CN1303848A - Method for synthesizing beta-biphenyl diester - Google Patents
Method for synthesizing beta-biphenyl diester Download PDFInfo
- Publication number
- CN1303848A CN1303848A CN 99125620 CN99125620A CN1303848A CN 1303848 A CN1303848 A CN 1303848A CN 99125620 CN99125620 CN 99125620 CN 99125620 A CN99125620 A CN 99125620A CN 1303848 A CN1303848 A CN 1303848A
- Authority
- CN
- China
- Prior art keywords
- reaction
- synthetic method
- biphenylylmethylcarbinol
- alcohol
- temperature
- 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.)
- Granted
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to a new method for synthesizing beta-biphenyldicarboxylate which is a medicine for reducing transminase. Said invented method uses gallic acid or tannic acid as raw material, and adopts the processes of esterification, etherification, selective nitration, reduction, diazotization and ullmann reaction in turn so as to obtain the invented product. Said product also is an important intermediate for synthesizing schizandrin so that it has high application value. Said method possesses relatively high yield.
Description
The present invention relates to a kind of synthetic method of active drug of transaminase lowering, particularly a kind of Biphenylylmethylcarbinol of β-type (6,6 '-dimethoxy-4 ', 5,4 ', 5 '-secondary methylenedioxy group-2,2 '-dicarboxylic ester biphenyl) is synthetic.
Biphenylylmethylcarbinol has through pharmacological screening and falls high serum glutamic pyruvic transminase effect, is acknowledged as a kind of active drug of transaminase lowering.It has three kinds of isomer, and chemical name is respectively: 4, and 4 '-dimethoxy-5,6,5 ', 6 '-secondary methylenedioxy group-2,2 '-dimethoxycarbonyl biphenyl (α-Biphenylylmethylcarbinol, α-DDB), 6,6 '-dimethoxy-4 ', 5,4 ', 5 '-secondary methylenedioxy group-2,2 '-dimethoxycarbonyl biphenyl (β-Biphenylylmethylcarbinol, β-DDB), 6,4 '-dimethoxy-4 ', 5,5 ', 6 '-secondary methylenedioxy group-2,2 '-dimethoxycarbonyl biphenyl (γ-Biphenylylmethylcarbinol, γ-DDB), chemical structural formula is respectively:
Since β-Biphenylylmethylcarbinol on the structure than α-Biphenylylmethylcarbinol more near their agent structure of analogue-natural product Wuweizisu C, so its pharmacological action than α-Biphenylylmethylcarbinol, γ-Biphenylylmethylcarbinol has bigger activity.β-Biphenylylmethylcarbinol is the important intermediate of synthetic Wuweizisu C still, has higher using value.
The acquisition of β-Biphenylylmethylcarbinol at present obtains during by synthetic α-Biphenylylmethylcarbinol, it is the by product of α-Biphenylylmethylcarbinol, the synthetic method of α-Biphenylylmethylcarbinol (" Acta Pharmaceutica Sinica " the 17th the 1st phase of volume, the 23rd page, January nineteen eighty-two) be to be starting raw material with gallic acid (I), get II through esterification, with dihydroxyl chelating in ortho position on borax and the phenyl ring again monomethyl etherization get III, carry out ring-closure reaction with methylene iodide as cyclizing agent and get (IV), bromination gets the 2-bromo-derivative, and (Ullmann Reaction) makes α-Biphenylylmethylcarbinol through Ullmann reaction.In bromination reaction, the mixed crystal of from mother liquor, having told mixed crystal 6-bromo-derivative and 2-bromo-derivative carry out Ullmann react α, β and γ three's mixed isomers.Wherein β-Biphenylylmethylcarbinol content is very low, can't carry out suitability for industrialized production, and the synthetic of its derivative just can not be realized.
The object of the present invention is to provide the new synthetic method that a kind of yield is higher, can carry out the β-Biphenylylmethylcarbinol of suitability for industrialized production.
In order to realize the object of the invention, the synthetic route of β-Biphenylylmethylcarbinol is as follows:
R=-CH
3,-CH
2CH
3,-CH (CH
3)
2, C (CH
3)
3,-CH
2CH
2CH
3,-CH
2CH
2CH
2CH
3X=Br, I
Step (1) abbreviates esterification as, and the product that obtains (II) abbreviates carboxylate as; Step (2) abbreviates the methyl-etherified reaction as, and the product that obtains (III) is a monomethyl ether; Step (3) abbreviates ring-closure reaction as, and the product that obtains (IV) abbreviates cyclocomplex as; The product that step (4) obtains for nitration reaction is a 6-nitro thing (V); The product that step (5) obtains for reduction reaction is 6-amino substance (VI); Step (6) is that the product that diazotization reaction (claiming the Sandmeyer reaction again) obtains is a 6-halo carboxylate (VII); Step (7) is Ullmann reaction (Ullmann Reaction), and the product that obtains is β-Biphenylylmethylcarbinol.
The invention reside in by selective nitration in the 6-position, directly obtained pure 6-bromo or 6-iodo coupling monomer by reduction, diazotization reaction.Further carry out the Ullmann reaction, the direct synthetic pure β-Biphenylylmethylcarbinol that obtained.
The present invention also can obtain the other different coupling monomer of several ester substituting groups by coupling monomer 6-halo carboxylate (VII) is modified, and then synthesizes their β-Biphenylylmethylcarbinol, and its synthetic route is as follows:
R=-CH
3,-CH
2CH
3,-CH (CH
3)
2,-C (CH
3)
3,-CH
2CH
2CH
3,-CH
2CH
2CH
2CH
3R
1And R
2It is different R groups
Wherein step (1) is a saponification reaction, and the product that obtains is the halogenated carboxylic acid thing; Step (2) is an esterification, and the product that obtains is the halo carboxylate; Step C is Ullmann reaction (Ullmann reaction), and the product that obtains is β-Biphenylylmethylcarbinol.
Esterification feed ratio of the present invention (mol ratio): gallic acid: alcohol: the vitriol oil=1: 8～25: 0.1～0.6, described methyl-etherified reaction feed ratio (weight ratio): gallic acid ester: sodium hydroxide: borax: methyl-sulfate: water=1: 0.5～0.9: 0.8～1.5: 1.6～2: 10～14, the temperature of described methyl-etherified reaction is controlled at 6～30 ℃.
In aforesaid method, described nitration reaction temperature is controlled at 0～10 ℃, and the weight that feeds intake (g) of reactant: volume ratio (ml) is: myristicic acid methylester: HNO
3=1: 8～15.
Utilize the Sn/HCl system to carry out reduction reaction, temperature is controlled at 0～90 ℃, and it is low-carbon alcohol such as ethanol, propyl alcohol that institute adds organic solvent, and the mol ratio of compound V and Sn is 1: 2～5.Also can adopt the method for shortening to reduce, solvent is: pyridine, ethanol, methyl alcohol etc., temperature is controlled within 0～40 ℃ of scope.
Diazotization reaction of the present invention (or claiming the Sandmeyer reaction) temperature is controlled at-1～5 ℃, and the intermediate decomposition temperature is 10～80 ℃.
Being reflected in the oil bath of Wu Ermen coupled reaction of the present invention (Ullmann coupling) carried out, and solvent for use is dry DMF, and temperature is controlled at 150～180 ℃.
The saponification reaction that the monomeric ester group house of correction of 6-halo carboxylate coupling is carried out of the present invention is carried out in alkaline aqueous solution, and the one-tenth ester catalyst of the carboxylic acid thing after the acidifying is the vitriol oil.
Synthetic method of the present invention, highway route design are rationally feasible, and raw material is easy to get, and per step yield all reaches more than 60%, and total recovery is up to more than 35%, and purity is higher, is suitable for suitability for industrialized production.
The present invention is described in detail below in conjunction with embodiment.
Embodiment 1
To synthesize the two methyl esters whole processes of β-biphenyl is divided into seven steps and is narrated.(1) through esterification synthesizing gallic acid methyl esters (II)
With 25g (0.133mol) gallic acid and 75ml methyl alcohol suspendible, gradation adds 4ml (0.075mol) vitriol oil, heated and stirred, and 4～5hr refluxes, normal pressure reclaims 50～55ml methyl alcohol (rate of recovery is 67～73%, and the methyl alcohol after the recovery can be directly used in same reaction after drying).Add frozen water, raffinate has solid to separate out to be methyl gallate (II).(2) synthesize 3 through etherificate, 4-dihydroxyl-5-methoxyl methyl benzoate (III)
The product II is added water 200ml suspendible, cooling, gradation adds in the solution that sodium hydroxide 7g (0.175mol) and 50ml water is made into and the used sulfuric acid of esterification, after the solid dissolving, add 33g (0.087mol) borax, stir 1hr, the frozen water cooling, keep reacting liquid temperature at 8～12 ℃, dropping sodium solution (10gNaOH (0.25mol+50ml water)) slowly, about 1.5hr adds.In 15～20min when beginning hydro-oxidation sodium solution gradation add the 32ml methyl-sulfate (42.6g, 0.34mol), treat that sodium hydroxide solution adds after, under uniform temp, stir 1～2hr, be warmed up to room temperature (25～35 ℃) then naturally, restir 2～3hr, place a few hours, this moment, the pH value of reaction solution was 7～8, added an amount of sodium hydroxide solution, transferring pH is 8～9, with the 50ml chloroform extraction once, remove the by product 3,4 of generation, the 5-tri-methoxybenzoate, heavy 2g.
Mother liquor concentrated hydrochloric acid acidifying, pH is 3～4, divides 4～5 extractions with the 250ml N-BUTYL ACETATE, united extraction liquid, 230ml N-BUTYL ACETATE (can use again) is reclaimed in underpressure distillation.Raffinate places refrigerator to preserve, monomethyl ether (III) promptly 3,4-dihydroxyl-5-methoxyl methyl benzoate filters and washes secondary with an amount of N-BUTYL ACETATE, dry back weighs 22g, 110～112 ℃ of fusing points, two go on foot yields counts 83.5% with gallic acid.
Above-mentioned steps can not separated by product three methyl ethers earlier yet, but with the direct acidification reaction liquid of hydrochloric acid, extracts with N-BUTYL ACETATE, obtain the 42g monomethyl ether, fusing point is 107～110 ℃, with the mother liquor decompressing and extracting, be dissolved in and use the chloroform extraction secondary in the diluted sodium hydroxide solution, reclaim chloroform, get by product three methyl ethers, the mother liquor hcl acidifying, N-BUTYL ACETATE extracts, monomethyl ether again, and Rf is the same with fore portion to be same product, gross weight 43g, yield 81.6%.(3) synthesize 3 through cyclization, 4-methylenedioxy group-5-methoxyl methyl benzoate (IV)
3,4-dihydroxyl-5-methoxyl methyl benzoate (monomethyl ether) 10g, methylene iodide 45g, Anhydrous potassium carbonate 50g, dry acetone 300ml, backflow 40h, elimination solid pressure reducing and steaming acetone gets dope.Get the yellowish brown solid product after the washing, heavy 8.2g (productive rate 69%).Product gets 7.0g through the dehydrated alcohol recrystallization, and 86～88 ℃ of fusing points get the compound IV.The methylene iodide that settles out in the water lotion is recyclable after with the calcium chloride drying to be used again.(4) nitrated synthetic 6-nitro-3,4-methylenedioxy group-5-methoxyl group formic acid methyl esters (V)
Compound IV 10g joins the dense HNO of 100ml in three batches in 0 ℃ of following 1h
3In, continuing to stir 1h, in the impouring frozen water, suction filtration gets crude product 11.2g, gets the faint yellow needle crystal 9.4g of photosensitivity (productive rate 80%) with re-crystallizing in ethyl acetate, and 124～126 ℃ of fusing points get the compound V.(5) the synthetic 6-amino-3 of reduction, 4-methylenedioxy group-5-methoxyl group formic acid methyl esters (VI)
Compound V 10g once adds among Sn (grain) 10g and the concentrated hydrochloric acid 100ml, adds ethanol 50ml, reflux 5h, be chilled to room temperature, separate out the paste solid, add NaOH10% and be neutralized to alkalescence, suction filtration, use hexanaphthene reflux extraction, filter, separate out crystal 4 .0g (productive rate 40%), 88～90 ℃ of fusing points, get compound 6-ammonia-3,4-methylenedioxy group-5-methoxyl methyl benzoate (VI), it also can be synthetic by shortening.(6) through the synthetic 6-halo myristicic acid methylester (VII) of diazotization
Compound VI 1g is 0 ℃ of diazotization, and the back adds 2gCuSO fully
45H
2O and Potassium Bromide 1g and 0.6gNaOH, 0.6gNaHSO
3The new system CuBr that generates, precipitation is gently stirred, and places, and 50 ℃ of water-baths are decomposed, with benzene extraction, anhydrous CaCl
2Drying, knot do crude product 0.9g, recrystallization gets 0.89g (productive rate 70%), 80～82 ℃ of fusing points, the compound VII.
Perhaps, after compound VI 1g diazotization is finished, add the aqueous solution that 1gKI is made into, stir, place, boiling water bath decomposes, with benzene extraction, NaOH solution washing, anhydrous CaCl
2The dry crude product that gets.The dehydrated alcohol recrystallization gets 0.5g, 88～89 ℃ of fusing points.(7) through the two methyl esters of the synthetic β-biphenyl of Ullmann reaction
2g compound VII adds 2g activation bronze powder, adds dry DMF10ml reflux 4h, stops, and adds benzene, filters, and recrystallization gets the two methyl esters 0.6g (productive rate 40%) of colourless transparent crystal β-biphenyl, 207～208 ℃ of fusing points in the ethanol.
Embodiment 2
Synthesizing of the two ethyl esters of β-biphenyl
Compound VII 5g among the embodiment is added 5%KOH aqueous solution 10ml, and reflux stops, add the acid neutralization, suction filtration gets 4.3g (productive rate 90%) compound VIII, 240 ℃ of fusing points, 2g adds 10ml ethanol, vitriol oil 0.5ml, reflux, pour in the frozen water, suction filtration goes out precipitation, gets white solid, 80 ℃ of fusing points get compound VII a.
Compound VII a2g adds 2g activation bronze powder and adds dry DMF10ml, and reflux 4h stops, and adds benzene, filters, and recrystallization gets colourless transparent crystal 0.6g (productive rate 40%) in the ethanol, and 156～158 ℃ of fusing points get the two ethyl esters of β-biphenyl.
Embodiment 3
The two isopropyl ester synthetic methods of β-biphenyl also can take the method for embodiment 2 synthetic with embodiment 1.Fusing point: 123～125 ℃.
Claims (10)
1. the synthetic method of a Biphenylylmethylcarbinol (6,6 '-dimethoxy-4 ', 5,4 ', 5 '-secondary methylenedioxy group-2,2 '-dicarboxylic ester biphenyl), this method realizes as follows:
1) under acidic conditions, gallic acid (I) and pure heating reflux reaction are obtained gallic acid ester (II);
2) carboxylate (II) that obtains in the step (1) being added temperature is 15-30 ℃ water cooling, under alkaline condition, with borax and methyl-sulfate reaction, obtains monomethyl ether (III) (3,4-dihydroxyl-5-methoxyl methyl benzoate);
3) make solvent with DMF (N, dinethylformamide), acetone or DMSO (methyl-sulphoxide),, obtain 3,4-methylenedioxy group-5-methoxybenzoic acid ester (IV) monomethyl ether (III) and methylene dichloride and Anhydrous potassium carbonate heating reflux reaction; It is characterized in that then carrying out following reaction:
4) the compound IV is joined in 0 ℃ the concentrated nitric acid, carry out the selective nitration reaction in the 6-position, obtain 6-nitro-3,4-methylenedioxy group-5-methoxybenzoic acid ester (V);
5) making reductive agent with Sn+HCl, is solvent with acid, alcohol, then carries out reduction reaction and gets 6-amino-3, and 4-methylenedioxy group-5-methoxyl methyl benzoate (VI) also can adopt the shortening method to carry out reduction reaction;
6) under alkaline condition, add hydrogen halide and carry out diazotization reaction, get 6-halo carboxylate coupling monomer (VII);
7), get β-Biphenylylmethylcarbinol again through Ullmann reaction.
2. synthetic method as claimed in claim 1 is characterized in that the nitration reaction temperature is controlled at 0～10 ℃, and the volume (ml) of the weight of compound IV (g) and nitric acid is than being 1: 8～15.
3. synthetic method as claimed in claim 1 is characterized in that the reduction reaction of utilizing the Sn/HCL system to be carried out, and temperature is controlled at 0～90 ℃, and organic solvent alcohol is low-carbon alcohol such as ethanol, propyl alcohol, and the mol ratio of compound V and Sn is 1: 2～5.
4. synthetic method as claimed in claim 1 is characterized in that the diazotization reaction temperature is controlled at-1～5 ℃.
5. synthetic method as claimed in claim 1 is characterized in that Ullmann reaction (Ullmann) carries out in oil bath, temperature is controlled at 150～180 ℃, and (mol ratio of (VII) is 0.8～3.5: 1 for copper powder and coupling monomer.
6. synthetic method as claimed in claim 1 is characterized in that the esterification molar ratio is a gallic acid: alcohol: the vitriol oil=1: 8～25: 0.1～0.6.
7. synthetic method as claimed in claim 1 is characterized in that the etherification reaction feed ratio is a gallic acid ester: sodium hydroxide: borax: methyl-sulfate: water=1: 0.5～0.9: 0.8～1.5: 1.6～2: 10～14.Temperature of reaction is controlled at 6～30 ℃.
8. Biphenylylmethylcarbinol (6,6 '-dimethoxy-4 ', 5,4 ', 5 '-secondary methylenedioxy group-2,2 '-dicarboxylic ester biphenyl) synthetic method is characterized in that also can realizing as follows: the compound 6-halo carboxylate coupling monomer (VII) that (1) utilizes claim 1 gained gets 6-halogenated carboxylic acid thing (VIII) (2) through saponification reaction then to carry out esterification and gets the different 6-halo carboxylate coupling monomer of ester substituting group (VII a): (3) and then get their β-Biphenylylmethylcarbinol again through Ullmann reaction.
9. synthetic method as claimed in claim 8 is characterized in that with the vitriol oil as becoming ester catalyst.
10. synthetic method as claimed in claim 8, alcohol is 1-5 with volume (ml), weight (g) ratio of 6-halogenated carboxylic acid thing when it is characterized in that esterification: 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB991256204A CN1140523C (en) | 1999-11-25 | 1999-11-25 | Method for synthesizing beta-biphenyl diester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB991256204A CN1140523C (en) | 1999-11-25 | 1999-11-25 | Method for synthesizing beta-biphenyl diester |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1303848A true CN1303848A (en) | 2001-07-18 |
| CN1140523C CN1140523C (en) | 2004-03-03 |
Family
ID=5284043
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB991256204A Expired - Fee Related CN1140523C (en) | 1999-11-25 | 1999-11-25 | Method for synthesizing beta-biphenyl diester |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1140523C (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102250085A (en) * | 2010-05-21 | 2011-11-23 | 四川大学 | Bifendate derivative and use thereof in preparation of drugs for treating autoimmune diseases |
| CN103193651A (en) * | 2013-04-12 | 2013-07-10 | 张家港威胜生物医药有限公司 | Synthesis of medical intermediate 3,5-dihydroxy methyl benzoate and industrial production process |
| CN105732375A (en) * | 2016-01-30 | 2016-07-06 | 张家界久瑞生物科技有限公司 | Method for synthesizing methyl 3,4,5-trimethoxybenzoate from gallic acid |
| CN111018825A (en) * | 2019-12-12 | 2020-04-17 | 苏州诚和医药化学有限公司 | Synthetic method of 2-bromo-3, 4-methylenedioxy-5-methoxybenzoic acid methyl ester |
| CN114085205A (en) * | 2021-11-29 | 2022-02-25 | 沧州普瑞东方科技有限公司 | Improved synthetic method of biphenyl diester |
-
1999
- 1999-11-25 CN CNB991256204A patent/CN1140523C/en not_active Expired - Fee Related
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102250085A (en) * | 2010-05-21 | 2011-11-23 | 四川大学 | Bifendate derivative and use thereof in preparation of drugs for treating autoimmune diseases |
| CN102250085B (en) * | 2010-05-21 | 2014-01-22 | 四川大学 | Bifendate derivative and use thereof in preparation of drugs for treating autoimmune diseases |
| CN103193651A (en) * | 2013-04-12 | 2013-07-10 | 张家港威胜生物医药有限公司 | Synthesis of medical intermediate 3,5-dihydroxy methyl benzoate and industrial production process |
| CN105732375A (en) * | 2016-01-30 | 2016-07-06 | 张家界久瑞生物科技有限公司 | Method for synthesizing methyl 3,4,5-trimethoxybenzoate from gallic acid |
| CN105732375B (en) * | 2016-01-30 | 2018-04-06 | 张家界久瑞生物科技有限公司 | A kind of method that gallic acid synthesizes 3,4,5-tri-methoxybenzoate |
| CN111018825A (en) * | 2019-12-12 | 2020-04-17 | 苏州诚和医药化学有限公司 | Synthetic method of 2-bromo-3, 4-methylenedioxy-5-methoxybenzoic acid methyl ester |
| CN111018825B (en) * | 2019-12-12 | 2020-12-22 | 苏州诚和医药化学有限公司 | Synthetic method of 2-bromo-3, 4-methylenedioxy-5-methoxybenzoic acid methyl ester |
| CN114085205A (en) * | 2021-11-29 | 2022-02-25 | 沧州普瑞东方科技有限公司 | Improved synthetic method of biphenyl diester |
| CN114085205B (en) * | 2021-11-29 | 2023-03-03 | 沧州普瑞东方科技有限公司 | Improved synthetic method of biphenyl diester |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1140523C (en) | 2004-03-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2001027060A1 (en) | Method for production of aryl alkyl ethers | |
| US4127604A (en) | Process for the preparation of acetic acid derivatives | |
| CN101153012A (en) | Novel method of producing dronedarone key intermediate | |
| CN112707836A (en) | Preparation method of m-diamide compound | |
| CN114044739B (en) | Synthetic method for preparing 5-bromo-2-chloro-4' -ethoxy diphenylmethane | |
| CN1140523C (en) | Method for synthesizing beta-biphenyl diester | |
| CN100410230C (en) | Method for preparing 1-chloro-2-methyl-4-alkylacyloxy-2-butene | |
| CN110818634B (en) | Refining method of lervatinib mesylate | |
| US4806683A (en) | Preparation process of cinnamic acids | |
| CN112441932A (en) | Preparation method of bisoprolol fumarate impurity | |
| CN103965058B (en) | A kind of production technology of memantine | |
| CN111116319B (en) | Synthesis and refining method of 1, 6-dihydroxynaphthalene | |
| CN100500648C (en) | Synthesizing process of nitro iodo phenol cyanide | |
| CN108947801B (en) | Preparation of biphenyldicarboxylic acid by coupling of 4-chlorobenzoic acid in ionic liquid | |
| CN116284020B (en) | Preparation method of pranoprofen | |
| CN101270048B (en) | Process for synthesizing 1-chlorine-2-methyl-4-acetoxy-2-butylene | |
| US6489507B1 (en) | Process for the synthesis of 3,5-bis(trifluoromethyl)benzoic acid | |
| US4264500A (en) | Process of making 6-chloro-α-methyl-carbazole-2-acetic acid | |
| CN115160134B (en) | Preparation method of 4-bromo-2-methyl benzoate | |
| CN112552299B (en) | Preparation method of linagliptin for treating type II diabetes | |
| US4408074A (en) | Process for preparing 1-(3,5-dimethoxy-4-hydroxy phenyl)-2-(N-methylamino) ethanol hydrochloride | |
| KR950005737B1 (en) | Separating method of component from gingkolide complex | |
| CN117986178A (en) | Preparation method of Fu Kasai di-substituted impurity | |
| JP3159405B2 (en) | Method for producing thienyl ether derivative | |
| JP2635632B2 (en) | Method for producing triazole derivative |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CI01 | Correction of invention patent gazette |
Correction item: Classification number Correct: C07D317/46 False: C07C317/46 Number: 29 Page: 46 Volume: 17 |
|
| CI02 | Correction of invention patent application |
Correction item: Classification number Correct: C07D317/46 False: C07C317/46 Number: 29 Page: The title page Volume: 17 |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: CLASSIFICATION NUMBER; FROM: C07C317/46 TO: C07D317/46 |
|
| ERR | Gazette correction |
Free format text: CORRECT: CLASSIFICATION NUMBER; FROM: C07C317/46 TO: C07D317/46 |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |