A (en) * | 2021-11-18 | 2022-02-25 | 河南大学 | Succinimidyl ionic liquid and method for catalytically synthesizing quinazoline-2, 4(1H,3H) -diketone by using same |
| CN114082442B (en) * | 2021-11-18 | 2024-01-19 | 河南大学 | Succinimidyl ionic liquid and method for synthesizing quinazoline-2, 4 (1H, 3H) -diketone by using same as catalyst |
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