CN106810550A - A kind of preparation method of 7-naphthyridine derivatives - Google Patents
A kind of preparation method of 7-naphthyridine derivatives Download PDFInfo
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- CN106810550A CN106810550A CN201710017410.0A CN201710017410A CN106810550A CN 106810550 A CN106810550 A CN 106810550A CN 201710017410 A CN201710017410 A CN 201710017410A CN 106810550 A CN106810550 A CN 106810550A
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- trifluoromethyl
- reaction
- naphthyridines
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- chloro
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- 238000002360 preparation method Methods 0.000 title abstract description 4
- 238000005660 chlorination reaction Methods 0.000 claims abstract description 12
- 238000006722 reduction reaction Methods 0.000 claims abstract description 10
- 239000000463 material Substances 0.000 claims abstract description 5
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 5
- 230000000977 initiatory effect Effects 0.000 claims abstract description 4
- 230000009467 reduction Effects 0.000 claims abstract description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 27
- 238000003786 synthesis reaction Methods 0.000 claims description 27
- -1 5- (trifluoromethyl) -1,8- naphthyridines Chemical class 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 17
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 11
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 8
- 238000010992 reflux Methods 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 7
- 229940126214 compound 3 Drugs 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 5
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 claims description 4
- YWOWJQMFMXHLQD-UHFFFAOYSA-N 3-(trifluoromethyl)pyridin-2-amine Chemical compound NC1=NC=CC=C1C(F)(F)F YWOWJQMFMXHLQD-UHFFFAOYSA-N 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 229910019213 POCl3 Inorganic materials 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 239000007810 chemical reaction solvent Substances 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 239000012320 chlorinating reagent Substances 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 5
- 239000000203 mixture Substances 0.000 claims 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims 1
- 150000001335 aliphatic alkanes Chemical class 0.000 claims 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims 1
- 229910052763 palladium Inorganic materials 0.000 claims 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 claims 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 claims 1
- 239000011591 potassium Substances 0.000 claims 1
- 229910052700 potassium Inorganic materials 0.000 claims 1
- 239000012279 sodium borohydride Substances 0.000 claims 1
- 229910000033 sodium borohydride Inorganic materials 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract description 4
- 150000005054 naphthyridines Chemical class 0.000 abstract description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 abstract 2
- 229910052801 chlorine Inorganic materials 0.000 abstract 2
- 239000000460 chlorine Substances 0.000 abstract 2
- ATRQECRSCHYSNP-UHFFFAOYSA-N 2-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=CC=N1 ATRQECRSCHYSNP-UHFFFAOYSA-N 0.000 abstract 1
- 150000001412 amines Chemical class 0.000 abstract 1
- 238000009509 drug development Methods 0.000 abstract 1
- 239000002547 new drug Substances 0.000 abstract 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000010189 synthetic method Methods 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 108091000080 Phosphotransferase Proteins 0.000 description 3
- 102000020233 phosphotransferase Human genes 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 102000001253 Protein Kinase Human genes 0.000 description 2
- 230000004715 cellular signal transduction Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 108060006633 protein kinase Proteins 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
- BPNQKPULYOCRAN-UHFFFAOYSA-N 2-(trifluoromethyl)-1,8-naphthyridine Chemical class C1=CC=NC2=NC(C(F)(F)F)=CC=C21 BPNQKPULYOCRAN-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- IYXGSMUGOJNHAZ-UHFFFAOYSA-N Ethyl malonate Chemical class CCOC(=O)CC(=O)OCC IYXGSMUGOJNHAZ-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 102000004195 Isomerases Human genes 0.000 description 1
- 108090000769 Isomerases Proteins 0.000 description 1
- 125000002842 L-seryl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])O[H] 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 108010006519 Molecular Chaperones Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
- 102000009097 Phosphorylases Human genes 0.000 description 1
- 108010073135 Phosphorylases Proteins 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- XFDJMIHUAHSGKG-UHFFFAOYSA-N chlorethoxyfos Chemical compound CCOP(=S)(OCC)OC(Cl)C(Cl)(Cl)Cl XFDJMIHUAHSGKG-UHFFFAOYSA-N 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000008467 tissue growth Effects 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The invention discloses a kind of (trifluoromethyl) 1 of 5 chlorine of 7-naphthyridine derivatives 3, the preparation method of 8 naphthyridines, it is initiation material with the amine of (trifluoromethyl) pyridine 2, (trifluoromethyl) 1 of 5 chlorine 3 is obtained by cyclization, chlorination, reduction, 8 naphthyridines, the compound is the important intermediate of new drug development.
Description
Technical field
The present invention relates to a kind of preparation method of important medicine intermediate, the chloro- 3- (fluoroforms of more particularly to compound 5-
Base) -1,8- naphthyridines and its synthetic method.
Technical background
The chloro- 3- of compound 5- (trifluoromethyl) -1,8- naphthyridines, structural formula is：
The compound is the important intermediate for synthesizing naphthyridines analog derivative.7-naphthyridine derivatives are by consuming the protein of ATP
The suppression of the signal transduction carried out such as kinases, adjust and/or regulate and control its effect.Change with reference to ATP and using its energy conformation,
Make the protein of substrate phosphorylation and enabling signal Cascaded amplification known from many types, such as kinases, phosphatase, chaperone
Or isomerase.ATP- associated proteins can be enriched with using specific instrument and technology.As the mechanism part of cancer markers,
Ser/Thr kinases and receptor tyrosine kinase are required phosphorylases in cellular signal transduction.Cell cycle, survival, increment
The cell processes that are adjusted by cellular signal transduction with cell death, with allow tissue growth, regeneration and in homeostasis or
Degenerate.Therefore, some kinases are the sensitive targets of mammalian therapeutic.In swashing for the different parts as human kinase group
In enzyme system row, receptor tyrosine KDR can be survived and be bred with stimulating endothelial cell, and condition is by the extracellular connections of VEGF.Then, match somebody with somebody
Body combination can cause intracellular phosphorylation event, i.e. signal cascade to amplify, and ultimately result in propagation.
At present, other patent literatures compound and its synthetic method be there are no.
The content of the invention
The invention discloses a kind of synthetic method of the chloro- 3- of 5- (trifluoromethyl) -1,8- naphthyridines, with (trifluoromethyl) pyrrole
Pyridine -2- amine is initiation material, and the chloro- 3- of 5- (trifluoromethyl) -1,8- naphthyridines is obtained by cyclization, chlorination, reduction three-step reaction, should
Compound is the important intermediate for synthesizing 7-naphthyridine derivatives.Synthesis step is as follows：
(1) it is initiation material with (trifluoromethyl) pyridine -2- amine, 2 is obtained with diethyl malonate reaction,
(2) 2 and chlorination reaction, 3 are obtained；
(3) reduced 3, obtained 4
One preferred embodiment in, described synthesis compound (trifluoromethyl) -1,8- naphthyridines -2,4- glycol it is anti-
Cyclization reagent that should be used is selected from diethyl malonate；Chlorinating agent used by described chlorination reaction synthesis compound 3 is selected from three
Chlorethoxyfos；Reducing agent used by described reduction reaction synthesis 5- chloro- 3- (trifluoromethyl) -1,8- naphthyridines is selected from Pd/C- hydrogen.
In another preferred embodiment, it is characterised in that described synthesis compound (trifluoromethyl) -1,8- naphthalenes
The reaction solvent for use of pyridine -2,4- glycol is selected from tetrahydrofuran；Solvent used by described chlorination reaction synthesis compound 3 is selected from
POCl3；Solvent used by described reduction reaction synthesis 5- chloro- 3- (trifluoromethyl) -1,8- naphthyridines is selected from methyl alcohol.
In further preferred embodiment, it is characterised in that described synthesis compound (trifluoromethyl) -1,8- naphthalenes
The reaction temperature of pyridine -2,4- glycol is the reflux temperature of solvent；Reaction temperature used by described chlorination reaction synthesis compound 3
It is the reflux temperature of solvent；The reaction temperature of described reduction reaction synthesis 5- chloro- 3- (trifluoromethyl) -1,8- naphthyridines is room
Temperature.
The present invention relates to the chloro- 3- of 5- (trifluoromethyl) -1,8- naphthyridines and its synthetic method, the compound is synthesis synthesis naphthalene
The important intermediate of piperidine derivatives, currently without other Patents documents report.
The present invention is further described by the following embodiment, and these descriptions are not present invention to be made into one
The restriction of step.It should be understood by those skilled in the art that the equivalent made to technical characteristic of the invention, or change accordingly
Enter, still fall within protection scope of the present invention.
Specific embodiment mode
Embodiment 1
(1) synthesis of (trifluoromethyl) -1,8- naphthyridines -2,4- glycol
(trifluoromethyl) pyridine -2- amine, 24ml diethyl malonates 30g are added in 160ml tetrahydrofurans, are stirred
Mix, heat, flow back 4 hours, cooling is concentrated under reduced pressure, the residue isolated 37g products of chromatographic column.
(2) synthesis of 2,4- bis- chloro- 6- (trifluoromethyl) -1,8- naphthyridines
First step products therefrom 35g is dissolved in 200ml POCl3s, is heated to reflux, reacted 12 hours, reaction solution is poured into
In frozen water, it is extracted with ethyl acetate, organic phase is washed three times with saturated common salt, then with anhydrous sodium sulfate drying, is concentrated under reduced pressure, remains
The excess isolated product 18g grease of chromatographic column.
(3) synthesis of the chloro- 3- of 5- (trifluoromethyl) -1,8- naphthyridines
15g 1,8- benzodiazine -2,4- dichloros are added in 200ml methyl alcohol, 3g 10%Pd/C are added, hydrogen is passed through
Filtrate, concentration, the residue isolated product 7.8g of chromatographic column are collected in gas, room temperature reaction 2 hours, filtering.
Claims (6)
1. the method that one kind prepares the chloro- 3- of 5- (trifluoromethyl) -1,8- naphthyridines, with (trifluoromethyl) pyridine -2- amine as initial former
Material, the chloro- 3- of 5- (trifluoromethyl) -1,8- naphthyridines is obtained by cyclization, chlorination, reduction three-step reaction, and synthetic route is as follows,
2. method according to claim 1, it is characterized by described 3 steps reaction is,
(1) it is initiation material with (trifluoromethyl) pyridine -2- amine, 2 is obtained with diethyl malonate reaction,
(2) 2 and chlorination reaction, 3 are obtained；
(3) reduced 3, obtained 4
3. method according to claim 1, it is characterised in that described synthesis compound (trifluoromethyl) -1,8- naphthyridines -2,4-
Cyclization reagent used by the reaction of glycol is selected from one or two the mixture in diethyl malonate or dimethyl malenate；
Chlorinating agent used by described chlorination reaction synthesis compound 3 is selected from hydrogen chloride, phosphorus trichloride, phosphorus pentachloride, POCl3
The mixture of one or more；Reducing agent used by described reduction reaction synthesis 5- chloro- 3- (trifluoromethyl) -1,8- naphthyridines
Selected from the mixing of one or more in Pd/C- hydrogen, palladium dydroxide/C- hydrogen, iron powder, zinc powder, sodium borohydride, potassium borohydride
Thing.
4. method according to claim 1, it is characterised in that described synthesis compound (trifluoromethyl) -1,8- naphthyridines -2,4-
The reaction solvent for use of glycol is selected from tetrahydrofuran, N,N-dimethylformamide, toluene, methyl alcohol, ethanol, normal propyl alcohol, isopropanol
In the mixture of one or more；Solvent used by described chlorination reaction synthesis compound 3 is selected from tetrahydrofuran, dichloromethane
The mixture of one or more in alkane, chloroform, carbon tetrachloride, thionyl chloride, POCl3；Described reduction reaction synthesis 5-
Solvent used by chloro- 3- (trifluoromethyl) -1,8- naphthyridines is selected from one or more in methyl alcohol, ethanol, normal propyl alcohol, isopropanol
Mixture.
5. method according to claim 1, it is characterised in that described synthesis compound (trifluoromethyl) -1,8- naphthyridines -2,4-
The reaction temperature of glycol is the reflux temperature of 0 DEG C-solvent；Reaction temperature used by described chlorination reaction synthesis compound 3 is 0
DEG C-reflux temperature of solvent；The reaction temperature of described reduction reaction synthesis 5- chloro- 3- (trifluoromethyl) -1,8- naphthyridines is 0
DEG C-reflux temperature of solvent.
6. method according to claim 1, it is characterised in that described synthesis compound (trifluoromethyl) -1,8- naphthyridines -2,4-
The reaction temperature of glycol is the reflux temperature of solvent；Reaction temperature used by described chlorination reaction synthesis compound 3 is solvent
Reflux temperature；The reaction temperature of described reduction reaction synthesis 5- chloro- 3- (trifluoromethyl) -1,8- naphthyridines is room temperature.
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| CN201710017410.0A CN106810550A (en) | 2017-01-10 | 2017-01-10 | A kind of preparation method of 7-naphthyridine derivatives |
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| CN201710017410.0A CN106810550A (en) | 2017-01-10 | 2017-01-10 | A kind of preparation method of 7-naphthyridine derivatives |
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| CN201710017410.0A Pending CN106810550A (en) | 2017-01-10 | 2017-01-10 | A kind of preparation method of 7-naphthyridine derivatives |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113620946A (en) * | 2021-09-03 | 2021-11-09 | 山东明化新材料有限公司 | Preparation method of 2-chloro-1, 8-naphthyridine derivatives |
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| CN1802379A (en) * | 2003-06-04 | 2006-07-12 | 拜尔农作物科学股份公司 | Triazolopyrimidines |
| CN1839136A (en) * | 2003-06-27 | 2006-09-27 | 拜尔农作物科学股份公司 | Pyrazolopyrimidines |
| CN101754681A (en) * | 2007-06-08 | 2010-06-23 | 海利空医疗公司 | Pyrazolonaphthyridine derivatives for therapeutic use |
| CN102958930A (en) * | 2010-06-28 | 2013-03-06 | 默克专利有限公司 | 2,4- diaryl - substituted [1,8] naphthyridines as kinase inhibitors for use against cancer |
| CN104086543A (en) * | 2014-06-19 | 2014-10-08 | 湖南华腾制药有限公司 | Method for preparing 4-chloro-1,8-naphthyridine |
-
2017
- 2017-01-10 CN CN201710017410.0A patent/CN106810550A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1802379A (en) * | 2003-06-04 | 2006-07-12 | 拜尔农作物科学股份公司 | Triazolopyrimidines |
| CN1839136A (en) * | 2003-06-27 | 2006-09-27 | 拜尔农作物科学股份公司 | Pyrazolopyrimidines |
| CN101754681A (en) * | 2007-06-08 | 2010-06-23 | 海利空医疗公司 | Pyrazolonaphthyridine derivatives for therapeutic use |
| CN102958930A (en) * | 2010-06-28 | 2013-03-06 | 默克专利有限公司 | 2,4- diaryl - substituted [1,8] naphthyridines as kinase inhibitors for use against cancer |
| CN104086543A (en) * | 2014-06-19 | 2014-10-08 | 湖南华腾制药有限公司 | Method for preparing 4-chloro-1,8-naphthyridine |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113620946A (en) * | 2021-09-03 | 2021-11-09 | 山东明化新材料有限公司 | Preparation method of 2-chloro-1, 8-naphthyridine derivatives |
| CN113620946B (en) * | 2021-09-03 | 2022-06-21 | 山东明化新材料有限公司 | Preparation method of 2-chloro-1, 8-naphthyridine derivatives |
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