CN106866528A - A kind of method for preparing 4 amino quinoline derivatives - Google Patents
A kind of method for preparing 4 amino quinoline derivatives Download PDFInfo
- Publication number
- CN106866528A CN106866528A CN201710146395.XA CN201710146395A CN106866528A CN 106866528 A CN106866528 A CN 106866528A CN 201710146395 A CN201710146395 A CN 201710146395A CN 106866528 A CN106866528 A CN 106866528A
- Authority
- CN
- China
- Prior art keywords
- amino
- unsubstituted
- reaction
- added
- substitution
- 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.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The invention discloses a kind of method for preparing 4 amino quinoline derivatives, cuprous catalysis agent is added in a reaction vessel, additive and o-amino benzonitride, described additive is triethylamine, tetramethylethylenediamine, 1, the alkene of 8 diazabicylo, 11 carbon 7, any one in potassium carbonate or cesium carbonate, it is subsequently adding organic solvent, finally by terminal alkyne compound, p-toluene sulfonyt azide is added into reaction vessel, reactant mixture is in room temperature to 100 DEG C, heating response 3h ~ 6h, reaction process is tracked with thin-layer chromatography, filter out optimum reaction condition, after reaction terminates, mixture is filtered, filter cake is washed, filtrate concentrates after merging, carry out column chromatography for separation, obtain final product quinolines.4 amino quinoline derivatives are prepared present invention employs " one kettle way ", reaction efficiency is substantially increased, post processing is simple, with preferable industrial applications prospect.
Description
Technical field
The invention belongs to organic chemistry filed, it is related to a kind of 4-aminoquinoline derivatives, specifically one kind prepares 4-
The method of amino quinoline derivatives.
Background technology
Quinoline is widely present in living nature, and quinoline can be extracted from the washing oil of coal tar or naphtalene oil.Quinoline system naphthalene shape is nitrogenous
Heterocyclic compound.N atoms instead of CH i.e. on 1- positions, therefore also known as azanaphthalene, quinoline has emphatically in medicine and dye industry
The application wanted.At present, the synthetic route of document report quinoline has a plurality of, wherein traditional industrialized production route is carried for coal tar
Follow the example of.Due to complicated by resource constraint and extraction equipment, quinoline and its homologue kind in coal tar are added limited, it is impossible to
To the compound containing quinoline ring for wanting to obtain, chemical synthesis is arisen at the historic moment.Various effective works are developed at present
Industry chemical synthesis route, the report on quinolines is, using conditions such as high temperature, strong acid, to obtain final product.
This method condition is harsh, and process is cumbersome, post processing trouble etc..Therefore, a kind of reaction of efficient synthesis of quinoline compound is
There is very much application prospect.
The content of the invention
For above-mentioned technical problem of the prior art, the invention provides a kind of side for preparing 4-aminoquinoline derivatives
Method, the described this method for preparing 4-aminoquinoline derivatives will solve of the prior art to prepare 4-aminoquinoline derivatives
Method complex process, process it is cumbersome, post processing trouble, the technical problem of high energy consumption.
The invention provides a kind of method for preparing 4-aminoquinoline derivatives, comprise the following steps：
（1）Weigh cuprous catalysis agent, o-amino benzonitride, additive, unsubstituted or band substitution cardinal extremity alkine compounds, unsubstituted
Base or band substitution base benzenesulfonyl azide, described additive is triethylamine, tetramethylethylenediamine, 1,8- diazabicylos 11
Any one in carbon -7- alkene, potassium carbonate or cesium carbonate, the Terminal Acetylenes of described band substitution base is 2- Methoxy-phenylacetylenes, 3-
Methyl phenylacetylene, 4- methyl phenylacetylene, 2- chlorobenzenes acetylene, 3- chlorobenzenes acetylene, 4- Methoxy-phenylacetylenes, 4- Liquid Crystal Compounds Intermediate p-Ethyl-phenylacetylenes, 4-
Any one in fluorobenzene acetylene, phenylacetylene, 1- hexins or 1- octynes；The benzenesulfonyl azide of described band substitution base is 4- first
Base benzenesulfonyl azide；Described unsubstituted or the benzenesulfonyl azide with substitution base, unsubstituted or Terminal Acetylenes, neighbour with substitution base
The mol ratio of anthranilo nitrile is 1 ~ 1.2：1~1.2：1 ~ 1.2, the molal quantity of described cuprous catalysis agent is unsubstituted or band
The 5% ~ 10% of substitution cardinal extremity alkine compounds molal quantity, the molal quantity of described additive is unsubstituted or band substitution cardinal extremity alkynes
1-2 times of the molal quantity of compound；
（2）Add cuprous catalysis agent, o-amino benzonitride in a reaction vessel, added after nitrogen displacement three times organic molten
Agent, finally adds unsubstituted or the benzenesulfonyl azide with substitution cardinal extremity alkine compounds, unsubstituted or with substitution base, nitrogen
Lower addition additive, in room temperature at 100 DEG C, reacting 3h ~ 6h after completion of dropping, reaction process carried out with thin-layer chromatography with
Track；
（3）After reaction terminates, mixture is filtered, then concentrated, then carry out column chromatography for separation, obtain final product 4- amino quinolines
Quinoline derivant.
Further, described copper salt catalyst is CuCl, CuBr, CuI, Cu2O。
Further, described organic solvent is Isosorbide-5-Nitrae-dioxane.
Further, in step 3）In, washed with petrol ether/ethyl acetate, to wash 2 ~ 4 times, filtrate is dense after merging
Contracting, then column chromatography for separation is carried out, obtain final product 4-aminoquinoline derivatives.
Reaction equation of the invention is described below：
The present invention is using Terminal Acetylenes, o-amino benzonitride and p-toluene sulfonyt azide（TsN3）Single step reaction method, obtains with difference
The amino-compound of substituted base.Under the cuprous catalysis of metal, nitrogen protection is lower to be added dropwise triethylamine, Isosorbide-5-Nitrae-dioxane for reaction
Heating obtains product in solvent.
Substitution base of the invention：R1Mainly there are the electron-donating groups such as methyl, ethyl, fluorine, chlorine, bromine, iodine and electron-withdrawing group； R 2
Mainly methyl electron-donating group.
The present invention is compared with prior art, and its technological progress is significant.4- ammonia is prepared present invention employs " one kettle way "
Base quinoline, substantially increases reaction efficiency, and post processing is simple, with preferable industrial applications prospect.
Brief description of the drawings
Fig. 1 is N-（4- amino -3- benzene yl-quinoline -2- bases）The proton nmr spectra of -4- methyl benzenesulfonamides.
Fig. 2 is N-（4- amino -3- benzene yl-quinoline -2- bases）The carbon-13 nmr spectra of -4- methyl benzenesulfonamides.
Specific embodiment
The present invention is expanded on further below by embodiment, but is not intended to limit the present invention.
Embodiment 1
CuCl catalyst 2mg, o-amino benzonitride 23mg, the μ L of phenylacetylene 22 are added in the reaction tube of 10ml and to toluene sulphur
The μ L of acyl azide 20, are subsequently adding Isosorbide-5-Nitrae-dioxane 1ml, and triethylamine 40mg is added dropwise into reaction tube after nitrogen displacement.Reaction is mixed
Compound heats 4h at 70 DEG C, and mixture is filtered, and uses petrol ether/ethyl acetate（Volume ratio 5/1,10mL）Washing three times is carried out,
Filtrate concentrates after merging, and carries out column chromatography for separation, and eluant, eluent is petrol ether/ethyl acetate（Volume ratio 2/1）600ml, obtains most
End-product N-（4- amino -3- benzene yl-quinoline -2- bases）- 4- methyl benzenesulfonamides, yield is 85%.
1H NMR (500 MHz, CDCl3) δ = 11.61 (s, 1H), 7.71 (t, J=10.0 Hz, 3H),
7.51 (t, J=7.5 Hz, 1H), 7.29 (t, J=7.5 Hz, 3H), 7.21 (t, J=7.5 Hz, 1H), 7.20
– 7.14 (m, 3H), 7.11 (d, J=7.5 Hz, 2H), 5.34 (s, 2H), 2.35 (s, 3H); 13C NMR
(126 MHz, CDCl3) δ = 153.0, 150.8, 141.8, 141.5, 136.0, 133.1, 131.5, 130.9,
129.1, 129.0, 127.9, 125.8, 123.8, 122.7, 117.3, 114.3, 107.9, 21.4; HRMS (m/
z) [M + H]+ calcd for C22H19N3O2S 390.1285, found 390.1276
Fig. 1, Fig. 2 be respectively compound N-（4- amino -3- benzene yl-quinoline -2- bases）The nuclear magnetic resonance of -4- methyl benzenesulfonamides
Hydrogen is composed and carbon-13 nmr spectra.
Embodiment 2
Added in the reaction tube of 10ml the μ L of CuCl catalyst 2mg, o-amino benzonitride 23mg, 4- Methoxy-phenylacetylene 39 and
The μ L of p-toluene sulfonyt azide 20, are subsequently adding Isosorbide-5-Nitrae-dioxane 1ml, and triethylamine 40mg is added dropwise into reaction after nitrogen displacement
Pipe.Reactant mixture heats 4h at 70 DEG C, and mixture is filtered, and uses petrol ether/ethyl acetate（Volume ratio 5/1,10mL）Carry out
Washing three times, filtrate concentrates after merging, and carries out column chromatography for separation, and eluant, eluent is petrol ether/ethyl acetate（Volume ratio 2/1）
600ml, obtains final product N- [4- amino -3-（4- methoxyphenyls）- quinoline -2- bases] -4- methyl benzenesulfonamides, produce
Rate is 42%.
1H NMR (500 MHz, DMSO) δ = 11.42 (s, 1H), 8.22 (d, J=10.0 Hz, 1H),
7.73 (d, J=10.0 Hz, 1H), 7.68 – 7.57 (m, 3H), 7.35 (t, J=7.5 Hz, 1H), 7.26
(d, J=10.0 Hz, 2H), 7.03 (q, J=10.0 Hz, 4H), 6.69 (s, 2H), 3.81 (s, 3H), 2.31
(s, 3H); 13C NMR (126 MHz, DMSO) δ = 158.5, 152.5, 151.7, 141.9, 141.0, 135.8,
132.1, 131.5, 129.0, 125.6, 125.3, 123.5, 123.2, 117.7, 114.3, 114.1, 105.8,
55.0, 20.8; HRMS (m/z) [M + H]+ calcd for C23H21N3O3S 420.1382, found 420.1380
Embodiment 3
CuCl catalyst 2mg, μ L of o-amino benzonitride 23mg, 3- methyl phenylacetylene 25 and right are added in the reaction tube of 10ml
The μ L of tosyl nitrine 20, are subsequently adding Isosorbide-5-Nitrae-dioxane 1ml, and triethylamine 40mg is added dropwise into reaction tube after nitrogen displacement.
Reactant mixture heats 4h at 70 DEG C, and mixture is filtered, and uses petrol ether/ethyl acetate（Volume ratio 5/1,10mL）Washed
Wash three times, filtrate concentrates after merging, and carries out column chromatography for separation, and eluant, eluent is petrol ether/ethyl acetate（Volume ratio 2/1）600ml,
Obtain final product N-（Toluene yl-quinoline -2- bases between 4- amino -3-）- 4- methyl benzenesulfonamides, yield is 68%.
1H NMR (500 MHz, CDCl3) δ = 11.72 (s, 1H), 7.73 (d, J=10.0 Hz, 2H),
7.69 (d, J=5.0 Hz, 1H), 7.56 (t, J=7.5 Hz, 1H), 7.32 (d, J=10.0 Hz, 1H), 7.26
– 7.17 (m, 4H), 7.09 (d, J=5.0 Hz, 1H), 6.95 (s, 2H), 5.24 (s, 2H), 2.37 (s,
3H), 2.29 (s, 3H); 13C NMR (126 MHz, CDCl3) δ = 153.1, 150.4, 141.8, 138.7,
136.2, 132.9, 131.6, 129.1, 127.8, 126.0, 123.9, 122.3, 117.5, 114.4, 108.6,
21.5; HRMS (m/z) [M + H]+ calcd for C23H21N3O2S 404.1432, found 404.1436
Embodiment 4
Added in the reaction tube of 10ml the μ L of CuCl catalyst 2mg, o-amino benzonitride 23mg, 2- Methoxy-phenylacetylene 25 and
The μ L of p-toluene sulfonyt azide 20, are subsequently adding Isosorbide-5-Nitrae-dioxane 1ml, and triethylamine 40mg is added dropwise into reaction after nitrogen displacement
Pipe.Reactant mixture heats 4h at 70 DEG C, and mixture is filtered, and uses petrol ether/ethyl acetate（Volume ratio 5/1,10mL）Carry out
Washing three times, filtrate concentrates after merging, and carries out column chromatography for separation, and eluant, eluent is petrol ether/ethyl acetate（Volume ratio 2/1）
600ml, obtains final product N- [4- amino -3-（2- methoxyphenyls）- quinoline -2- bases] -4- methyl benzenesulfonamides, produce
Rate is 45%.
1H NMR (500 MHz, CDCl3) δ = 11.78 (s, 1H), 7.71 (d, J=10.0 Hz, 2H),
7.63 (d, J=10.0 Hz, 1H), 7.55 (t, J=7.5 Hz, 1H), 7.32 (t, J=5.0 Hz, 2H), 7.24
(d, J=7.5 Hz, 1H), 7.15 (d, J=5.0 Hz, 2H), 7.07 (d, J=5.0 Hz, 1H), 6.98 (t, J
=7.5 Hz, 1H), 6.91 (d, J=10.0 Hz, 1H), 5.01 (s, 2H), 3.53 (s, 3H), 2.34 (s,
3H) ; 13C NMR (125 MHz, CDCl3) δ = 157.6, 153.3, 150.1, 141.7, 141.5, 136.3,
132.3, 131.3, 123.0, 128.9, 125.9, 123.6, 121.8, 121.4, 121.3, 117.6, 114.3,
111.7, 105.7, 55.5, 21.4. HRMS (m/z) [M + H]+ calcd for C23H21N3O3S 420.1382,
found 420.1383
Embodiment 5
CuCl catalyst 2mg, μ L of o-amino benzonitride 23mg, 2- chlorobenzene acetylene 23 and to first are added in the reaction tube of 10ml
The μ L of benzenesulfonyl azide 20, are subsequently adding Isosorbide-5-Nitrae-dioxane 1ml, and triethylamine 40mg is added dropwise into reaction tube after nitrogen displacement.Instead
Answer mixture to heat 4h at 70 DEG C, mixture is filtered, use petrol ether/ethyl acetate（Volume ratio 5/1,10mL）Washed
Three times, filtrate concentrates after merging, and carries out column chromatography for separation, and eluant, eluent is petrol ether/ethyl acetate（Volume ratio 2/1）600ml, obtains
To final product N- [4- amino -3-（The chloro- phenyl of 2-）- quinoline -2- bases] -4- methyl benzenesulfonamides, yield is 74%.
1H NMR (500 MHz, DMSO) δ = 11.39 (s, 1H), 8.25 (d, J=5.0 Hz, 1H),
7.76 (d, J=10.0 Hz, 1H), 7.67 (t, J=7.5 Hz, 1H), 7.58 (t, J=10.0 Hz, 3H),
7.45 – 7.33 (m , 3H), 7.25 – 7.16 (m, 3H), 6.79 (s, 2H), 2.30 (s, 3H); 13C NMR
(126 MHz, DMSO) δ = 152.3, 151.6, 141.8, 141..0, 136.2, 134.6, 133.2, 132.7,
131.7, 129.6, 128.9, 127.6, 125.4, 123.5, 123.2, 117.8, 114.0, 103.6, 20.8;
HRMS (m/z) [M + H]+ calcd for C22H18ClN3O2S 424.0886, found 424.0917
Embodiment 6
CuCl catalyst 2mg, μ L of o-amino benzonitride 23mg, 3- chlorobenzene acetylene 23 and to first are added in the reaction tube of 10ml
The μ L of benzenesulfonyl azide 20, are subsequently adding Isosorbide-5-Nitrae-dioxane 1ml, and triethylamine 40mg is added dropwise into reaction tube after nitrogen displacement.Instead
Answer mixture to heat 4h at 70 DEG C, mixture is filtered, use petrol ether/ethyl acetate（Volume ratio 5/1,10mL）Washed
Three times, filtrate concentrates after merging, and carries out column chromatography for separation, and eluant, eluent is petrol ether/ethyl acetate（Volume ratio 2/1）600ml, obtains
To final product N- [4- amino -3-（The chloro- phenyl of 3-）- quinoline -2- bases] -4- methyl benzenesulfonamides, yield is 70%.
1H NMR (501 MHz, DMSO) δ = 11.42 (s, 1H), 8.25 (d, J=10.0 Hz, 1H),
7.76 (d, J=10.0 Hz, 1H), 7.66 (t, J=7.5 Hz, 1H), 7.59 (d, J=10.0 Hz, 2H),
7.47 (t, J=7.5 Hz, 1H), 7.42 (d, J=10.0 Hz, 1H), 7.37 (t, J=7.5 Hz, 1H), 7.26
(d, J=10.0 Hz, 2H), 7.10 (d, J=10.0 Hz, 2H), 6.88 (s, 2H), 2.31 (s, 3H); 13C
NMR (126 MHz, DMSO) δ = 152.1, 151.7, 141.9, 141.0, 136.1, 133.1, 131.7,
131.1, 130.5, 129.7, 129.0, 127.4, 125.2, 123.5, 123.3, 117.9, 114.1, 104.7,
20.8; HRMS (m/z) [M + H]+ calcd for C22H18ClN3O2S 424.0886, found 424.0881
Embodiment 7
CuCl catalyst 2mg, μ L of o-amino benzonitride 23mg, 4- fluorobenzene acetylene 38 and to first are added in the reaction tube of 10ml
The μ L of benzenesulfonyl azide 20, are subsequently adding Isosorbide-5-Nitrae-dioxane 1ml, and triethylamine 40mg is added dropwise into reaction tube after nitrogen displacement.Instead
Answer mixture to heat 4h at 70 DEG C, mixture is filtered, use petrol ether/ethyl acetate（Volume ratio 5/1,10mL）Washed
Three times, filtrate concentrates after merging, and carries out column chromatography for separation, and eluant, eluent is petrol ether/ethyl acetate（Volume ratio 2/1）600ml, obtains
To final product N- [4- amino -3-（4- fluorophenyls）- quinoline -2- bases] -4- methyl benzenesulfonamides, yield is 50%.
1H NMR (500 MHz, CDCl3) δ = 11.77 (s, 1H), 7.69 (d, J=10.0 Hz, 2H),
7.64 (d, J=5.0 Hz, 1H), 7.59 (t, J=7.5 Hz, 1H), 7.35 (d, J=10.0 Hz, 1H), 7.30
(d, J=7.5 Hz, 1H), 7.17 (d, J=5.0 Hz, 4H), 7.08 (t, J=10.0 Hz, 2H), 5.05 (s,
2H), 2.35 (s, 3H); 13C NMR (126 MHz, CDCl3) δ = 163.6, 161.6, 153.3, 150.1,
141.9, 141.5, 136.3, 132.9, 132.8, 131.8, 129.20, 128. 9, 128.9, 125.9,
124.0, 121.9, 117.8, 116.4, 116.2, 114.3, 107.7, 21.5; HRMS (m/z) [M + H]+
calcd for C22H18FN3O2S 408.1182, found 408.1170
Embodiment 8
μ L of CuCl catalyst 2mg, o-amino benzonitride 23mg, 4- Liquid Crystal Compounds Intermediate p-Ethyl-phenylacetylene 42 and right are added in the reaction tube of 10ml
The μ L of tosyl nitrine 20, are subsequently adding Isosorbide-5-Nitrae-dioxane 1ml, and triethylamine 40mg is added dropwise into reaction tube after nitrogen displacement.
Reactant mixture heats 4h at 70 DEG C, and mixture is filtered, and uses petrol ether/ethyl acetate（Volume ratio 5/1,10mL）Washed
Wash three times, filtrate concentrates after merging, and carries out column chromatography for separation, and eluant, eluent is petrol ether/ethyl acetate（Volume ratio 2/1）600ml,
Obtain final product N- [4- amino -3-（4- ethyls-phenyl）- quinoline -2- bases] -4- methyl benzenesulfonamides, yield is
68%。
1H NMR (500 MHz, DMSO) δ = 11.45 (s, 1H), 8.23 (d, J=5.0 Hz, 1H),
7.73 (d, J=10.0 Hz, 1H), 7.63 (dd, J=5.0, 5.0 Hz, 3H), 7.36 (t, J=7.5 Hz,
1H), 7.27 (dd, J=10.0, 7.5 Hz, 4H), 7.05 (d, J=5.0 Hz, 2H), 6.66 (s, 2H),
2.67 (q, J=7.5 Hz, 2H), 2.31 (s, 3H), 1.26 (t, J=7.5 Hz, 3H); 13C NMR (126
MHz, DMSO) δ = 152.4, 151.5, 142.6, 141.9, 141.0, 135.8, 131.5, 130.9, 130.8,
129.0, 128.1, 125.3, 123.5, 123.2, 117.7, 114.1, 106.1, 27.9, 20.8, 15.1;
HRMS (m/z) [M + H]+ calcd for C24H23N3O2S 418.1589, found 418.1592
Embodiment 9
CuCl catalyst 2mg, μ L of o-amino benzonitride 23mg, 4- methyl phenylacetylene 25 and right are added in the reaction tube of 10ml
The μ L of tosyl nitrine 20, are subsequently adding Isosorbide-5-Nitrae-dioxane 1ml, and triethylamine 40mg is added dropwise into reaction tube after nitrogen displacement.
Reactant mixture heats 4h at 70 DEG C, and mixture is filtered, and uses petrol ether/ethyl acetate（Volume ratio 5/1,10mL）Washed
Wash three times, filtrate concentrates after merging, and carries out column chromatography for separation, and eluant, eluent is petrol ether/ethyl acetate（Volume ratio 2/1）600ml,
Obtain final product N-（4- amino -3- p-methylphenyls-quinoline -2- bases）- 4- methyl benzenesulfonamides, yield is 60%.
1H NMR (500 MHz, CDCl3) δ = 11.72 (s, 1H), 7.71 (d, J=5.0 Hz, 2H),
7.64 (d, J=10.0 Hz, 1H), 7.55 (t, J=7.5 Hz, 1H), 7.31 (d, J=10.0 Hz, 1H),
7.23 (t, J=7.5 Hz, 1H), 7.16 (t, J=7.5 Hz, 4H), 7.04 (d, J=5.0 Hz, 2H), 5.15
(s, 2H), 2.34 (s, 3H), 2.32 (s, 3H); 13C NMR (126 MHz, CDCl3) δ = 153.3,
150.2, 141.8, 141.6, 137.9, 136.2, 131.6, 130.7, 129.9, 129. 9, 129.1, 126.0,
123.8, 122.1, 117.6, 114.4, 108.6, 21.5, 21.4; HRMS (m/z) [M + H]+ calcd for
C23H21N3O2S 404.1432, found 404.1427
Embodiment 10
The μ L of CuCl catalyst 2mg, o-amino benzonitride 23mg, 1- hexin 23 are added in the reaction tube of 10ml and to toluene sulphur
The μ L of acyl azide 20, are subsequently adding Isosorbide-5-Nitrae-dioxane 1ml, and triethylamine 40mg is added dropwise into reaction tube after nitrogen displacement.Reaction is mixed
Compound heats 4h at 70 DEG C, and mixture is filtered, and uses petrol ether/ethyl acetate（Volume ratio 5/1,10mL）Washing three times is carried out,
Filtrate concentrates after merging, and carries out column chromatography for separation, and eluant, eluent is petrol ether/ethyl acetate（Volume ratio 2/1）600ml, obtains most
End-product N-（4- amino -3- first yl-quinoline -2- bases）- 4- methyl benzenesulfonamides, yield is 40%.
1H NMR (500 MHz, DMSO) δ = 11.35 (s, 1H), 8.14 (d, J=10.0 Hz, 1H),
7.70 (d, J=5.0 Hz, 2H), 7.67 (d, J=5.0 Hz, 1H), 7.59 (t, J=7.5 Hz, 1H), 7.33
(t, J=7.5 Hz, 1H), 7.26 (d, J=10.0 Hz, 2H), 7.08 (s, 2H), 2.30 (s, 3H), 1.23
(s, 6H), 0.79 (d, J=5.0 Hz, 3H); 13C NMR (126 MHz, DMSO) δ = 152.3, 150.9,
142.1, 141.0, 135.2, 130.8, 129.0, 125.3, 123.2, 122.6, 117.6, 114.1, 104.8,
29.3, 23.4, 22.0, 20.8, 14.0; HRMS (m/z) [M + H]+ calcd for C20H23N3O2S
370.1589, found 370.1587
Embodiment 11
The μ L of CuCl catalyst 2mg, o-amino benzonitride 23mg, 1- octyne 29 are added in the reaction tube of 10ml and to toluene sulphur
The μ L of acyl azide 20, are subsequently adding Isosorbide-5-Nitrae-dioxane 1ml, and triethylamine 40mg is added dropwise into reaction tube after nitrogen displacement.Reaction is mixed
Compound heats 4h at 70 DEG C, and mixture is filtered, and uses petrol ether/ethyl acetate（Volume ratio 5/1,10mL）Washing three times is carried out,
Filtrate concentrates after merging, and carries out column chromatography for separation, and eluant, eluent is petrol ether/ethyl acetate（Volume ratio 2/1）600ml, obtains most
End-product N-（4- amino -3- first yl-quinoline -2- bases）- 4- methyl benzenesulfonamides, yield is 40%.
1H NMR (501 MHz, CDCl3) δ = 11.75 (s, 1H), 7.86 (d, J=7.5 Hz, 2H),
7.62 (d, J=8.0 Hz, 1H), 7.55 (t, J=7.5 Hz, 1H), 7.31 (t, J=7.5 Hz, 2H), 7.22
(d, J=5.0 Hz, 2H), 5.06 (s, 2H), 2.63 (t, J=7.5 Hz, 2H), 2.38 (s, 3H), 1.46 –
1.37(m, 2H), 1.35 – 1.27 (m, 4H), 1.22 (s, 2H), 0.85 (t, J=6.0, 3H); 13C NMR
(126 MHz, CDCl3) δ = 153.6, 148.8, 141.8, 135.5, 130.9, 129.2, 126.0, 123.8,
121.0, 117.6, 114.4, 108.3, 31.9, 29.5, 27.2, 24.8, 22.7, 21.5, 14.2; HRMS
(m/z) [M + H]+ calcd for C22H27N3O2S 398.1902, found 398.1900
Embodiment 12
Add CuCl catalyst 2mg, o-amino benzonitride 23mg, the μ L of phenylacetylene 22 and benzene sulfonyl folded in the reaction tube of 10ml
The μ L of nitrogen 19, are subsequently adding Isosorbide-5-Nitrae-dioxane 1ml, and triethylamine 40mg is added dropwise into reaction tube after nitrogen displacement.Reactant mixture
4h is heated at 70 DEG C, mixture is filtered, use petrol ether/ethyl acetate（Volume ratio 5/1,10mL）Carry out washing three times, filtrate
Concentrated after merging, carry out column chromatography for separation, eluant, eluent is petrol ether/ethyl acetate（Volume ratio 2/1）600ml, is finally produced
Thing N-（4- amino -3- benzene yl-quinoline -2- bases）- benzsulfamide, yield is 70%.
1H NMR (500 MHz, DMSO) δ = 11.51 (s, 1H), 8.25 (d, J=8.5 Hz, 1H),
7.74 (dd, J=8.5, 7.0 Hz, 3H), 7.65 (t, J=7.0 Hz, 1H), 7.46 (dd, J=7.0, 7.0
Hz, 5H), 7.37 (dd, J=6.5, 8.0 Hz, 2H), 7.14 (d, J=7.5 Hz, 2H), 6.71 (s, 2H);13C NMR (126 MHz, DMSO) δ = 152.3, 151.7, 144.7, 136.0, 133.7, 131.6, 131.0,
128.8, 128.6, 127.4, 125.2, 123.6, 123.3, 117.9, 114.1, 106.3; HRMS (m/z) [M
+ H]+ calcd for C21H17N3O2S 376.1119, found 376.1128
Embodiment 13
Added in the reaction tube of 10ml the μ L of CuCl catalyst 2mg, o-amino benzonitride 23mg, 4- Methoxy-phenylacetylene 39 and
The μ L of benzenesulfonyl azide 19, are subsequently adding Isosorbide-5-Nitrae-dioxane 1ml, and triethylamine 40mg is added dropwise into reaction tube after nitrogen displacement.Instead
Answer mixture to heat 4h at 70 DEG C, mixture is filtered, use petrol ether/ethyl acetate（Volume ratio 5/1,10mL）Washed
Three times, filtrate concentrates after merging, and carries out column chromatography for separation, and eluant, eluent is petrol ether/ethyl acetate（Volume ratio 2/1）600ml, obtains
To final product N- [4- amino -3-（4- methoxyphenyls）- quinoline -2- bases]-benzsulfamide, yield is 35%.
1H NMR (500 MHz, DMSO) δ = 11.45 (s, 1H), 8.22 (d, J=8.0 Hz, 1H),
7.74 (d, J=8.5 Hz, 1H), 7.70 (d, J=8.5 Hz, 2H), 7.65 (t, J=7.5 Hz, 1H), 7.50
– 7.44 (m, 3H), 7.36 (t, J=8.0 Hz, 1H), 7.02 (q, J=9.0 Hz, 4H), 3.81 (s, 3H);13C NMR (126 MHz, DMSO) δ = 158.5, 152.5, 151.9, 144.8, 135.8, 132.1, 131.5,
131.0, 128.6, 125.6, 125.2, 123.5, 123.2, 117.8, 114.3, 114.1, 105.9, 55.0;
HRMS (m/z) [M + H]+ calcd for C22H19N3O3S 406.1225, found 406.1219
Embodiment 14
CuCl catalyst 2mg, the μ L of o-amino benzonitride 23mg, 3- chlorobenzene acetylene 24 and benzene sulphur are added in the reaction tube of 10ml
The μ L of acyl azide 19, are subsequently adding Isosorbide-5-Nitrae-dioxane 1ml, and triethylamine 40mg is added dropwise into reaction tube after nitrogen displacement.Reaction is mixed
Compound heats 4h at 70 DEG C, and mixture is filtered, and uses petrol ether/ethyl acetate（Volume ratio 5/1,10mL）Washing three times is carried out,
Filtrate concentrates after merging, and carries out column chromatography for separation, and eluant, eluent is petrol ether/ethyl acetate（Volume ratio 2/1）600ml, obtains most
End-product N- [4- amino -3-（3- chlorphenyls）- quinoline -2- bases]-benzsulfamide, yield is 75%.
1H NMR (500 MHz, DMSO) δ 11.46 (s, 1H), 8.26 (d, J=8.0 Hz, 1H), 7.78
(d, J=8.5 Hz, 1H), 7.69 (t, J=8.5 Hz, 3H), 7.51 – 7.45 (m, 4H), 7.42 (d, J=
8.5 Hz, 1H), 7.38 (t, J=7.5 Hz, 1H), 7.12 – 7.08 (t, J=7.5 Hz, 2H), 6.90 (s,
2H); 13C NMR (126 MHz, DMSO) δ = 152.1, 151.8, 144.7, 136.0, 133.1, 131.7,
131.1, 131.0, 130.5, 129.7, 128.6, 127.4, 125.1, 123. 6, 123.3, 117.9, 114.1,
104.7; HRMS (m/z) [M + H]+ calcd for C21H16ClN3O2S 410.0730, found 410.0725
Embodiment 15
CuCl catalyst 2mg, μ L of o-amino benzonitride 23mg, 3- methyl phenylacetylene 25 and right are added in the reaction tube of 10ml
The μ L of tosyl nitrine 19, are subsequently adding Isosorbide-5-Nitrae-dioxane 1ml, and triethylamine 40mg is added dropwise into reaction tube after nitrogen displacement.
Reactant mixture heats 4h at 70 DEG C, and mixture is filtered, and uses petrol ether/ethyl acetate（Volume ratio 5/1,10mL）Washed
Wash three times, filtrate concentrates after merging, and carries out column chromatography for separation, and eluant, eluent is petrol ether/ethyl acetate（Volume ratio 2/1）600ml,
Obtain final product N-（Toluene yl-quinoline -2- bases between 4- amino -3-）- benzsulfamide, yield is 80%.
1H NMR (500 MHz, CDCl3) δ = 11.68 (s, 1H), 7.82 (d, J=7.0 Hz, 2H),
7.67 (d, J=7.5 Hz, 1H), 7.54 (t, J=7.5 Hz, 1H), 7.39 (dd, J=6.5, 7.0 Hz, 3H),
7.30 (d, J=8.0 Hz, 1H), 7.20 (d, J=7.5 Hz, 2H), 7.06 (d, J=7.0 Hz, 1H), 6.91
(s, 2H), 5.22 (s, 2H), 2.25 (s, 3H); 13C NMR (126 MHz, CDCl3) δ = 153.1,
150.5, 144.5, 138.7, 136.1, 132.9, 131.6, 131.3, 129.0, 128.9, 128.5, 127.7,
125.9, 123.9, 122.3, 117.6, 114.6, 108.6, 21.5; HRMS (m/z) [M + H]+ calcd for
C22H19N3O2S 390.1276, found 390.1275
Above said content is only the basic explanation under present inventive concept, and according to technical scheme done it is any etc.
Effect conversion, all should belong to protection scope of the present invention.
Claims (4)
1. a kind of method for preparing 4-aminoquinoline derivatives, it is characterised in that comprise the following steps：
（1）Cuprous catalysis agent, o-amino benzonitride, additive, unsubstituted or the terminal alkyne compound with substitution base, nothing is weighed to take
Benzenesulfonyl azide for base or with substitution base, described additive is triethylamine, tetramethylethylenediamine, 1,8- diazabicylos ten
Any one in one carbon -7- alkene, potassium carbonate or cesium carbonate, the Terminal Acetylenes of described band substitution base is 2- Methoxy-phenylacetylenes,
3- methyl phenylacetylene, 4- methyl phenylacetylene, 2- chlorobenzenes acetylene, 3- chlorobenzenes acetylene, 4- Methoxy-phenylacetylenes, 4- Liquid Crystal Compounds Intermediate p-Ethyl-phenylacetylenes,
Any one in 4- fluorobenzene acetylene, phenylacetylene, 1- hexins or 1- octynes；The benzenesulfonyl azide of described band substitution base is right
Tosyl nitrine；Described unsubstituted or the benzenesulfonyl azide with substitution base, unsubstituted or Terminal Acetylenes, neighbour with substitution base
The mol ratio of anthranilo nitrile is 1 ~ 1.2：1~1.2：1 ~ 1.2, the molal quantity of described cuprous catalysis agent is unsubstituted or band
The 5% ~ 10% of substitution cardinal extremity alkine compounds molal quantity, the molal quantity of described additive is unsubstituted or band substitution cardinal extremity alkynes
1-2 times of the molal quantity of compound；
（2）Cuprous catalysis agent, o-amino benzonitride are added in a reaction vessel, organic solvent is added after nitrogen displacement, most
Unsubstituted or the benzenesulfonyl azide with substitution cardinal extremity alkine compounds, unsubstituted or with substitution base are added afterwards, is added under nitrogen
Enter additive, 3h ~ 6h is reacted at 100 DEG C in room temperature after completion of dropping, reaction process is tracked with thin-layer chromatography；
（3）After reaction terminates, mixture is filtered, then concentrated, then carry out column chromatography for separation, obtain final product 4- amino quinolines
Quinoline derivant.
2. a kind of method for preparing quinoline compound according to claim 1, it is characterised in that：Described cuprous catalysis agent
It is CuCl, CuBr, CuI or Cu2Any one in O.
3. a kind of method for preparing 4-aminoquinoline derivatives according to claim 1, it is characterised in that：Described is organic
Solvent is 1,4- dioxane.
4. a kind of method for preparing 4-aminoquinoline derivatives according to claim 1, it is characterised in that：In step 3）
In, washed with petrol ether/ethyl acetate, to wash 2 ~ 4 times, filtrate concentrates after merging, then carries out column chromatography for separation, obtains most
End-product 4-aminoquinoline derivatives.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710146395.XA CN106866528A (en) | 2017-03-13 | 2017-03-13 | A kind of method for preparing 4 amino quinoline derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710146395.XA CN106866528A (en) | 2017-03-13 | 2017-03-13 | A kind of method for preparing 4 amino quinoline derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106866528A true CN106866528A (en) | 2017-06-20 |
Family
ID=59170800
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710146395.XA Pending CN106866528A (en) | 2017-03-13 | 2017-03-13 | A kind of method for preparing 4 amino quinoline derivatives |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106866528A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108658943A (en) * | 2018-06-08 | 2018-10-16 | 浙江树人学院 | A kind of benzene sulfonamide class compound with anti-tumor activity and its preparation and application |
| CN112724083A (en) * | 2021-01-06 | 2021-04-30 | 常州工学院 | Method for synthesizing secondary sulfonamide compound from benzamide compound and direct ortho-amine and application |
| CN113234015A (en) * | 2021-05-19 | 2021-08-10 | 广东医科大学 | 3-acyl dihydroquinoline derivative and preparation method and application thereof |
| CN114315708A (en) * | 2022-02-07 | 2022-04-12 | 广东湛江海洋医药研究院 | Preparation method of 2-sulfamide pyridine derivative |
| CN115197135A (en) * | 2022-08-30 | 2022-10-18 | 鲁东大学 | Method for preparing polysubstituted quinoline compound by zinc catalysis |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104892599A (en) * | 2015-05-26 | 2015-09-09 | 华南理工大学 | Preparation method of imidazopyridine compound |
| CN106146447A (en) * | 2016-07-18 | 2016-11-23 | 上海应用技术学院 | A kind of method preparing 4 amido imide coumarin derivatives |
-
2017
- 2017-03-13 CN CN201710146395.XA patent/CN106866528A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104892599A (en) * | 2015-05-26 | 2015-09-09 | 华南理工大学 | Preparation method of imidazopyridine compound |
| CN106146447A (en) * | 2016-07-18 | 2016-11-23 | 上海应用技术学院 | A kind of method preparing 4 amido imide coumarin derivatives |
Non-Patent Citations (3)
| Title |
|---|
| FENGPING YI ET AL.: "An Efficient One-Pot Protocol for the Synthesis of Polysubstituted 4-Amino-iminocoumarins and 4-Aminoquinolines by a Copper-Catalyzed Three-Component Reaction", 《EUR. J. ORG. CHEM.》 * |
| SATOSHI UEDA ET AL.: "Facile Synthesis of 1,2,4-Triazoles via a Copper-Catalyzed Tandem Addition-Oxidative Cyclization", 《J.AM.CHEM.SOC.》 * |
| SUN-LIANG CUI ET AL.: "Novel and Efficient Synthesis of Iminocoumarins via Copper-Catalyzed Multicomponent Reaction", 《ORGANIC LETTERS》 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108658943A (en) * | 2018-06-08 | 2018-10-16 | 浙江树人学院 | A kind of benzene sulfonamide class compound with anti-tumor activity and its preparation and application |
| CN108658943B (en) * | 2018-06-08 | 2021-04-30 | 浙江树人学院 | Phenyl sulfonamide compound with anti-tumor activity and preparation and application thereof |
| CN112724083A (en) * | 2021-01-06 | 2021-04-30 | 常州工学院 | Method for synthesizing secondary sulfonamide compound from benzamide compound and direct ortho-amine and application |
| CN112724083B (en) * | 2021-01-06 | 2022-09-02 | 常州工学院 | Method for synthesizing secondary sulfonamide compound from benzamide compound and direct ortho-amine and application |
| CN113234015A (en) * | 2021-05-19 | 2021-08-10 | 广东医科大学 | 3-acyl dihydroquinoline derivative and preparation method and application thereof |
| CN113234015B (en) * | 2021-05-19 | 2022-02-18 | 广东医科大学 | 3-acyl dihydroquinoline derivative and preparation method and application thereof |
| CN114315708A (en) * | 2022-02-07 | 2022-04-12 | 广东湛江海洋医药研究院 | Preparation method of 2-sulfamide pyridine derivative |
| CN114315708B (en) * | 2022-02-07 | 2023-02-17 | 广东湛江海洋医药研究院 | Preparation method of 2-sulfamide pyridine derivative |
| CN115197135A (en) * | 2022-08-30 | 2022-10-18 | 鲁东大学 | Method for preparing polysubstituted quinoline compound by zinc catalysis |
| CN115197135B (en) * | 2022-08-30 | 2023-09-19 | 鲁东大学 | Method for preparing polysubstituted quinoline compound by zinc catalysis |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106866528A (en) | A kind of method for preparing 4 amino quinoline derivatives | |
| Cao et al. | Manganese (iii)-mediated direct C sp2–H radical trifluoromethylation of coumarins with sodium trifluoromethanesulfinate | |
| CN108314658B (en) | A kind of preparation method of polysubstituted oxazole derivatives | |
| CN105801575A (en) | Synthetic method of imidazo[1,2-a]pyridine | |
| CN104262213A (en) | Method for synthesizing alpha-aryl-beta-sulfonyl amide | |
| CN106146447B (en) | A method of preparing 4- amido imide coumarin derivative | |
| CN101346373A (en) | 2,2',6,6'-four oxazolines biphenyl ligand and preparation method thereof | |
| CN111704575B (en) | Synthesis method of quinoline-2-thiocarboxamide compound under conditions of no catalyst and no additive | |
| CN112592352A (en) | Polysubstituted benzothienopyridine compound and preparation method thereof | |
| CN106883229B (en) | A kind of preparation method of 3- hydroxy imidazoles simultaneously [1,2-a] pyridine derivate | |
| CN110156710A (en) | A kind of polysubstituted preparation method for disliking azole compounds | |
| Yin et al. | Assembly of N, N-disubstituted-N′-arylureas via a copper-catalyzed one-pot three-component reaction of aryl bromides, potassium cyanate, and secondary amines | |
| CN108299384A (en) | Trifluoromethylthio transfering reagent compound and its synthetic method | |
| CN109265409B (en) | Synthesis method of 2-substituted benzoxazole, 2-substituted benzothiazole and derivatives thereof | |
| CN109265403B (en) | Synthesis method of benzimidazole and derivatives thereof | |
| CN110963981B (en) | Benzothiazole aryl compound derivatives and preparation method thereof | |
| CN106316871A (en) | Chiral beta 2-amino acid derivative and preparing method thereof | |
| CN106543040B (en) | A kind of synthetic method of medicine intermediate carbamate compounds | |
| CN102827080B (en) | Novel synthetic method of ivabradine and novel intermediate product of ivabradine | |
| CN104860880A (en) | Method for synthesizing 8-(nitro methyl) quinoline compounds | |
| CN106146417B (en) | A method of 4- aryl-NH-1,2,3- triazole is prepared using aldehyde sodium bisulfite adduct | |
| CN104860881A (en) | Methods for synthesizing 8-(nitro methyl) quinoline compounds and 8-methylamino tetrahydroquinoline compounds | |
| CN104059075A (en) | 8, 9-mono and/or di-substituted imidazo[1, 2-c]quinazolin-3(2H)-one fused heterocyclic compound and preparation method thereof | |
| CN109535061A (en) | A kind of 3- nitroso-indol derivative and preparation method thereof | |
| CN109438349A (en) | 6- (alpha-cyano imines) base phenanthridines class compound and its synthetic method |
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 | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20170620 |