CN105001132A - (Z)-3-dimethylamino-alpha-4'-substituted benzene sulfydryl-alpha, beta-unsaturated aromatic amide compound and preparation method thereof - Google Patents
(Z)-3-dimethylamino-alpha-4'-substituted benzene sulfydryl-alpha, beta-unsaturated aromatic amide compound and preparation method thereof Download PDFInfo
- Publication number
- CN105001132A CN105001132A CN201510480331.4A CN201510480331A CN105001132A CN 105001132 A CN105001132 A CN 105001132A CN 201510480331 A CN201510480331 A CN 201510480331A CN 105001132 A CN105001132 A CN 105001132A
- Authority
- CN
- China
- Prior art keywords
- substituted benzene
- dimethylamino
- alpha
- preparation
- unsaturated aromatic
- 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
Disclosed is a (Z)-3-dimethylamino-alpha-4'-substituted benzene sulfydryl-alpha, beta-unsaturated aromatic amide compound. Under the existence of proper temperature, corresponding solvent and alkali, aromatic amidine 1 reacts with an alpha-4'-substituted benzene sulfydryl acetylchloride compound 2, and (Z)-3-dimethylamino-alpha-4'-substituted benzene sulfydryl-alpha, beta-unsaturated aromatic amide is obtained after purification. The reaction process is simple, safe and environmentally friendly. A newly-formed carbon-carbon double bond is high in stereo selection performance (only Z-type olefin is generated), few reaction steps exist, the conditions are mild, the price of raw materials is low, and operation is convenient. An obtained product is high in purity and fully meets the quality requirements for a drug intermediate, and beneficial conditions are provided for industrial production.
Description
Technical field
The invention belongs to the synthesis technical field of amides organic compound, be specifically related to one and prepare ((Z)-3-dimethylamino-α – 4 '-substituted benzene sulfydryl-α, β-unsaturated aromatic amides and preparation method thereof.
Background technology
α is contained, beta-unsaturated acyl amine in many medicines and agricultural chemicals.Such as anticonvulsion, antidepressant, anti-female hormone, pain relieving and germ resistance etc., α, beta-unsaturated acyl amine is also widely used in the key areas such as agricultural, materials industry.α, beta-unsaturated acyl aminated compounds, with its multi-functional constructional feature, has become the intermediate that in organic synthesis, a class is important, may be used for preparing the multiple heterocycles compounds such as quinoline, quinolinone, furans, piperidone, pyridine, pyridone, pyrroles.In general, α, the reaction of beta-unsaturated acyl aminated compounds mainly contains: with the reaction of electrophilic reagent, with the reaction of nucleophilic reagent, electrocyclic reaction, reduction and oxidizing reaction.From structure, this α, the existing nucleophilicity of beta-unsaturated acyl amine also has Electron Affinities, not only can react with nucleophilic reagent but also can react with electrophilic reagent.α, the preparation method of beta-unsaturated acyl aminated compounds, patent 1 (United States Patent (USP) the 2nd, 451, No. 436), patent 2(Japanese Unexamined Patent Publication 4-208258 publication) and Japanese Unexamined Patent Publication 6-199752 publication) disclose the method for N,N-DMAA using acrylate.But, not only need vinylformic acid to carry out esterification in this method, but also need the step ester group of gained ester cpds being converted into amide group.Usually, by ester group in the conversion of amide group, need the polyol compounds such as glycerol as solvent, therefore need the step be separated from solvent by resultant after the completion of reaction.Therefore, in yield, expense, there is too high problem.
In prior art, other prepares α, and the method for beta-unsaturated acyl amine is: first unsaturated acid is made acyl chlorides, and then carries out amidate action with secondary amine and obtain product.Produce that acyl chlorides generally needs to use that oxalyl chloride, phosphorus trichloride, phosphorus oxychloride or sulfur oxychloride etc. are volatile by unsaturated acid, pungency and corrodibility is strong, toxicity is larger pharmaceutical chemicals, not only environment is produced and pollute, and too increase the difficulty of the abstraction and purification in production process.Saturated amide compound can at α; α is prepared in the dehydration of β position; beta-unsaturated acyl amine compound; such as; patent CN1826314 A(2006) disclose a kind of α; the preparation method of beta-unsaturated acyl amine compound; first blocking group is introduced saturated amide compound; dewater under the existence of dehydrogenation catalyst and applicable oxygenant, react and form double bond; finally remove blocking group and obtain final product; but needed for whole reaction process, chemical reagent is many, long reaction time, complicated condition.2013 European organic chemistry magazine [(Eur.J.Org.Chem., 2013 (7): 1218)] report and use cupric perchlorate catalysis phenylformic acid and Carbox amide synthesis acid amide compounds.But this catalyst system to substrate requirements high and reaction needed carry out under the high temperature of 100 ° of C.Chinese patent CN103232357B in 2014 has reported one and has prepared α, the method of beta-unsaturated acyl amine, in an inert atmosphere, with cinnamic acid compound and Carbox amide for reactant, with molysite and oxygenant for catalyst system, product α is prepared, beta-unsaturated acyl amine by amidate action.The method not only uses various molysite as catalyzer, but also wants tertbutyl peroxide etc. to be oxygenant.
Huang Zhizhen, Wu Luling are at Chin. J. Org. Chem., and 1996,16 (4): 340-343 report (E)-α, the Stereo-selective synthesis of beta-unsaturated acyl amine.This method is that bromo acetamide and aldehyde generate target compound by azaWittig reaction under palladium metal and dibutyl tellurid effect.(Z)-3-dimethylamino-α – 4 '-substituted benzene sulfydryl-α, β-unsaturated aromatic amides there is no report in the literature.(Z) compound of-N-benzyl-2-(benzylthio)-3-(dimethylamino) acrylamide class has been reported.
the starting raw material [(Z)-N-benzyl-2-(benzylthio)-3-chloroacrylamide] of the method can must obtain through multistep synthesis.Further, benzyl-mercapto compound [Organic & Biomolecular Chemistry, 2452-2472,2011] is only.In addition, (Z)-3-morpholino-2-(phenylthio)-N-(p-tolyl) acrylamide obtains [Tetrahedron, 5494-5499,2011] through high temperature, tube sealing and polystep reaction.
Summary of the invention
The object of this invention is to provide that a kind of highly selective, reaction process are simple, safety, environmental protection preparation one class (Z)-3-dimethylamino-α – 4 '-substituted benzene sulfydryl-α, the method for β-unsaturated aromatic amides.
For achieving the above object, the technical solution used in the present invention is:
One class (Z)-3-dimethylamino-α –, 4 '-substituted benzene sulfydryl-α, β-unsaturated aromatic amides is the compound 3 represented in following general formula;
In general formula: fragrant amidine
1in: R
1for independently-H ,-F ,-Cl, Br ,-I ,-CN ,-NO
2,-OH ,-CO
2me ,-CO
2et ,-CONHMe ,-CONHEt, C
1-C
6alkyl; R
2for independently H ,-F ,-OH ,-CN; R
3for independently-H ,-CN ,-NO
2;
In α-4 '-substituted benzene mercaptoacetyl chlorine compound 2: R
4for independently-F ,-Cl, Br ,-I ,-CN ,-NO
2,-CO
2me ,-CO
2et.
One class (Z)-3-dimethylamino-α –, 4 '-substituted benzene sulfydryl-α, the preparation method of β-unsaturated aromatic amides, comprise the steps: under the existence of proper temperature, coordinative solvent and alkali, fragrant amidine 1 Yu α – 4 '-substituted benzene mercaptoacetyl chlorine compound
2reaction, obtains (Z)-3-dimethylamino-α – 4 '-substituted benzene sulfydryl-α after purified, β-unsaturated aromatic amides.
Described proper temperature is-78
oc---5
oc.
Described coordinative solvent is methylene dichloride, 1,2-ethylene dichloride, tetracol phenixin, chloroform, tetrahydrofuran (THF), ethyl acetate, toluene, benzene, any one of acetonitrile.
The mol ratio of described fragrant amidine 1 Yu α – 4 '-substituted benzene mercaptoacetyl chlorine compound 2 is 1:1 4.
The described alkali stated be triethylamine, diisopropylethylamine, pyridine, 3,5-lutidine, 4-N, N-lutidine, sodium carbonate, sodium bicarbonate, salt of wormwood, saleratus, sodium hydroxide, potassium hydroxide, sodium phosphate any one.
The method of described purifying is for steaming solvent, recrystallization, silica gel column chromatography, underpressure distillation.
The invention has the beneficial effects as follows: reaction process of the present invention is simple, safety, environmental protection; The selecting property of solid of the carbon-to-carbon double bond of new formation is high (only having Z-formula alkene to generate), and reactions steps is few, mild condition, low in raw material price, convenient operation; And products obtained therefrom purity is high, meet specification of quality as pharmaceutical intermediate completely, for its suitability for industrialized production provides favourable condition.
Embodiment
Below in conjunction with specific embodiment, the invention will be further described.
Embodiment one
by (E)-N '-(4-phenelyl)-N, N-dimethylamino carbonamidine (7.69 grams, 0.04 mole), tetracol phenixin (30 milliliters), (6.91 grams, salt of wormwood, 0.05 mole) and a magneton join in the single necked round bottom flask of 100 milliliters, start magnetic stirring apparatus, reaction flask is placed in 5
oin the cryostat of C.2-(4 '-chlorobenzene sulfydryl is slowly dripped with syringe) Acetyl Chloride 98Min. (13.3 grams, 0.06 mole), whole dropping process lasts about 50 minutes.After dripping, reaction mixture is at room temperature stirred and spends the night.Revolve and steam except desolventizing.Then in reaction flask, add ethyl acetate (20 milliliters) and water (20 milliliters) and stir 10 minutes, being transferred in a separating funnel, separate lower floor's inorganic phase.Inorganic phase ethyl acetate (10 milliliters) extracts.Merge organic phase and wash respectively with saturated aqueous common salt (20 milliliters) and water (20 milliliters).Organic phase anhydrous sodium sulfate drying.Revolve after steaming recycling design, residue over silica gel column chromatography (ethyl acetate/normal hexane: 1:7) obtains product (Z)-3-(dimethylamino)-N-(4-phenelyl)-α-(4 ' chlorobenzene sulfydryl) acrylamide [(Z)-2-((4-chlorophenyl) thio)-3-(dimethylamino)-N-(4-ethoxyphenyl) acrylamide] 6.93 grams, productive rate 46%.
1H NMR (CDCl
3),300 MHz (
ppm ): 10.04 (1H, s， -NH), 7.68 (2H, m), 7.40-7.51(4H, m), 7.01 (1H, s), 6.83 (2H, d), 3.73 (2H, q), 2.99 (3H, s), 3.02 (3H, s), 1.35 3H, t); MS: m/z（M+1） 377.12。
Embodiment two
By (E)-N '-(4-phenelyl)-N, N-dimethylamino carbonamidine (3.84 grams, 0.02 mole), toluene (20 milliliters), (0.8 gram, sodium hydroxide, 0.02 mole) and a magneton join in the single necked round bottom flask of 100 milliliters, start magnetic stirring apparatus, reaction flask be placed in--45
oin the cryostat of C.2-(4 '-chlorobenzene sulfydryl is slowly dripped with syringe) Acetyl Chloride 98Min. (6.6 grams, 0.03 mole), whole dropping process lasts about 35 minutes.After dripping, reaction mixture is at room temperature stirred and spends the night.Revolve and steam except desolventizing.Then in reaction flask, add ethyl acetate (20 milliliters) and water (20 milliliters) and stir 10 minutes, being transferred in a separating funnel, separate lower floor's inorganic phase.Inorganic phase ethyl acetate (10 milliliters) extracts.Merge organic phase and wash respectively with saturated aqueous common salt (20 milliliters) and water (20 milliliters).Organic phase anhydrous sodium sulfate drying.Revolve after steaming recycling design, residue over silica gel column chromatography (ethyl acetate/normal hexane: 1:7) obtains product (Z)-3-(dimethylamino)-N-(4-phenelyl)-α-(4 ' chlorobenzene sulfydryl) acrylamide [(Z)-2-((4-chlorophenyl) thio)-3-(dimethylamino)-N-(4-ethoxyphenyl) acrylamide] 3.01 grams, productive rate 40%.
Embodiment three
By (E)-N '-(4-phenelyl)-N, N-dimethylamino carbonamidine (3.84 grams, 0.02 mole), ethyl acetate (20 milliliters), sodium phosphate (4.92 grams, 0.03 mole) and a magneton join in the single necked round bottom flask of 100 milliliters, start magnetic stirring apparatus, reaction flask is placed in 0
oin the frozen water cryostat of C.Then 2-(4 '-chlorobenzene sulfydryl is slowly dripped with syringe) Acetyl Chloride 98Min. (8.84 grams, 0.04 mole), whole dropping process lasts about 40 minutes.Dripping 2-(4 '-chlorobenzene sulfydryl) after Acetyl Chloride 98Min., reaction mixture is at room temperature stirred and spends the night.Revolve and steam except desolventizing.Then in reaction flask, add ethyl acetate (20 milliliters) and water (20 milliliters) and stir 10 minutes, being transferred in a separating funnel, separate lower floor's inorganic phase.Inorganic phase ethyl acetate (10 milliliters) extracts.Merge organic phase and wash respectively with saturated aqueous common salt (20 milliliters) and water (20 milliliters).Organic phase anhydrous sodium sulfate drying.Revolve after steaming recycling design, residue over silica gel column chromatography (ethyl acetate/normal hexane: 1:7) obtains product (Z)-3-(dimethylamino)-N-(4-phenelyl)-2-(4 ' chlorobenzene sulfydryl) acrylamide [(Z)-α-((4-chlorophenyl) thio)-3-(dimethylamino)-N-(4-ethoxyphenyl) acrylamide] 4.59 grams, productive rate 61%.
Embodiment four
By (E)-N '-(4-phenelyl)-N, N-dimethylamino carbonamidine (1.92 grams, 0.01 mole), methylene dichloride (10 milliliters), (4.14 grams, salt of wormwood, 0.03 mole) and a magneton join in the single necked round bottom flask of 50 milliliters, start magnetic stirring apparatus, reaction flask is placed in-78
oin the cryostat of C.Then 2-(4 '-chlorobenzene sulfydryl is slowly dripped with syringe) Acetyl Chloride 98Min. (6.63 grams, 0.03 mole), whole dropping process lasts about 20 minutes.After dripping, reaction mixture is at room temperature stirred and spends the night.Revolve and steam except desolventizing.Then in reaction flask, add ethyl acetate (20 milliliters) and water (20 milliliters) and stir 10 minutes, being transferred in a separating funnel, separate lower floor's inorganic phase.Inorganic phase ethyl acetate (10 milliliters) extracts.Merge organic phase and wash respectively with saturated aqueous common salt (20 milliliters) and water (20 milliliters).Organic phase anhydrous sodium sulfate drying.Revolve after steaming recycling design, (Z)-3-(dimethylamino)-N-(4-phenelyl)-2-(4 ' chlorobenzene sulfydryl) acrylamide [(Z)-α-((4-chlorophenyl) thio)-3-(dimethylamino)-N-(4-ethoxyphenyl) acrylamide] 2.34 grams, productive rate 62%.
Embodiment five
By (E)-N '-(4-phenelyl)-N, N-dimethylamino carbonamidine (3.84 grams, 0.02 mole), chloroform (40 milliliters), (0.8 gram, sodium hydroxide, 0.02 mole) and a magneton join in the single necked round bottom flask of 100 milliliters, start magnetic stirring apparatus, reaction flask is placed in-20
oin the cryostat of C.Then 2-(4 '-chlorobenzene sulfydryl is slowly dripped with syringe) Acetyl Chloride 98Min. (15.5 grams, 0.07 mole), whole dropping process lasts about 60 minutes.After dripping, reaction mixture is at room temperature stirred and spends the night.Revolve and steam except desolventizing.Then in reaction flask, add ethyl acetate (20 milliliters) and water (20 milliliters) and stir 10 minutes, being transferred in a separating funnel, separate lower floor's inorganic phase.Inorganic phase ethyl acetate (10 milliliters) extracts.Merge organic phase and wash respectively with saturated aqueous common salt (20 milliliters) and water (20 milliliters).Organic phase anhydrous sodium sulfate drying.Revolve after steaming recycling design, resistates obtains product (Z)-3-(dimethylamino)-N-(4-phenelyl through recrystallization)-2-(4 ' chlorobenzene sulfydryl) acrylamide [(Z)-α-((4-chlorophenyl) thio)-3-(dimethylamino)-N-(4-ethoxyphenyl) acrylamide] 4.75 grams, productive rate 63%.
Embodiment six
By (E)-N '-(4-phenelyl)-N, N-dimethylamino carbonamidine (7.69 grams, 0.04 mole), acetonitrile (20 milliliters), (2.8 grams, potassium hydroxide, 0.05 mole) and a magneton join in the single necked round bottom flask of 100 milliliters, start magnetic stirring apparatus, reaction flask is placed in 0
oin the frozen water cryostat of C.Then 2-(4 '-chlorobenzene sulfydryl is slowly dripped with syringe) Acetyl Chloride 98Min. (17.7 grams, 0.08 mole), whole dropping process lasts about 80 minutes.After dripping, reaction mixture is at room temperature stirred and spends the night.Revolve and steam except desolventizing.Then in reaction flask, add ethyl acetate (20 milliliters) and water (20 milliliters) and stir 10 minutes, being transferred in a separating funnel, separate lower floor's inorganic phase.Inorganic phase ethyl acetate (10 milliliters) extracts.Merge organic phase and wash respectively with saturated aqueous common salt (20 milliliters) and water (20 milliliters).Organic phase anhydrous sodium sulfate drying.Revolve after steaming recycling design, residue over silica gel column chromatography (ethyl acetate/normal hexane: 1:6) obtains product (Z)-3-(dimethylamino)-N-(4-phenelyl)-2-(4 ' chlorobenzene sulfydryl) acrylamide [(Z)-α-((4-chlorophenyl) thio)-3-(dimethylamino)-N-(4-ethoxyphenyl) acrylamide] 8.44 grams, productive rate 56%.
Obviously, embodiment described above is only the present invention's part embodiment, instead of whole embodiments.Based on the embodiment in the present invention, those of ordinary skill in the art, not making the every other embodiment obtained under creative work prerequisite, belong to the scope of protection of the invention.
Claims (7)
1. a class (Z)-3-dimethylamino-α – 4 '-substituted benzene sulfydryl-α, β-unsaturated aromatic amides, is characterized in that, is the compound 3 represented in following general formula;
In general formula: fragrant amidine
1in: R
1for independently-H ,-F ,-Cl, Br ,-I ,-CN ,-NO
2,-OH ,-CO
2me ,-CO
2et ,-CONHMe ,-CONHEt, C
1-C
6alkyl; R
2for independently H ,-F ,-OH ,-CN; R
3for independently-H ,-CN ,-NO
2;
In α-4 '-substituted benzene mercaptoacetyl chlorine compound 2: R
4for independently-F ,-Cl, Br ,-I ,-CN ,-NO
2,-CO
2me ,-CO
2et.
2. a class (Z) as claimed in claim 1-3-dimethylamino-α – 4 '-substituted benzene sulfydryl-α, the preparation method of β-unsaturated aromatic amides, it is characterized in that, comprise the steps: under the existence of proper temperature, coordinative solvent and alkali, fragrant amidine 1 Yu α – 4 '-substituted benzene mercaptoacetyl chlorine compound
2reaction, obtains (Z)-3-dimethylamino-α – 4 '-substituted benzene sulfydryl-α after purified, β-unsaturated aromatic amides.
3. preparation method as claimed in claim 2, it is characterized in that, described proper temperature is-78
oc---5
oc.
4. preparation method as claimed in claim 2, it is characterized in that, described coordinative solvent is methylene dichloride, 1,2-ethylene dichloride, tetracol phenixin, chloroform, tetrahydrofuran (THF), ethyl acetate, toluene, benzene, any one of acetonitrile.
5. preparation method as claimed in claim 2, it is characterized in that, the mol ratio of described fragrant amidine 1 Yu α – 4 '-substituted benzene mercaptoacetyl chlorine compound 2 is 1:1 4.
6. preparation method as claimed in claim 2, it is characterized in that, described alkali is triethylamine, diisopropylethylamine, pyridine, 3, any one of 5-lutidine, 4-N, N-lutidine, sodium carbonate, sodium bicarbonate, salt of wormwood, saleratus, sodium hydroxide, potassium hydroxide, sodium phosphate.
7. preparation method as claimed in claim 2, it is characterized in that, the method for described purifying is for steaming solvent, recrystallization, silica gel column chromatography, underpressure distillation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510480331.4A CN105001132B (en) | 2015-08-08 | 2015-08-08 | One class (Z)-3-dimethylamino-α 4 '-substituted benzene sulfydryl-α, β-discord aromatic amides and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510480331.4A CN105001132B (en) | 2015-08-08 | 2015-08-08 | One class (Z)-3-dimethylamino-α 4 '-substituted benzene sulfydryl-α, β-discord aromatic amides and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105001132A true CN105001132A (en) | 2015-10-28 |
| CN105001132B CN105001132B (en) | 2016-08-31 |
Family
ID=54374045
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510480331.4A Active CN105001132B (en) | 2015-08-08 | 2015-08-08 | One class (Z)-3-dimethylamino-α 4 '-substituted benzene sulfydryl-α, β-discord aromatic amides and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105001132B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109053619A (en) * | 2018-10-08 | 2018-12-21 | 枣庄学院 | A kind of intermediate and method for preparing 2- and replacing benzoxazoles class compound |
-
2015
- 2015-08-08 CN CN201510480331.4A patent/CN105001132B/en active Active
Non-Patent Citations (1)
| Title |
|---|
| MARIE KISSANE等: "Addition-substitution reactions of 2-thio-3-chloroacrylamides with carbon,nitrogen, oxygen, sulfur and selenium nucleophiles", 《ORGANIC & BIOMOLECULAR CHEMISTRY》, vol. 9, no. 7, 31 December 2011 (2011-12-31), pages 2452 - 2472 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109053619A (en) * | 2018-10-08 | 2018-12-21 | 枣庄学院 | A kind of intermediate and method for preparing 2- and replacing benzoxazoles class compound |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105001132B (en) | 2016-08-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Li et al. | Regioselective and stereoselective sulfonylation of alkynylcarbonyl compounds in water | |
| EP3302441A1 (en) | Processes to produce brivaracetam | |
| JP6434980B2 (en) | Method for producing adamantane amide | |
| Tarui et al. | Ni-catalyzed α-arylation of secondary α-bromo-α-fluoro-β-lactam: cross-coupling of a secondary fluorine-containing electrophile | |
| CN104370755A (en) | Preparation method for optical activity active 3-amino butanol and optical activity 3-amino butyric acid | |
| CN101792400A (en) | Synthetic method for agomelatine | |
| Li et al. | An efficient enantioselective synthesis of florfenicol via a vanadium-catalyzed asymmetric epoxidation | |
| Xiang et al. | Iron-mediated cross dehydrogenative coupling (CDC) of terminal alkynes with benzylic ethers and alkanes | |
| CN105148988A (en) | Chiral pyridoxal catalysts and synthetic method therefor and application thereof | |
| CN105001132A (en) | (Z)-3-dimethylamino-alpha-4'-substituted benzene sulfydryl-alpha, beta-unsaturated aromatic amide compound and preparation method thereof | |
| Zhao et al. | Organocatalytic asymmetric cyclopropanation of α, β-unsaturated aldehydes with arsonium ylides | |
| CN104926674A (en) | (Z)-3-dimethylamino-2-phenoxy-alpha, beta-unsaturated amide and preparation method thereof | |
| CN110483469B (en) | Method for synthesizing iodo-benzoxepin heptacyclic lactone without metal catalysis | |
| CN104689849A (en) | Phosphamide-(di) secondary amine dual-functional catalyst and synthesis method thereof | |
| CN105085337A (en) | (Z)-3-dimethylamino-alpha-mercaptophenyl-alpha,beta-unsaturated amide compound and preparing method thereof | |
| CN102875421A (en) | Aziridine compound loop opening method based on p-nitrobenzoic acid | |
| David et al. | Ethyl dibromofluoroacetate: a versatile reagent for the synthesis of fluorinated molecules | |
| Ye et al. | Tandem Michael addition/ylide olefination reaction for the synthesis of highly functionalized cyclohexadiene derivatives | |
| Tang et al. | Silver (i)-catalyzed addition of pyridine-N-oxides to alkynes: a practical approach for N-alkenoxypyridinium salts | |
| KR101617121B1 (en) | Novel Chiral Cyclopropane Fused Tetrahydroquinoline Derivatives and Methods of Preparation Thereof | |
| CN103183680A (en) | Method for preparing asenapine | |
| CN113493386B (en) | Novel high-selectivity asymmetric synthesis process of 2-fluorocyclopropylamine | |
| CN109867694A (en) | A kind of synthetic method of the 7- alkynyl Benzazole compounds of oxygen guiding | |
| CN103848830A (en) | Simple method for synthesizing imidazo (1,2-a) pyridine derivatives | |
| CN114751800B (en) | Synthesis method of 5-sulfonyl-penta-2, 3-diene nitrile compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| CB03 | Change of inventor or designer information |
Inventor after: Liu Xuejing Inventor after: Han Ying Inventor after: Cao Han Inventor after: Zhou Li Inventor before: Liu Xuejing Inventor before: Cao Han Inventor before: Zhou Li |
|
| COR | Change of bibliographic data | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20160726 Address after: 277100 Bei'an West Road, Zaozhuang, Shandong Applicant after: Zaozhuang University Applicant after: Southern Shandong coal chemical industry engineering Institute for Research and Technology of Shandong Province Address before: 277100, Shandong, Zaozhuang, Zaozhuang University (Zaozhuang District, Bei'an Road, No. 1) building on the third floor Applicant before: Southern Shandong coal chemical industry engineering Institute for Research and Technology of Shandong Province |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20200923 Address after: 3 / F, building 2, No. 115, Yangpu Road, Suzhou Industrial Park, Suzhou area, China (Jiangsu) pilot Free Trade Zone, Suzhou City, Jiangsu Province Patentee after: Best (Suzhou) Pharmaceutical Co., Ltd Address before: 277100 Bei'an West Road, Zaozhuang, Shandong Patentee before: ZAOZHUANG University Patentee before: ENGINEERING AND TECHNOLOGY INSTITUTE OF LUNAN COAL CHEMICAL ENGINEERING |
|
| TR01 | Transfer of patent right |