CN102976966B - Synthetic method for high-steric-hindrance tertiary amides - Google Patents
Synthetic method for high-steric-hindrance tertiary amides Download PDFInfo
- Publication number
- CN102976966B CN102976966B CN201210493402.0A CN201210493402A CN102976966B CN 102976966 B CN102976966 B CN 102976966B CN 201210493402 A CN201210493402 A CN 201210493402A CN 102976966 B CN102976966 B CN 102976966B
- Authority
- CN
- China
- Prior art keywords
- acid amides
- high steric
- grades
- hindrance
- synthetic method
- 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.)
- Expired - Fee Related
Links
Abstract
The invention provides a synthetic method for high-steric-hindrance tertiary amides. The method comprises the following steps of: dispersing secondary amides, high-steric-hindrance halogenated hydrocarbon and alkali into an organic solvent to form a turbid liquid; adding copper salt and a ligand with the catalysis amount into the turbid liquid for heating to 60-140 DEG C to react; and performing post-processing on a mixed liquid to obtain the high-steric-hindrance tertiary amides after the reaction is finished. By the synthetic method, the coupling between the secondary amides and the high-steric-hindrance halogenated hydrocarbon C-N bonds is realized in the presence of ligand and alkali by using the copper salt as a catalyst; and the method is easy to operate, wide in practicability of substrates, high in yield, available in reactive raw materials, and suitable for laboratory preparation and industrial scale production.
Description
Technical field
The invention belongs to organic compound Intermediate Preparation field, be specifically related to the synthetic method of a kind of high steric-hindrance amino three grades of acid amides.
Background technology
Nineteen thirty-seven, the people such as Margaret report aryl imine ether and obtain through Cha Puman rearrangement reaction the N that ortho position replaces with carboxyl or ester group, N-disubstituted benzenes Carbox amide.(SomeDerivatives of Diphenylamine and a New Synthesis of N-ArylnnthrnniZicAcids and of Acridones, J.Chem.Soc., 1937,1954), concrete reaction formula is as follows:
At present, N, N-disubstituted benzenes methane amide or N, N-bis-replace acetamides and are widely used in organic synthesis, agricultural chemicals, medicine and other fields, are the structural units of Chemicals important in these fields.Have in the molecule of physiologically active also containing these structural units many.Such as: in medicine such as one of anti-insomnia medicine Zaleplone (Zaleplon), clinical treatment tuberculosis medicine brucine (Strychnine) and anodyne fentanyl (Fentanyl) etc., all contain multiple carbonnitrogen bond.
A kind of method being applicable to the comparatively general gentleness of above compound is also more rare, the method of existing this compounds of preparation has: enamine under oxygenant (such as: metachloroperbenzoic acid etc.) effect, rearrangement reaction occurs and generates N, N-disubstituted amide; There is protonation reaction in ketoxime, the group being simultaneously in antiposition with hydroxyl moves on the nitrogen-atoms of electron deficiency, and the carbonium ion formed and water are obtained by reacting acid amides under the effect such as sulfuric acid, Tripyrophosphoric acid; There is rearrangement reaction and generate corresponding N in the heating of aryl imine ether, N-disubstituted aryl acid amides, (Some Derivatives of Diphenylamine and aNew Synthesis of N-ArylnnthrnniZic Acids and of Acridones, J.Chem.Soc., 1937,1954; Oxidative Rearrangement of Ketimines to Amides by MCPBA andBF
3oEt
2.Synlett 2003,112; Structural Analysis of.beta.-Turn MimicsContaining a Substituted 6-Aminocaproic Acid Linker.J.Am.Chem.Soc.1995,117,5169).The major defect that these class methods exist realizes suitability for industrialized production for being difficult to, and the restriction of poisonous and non-available reagent, low-yield, polystep reaction and reaction substrate are limited.
In recent years, also someone reports and adopts the method for coupling to prepare three grades of amidess, but seldom relate to the coupling reagent of high steric-hindrance amino in selected substrate, particularly electrophilic reagent seldom select ortho position have substituent (such as: A Simple Copper-Catalyzed Synthesis of Tertiary AcyclicAmides, Org.Lett., 2011,13,2818; Pd-Catalyzed N-Arylation of SecondaryAcyclic Amides:Catalyst Development, Scope, and Computational Study, J.Am.Chem.Soc.2009,131,16720.).
Summary of the invention
The invention provides the synthetic method of a kind of high steric-hindrance amino three grades of acid amides, it is less and be applicable to the advantage of high steric-hindrance amino substrate that this synthetic method has high, the raw materials used toxicity of reaction yield.
A synthetic method for high steric-hindrance amino three grades of acid amides, comprises the following steps:
Secondary acid amides, high steric-hindrance amino halohydrocarbon and alkali are scattered in organic solvent and form suspension liquid, mantoquita and the part of catalytic amount is added in described suspension liquid, react after being heated to 60-140 DEG C, after reacting completely, aftertreatment obtains described high steric-hindrance amino three grades of acid amides;
The structure of described secondary acid amides is such as formula shown in (I):
The structure of described high steric-hindrance amino halohydrocarbon is such as formula shown in (II):
The structure of described high steric-hindrance amino three grades of acid amides is such as formula shown in (III):
In formula (I), formula (II) and formula (III), R
1, R
2and R
3independently selected from C
1~ C
10alkyl or the aryl replaced arbitrarily;
Substituting group on described phenyl is selected from H, CH
3o-, CH
3-, F, Cl or-NO
2;
In formula (II), X is I or Br.
Described synthetic method reaction formula is expressed as follows:
In the present invention, described aftertreatment is: after question response terminates, and adds a certain amount of cold water, extracts by ethyl acetate to reaction solution, and merge organic layer, separatory abandons water layer; Organic layer saturated sodium bicarbonate solution, saturated nacl aqueous solution are washed successively, then use anhydrous sodium sulfate drying, filter, removal of solvent under reduced pressure, obtains thick product, this thick product column chromatography is separated.
The present invention, using mantoquita as catalyzer, under part and alkali existent condition, directly achieves the fracture of C-X key in high steric-hindrance amino halohydrocarbon, furthermore achieved that the C-N key linked reaction of secondary acid amides and high steric-hindrance amino halohydrocarbon, obtains high steric-hindrance amino three grades of acid amides.The secondary acid amides used and high steric-hindrance amino halohydrocarbon toxicity less, easily obtain, this synthetic method is simple to operate, and reaction substrate is extensive, and the productive rate of high steric-hindrance amino three grades of acid amides is high.
As preferably, described aryl is phenyl, and now, reaction yield is high, and various raw material is easy to obtain.
Described mantoquita, as catalyzer, can activate the C-X key in described high steric-hindrance amino halohydrocarbon, and promote the carrying out of reaction, described mantoquita is preferably CuI, CuBr or CuCl, and these mantoquitas have higher catalytic activity.
Described part is the organic micromolecule compound containing N, electron pair in atom N can carry out coordination with described mantoquita, improve dissolving power and the catalytic activity of described mantoquita, as preferably, described part is N, N '-dimethyl quadrol, L-PROLINE or 1,4-dimethyl-3,4-dihydro-1 hydrogen-benzo [e]-Isosorbide-5-Nitrae-diazepine-5 (2H)-one, all contain the atom N that two have coordination function in these parts, the coordination ability of described part can be improved.
As preferably, the mol ratio of described mantoquita, part and secondary acid amides is 0.05-0.30: 0.1-0.6: 1, and the consumption of described part is generally described mantoquita twice, and mantoquita can be made to keep good catalytic activity; The consumption of described mantoquita is too little, and can reduce the yield of product, consumption is excessive, can increase the cost of the method.
In the present invention, described organic solvent is the solvent that raw material can be made fully to dissolve, and be preferably toluene, dimethylbenzene or DMF, now, the productive rate of the product obtained is high.
Described alkali can remove the HX generated in reaction process, promotes the carrying out of reaction, and improve the productive rate of product, described alkali is preferably salt of wormwood, sodium carbonate, Quilonum Retard or cesium carbonate, and these alkali are cheaply easy to get.
In the present invention, described high steric-hindrance amino halohydrocarbon price is more cheap relative to acid amides, and it is excessive that the consumption of high steric-hindrance amino halohydrocarbon is generally, and as preferably, the mol ratio of described secondary acid amides, high steric-hindrance amino halohydrocarbon and alkali is 1: 2 ~ 5: 3 ~ 6.
The raising of the temperature of reaction is conducive to the carrying out reacted, and the temperature of described reaction is preferably 100-140 DEG C.
React the degree of carrying out to be monitored by TLC (thin-layer chromatography), the time of reaction is generally 10 ~ 40 hours.
Compared with the existing technology, beneficial effect of the present invention is embodied in:
(1) many structural units had containing three grades of acid amides in the molecule of biology and physiologically active.As, all contain the basic structural unit of three grades of acid amides in medicine such as one of anti-insomnia medicine Zaleplone (Zaleplon), clinical treatment tuberculosis medicine brucine (Strychnine) and anodyne fentanyl (Fentanyl) etc.Adopt the present invention high productivity synthesis can have three grades of sterically hindered acid amides;
(2) this synthetic method can synthesize three grades of known amide compounds, as: 2-(N-phenyl-benzamide base) methyl benzoate;
(2) this synthetic method is simple to operate, and substrate practicality is comparatively wide, and productive rate is high, and reaction raw materials is easy to get, and is applicable to laboratory preparation and industrial-scale production.
Embodiment
Embodiment 1:
To with adding N-phenylbenzamaide 1a (No. CAS: 93-98-1,0.25mmol) in the reaction flask of magneton, 2-iodo-benzoic acid methyl esters 2a (No. CAS: 610-97-9,0.5mmol), K
2cO
3(0.1g, 0.75mmol) and 2mL dimethylbenzene, then in this reaction solution, CuI (0.025mmol) and 1 is added, 4-dimethyl-3, 4-dihydro-1 hydrogen-benzo [e]-1, 4-diazepine-5 (2H)-one (No. CAS: 500734-45-2, 0.05mmol), react 24 hours under 130 DEG C of oil bath conditions, stopped reaction, 10mL cold water is added by after reaction solution cool to room temperature, fully extract (3x20mL) by ethyl acetate, combining extraction liquid also uses saturated sodium bicarbonate solution, saturated nacl aqueous solution washs successively, then anhydrous sodium sulfate drying is used, filter, decompression precipitation, obtain thick product, this thick product column chromatography is carried out separation to obtain light yellow solid 3aa 2-(N-phenyl-benzamide base) methyl benzoate (this compound is known compound, No. CAS: 409111-58-6, 70mg, 85%).
Attached 3aa detects data:
1h NMR (500MHz, CDCl
3) δ 7.93 (s, 1H), 7.47 (dd, J=18.3,7.4Hz, 3H), 7.36-7.02 (m, 10H), 3.80 (s, 3H);
13c NMR (126MHz, CDCl
3) δ 170.6,166.4,143.8,143.2,135.9,132.9,131.1,130.1,129.1,128.9,127.8,127.5,126.8,126.2,52.4; HRMS (EI) calcd for C
21h
17nO
3(M
+), 331.1208; Found, 331.1205.
Reaction formula is as follows:
Embodiment 2:
To with adding N-phenylbenzamaide 1a (0.25mmol) in the reaction flask of magneton, 2-iodo-benzoic acid methyl esters 2a (0.5mmol), K
2cO
3(0.1g, 0.75mmol) and 2mL dimethylbenzene, then in this reaction solution, CuI (0.025mmol) and DMEDA (0.05mmol) is added, react 24 hours under 130 DEG C of oil bath conditions, stopped reaction, 10mL cold water is added by after reaction solution cool to room temperature, fully extract (3x20mL) by ethyl acetate, combining extraction liquid also uses saturated sodium bicarbonate solution, saturated nacl aqueous solution washs successively, then anhydrous sodium sulfate drying is used, filter, decompression precipitation, obtain thick product, this thick product column chromatography is carried out separation and obtain light yellow solid 3aa 2-(N-phenyl-benzamide base) methyl benzoate (58mg, 70%), product warp
1hNMR confirms.
Reaction formula is as follows:
Embodiment 3:
To with adding N-phenylbenzamaide 1a (0.25mmol) in the reaction flask of magneton, 2-iodo-benzoic acid methyl esters 2a (0.5mmol), K
2cO
3(0.1g, 0.75mmol) and 2mL dimethylbenzene, then in this reaction solution, CuI (0.025mmol) and L-PROLINE (0.05mmol) is added, react 24 hours under 130 DEG C of oil bath conditions, stopped reaction, 10mL cold water is added by after reaction solution cool to room temperature, fully extract (3x20mL) by ethyl acetate, combining extraction liquid also uses saturated sodium bicarbonate solution, saturated nacl aqueous solution washs successively, then anhydrous sodium sulfate drying is used, filter, decompression precipitation, obtain thick product, this thick product column chromatography is carried out separation and obtain light yellow solid 3aa 2-(N-phenyl-benzamide base) methyl benzoate (56mg, 68%), product warp
1mR confirms.
Reaction formula is as follows:
Embodiment 4:
To with adding N-phenylbenzamaide 1a (0.25mmol) in the reaction flask of magneton, 2-iodo-benzoic acid methyl esters 2a (0.5mmol), K
2cO
3(0.1g, 0.75mmol) and 2mL toluene, then in this reaction solution, CuI (0.025mmol) and DMEDA (0.05mmo1) is added, react 40 hours under 100 DEG C of oil bath conditions, stopped reaction, 10mL cold water is added by after reaction solution cool to room temperature, fully extract (3x20mL) by ethyl acetate, combining extraction liquid also uses saturated sodium bicarbonate solution, saturated nacl aqueous solution washs successively, then anhydrous sodium sulfate drying is used, filter, decompression precipitation, obtain thick product, this thick product column chromatography is carried out separation and obtain light yellow solid 3aa 2-(N-phenyl-benzamide base) methyl benzoate (52mg, 62%), product warp
1mR confirms.
Reaction formula is as follows:
Embodiment 5:
To with adding N-(4-p-methoxy-phenyl) benzamide 1b (CAS:7472-54-0,0.25mmol), 2-iodo-benzoic acid methyl esters 2a (0.5mmol) in the reaction flask of magneton, K
2cO
3(0.1g, 0.75mmol) and 2mL dimethylbenzene, then in this reaction solution, CuI (0.025mmol) and 1 is added, 4-dimethyl-3, 4-bis--hydrogen-1 hydrogen-benzo [e]-1, 4-bis--azatropylidene-5 (2H)-one (0.05mmol), react 24 hours under 130 DEG C of oil bath conditions, stopped reaction, 10mL cold water is added by after reaction solution cool to room temperature, fully extract (3x20mL) by ethyl acetate, combining extraction liquid also uses saturated sodium bicarbonate solution, saturated nacl aqueous solution washs successively, then anhydrous sodium sulfate drying is used, filter, decompression precipitation, obtain thick product, this thick product column chromatography is carried out separation to obtain light yellow solid 3ba 2-(N-(4-p-methoxy-phenyl) benzoylamino) (this compound is known compound to methyl benzoate, No. CAS: 1103-25-9, 84mg, 93%).
Attached 3ba detects data:
1h NMR (500MHz, CDCl
3) δ 7.97 (s, 1H), 7.47 (s, 3H), 7.36-7.15 (m, 5H), 7.08 (d, J=32.2Hz, 2H), 6.71 (s, 2H), 3.82 (s, 3H), 3.74 (s, 3H);
13c NMR (126MHz, CDCl
3) δ 170.59,166.51,157.82,136.01,132.85,130.98,129.94,129.01,127.78,126.64,114.19,55.36,52.38; HRMS (EI) calcd for C
22h
19nO
4(M
+), 361.1314; Found, 361.1319.
Reaction formula is as follows:
Embodiment 6:
To with adding N-phenylbenzamaide 1a (0.25mmol) in the reaction flask of magneton, 2-iodo ethyl benzoate 2c (No. CAS: 1829-28-3,0.5mmol), K
2cO
3(0.1g, 0.75mmol) and 2mL dimethylbenzene, then in this reaction solution, CuI (0.04mmol) and 1 is added, 4-bis--methyl-3, 4-dihydro-1 hydrogen-benzo [e]-1, 4-diazepine-5 (2H)-one (0.08mmol), react 24 hours under 130 DEG C of oil bath conditions, stopped reaction, 10mL cold water is added by after reaction solution cool to room temperature, fully extract (3x20mL) by ethyl acetate, combining extraction liquid also uses saturated sodium bicarbonate solution, saturated nacl aqueous solution washs successively, then anhydrous sodium sulfate drying is used, filter, decompression precipitation, obtain thick product, this thick product column chromatography is carried out separation and obtain light yellow solid 3ac 2-(N-phenyl-benzamide base) ethyl benzoate (74mg, 85%).
Attached 3ac detects data: NMR (500MHz, CDCl
3) δ 7.90 (s, 1H), 7.49 (d, J=7.6Hz, 2H), 7.43 (t, J=7.0Hz, 1H), 7.35-7.24 (m, 3H), 7.19 (t, J=7.6Hz, 4H), 7.12 (d, J=7.6Hz, 3H), (4.26 d, J=6.3Hz, 2H), (1.27 t, J=7.0Hz, 3H);
13cNMR (126MHz, CDCl
3) δ 170.49,165.96,143.82,143.17,135.98,132.77,131.00,130.11,129.35,129.12,128.90,127.79,127.53,126.87,126.22,61.39,14.20; HRMS (EI) calcd for C
22h
19nO
3(M
+), 345.1365; Found, 345.1364.
Reaction formula is as follows:
Finally, it is also to be noted that enumerate above be only some embodiments of the present invention son.Obviously, the invention is not restricted to above embodiment, many distortion can also be had.Those of ordinary skill in the art can directly derive from book disclosure of invention or associate all distortion, all should think protection scope of the present invention.
Claims (6)
1. a synthetic method for high steric-hindrance amino three grades of acid amides, is characterized in that, comprise the following steps:
Secondary acid amides, high steric-hindrance amino halohydrocarbon and alkali are scattered in organic solvent and form suspension liquid, mantoquita and the part of catalytic amount is added in described suspension liquid, react after being heated to 60-140 DEG C, after reacting completely, aftertreatment obtains described high steric-hindrance amino three grades of acid amides;
The structure of described secondary acid amides is such as formula shown in (I):
The structure of described high steric-hindrance amino halohydrocarbon is such as formula shown in (II):
The structure of described high steric-hindrance amino three grades of acid amides is such as formula shown in (III):
In formula (I), formula (II) and formula (III), R
1, R
2and R
3independently selected from C
1~ C
10alkyl or the phenyl replaced arbitrarily;
Substituting group on described phenyl is selected from H, CH
3o-, CH
3-, F, Cl or-NO
2;
In formula (II), X is I or Br;
Described mantoquita is CuI, CuBr or CuCl;
Described part is Isosorbide-5-Nitrae-dimethyl-3,4-dihydro-1 hydrogen-benzo [e]-Isosorbide-5-Nitrae-diazepine-5 (2H)-one.
2. the synthetic method of high steric-hindrance amino according to claim 1 three grades of acid amides, is characterized in that, the mol ratio of described mantoquita, part and secondary acid amides is 0.05-0.30:0.1-0.6:1.
3. the synthetic method of high steric-hindrance amino according to claim 1 three grades of acid amides, is characterized in that, described organic solvent is toluene, dimethylbenzene or DMF.
4. the synthetic method of high steric-hindrance amino according to claim 1 three grades of acid amides, is characterized in that, described alkali is salt of wormwood, sodium carbonate, Quilonum Retard or cesium carbonate.
5. the synthetic method of the high steric-hindrance amino three grades of acid amides according to claim 1 or 4, is characterized in that, the mol ratio of described secondary acid amides, high steric-hindrance amino halohydrocarbon and alkali is 1:2 ~ 5:3 ~ 6.
6. the synthetic method of high steric-hindrance amino according to claim 1 three grades of acid amides, is characterized in that, the temperature of described reaction is 100-140 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210493402.0A CN102976966B (en) | 2012-11-27 | 2012-11-27 | Synthetic method for high-steric-hindrance tertiary amides |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210493402.0A CN102976966B (en) | 2012-11-27 | 2012-11-27 | Synthetic method for high-steric-hindrance tertiary amides |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102976966A CN102976966A (en) | 2013-03-20 |
| CN102976966B true CN102976966B (en) | 2015-01-28 |
Family
ID=47851371
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210493402.0A Expired - Fee Related CN102976966B (en) | 2012-11-27 | 2012-11-27 | Synthetic method for high-steric-hindrance tertiary amides |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102976966B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101570490A (en) * | 2009-06-12 | 2009-11-04 | 华东理工大学 | Method for synthesizing copper-catalyzed substituted diphenylamine |
| CN102766004A (en) * | 2012-08-13 | 2012-11-07 | 成都理工大学 | Method for synthesizing aminoacyl arylamine |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2275395B1 (en) * | 2001-04-24 | 2016-11-09 | Massachusetts Institute of Technology (MIT) | Copper-catalyzed formation of carbon-carbon bonds |
-
2012
- 2012-11-27 CN CN201210493402.0A patent/CN102976966B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101570490A (en) * | 2009-06-12 | 2009-11-04 | 华东理工大学 | Method for synthesizing copper-catalyzed substituted diphenylamine |
| CN102766004A (en) * | 2012-08-13 | 2012-11-07 | 成都理工大学 | Method for synthesizing aminoacyl arylamine |
Non-Patent Citations (3)
| Title |
|---|
| A General and Efficient CuBr2-Catalyzed N-Arylation of Secondary Acyclic Amides;Wang, Mangang等;《Chin. J. Chem.》;20121023;第30卷(第10期);第2357页Table 1 Entry 3-7、13，第2358页Table 3 Entry 11，第2360页实验部分 * |
| A Simple Copper-Catalyzed Synthesis of Tertiary Acyclic Amides;Emilie Racine等;《Org. Lett.》;20110506;第13卷(第10期);第2818页最后一段，第2819页Table 2 * |
| 王晔峰,曾京辉,崔晓瑞.铜催化C-N 交叉偶联反应的研究进展.《有机化学》.2010,第30卷(第2期),第181-199页. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102976966A (en) | 2013-03-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111925381B (en) | Synthesis method of baroxavir key intermediate | |
| CN103224436B (en) | The preparation method of the amino diaryl ketone compound of a kind of neighbour | |
| CN111675662A (en) | Preparation method of 2-trifluoromethyl substituted quinazolinone compound | |
| CN103601686A (en) | Method for synthesizing fluorine-containing pyrimidine compounds by virtue of one-pot method | |
| CN110204487A (en) | A kind of synthetic method of quinoline | |
| CN106146334B (en) | 2,3- diaryl -2- alkynes propionamido- -3- arylamino methyl propionate derivative and its preparation method and application | |
| CN106831792A (en) | A kind of preparation method of PARP inhibitor Rucaparib intermediates | |
| CN105949118A (en) | Preparation method of 2-aryl quinoline derivatives | |
| CN113045503B (en) | Preparation method of 2-trifluoromethyl substituted quinazolinone compound and application of compound in synthesis of drug molecules | |
| CN102976966B (en) | Synthetic method for high-steric-hindrance tertiary amides | |
| CN103012350A (en) | Synthetic method of benzopyran chiral compound | |
| CN106008305A (en) | Synthetic method of penta-substituted 2-amino pyrrole derivatives | |
| CN102127014B (en) | Azaphenanthrone compound and preparation method thereof | |
| CN102260213B (en) | Method for preparing tolvaptan | |
| CN103755715B (en) | Cumarone is [2,3-c] pyridine compounds and synthetic method thereof also | |
| CN109988108A (en) | A kind of rich preparation method for Buddhist nun of card | |
| CN105153048B (en) | A kind of preparation method of 2,4 quinazoline diones class compound | |
| KR100574350B1 (en) | Process for preparation of 2-aminopyridine derivatives | |
| CN102351870B (en) | Method for preparing benzacridine derivative and application of benzacridine derivative as anti-cancer medicine | |
| CN106496118B (en) | A kind of quinolines enamine ketone compound and preparation method thereof | |
| CN104592222A (en) | Preparation method for antiplatelet medicine AZD6482 | |
| CN101088999A (en) | Process of synthesizing 3-amino quinine dihydrochloride | |
| CN104447534A (en) | 6-[(7-chloroquinoline-4-oxyl) phenolic ether]-2-naphthamide derivative as well as preparation method and application thereof | |
| CN109134351A (en) | S-3-(4- aminophenyl) piperidines synthetic method | |
| CN103848773B (en) | A kind of method preparing two indyl fluorene derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20150128 Termination date: 20181127 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |