CN113735799B - Synthesis method of dyclonine hydrochloride - Google Patents
Synthesis method of dyclonine hydrochloride Download PDFInfo
- Publication number
- CN113735799B CN113735799B CN202010473380.6A CN202010473380A CN113735799B CN 113735799 B CN113735799 B CN 113735799B CN 202010473380 A CN202010473380 A CN 202010473380A CN 113735799 B CN113735799 B CN 113735799B
- Authority
- CN
- China
- Prior art keywords
- compound
- reaction
- hydrochloride
- dyclonine hydrochloride
- dyclonine
- 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.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/10—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
- C07D295/104—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/108—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Hydrogenated Pyridines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The application discloses a brand new synthesis method of dyclonine hydrochloride. The method takes bromoacetophenone as a starting material and produces dyclonine hydrochloride through Mannich reaction and C-O crosslinking reaction. Compared with the prior art, the method has the advantages of easily obtained starting materials, controllable reaction temperature, higher purity, shortened time, improved yield and the like, avoids the use of highly toxic reagents such as acetyl chloride, 3-chloropropionyl chloride and the like, and is more beneficial to the safety of medicines and industrialized mass production.
Description
Technical Field
The application relates to the technical field of medicine synthesis, in particular to a method for synthesizing dyclonine hydrochloride.
Background
Dyclonine hydrochloride (english name Dyclonine hydrochloride); the chemical name is 4-butoxy-beta-piperidyl propiophenone hydrochloride, and the structural formula is as follows:
dyclonine hydrochloride has local anesthetic effect, can block the conduction of nerve impulses or stimulus, inhibit touch sense and pain sense, and has analgesic, antipruritic and antibacterial effects on skin. The product was first developed in 1932 U.S. Sharp & Dohme, and there was little report of dyclonine abroad until the 21 st century.
Indian patent IN172270A IN 1993 reported a route for the synthesis of dyclonine hydrochloride, which is as follows:
the yield of butoxyacetophenone in this route was low (up to 75%) and thus affected the overall yield; in addition, in the process, in the isopropanol solution of HCl, the process steps are added, the amount of three wastes in the post-treatment is high, and the production cost of the bulk drug is increased.
The patent No. CN200810087761.X of Yangjiang pharmaceutical industry group IN 2009 discloses a novel synthesis method of dyclonine hydrochloride, which is improved on the basis of the patent IN172270A document, and the specific route is as follows:
although the technology improves the reported synthesis technology, the technology still has the technical problems of long acylation reaction time, high toxicity of the used anhydride, long-time high-temperature distillation during the purification of the phenylbutyl ether and the p-butoxyacetophenone, low yield and the like.
Another method for synthesizing dyclonine hydrochloride is disclosed in patent CN201710475386.5 in the pharmaceutical industry of magical, guizhou in 2017, and the specific route is as follows:
the method is further improved in the route reported by the patent CN200810087761.X, mainly uses 3-chloropropionyl chloride, is inflammable, can react violently when meeting water, has harsh storage conditions and has potential safety hazard.
The application discloses a method patent CN201710438702.1 of dyclonine hydrochloride in 2017 Tianhua pharmaceutical in Changzhou, and the specific synthetic route is as follows:
the method shortens the route disclosed in the patent CN200810087761.X, the starting materials of the method are relatively expensive to hydroxyacetophenone and bromobutane, the reaction is difficult to carry out in two phases, and a phase transfer catalyst is needed.
Disclosure of Invention
Aiming at the defects of the prior art, the application aims to provide a novel method for synthesizing dyclonine hydrochloride.
The technical scheme of the application is as follows:
a synthesis method of dyclonine hydrochloride comprises the following synthesis routes:
wherein X is F, cl, br or I; n is 3-100;
the synthesis method comprises the following steps:
1) In the presence of an organic solvent, carrying out Mannich reaction on the compound I and piperidine hydrochloride and paraformaldehyde to obtain a compound II;
2) Under the protection of nitrogen, under the existence of ligand and the action of catalyst, compound II and n-butanol undergo the C-O crosslinking reaction to obtain compound III, namely dyclonine hydrochloride.
Preferably, the method comprises the steps of,
in the step 1) described above, the step of,
compound i: piperidine hydrochloride: the molar ratio of paraformaldehyde is 1:1.2 to 1.8:3.0 to 4.0 percent of the total weight of the composite,
the reaction temperature is 50-95 ℃; the reaction time is 3-7 h;
the organic solvent is any one of ethanol, isopropanol and acetic acid.
Preferably, the method comprises the steps of,
in the step 1), X is Br; n is 3.
In the step 2) described above, the step of,
compound II: the molar ratio of n-butanol is 1:5.0 to 10.0;
the reaction temperature is 60-120 ℃; the reaction time is 5-15 h;
the ligand is any one of phenanthroline and derivatives, acetylacetone and trans-4-hydroxy-L-proline;
the catalyst is any one of cuprous iodide, copper powder and metallic palladium.
More preferably, the process is carried out,
in the step 1) described above, the step of,
the compound I is p-bromoacetophenone; compound i: piperidine hydrochloride: the molar ratio of paraformaldehyde is 1:1.2:3.0;
the reaction condition is 60 ℃ for 4 hours;
the organic solvent used is preferably ethanol.
In the step 2) described above, the step of,
compound ii is 4-bromo- β -piperidinyl propiophenone hydrochloride; compound II: the molar ratio of n-butanol is 1:5, a step of;
the reaction condition is that the reaction is carried out for 7 hours at 80 ℃;
the ligand used is preferably trans-4-hydroxy-L-proline;
the catalyst used is preferably cuprous iodide.
In the step 1), the compound I is obtained by reacting halogenated benzene with acetyl chloride, wherein the halogenated benzene is any one of fluorobenzene, chlorobenzene, bromobenzene and iodobenzene. The halogenated benzene is preferably bromobenzene.
The preferred technical route of the application is to take p-bromoacetophenone as a starting material, and the method comprises the following steps: reacting p-bromoacetophenone, piperidine hydrochloric acid and paraformaldehyde with ethanol as a solvent to generate 4-bromo-beta-piperidyl propiophenone hydrochloride; and a second step of: and (3) reacting the obtained product with n-butanol under the catalysis of CuI to obtain the final product dyclonine hydrochloride.
The application has the following technical effects:
1) Compared with the prior art, the method has the advantages of easily obtained starting materials, controllable reaction temperature, higher purity, shortened time, improved yield and the like, simultaneously avoids the use of high-toxicity reagents such as acetyl chloride, 3-chloropropionyl chloride and the like, and is more beneficial to the safety and industrialized mass production of medicines because the solvent reagents used in the process are low in toxicity.
2) The reaction is preferably carried out in the forward direction by using cuprous iodide as a catalyst and trans-4-hydroxy-L-proline as a ligand, thereby improving the reaction yield.
3) Less three wastes and more environment protection.
Drawings
FIG. 1 is an HPLC chart of the product obtained in example 1.
FIG. 2 is an MS spectrum of the product obtained in example 1.
FIG. 3 is an H-NMR spectrum of the product obtained in example 1.
Detailed Description
Paraformaldehyde used in the following examples and comparative examples were purchased from national pharmaceutical chemicals Co., ltd, product number 80096618, CAS:30525-89-4.
EXAMPLE 1 preparation of dyclonine hydrochloride
(1) Preparation of 4-bromo- β -piperidyl propiophenone hydrochloride: to a 250mL three-necked flask, 19.9g of p-bromoacetophenone, 100mL of ethanol, 14.6g of piperidine hydrochloride (1.2 eq), 8.9g of paraformaldehyde (3.0 eq) and 2mL of hydrochloric acid were added, the mixture was stirred and heated to 60 ℃ to react for 4 hours, then the heating was stopped, the mixture was cooled and crystallized at 0 ℃ for 4 hours, suction filtration was performed, the filter cake was rinsed with isopropanol, and vacuum-dried at 60 ℃ to obtain 30.6kg of a white solid with an HPLC purity of 97% and a yield of 92%.
(2) Preparation of dyclonine hydrochloride: to a 500mL three-necked flask under nitrogen atmosphere were added 183mL of dimethyl sulfoxide, 16.6g of 4-bromo- β -piperidyl propiophenone hydrochloride, 1.9g of cuprous iodide (0.2 eq), 2.6g of trans-4-hydroxy-L-proline (0.4 eq), 13.8g of potassium carbonate (2.0 eq), 3.1g of tetrabutylammonium bromide (0.19 eq), 33mL of acetonitrile, and the temperature in the flask was controlled at 50 ℃. 18.5g of n-butanol (5.0 eq) was added rapidly, and the kettle temperature was controlled at 80℃and maintained for 7h. After the reaction, quench with ice water, add dichloromethane, filter, layer, wash the organic phase twice, concentrate the organic phase to half volume, add ethyl acetate to crystallize, filter. The filter cake obtained was refined once with ethanol. After drying in vacuo at 50℃for 6h, 13.2g of a white solid powder were obtained with an HPLC purity of 99.9%, yield 81%, mp:173 ℃.
From the above results, it can be seen that: in the reaction system of the step 2) of the embodiment, the catalyst cuprous iodide is used, and meanwhile, the ligand trans-4-hydroxy-L-proline is used, so that the reaction yield is high.
EXAMPLE 2 preparation of dyclonine hydrochloride
(1) Preparation of 4-bromo- β -piperidyl propiophenone hydrochloride: to a 250mL three-necked flask, 19.9g of p-bromoacetophenone, 100mL of isopropanol, 14.6g of piperidine hydrochloride (1.2 eq), 8.9g of paraformaldehyde (3.0 eq) and 2mL of hydrochloric acid were added, the mixture was stirred and heated to 60 ℃ to react for 4 hours, then the heating was stopped, the mixture was cooled and crystallized at 0 ℃ for 4 hours, suction filtration was performed, the filter cake was rinsed with isopropanol, and vacuum-dried at 60 ℃ to obtain 27.9kg of a white solid with an HPLC purity of 90% and a yield of 84%.
(2) Preparation of dyclonine hydrochloride: the reaction conditions were the same as in example 1 to obtain 12.5g of a white solid powder with a purity of 99.2% and a yield of 77%.
From the above results, it can be seen that: in the reaction system of the step 2) of the embodiment, the catalyst cuprous iodide is used, and meanwhile, the ligand trans-4-hydroxy-L-proline is used, so that the reaction yield is high.
Comparative example 1 preparation of dyclonine hydrochloride
(1) Preparation of 4-bromo- β -piperidyl propiophenone hydrochloride: the reaction conditions were the same as in example 1.
(2) Preparation of dyclonine hydrochloride: to a 500mL three-necked flask under nitrogen atmosphere were added 183mL of dimethyl sulfoxide, 16.6g of 4-bromo- β -piperidyl propiophenone hydrochloride, 2.6g of trans-4-hydroxy-L-proline (0.4 eq), 13.8g of potassium carbonate (2.0 eq), 3.1g of tetrabutylammonium bromide (0.19 eq) and 33mL of acetonitrile, and the temperature in the flask was controlled at 50 ℃. 18.5g of n-butanol (5.0 eq) was added rapidly, and the kettle temperature was controlled at 80℃and maintained for 7h. Detecting no product is generated.
From the above results, it can be seen that: in the reaction system of step 2) of this comparative example, no catalyst was used, and only the ligand trans-4-hydroxy-L-proline was used, and dyclonine hydrochloride was not successfully produced.
Comparative example 2 preparation of dyclonine hydrochloride
(1) Preparation of 4-bromo- β -piperidyl propiophenone hydrochloride: the reaction conditions were the same as in example 1.
(2) Preparation of dyclonine hydrochloride: to a 500mL three-necked flask under nitrogen atmosphere were added 183mL of dimethyl sulfoxide, 16.6g of 4-bromo- β -piperidyl propiophenone hydrochloride, 3.6g of 1, 10-phenanthroline (0.4 eq), 13.8g of potassium carbonate (2.0 eq), 3.1g of tetrabutylammonium bromide (0.19 eq), 33mL of acetonitrile, and the temperature in the flask was controlled at 50 ℃. 18.5g of n-butanol (5.0 eq) was added rapidly, and the kettle temperature was controlled at 80℃and maintained for 7h. After the reaction, quench with ice water, add dichloromethane, filter, layer, wash the organic phase twice, concentrate the organic phase to half volume, add ethyl acetate to crystallize, filter. The filter cake obtained was refined once with ethanol. After drying under vacuum at 50℃for 6 hours, 11.1g of a white solid powder was obtained, purity 99.5%, yield 68%.
From the above results, it can be seen that: in the reaction system of step 2) of the present comparative example, no catalyst was used, and only ligand 1, 10-phenanthroline was used, but the dyclonine hydrochloride product could be produced, but the yield was significantly lower than that of the reaction system using both the catalyst and the ligand.
Example 3 structural confirmation (using the sample prepared in example 1)
(1) Nuclear magnetic resonance hydrogen spectrum (1H-NMR)
Instrument model: BRUKER AV-400 type nuclear magnetic resonance instrument deuterated chloroform is used as a solvent.
1H-NMR(CDCl 3 ,400MHz)δ12.3(s,1H,H-Cl),8.0(d,2H,Ar-H),6.9(d,2H,Ar-H),4.0(t,2H,CH 2 ),3.7(t,2H,CH 2 ),3.5(m,2H,CH 2 ),3.4(m,2H,CH 2 ),2.7(s,2H,CH 2 ),2.2(m,2H,CH 2 ),1.9-1.0(m,8H,4×CH 2 ),1.0(m,3H,CH 3 )
( 2) Mass spectrometry (ESI, model: agilent 1260-6230 TOF LC-MS )
Dyclonine hydrochloride has a molecular weight of 325.9, wherein the free base has a molecular weight of 289.4, M is the standard, and a molecular ion peak (M+1) appears in the mass spectrum + 290.8, corresponding to the molecular weight of dyclonine hydrochloride free base.
(3) HPLC purity 99.9%, measured using HPLC area normalization method, i.e.: chromatographic column C18 column (4.6 mm. Times.250 mm,5 μm); detection wavelength 282nm; column temperature 40 ℃; flow rate: 1.0ul/min, mobile phase A:10mmol/L aqueous ammonium acetate, mobile phase B:100% acetonitrile.
Gradient elution for 70min:
the products of example 2 and comparative example 2 were identical to example 1, as confirmed by spot-plate control.
Although the embodiments of the present application are described above, the embodiments are only used for facilitating understanding of the present application, and are not intended to limit the present application. Any person skilled in the art can make any modification and variation in form and detail without departing from the spirit and scope of the present disclosure, but the scope of the present disclosure is to be determined by the appended claims.
Claims (6)
1. The synthesis method of dyclonine hydrochloride is characterized by comprising the following synthesis routes:
wherein X is F, cl, br or I; n is 3-100;
the synthesis method comprises the following steps:
1) In the presence of an organic solvent, carrying out Mannich reaction on the compound I and piperidine hydrochloride and paraformaldehyde to obtain a compound II;
2) Under the protection of nitrogen, under the existence of ligand and the action of catalyst, compound II and n-butanol undergo C-O crosslinking reaction to obtain compound III, namely dyclonine hydrochloride;
in the step 1) described above, the step of,
compound i: piperidine hydrochloride: the molar ratio of paraformaldehyde is 1:1.2 to 1.8:3.0 to 4.0 percent of the total weight of the composite,
the reaction temperature is 50-95 ℃; the reaction time is 3-7 h;
the organic solvent is any one of ethanol, isopropanol and acetic acid.
2. The method for synthesizing dyclonine hydrochloride according to claim 1,
in the step 2) described above, the step of,
compound II: the molar ratio of n-butanol is 1:5.0 to 10.0;
the reaction temperature is 60-120 ℃; the reaction time is 5-15 h;
the ligand is any one of phenanthroline and derivatives, acetylacetone and trans-4-hydroxy-L-proline; the catalyst is any one of cuprous iodide, copper powder and metallic palladium.
3. The method for synthesizing dyclonine hydrochloride according to claim 1 or 2, wherein in the step 1),
the compound I is p-bromoacetophenone; compound i: piperidine hydrochloride: the molar ratio of paraformaldehyde is 1:1.2:3.0;
the reaction condition is 60 ℃ for 4 hours;
the organic solvent used is preferably ethanol.
4. The method for synthesizing dyclonine hydrochloride according to claim 1 or 2, wherein in the step 2),
compound ii is 4-bromo- β -piperidinyl propiophenone hydrochloride; compound II: the molar ratio of n-butanol is 1:5, a step of;
the reaction condition is that the reaction is carried out for 7 hours at 80 ℃;
the ligand used is preferably trans-4-hydroxy-L-proline;
the catalyst used is preferably cuprous iodide.
5. The method for synthesizing dyclonine hydrochloride according to claim 1, wherein in the step 1), the compound i is obtained by reacting a halogenated benzene with acetyl chloride, and the halogenated benzene is any one of fluorobenzene, chlorobenzene, bromobenzene and iodobenzene.
6. The method for synthesizing dyclonine hydrochloride according to claim 5, wherein in the step 1), the halogenated benzene is bromobenzene.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010473380.6A CN113735799B (en) | 2020-05-29 | 2020-05-29 | Synthesis method of dyclonine hydrochloride |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010473380.6A CN113735799B (en) | 2020-05-29 | 2020-05-29 | Synthesis method of dyclonine hydrochloride |
Publications (2)
Publication Number | Publication Date |
---|---|
CN113735799A CN113735799A (en) | 2021-12-03 |
CN113735799B true CN113735799B (en) | 2023-08-29 |
Family
ID=78724447
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010473380.6A Active CN113735799B (en) | 2020-05-29 | 2020-05-29 | Synthesis method of dyclonine hydrochloride |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN113735799B (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN117986204B (en) * | 2024-04-02 | 2024-06-04 | 华泰民康(沈阳)科技有限公司 | Synthesis method of dyclonine hydrochloride |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107235930A (en) * | 2017-06-12 | 2017-10-10 | 常州市天华制药有限公司 | A kind of synthetic method of dyclonine hydrochloride |
CN107417643A (en) * | 2017-06-21 | 2017-12-01 | 贵州神奇药业有限公司 | A kind of synthesis technique of dyclonine hydrochloride |
-
2020
- 2020-05-29 CN CN202010473380.6A patent/CN113735799B/en active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107235930A (en) * | 2017-06-12 | 2017-10-10 | 常州市天华制药有限公司 | A kind of synthetic method of dyclonine hydrochloride |
CN107417643A (en) * | 2017-06-21 | 2017-12-01 | 贵州神奇药业有限公司 | A kind of synthesis technique of dyclonine hydrochloride |
Non-Patent Citations (1)
Title |
---|
Investigation of inhibitory properties of some hydrazone compounds on hCA I, hCA II and AChE enzymes;Kaan Kucukoglu等;《Bioorganic Chemistry》;20190228;第86卷;全文 * |
Also Published As
Publication number | Publication date |
---|---|
CN113735799A (en) | 2021-12-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7500102B2 (en) | Intermediate for synthesizing camptothecin derivatives, production method thereof and use thereof | |
WO2022242278A1 (en) | Preparation methods for upadacitinib and intermediate thereof | |
CN113735799B (en) | Synthesis method of dyclonine hydrochloride | |
KR102207333B1 (en) | Novel Production Method for Quadruple Cyclic Compounds | |
CN113416150A (en) | Novel synthesis method of lobaplatin intermediate | |
CN109134372A (en) | A kind of preparation method of pyrido indene compounds | |
CN114349609B (en) | Synthesis method of hexabenzocoronene dimer | |
CN107382910B (en) | Difluoromethyl aldehyde hydrazone compound and preparation method thereof | |
CN109651385A (en) | A kind of preparation method of pyrans [3,2-a] carbazole compound | |
CN110317172B (en) | Azafluorenone derivative and preparation method and application thereof | |
CN113698375A (en) | Synthesis method of 4-cyclohexylimine methyl substituted benzofuran derivative | |
EP3782977A1 (en) | Cyclopropanation method and reagent | |
CN111909098A (en) | hexahydro-5H-benzo [ d ] imidazole-5-ketone derivative and preparation method and application thereof | |
CN107445835B (en) | Synthesis method of 1, 2-dihydro cyclobuteno [ a ] naphthalene derivative and precursor thereof | |
CN112126941B (en) | Polysubstituted 10-hydroxy phenanthrene derivative and preparation method thereof | |
CN111333528B (en) | Synthesis method of multi-configuration O-phenyl-serine compound | |
CN110105361B (en) | Preparation method of Evodikine and derivative thereof | |
CN110577483B (en) | Green synthesis method of 3, 3-disubstituted-2-indolone | |
CN113354573B (en) | Method for large-scale production of alpha, alpha-terpyridine | |
TWI785816B (en) | 11-arylcinnolino[2,3-f]phenanthridin-9-ium salts and the manufacturing method thereof | |
EP4389732A1 (en) | Method for synthesizing 5,8-diamino-3,4-dihydro-2h-1-naphthalenone and intermediate compound used therein | |
Storli | Design and Synthesis of Carbazole Derivatives as Novel Therapeutic Candidates Against Acute Myeloid Leukaemia | |
CN115677775A (en) | Preparation method of dibenzophospholane pentadiene compound with electroluminescence function | |
CN113234083A (en) | Tetrahydroquinoline pyran compound and preparation method and application thereof | |
CN115677766A (en) | Preparation method of phosphorus-containing photoelectric functional material |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |