CN105646487B - A kind of 7-naphthyridine derivatives of bromo 1,8 and preparation method thereof - Google Patents
A kind of 7-naphthyridine derivatives of bromo 1,8 and preparation method thereof Download PDFInfo
- Publication number
- CN105646487B CN105646487B CN201610145831.7A CN201610145831A CN105646487B CN 105646487 B CN105646487 B CN 105646487B CN 201610145831 A CN201610145831 A CN 201610145831A CN 105646487 B CN105646487 B CN 105646487B
- Authority
- CN
- China
- Prior art keywords
- bromo
- methyl
- hydrogen
- bromine
- naphthyridine derivatives
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Abstract
The invention discloses a kind of 7-naphthyridine derivatives of bromo 1,8 and preparation method thereof, the general structure of such 7-naphthyridine derivatives of bromo 1,8 isWherein, R1For bromine, acetylamino, amino, R2For hydrogen, bromine, R3For methyl, hydrogen, bromomethyl, R4For hydrogen, bromine, R5For bromine, methyl, bromomethyl, pyridine radicals.The 7-naphthyridine derivatives of bromo 1,8 of a kind of high activity of the present invention have potential application value in biological medicine, field of optical functional material, have the function that to further exploitation drug resource, fluorescent material, catalysis material positive.The preparation method of the present invention has the characteristics that syntheti c route is short, reaction condition is gentle, simple to operate, product yield is high, purity is high, cost is low, is adapted to industrialized production.
Description
Technical field
The invention belongs to technical field of chemistry, and in particular to a kind of bromo 1,8- 7-naphthyridine derivatives and preparation method thereof.
Background technology
In recent decades, heterocyclic nitrogen compound and its transient metal complex are with its abundant Photophysics, good
The extensive concern of good biological medicine activity causes chemical research person, research are very active.Numerous studies are found：Indolizine derives
Thing can be used for anti-aging, antitumor, anti-inflammatory, analgesic, anti-malarial, antibacterial, anti-senile dementia disease and angiocardiopathy.1,8- naphthyridines
It is that most commonly used one kind is studied in heterocyclic nitrogen compound, the heterocycle being made up of two nitrogenous heteroatomic aromatic condensed rings
System, there is special rigid planar structure and show good optical physics, spectrochemical property.In biological medicine, You Jiguang
Electrical part material, fluorescence chemical sensor, organic catalysis material, Coordinative Chemistry etc. have a wide range of applications.
1,8- naphthyridines analog derivatives are used widely to be closely connected with the preparation of the derivative of a large amount of 1,8- naphthyridines.Its
In, 1, the 8- 7-naphthyridine derivatives of chlorine substitution have been produced and for the preparation site of other groups introducing, have such as prepared tripodia, chain
Shape, caged and macrocyclic compound, chlorine substitution 1, the 8- 7-naphthyridine derivatives structure such as formula A of part report.But chlorine substitutes 1,8- naphthyridines
Reactivity is relatively low when derivative introduces group as reaction site, as substitution reaction and coupling reaction (Heck,
Sonogashira, Suzuki, Stille react).Therefore, suitable method is found to prepare bromo 1,8- naphthyridine compounds tool
It is significant.
Under illumination or heating condition, with N-bromosuccinimide (NBS), Br2、CBrCl3, HBr etc. be bromating agent, enter
The substitution of row free radical, nucleophilic displacement of fluorine, electrophilic substitution reaction are to prepare the most frequently used method of bromoarene compound.1,8- naphthyridine types
Compound bromo caused by its special azepine ring structure is difficult, once had document report to make bromating agent using NBS, and was prepared more
Kind 1,8- naphthyridines methyl bromo derivatives, and prove radical reaction.
The content of the invention
It is an object of the invention to provide in it is relatively gentle, cost-effective and environmentally friendly under the conditions of obtained a kind of bromo 1 is prepared,
8- 7-naphthyridine derivatives and its corresponding preparation method.
The purpose of the present invention is achieved through the following technical solutions：
A kind of bromo 1, the preparation method of 8- 7-naphthyridine derivatives, the bromo 1, the general structure I of 8- 7-naphthyridine derivatives are：
Wherein：R1For bromine, acetylamino, amino,
R2For hydrogen, bromine,
R3For methyl, hydrogen, bromomethyl,
R4For hydrogen, bromine,
R5For bromine, methyl, bromomethyl, pyridine radicals；
Preparation method is as follows：
A, by the compound of structure shown in following structural formula II and tribromo oxygen phosphorus reaction, condition is that 30 points are reacted at 90 DEG C
Clock, wherein：R1For hydroxyl, acetylamino, amino, R3For methyl, hydrogen, R5For hydroxyl, methyl, pyridine radicals,
Obtain following 1-9 totally 9 bromo 1,8- 7-naphthyridine derivatives of the description of formula I：
B, by the compound of structure shown in following structural formula III and tribromo oxygen phosphorus reaction, condition is that reaction 1 is small at 110 DEG C
When, wherein：R3For hydrogen, methyl,
Obtain following 10-11 totally 2 bromo 1,8- 7-naphthyridine derivatives of the description of formula I：
C, by the compound of structure shown in following structural formula II and tribromo oxygen phosphorus reaction, condition is that reaction 2 is small at 140 DEG C
When, wherein：R1For hydroxyl, acetylamino, amino, R3For methyl, hydrogen, R5For hydroxyl, methyl, pyridine radicals,
Obtain following 12-19 totally 8 bromo 1,8- 7-naphthyridine derivatives of the description of formula I：
The present invention is with POBr3For bromating agent, in it is relatively gentle, cost-effective and environmentally friendly under the conditions of a kind of bromo 1,8- naphthalenes is prepared
Piperidine derivatives.Such compound is the derivative of indolizine, before having major application in terms of biological medicine, the optical function material
Scape, have the function that to further exploitation drug resource, fluorescent material, catalysis material positive.
Embodiment
The general structure I of a kind of bromo 1,8- 7-naphthyridine derivatives of the present invention is：
Wherein：R1For bromine, acetylamino, amino,
R2For hydrogen, bromine,
R3For methyl, hydrogen, bromomethyl,
R4For hydrogen, bromine,
R5For bromine, methyl, bromomethyl, pyridine radicals.
Several preparation methods difference of above-mentioned a kind of bromo 1,8- 7-naphthyridine derivatives is as follows：
A, by the compound of structure shown in following structural formula II and tribromo oxygen phosphorus reaction, condition is that 30 points are reacted at 90 DEG C
Clock, wherein：R1For hydroxyl, acetylamino, amino, R3For methyl, hydrogen, R5For hydroxyl, methyl, pyridine radicals,
Obtain following 1-9 totally 9 new bromo 1,8- 7-naphthyridine derivatives of the description of formula I：
B, by the compound of structure shown in following structural formula III and tribromo oxygen phosphorus reaction, condition is that reaction 1 is small at 110 DEG C
When, wherein：R3For hydrogen, methyl,
Obtain following 10-11 totally 2 new bromo 1,8- 7-naphthyridine derivatives of the description of formula I：
C, by the compound of structure shown in following structural formula II and tribromo oxygen phosphorus reaction, condition is that reaction 2 is small at 140 DEG C
When, wherein：R1For hydroxyl, acetylamino, amino, R3For methyl, hydrogen, R5For hydroxyl, methyl, pyridine radicals,
Obtain following 12-19 totally 8 new bromo 1,8- 7-naphthyridine derivatives of the description of formula I：
Specific preparation manipulation method is as follows：
The bromo- 7- acetylaminohydroxyphenylarsonic acids 1,8- naphthyridines (5) of 2-：
2- hydroxyl -7- acetylaminohydroxyphenylarsonic acids 1,8- naphthyridines (0.5g, 2.46mmol) and excessive tribromo are added in 50mL round-bottomed flasks
Oxygen phosphorus (2.0g, 6.97mmol).Nitrogen protects lower 90 DEG C of heating reflux reactions, and reaction terminates to obtain dark thick liquid, about 0.5h.Instead
Answer liquid to be cooled to room temperature, pour into the beaker of a small amount of trash ice, adjust pH value to neutrality with concentrated ammonia liquor, separate out a large amount of brown and consolidate
Body, it is filtered to remove solution and dry crude product.Crude by column chromatography silica gel 200-300 mesh isolates and purifies, and eluent is
VDichloromethane：VPetroleum ether=1:5, obtain white powder.Reaction equation is as follows：
The crystal structure of product is determined by X-ray single crystal diffraction.Bond distance：Br(1)-C(6),C(1)-N
(1),1.319；C(1)-N(3),1.387；C(5)-N(1),1.357；C(5)-N(2),1.365；C(6)-N(2),1.304；C
(9)-O(1),1.216；C(9)-N(3),1.378.Bond angle：N(1)-C(1)-N(3),114.1°；N(1)-C(1)-C(2),
123.1°；N(3)-C(1)-C(2),122.8°；N(1)-C(5)-N(2),115.7°；N(1)-C(5)-C(4),122.8°；N
(2)-C(5)-C(4),121.5°；N(2)-C(6)-C(7),126.2°；N(2)-C(6)-Br(1),117.2°；C(7)-C(6)-
Br(1),116.6°。1H NMR(400MHz,CDCl3) δ (ppm) 8.95 (s, 1H NH), 8.60 (d, J=8.9Hz, 1H Naph-
), H 8.21 (d, J=8.9Hz, 1H Naph-H), 7.97 (d, J=8.3Hz, 1H Naph-H), 7.56 (d, J=8.3Hz, 1H
Naph-H),2.34(s,3H CH3).13C NMR(101MHz,CDCl3)δ(ppm)170.03(s),154.63(s),154.56
(s),145.43(s),139.38(s),138.27(s),125.59(s),119.37(s),115.90(s),25.07(s).ESI-
MS calcd for C10H8BrN3O[M+H]+267.09,found 267.18,268.31。
The bromo- 1,8- naphthyridines (10) of 2- bromomethyls -7-：
2- methyl -7- hydroxyls -1,8- naphthyridines (0.5g, 3.12mmol) and excessive tribromo oxygen phosphorus are added in 50mL round-bottomed flasks
(2.0g,6.97mmol).Nitrogen protects lower 110 DEG C of heating reflux reactions, and reaction terminates to obtain dark thick liquid, about 1h.Reaction solution
Room temperature is cooled to, is poured into the beaker of a small amount of trash ice, pH value is adjusted to neutrality with concentrated ammonia liquor, separates out a large amount of brown solids, mistake
Filter out solution and dry crude product.Crude by column chromatography silica gel 200-300 mesh isolates and purifies, eluent VDichloromethane：
VPetroleum ether=1:10, obtain white powder.Reaction equation is as follows：
1H NMR (400MHz, CDCl3) δ (ppm) 8.21 (d, J=8.3Hz, 1H Naph-H), 8.01 (d, J=8.4Hz,
1H Naph-H), 7.73 (d, J=8.3Hz, 1H Naph-H), 7.64 (d, J=8.4Hz, 1H Naph-H), 4.73 (s, 2H
CH2Br).13C NMR (101MHz, CDCl3) δ (ppm) 161.45 (s), 154.92 (s), 145.88 (s), 138.27 (d, J=
16.1Hz),127.62(s),122.80(s),120.77(s),33.43(s).ESI-MS calcd for C9H6Br2N2[M+H]+
302.97,found 302.95。
The bromo- 1,8- naphthyridines (12) of the bromomethyl -7- of 2,4- bis-：
2,4- dimethyl -7- hydroxyls -1,8- naphthyridines (0.5g, 2.87mmol) and excessive tribromo are added in 50mL round-bottomed flasks
Oxygen phosphorus (2.0g, 6.97mmol).Nitrogen protects lower 140 DEG C of heating reflux reactions, and reaction terminates to obtain dark thick liquid, about 2h.Instead
Answer liquid to be cooled to room temperature, pour into the beaker of a small amount of trash ice, adjust pH value to neutrality with concentrated ammonia liquor, separate out a large amount of brown and consolidate
Body, it is filtered to remove solution and dry crude product.Crude by column chromatography silica gel 200-300 mesh isolates and purifies, and eluent is
VDichloromethane：VPetroleum ether=1:20, obtain white powder.Reaction equation is as follows：
1H NMR(400MHz,CDCl3) δ (ppm) 8.32 (d, J=8.7Hz, 1H Naph-H), 7.72 (t, J=4.3Hz,
2H Naph-H),4.79(s,2H CH2Br),4.71(s,2H CH2Br).13C NMR(101MHz,CDCl3)δ(ppm)161.49
(s),155.51(s),146.13(s),145.57(s),134.41(s),127.58(s),122.61(s),119.13(s),
33.01(s),26.38(s).ESI-MS calcd for C10H7Br3N2[M+H]+395.89,found 395.85,396.90,
398.90。
The bromo- 7- pyridine radicals -1,8- naphthyridines (19) of 2,3- bis-：
2- hydroxyl -7- pyridine radicals -1,8- naphthyridines (0.5g, 3.12mmol) and excessive tribromo oxygen are added in 50mL round-bottomed flasks
Phosphorus (2.0g, 6.97mmol).Nitrogen protects lower 140 DEG C of heating reflux reactions, and reaction terminates to obtain dark thick liquid, about 2h.Reaction
Liquid is cooled to room temperature, pours into the beaker of a small amount of trash ice, with concentrated ammonia liquor regulation pH value to neutrality, separates out a large amount of brown solids,
It is filtered to remove solution and dry crude product.Crude by column chromatography silica gel 200-300 mesh isolates and purifies, eluent VDichloromethane：
VPetroleum ether=1:20, obtain white powder.Reaction equation is as follows：
1H NMR(400MHz,CDCl3) δ 8.82 (dd, J=8.3,2.8Hz, 2H), 8.74 (d, J=4.3Hz, 1H), 8.43
(s, 1H), 8.24 (d, J=8.6Hz, 1H), 7.89 (t, J=7.7Hz, 1H), 7.44-7.38 (m, 1H)13C NMR(101MHz,
CDCl3)δ160.48(s),154.65(s),153.72(s),149.20(s),146.69(s),140.59(s),137.17(s),
136.56 (s), 125.07 (s), 122.78 (d, J=6.7Hz), 121.23 (d, J=19.7Hz) .ESI-MS calcd for
C13H7Br2N3[M+H]+366.02,found 366.21,367.07,368.17。
Claims (1)
1. a kind of bromo 1, the preparation method of 8- 7-naphthyridine derivatives, it is characterised in that the bromo 1, the knot of 8- 7-naphthyridine derivatives
Structure formula I is：
Wherein：R1For bromine, acetylamino, amino,
R2For hydrogen, bromine,
R3For methyl, hydrogen, bromomethyl,
R4For hydrogen, bromine,
R5For bromine, methyl, bromomethyl, pyridine radicals；
Preparation method is as follows：
A, by the compound of structure shown in following structural formula II and tribromo oxygen phosphorus reaction, condition is to be reacted 30 minutes at 90 DEG C, its
In：R1For hydroxyl, acetylamino, amino, R3For methyl, hydrogen, R5For hydroxyl, methyl, pyridine radicals,
Obtain following 1-9 totally 9 bromo 1,8- 7-naphthyridine derivatives of the description of formula I：
B, by the compound of structure shown in following structural formula III and tribromo oxygen phosphorus reaction, condition is to be reacted 1 hour at 110 DEG C, its
In：R3For hydrogen, methyl,
Obtain following 10-11 totally 2 bromo 1,8- 7-naphthyridine derivatives of the description of formula I：
C, by the compound of structure shown in following structural formula II and tribromo oxygen phosphorus reaction, condition is to be reacted 2 hours at 140 DEG C, its
In：R1For hydroxyl, acetylamino, amino, R3For methyl, hydrogen, R5For hydroxyl, methyl, pyridine radicals,
Obtain following 12-19 totally 8 bromo 1,8- 7-naphthyridine derivatives of the description of formula I：
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610145831.7A CN105646487B (en) | 2016-03-15 | 2016-03-15 | A kind of 7-naphthyridine derivatives of bromo 1,8 and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610145831.7A CN105646487B (en) | 2016-03-15 | 2016-03-15 | A kind of 7-naphthyridine derivatives of bromo 1,8 and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105646487A CN105646487A (en) | 2016-06-08 |
| CN105646487B true CN105646487B (en) | 2017-12-05 |
Family
ID=56493288
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610145831.7A Expired - Fee Related CN105646487B (en) | 2016-03-15 | 2016-03-15 | A kind of 7-naphthyridine derivatives of bromo 1,8 and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105646487B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4642308A (en) * | 1984-07-19 | 1987-02-10 | Rhone-Poulenc Sante | N-(1,8-naphthyridin-2-yl) amides and their pharmaceutical use |
| US5258356A (en) * | 1989-03-11 | 1993-11-02 | Basf Aktiengesellschaft | Substituted 1,8-naphthyridines, their preparation and their use as antidotes |
| CN103827123A (en) * | 2011-09-02 | 2014-05-28 | 德克萨斯A&M大学*** | Porous materials containing built-in single molecule traps for small molecule capture |
| CN104114556A (en) * | 2012-02-10 | 2014-10-22 | 埃科特莱茵药品有限公司 | Process for manufacturing a naphthyridine derivative |
-
2016
- 2016-03-15 CN CN201610145831.7A patent/CN105646487B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4642308A (en) * | 1984-07-19 | 1987-02-10 | Rhone-Poulenc Sante | N-(1,8-naphthyridin-2-yl) amides and their pharmaceutical use |
| US5258356A (en) * | 1989-03-11 | 1993-11-02 | Basf Aktiengesellschaft | Substituted 1,8-naphthyridines, their preparation and their use as antidotes |
| CN103827123A (en) * | 2011-09-02 | 2014-05-28 | 德克萨斯A&M大学*** | Porous materials containing built-in single molecule traps for small molecule capture |
| CN104114556A (en) * | 2012-02-10 | 2014-10-22 | 埃科特莱茵药品有限公司 | Process for manufacturing a naphthyridine derivative |
Non-Patent Citations (3)
| Title |
|---|
| 2016101458317;王瑞;《STN》;20160921 * |
| 2-甲基-1,8-萘啶衍生物的甲基溴代反应;苟高章等;《应用化学》;20141130;第31卷(第11期);第1268页Scheme 1 * |
| A palladium catalyzed new synthesis of N,N-dimethyl[1,8]-naphthyridine-2-amines: facile incorporation of N,N-dimethylamino group from DMF in aqueous medium;Goswami, Shyamaprosad 等;《 Journal of Heterocyclic Chemistry》;20090413;第46卷(第2期);第325页表1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105646487A (en) | 2016-06-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104926811B (en) | The synthetic method of 3-cyanoimidazole also [1,2-a] pyridine compounds and application thereof | |
| WO2011109932A1 (en) | Novel process for the manufacture of 5-halogenated-7-azaindoles | |
| CN106146560B (en) | A kind of refining methd of high-purity phosphoric acid specially azoles amine | |
| CN105646487B (en) | A kind of 7-naphthyridine derivatives of bromo 1,8 and preparation method thereof | |
| CN105085520A (en) | 3-(2-nitro-1-phenylethyl)-2-(2-phenyl-imidazo[1,2-alpha] pyridine) compound | |
| CN105820174B (en) | A kind of preparation method of polysubstituted thiophene diindyl derivative | |
| CN111686798A (en) | BINOL axis chiral thiourea organic catalyst for preparing spiro tetrahydrothiophene | |
| CN103172637A (en) | Pyrimido [1, 2-a] benzimidazole compound and method for preparing same | |
| CN104610267A (en) | Method for efficiently synthetizing 6-alkylpyrazol-[1,5-c]-quinazoline skeleton compounds under no catalytic condition | |
| CN102603621B (en) | Novel chiral sulfoxide compound and method for preparing esomeprazole by using novel chiral sulfoxide compound | |
| CN110330450A (en) | A kind of preparation method of asymmetry thiourea | |
| CN109897033A (en) | A kind of method synthesizing imidazo containing iodine [1,2a] pyridine compounds and their | |
| CN101220016A (en) | Method for synthesizing 4-hydroxyl coumarin and derivant thereof | |
| CN103073480A (en) | Preparation method for 2-(t-butyloxycarbonyl) octahydrocyclopenta [c] pyrrole-5-carboxylic acid | |
| CN100593538C (en) | Method for preparing N-substituted acryloyl-2,5-pyrrole-dione compound | |
| CN102718694B (en) | 3-cyan substituted indole compound and synthetic method thereof | |
| CN105061296B (en) | A kind of preparation method of 2 substituted carbazole class compound | |
| CN102584695A (en) | Preparing method of 5-methylnicotinicacid | |
| CN102010345A (en) | Method for preparing D-phenylalanine through dynamic kinetic resolution | |
| CN105418499A (en) | Preparation method of acridine compound | |
| CN106883185B (en) | Preparation method of 4-chloro-2-trifluoromethylpyrimidine | |
| CN105061421A (en) | Method for preparing 2-chloro-1, 8-naphthyridine derivative | |
| CN104151314A (en) | Naphthoimidazopyridine compound and preparation method thereof | |
| CN105418507A (en) | Preparation method for 1-(3-methyl-1-phenyl-1H-pyrazole-5-yl)piperazine | |
| CN109053736A (en) | A kind of preparation method of pyrrolo- [1,2- α] indoles -3- 01 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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20171205 Termination date: 20190315 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |