CN110105276A - A kind of 2- quinolinone compounds and preparation method thereof - Google Patents
A kind of 2- quinolinone compounds and preparation method thereof Download PDFInfo
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- CN110105276A CN110105276A CN201910547106.6A CN201910547106A CN110105276A CN 110105276 A CN110105276 A CN 110105276A CN 201910547106 A CN201910547106 A CN 201910547106A CN 110105276 A CN110105276 A CN 110105276A
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- dihydroquinoline
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- 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
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Abstract
A kind of 2- quinolinone compounds and preparation method thereof, the structural formula of the 2- quinolinone compounds are as follows:R1For substituted-phenyl, heterocycle or benzyl；R2For methyl or hydrogen.The present invention is using β-ketones with Enamino-esters and malonic acid as raw material, under the action of acetic anhydride, passes through the multifarious quinolinones compound of mixed anhydride method synthetic molecules.Synthetic method has many advantages, such as that raw material is simple and easy to get, reaction condition is mild, regioselectivity is high, target product yield is high, is advantageously implemented industrialized production.
Description
Technical field
The invention belongs to technical field of organic chemistry, and in particular to a kind of quinoline ketone derivative and preparation method thereof.
Background technique
Quinolinone and its derivative are important one of nitrogen-containing heterocycle compound, many natural products and pharmaceutical activity molecule
All contain quinolinone structural unit.In all quinolinone compounds, 2- quinolinones compound is special due to its special structure
Sign, acts not only as the polycyclic nitrogen heterocyclic of building block building molecular diversity, and shows extensive biology
Activity, including antibacterial, antitumor, anti-malarial, antiviral, AntiHIV1 RT activity, calmness, desinsection, anti-arrhythmia etc., treatment of cancer, Ah
Wurz sea write from memory disease, atherosclerosis, cardiovascular disease treatment in have important application.
2- quinolinone compounds according to the present invention are because it contains unique enol and potential 1,3- dicarbapentaborane piece
Section, can design and construct fused heterocyclic compound by cyclization reaction with other organic substrates.It is folded according to the activity in pharmaceutical chemistry
Add principle, when compound contains more activity factors, it is active a possibility that it is bigger.Therefore, design synthesizes in this way
Quinolinone building block of the one kind containing multiple reactivity sites, will promote development the new synthesis based on quinolinone for substrate
Methodology and building multi-ring heterocyclic compound library, facilitate the new lead compound based on quinolinone parent nucleus of discovery.The present invention
Related 2- quinolinone compounds design feature is as follows:
Compound involved in the present invention, has enol segment and 1, and 3- dicarbapentaborane segment can be designed and be tried with parents' electricity
Agent reaction, introduces furan nucleus, realizes the expansion of ring skeleton；Or active methylene group based on its keto-acid product and carbonyl is anti-
It answers, constructs other five yuan or hexa-atomic polycyclic nitrogen heterocyclics.
Summary of the invention
The purpose of the present invention is to provide a kind of 2- quinolinone compounds, which has potential source biomolecule activity, and makees
For an organic synthesis intermediate containing more active sites, it is active thick with potential source biomolecule to can be used for synthetic molecules diversity
Heterocyclic compound；2- quinoline is prepared based on the mixed anhydride method that β-ketones with Enamino-esters and malonic acid are substrate the present invention also provides a kind of
The method of ketone compound.
The purpose of the present invention is achieved through the following technical solutions:
A kind of 2- quinolinone compounds, structural formula are formula (1):
In formula (1), R1For substituted-phenyl, heterocycle or benzyl；R2For methyl or hydrogen；
The substituted-phenyl is monosubstituted or disubstituted halogen, nitro, hydrogen, C1-C2 alkane o-, m-, to three sites
Base, C1-C2 alkoxy；The heterocycle is unsubstituted furyl, thienyl and indyl.
As the further improvement of quinolinone compounds of the invention, the 2- quinolinone compounds are following any one
It is a:
1) -2,5 (1H, 6H)-diketone of 4- hydroxyl -1- (nitrobenzophenone) -7,8- dihydroquinoline
2) -2,5 (1H, 6H)-diketone of 1- (4- fluoro-phenyl) -4- hydroxyl -7,8- dihydroquinoline
3) -2,5 (1H, 6H)-diketone of 1- (the chloro- phenyl of 4-) -4- hydroxyl -7,8- dihydroquinoline
4) -2,5 (1H, 6H)-diketone of 1- (the bromo- phenyl of 4-) -4- hydroxyl -7,8- dihydroquinoline
5) -2,5 (1H, 6H)-diketone of 4- hydroxyl -1- phenyl -7,8- dihydroquinoline
6) 4- hydroxyl -1- (4- tolyl) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
7) 4- hydroxyl -1- (4- anisyl) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
8) -2,5 (1H, 6H)-diketone of 1- (2- fluoro-phenyl) -4- hydroxyl -7,8- dihydroquinoline
9) -2,5 (1H, 6H)-diketone of 1- (3- fluoro-phenyl) -4- hydroxyl -7,8- dihydroquinoline
10) -2,5 (1H, 6H)-diketone of 1- (the chloro- phenyl of 3-) -4- hydroxyl -7,8- dihydroquinoline
11) -2,5 (1H, 6H)-diketone of 1- (the chloro- phenyl of 2-) -4- hydroxyl -7,8- dihydroquinoline
12) -2,5 (1H, 6H)-diketone of 1- (the bromo- phenyl of 3-) -4- hydroxyl -7,8- dihydroquinoline
13) 4- hydroxyl -1- (3- tolyl) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
14) -2,5 (1H, 6H)-diketone of 1- (the chloro- 5- tolyl of 3-) -4- hydroxyl -7,8- dihydroquinoline
15) -2,5 (1H, 6H)-diketone of 1- (furans -2- base) -4- hydroxyl -7,8- dihydroquinoline
16) 4- hydroxyl -1- (thiophene -2- base) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
17) 4- hydroxyl -1- (1H- indol-3-yl) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
18) -2,5 (1H, 6H)-diketone of 1- benzyl -4- hydroxyl -7,8- dihydroquinoline
19) 4- hydroxyl -7,7- dimethyl -1- (4- nitrobenzophenone) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
20) -2,5 (1H, 6H)-diketone of 1- (4- fluorophenyl) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
21) -2,5 (1H, 6H)-diketone of 1- (4- chlorphenyl) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
22) -2,5 (1H, 6H)-diketone of 1- (4- bromophenyl) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
23) -2,5 (1H, 6H)-diketone of 4- hydroxyl -7,7- dimethyl -1- phenyl -7,8- dihydroquinoline
24) 4- hydroxyl -7,7- dimethyl -1- (4- tolyl) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
25) -2,5 (1H, 6H)-diketone of 4- hydroxyl -1- (4- anisyl) -7,7- dimethyl -7,8- dihydroquinoline
26) -2,5 (1H, 6H)-diketone of 1- (2- fluorophenyl) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
27) -2,5 (1H, 6H)-diketone of 1- (3- fluorophenyl) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
28) -2,5 (1H, 6H)-diketone of 1- (3- chlorphenyl) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
29) -2,5 (1H, 6H)-diketone of 1- (3- bromophenyl) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
30) 4- hydroxyl -7,7- dimethyl -1- (3- tolyl) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
31) -2,5 (1H, 6H)-diketone of 1- (the chloro- 5- tolyl of 2-) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
32) -2,5 (1H, 6H)-diketone of 1- (furans -2- base) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
33) 4- hydroxyl -7,7- dimethyl -1- (thiophene -2- base) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
34) -2,5 (1H, 6H)-diketone of 4- hydroxyl -1- (1H- indol-3-yl) -7,7- dimethyl -7,8- dihydroquinoline
35) -2,5 (1H, 6H)-diketone of 1- benzyl -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
The preparation method of 2- quinolinone compounds of the present invention, reaction equation are as follows:
Preparation method is to take β-ketones with Enamino-esters 1 and malonic acid 2 to be dissolved in acetic anhydride at 50 DEG C, thin-layer chromatography monitoring reaction
After the completion, saturated sodium bicarbonate solution neutralization reaction liquid is added；Reaction solution, dry concentration organic phase, silicon is extracted with ethyl acetate
Plastic column chromatography obtains 2- quinolinone compounds (1).
The present invention is using β-ketones with Enamino-esters and malonic acid as raw material, under the action of acetic anhydride, passes through mixed anhydride method synthesis point
The multifarious quinolinones compound of son.Synthetic method have raw material is simple and easy to get, reaction condition is mild, regioselectivity is high,
The advantages that target product yield is high, easy to operate, and regioselectivity is high, is advantageously implemented industrialized production.Synthesized 2- quinoline
Quinoline ketone compound has potential good biological activity, and contains enol and potential 1,3- dicarbapentaborane segment in molecular structure, can
Fused heterocyclic compound as organic synthesis building block building molecular diversity.
The present invention provides method for the first time to construct quinolinone compounds based on malonic acid and electron deficient enamine, realizes one
The synthesis of the novel 2- quinolinone compounds of class skeleton, such compound in medicament research and development or organic synthesis regardless of all having
It is very strong can be applied.
Specific embodiment
Further illustrate how the present invention realizes below by way of specific embodiment.
The structure of 2- quinolinone compounds of the present invention is formula (1):
In formula (1), R1 is substituted-phenyl, heterocycle or benzyl；R2For methyl or hydrogen；The substituted-phenyl be it is o-, m-,
To monosubstituted or disubstituted halogen, nitro, hydrogen, C1-C2 alkyl, C1-the C2 alkoxy in three sites；The heterocycle is
Unsubstituted furyl, thienyl and indyl.
The quinolinone compounds be it is following any one:
1) -2,5 (1H, 6H)-diketone of 4- hydroxyl -1- (nitrobenzophenone) -7,8- dihydroquinoline
2) -2,5 (1H, 6H)-diketone of 1- (4- fluoro-phenyl) -4- hydroxyl -7,8- dihydroquinoline
3) -2,5 (1H, 6H)-diketone of 1- (the chloro- phenyl of 4-) -4- hydroxyl -7,8- dihydroquinoline
4) -2,5 (1H, 6H)-diketone of 1- (the bromo- phenyl of 4-) -4- hydroxyl -7,8- dihydroquinoline
5) -2,5 (1H, 6H)-diketone of 4- hydroxyl -1- phenyl -7,8- dihydroquinoline
6) 4- hydroxyl -1- (4- tolyl) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
7) 4- hydroxyl -1- (4- anisyl) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
8) -2,5 (1H, 6H)-diketone of 1- (2- fluoro-phenyl) -4- hydroxyl -7,8- dihydroquinoline
9) -2,5 (1H, 6H)-diketone of 1- (3- fluoro-phenyl) -4- hydroxyl -7,8- dihydroquinoline
10) -2,5 (1H, 6H)-diketone of 1- (the chloro- phenyl of 3-) -4- hydroxyl -7,8- dihydroquinoline
11) -2,5 (1H, 6H)-diketone of 1- (the chloro- phenyl of 2-) -4- hydroxyl -7,8- dihydroquinoline
12) -2,5 (1H, 6H)-diketone of 1- (the bromo- phenyl of 3-) -4- hydroxyl -7,8- dihydroquinoline
13) 4- hydroxyl -1- (3- tolyl) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
14) -2,5 (1H, 6H)-diketone of 1- (the chloro- 5- tolyl of 3-) -4- hydroxyl -7,8- dihydroquinoline
15) -2,5 (1H, 6H)-diketone of 1- (furans -2- base) -4- hydroxyl -7,8- dihydroquinoline
16) 4- hydroxyl -1- (thiophene -2- base) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
17) 4- hydroxyl -1- (1H- indol-3-yl) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
18) -2,5 (1H, 6H)-diketone of 1- benzyl -4- hydroxyl -7,8- dihydroquinoline
19) 4- hydroxyl -7,7- dimethyl -1- (4- nitrobenzophenone) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
20) -2,5 (1H, 6H)-diketone of 1- (4- fluorophenyl) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
21) -2,5 (1H, 6H)-diketone of 1- (4- chlorphenyl) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
22) -2,5 (1H, 6H)-diketone of 1- (4- bromophenyl) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
23) -2,5 (1H, 6H)-diketone of 4- hydroxyl -7,7- dimethyl -1- phenyl -7,8- dihydroquinoline
24) 4- hydroxyl -7,7- dimethyl -1- (4- tolyl) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
25) -2,5 (1H, 6H)-diketone of 4- hydroxyl -1- (4- anisyl) -7,7- dimethyl -7,8- dihydroquinoline
26) -2,5 (1H, 6H)-diketone of 1- (2- fluorophenyl) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
27) -2,5 (1H, 6H)-diketone of 1- (3- fluorophenyl) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
28) -2,5 (1H, 6H)-diketone of 1- (3- chlorphenyl) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
29) -2,5 (1H, 6H)-diketone of 1- (3- bromophenyl) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
30) 4- hydroxyl -7,7- dimethyl -1- (3- tolyl) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
31) -2,5 (1H, 6H)-diketone of 1- (the chloro- 5- tolyl of 2-) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
32) -2,5 (1H, 6H)-diketone of 1- (furans -2- base) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
33) 4- hydroxyl -7,7- dimethyl -1- (thiophene -2- base) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
34) -2,5 (1H, 6H)-diketone of 4- hydroxyl -1- (1H- indol-3-yl) -7,7- dimethyl -7,8- dihydroquinoline
35) -2,5 (1H, 6H)-diketone of 1- benzyl -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
The reaction equation for preparing 2- quinolinone compounds of the present invention is as follows:
Preparation method is to take β-ketones with Enamino-esters 1 and malonic acid 2 in above formula to be dissolved in acetic anhydride, thin-layer chromatography at 50 DEG C
After the reaction was completed, saturated sodium bicarbonate solution neutralization reaction liquid is added in monitoring；Reaction solution is extracted with ethyl acetate, dry concentration has
Machine phase, silica gel column chromatography obtain quinolinone compounds (1).
The synthetic method of several 2- quinolinone compounds is illustrated in detail below.
The synthesis of -2,5 (1H, 6H)-diketone of embodiment 1:1- (the bromo- phenyl of 3-) -4- hydroxyl -7,8- dihydroquinoline:
By 3- ((3- bromophenyl) amino) cyclohexyl -2- ketenes 0.265g (1.0mmol) and malonic acid 0.104g
(1.0mmol) is added in reaction flask, 10mL acetic anhydride is added portionwise under stirring, heating reflux reaction 1 hour, end of reaction was used
Reaction solution is modulated alkalinity by saturated solution of sodium bicarbonate, and ethyl acetate extraction, organic phase is dry, is concentrated under reduced pressure, and concentrate passes through
Column chromatographs (petroleum ether: ethyl acetate=1:1), obtains white solid 1- (the bromo- phenyl of 3-) -4- hydroxyl -7,8- dihydroquinoline -2,
The synthesis 0.243g of 5 (1H, 6H)-diketone, yield 80%；1H NMR(400MHz,CDCl3): δ=12.46 (s, 1H, OH),
7.63-7.66 (m, 1H, ArH), 7.43 (d, J=8.0Hz, 1H, ArH), 7.37-7.39 (m, 1H, ArH), 7.14-7.17 (m,
1H, ArH), 5.88 (s, 1H, C=CH2),2.58-2.62(m,2H,CH2),2.47-2.52(m,2H,CH2),2.02-2.06(m,
2H,CH2)；13C NMR(100MHz,CDCl3): δ=201.3,167.6,164.0,161.5,158.7,133.0,129.8,
117.2,105.0,97.7,77.4,77.1,76.8,49.9,42.7,32.5,28.0；HRMS(ESI-TOF):m/z calcd
for C15H13BrNO3[(M+H)+],334.0073；found,334.0073.
The synthesis of embodiment 2:4- hydroxyl -1- (3- tolyl) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone:
3- ((3- bromophenyl) amino) cyclohexyl -2- ketenes is replaced with 3- (3- tolyl) cyclohexyl -2- ketenes, remaining is same
Embodiment 1 (proportion is according to molar ratio between raw material), yield: 81%；1H NMR(400MHz,CDCl3): δ=12.40 (s, 1H,
), OH 7.35 (t, J=8.0Hz, 1H, ArH), 7.22 (t, J=8.0Hz, 1H, ArH), 6.90-6.92 (m, 2H, ArH), 5.82
(s, 1H, C=CH2), 2.43 (d, J=4.0Hz, 1H, ArH), 2.49-2.53 (m, 2H, CH2),2.35-2.42(m,2H,CH2),
2.34(s,3H,CH3),1.91-1.98(m,2H,CH2)；13C NMR(100MHz,CDCl3): δ=200.5,166.6,162.9,
159.1,139.3,129.3,128.8,127.2,123.7,104.8,96.9,28.2,20.4,19.7；HRMS(ESI-TOF):
m/z calcd for C16H16NO3[(M+H)+],270.1125；found,270.1125.
- 2,5 (1H, 6H)-diketone of embodiment 3:1- (4- fluorophenyl) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
Synthesis:
3- ((3- bromophenyl) ammonia is replaced with 3- ((4- fluorophenyl) amino) cyclohexyl -5,5- Dimethylcyclohexyl -2- ketenes
Base) cyclohexyl -2- ketenes, remaining is the same as embodiment 1 (proportion is according to molar ratio between raw material), yield: 78%；1H NMR
(400MHz,CDCl3): δ=12.42 (s, 1H, OH), 7.22-7.28 (m, 2H, ArH), 7.13-7.16 (m, 2H, ArH), 5.87
(s, 1H, C=CH2),2.45(s,2H,CH2),2.33(s,2H,CH2),1.05(s,6H,CH3)；13C NMR(100MHZ,
CDCl3): δ=201.2,167.6,164.5,163.7,162.0,138.5,138.4,131.5,131.4,12 3.9,117.0,
116.7,115.9,105.0,97.8,50.0,42.6,32.6,28.1 28.0；HRMS(ESI-TOF):m/z calcd for
C17H17FNO3[(M+H)+],302.1187；found,302.1188.
- 2,5 (1H, 6H)-diketone of embodiment 4:1- (3- fluorophenyl) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
Synthesis:
3- ((3- bromophenyl) ammonia is replaced with 3- ((3- fluorophenyl) amino) cyclohexyl -5,5- Dimethylcyclohexyl -2- ketenes
Base) cyclohexyl -2- ketenes, remaining is the same as embodiment 1 (proportion is according to molar ratio between raw material), yield: 78%；1H NMR
(400MHz,CDCl3): δ=12.41 (s, 1H, OH), 7.51-7.57 (m, 1H, ArH), 7.21-7.27 (m, 1H, ArH),
6.91-6.99 (m, 2H, ArH), 5.88 (s, 1H, C=CH2),2.46(s,2H,CH2),2.34(s,2H,CH2),1.05(s,6H,
CH3)；13C NMR(100MHZ,CDCl3): δ=201.2,167.6,164.5,163.7,162.0,158.3,138.5,131.5,
123.9,117.0,116.8,115.9,115.7,105.0,97.8,50.0,42.6,32.6,28.1,28.0；HRMS(ESI-
TOF):m/z calcd for C17H17FNO3[(M+H)+],302.1187；found,302.1187.
Embodiment 5:4- hydroxyl -7,7- dimethyl -1- (3- tolyl) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
Synthesis:
3- ((3- bromophenyl) amino) cyclohexyl-is replaced with 5,5- dimethyl -3- (methylamino)-cyclohexyl -2- ketenes
2- ketenes, remaining is the same as embodiment 1 (proportion is according to molar ratio between raw material), yield: 83%；1H NMR(400MHz,CDCl3):δ
=12.40 (s, 1H, OH), 7.41-7.45 (m, 1H, ArH), 7.32 (d, J=8.0Hz, 1H, ArH), 6.94 (d, J=8.0Hz,
2H, ArH), 5.87 (s, 1H, C=CH2),2.44(s,2H,CH2),2.42(s,2H,CH3),2.34(s,2H,CH2),1.04(s,
6H,CH3)；13C NMR(100MHZ,CDCl3): δ=201.2,167.4,164.1,158.3,140.3,137.1,130.3,
129.9,128.2,124.7,104.7,97.7,50.0,42.6,32.5,27.9,21.4；HRMS(ESI-TOF):m/z calcd
for C18H20NO3[(M+H)+],298.1438；found,298.1438.
Claims (3)
1. a kind of 2- quinolinone compounds, which is characterized in that the structure of the 2- quinolinone compounds is that formula (1) is as follows:
In formula (1), R1For substituted-phenyl, heterocycle or benzyl；R2For methyl or hydrogen；The substituted-phenyl be it is o-, m-, to three
Monosubstituted or disubstituted halogen, nitro, hydrogen, C1-C2 alkyl, C1-the C2 alkoxy in a site；The heterocycle is not take
Furyl, thienyl and the indyl in generation.
2. 2- quinolinone compounds according to claim 1, which is characterized in that the 2- quinolinone compounds are following
Meaning one:
1) -2,5 (1H, 6H)-diketone of 4- hydroxyl -1- (nitrobenzophenone) -7,8- dihydroquinoline
2) -2,5 (1H, 6H)-diketone of 1- (4- fluoro-phenyl) -4- hydroxyl -7,8- dihydroquinoline
3) -2,5 (1H, 6H)-diketone of 1- (the chloro- phenyl of 4-) -4- hydroxyl -7,8- dihydroquinoline
4) -2,5 (1H, 6H)-diketone of 1- (the bromo- phenyl of 4-) -4- hydroxyl -7,8- dihydroquinoline
5) -2,5 (1H, 6H)-diketone of 4- hydroxyl -1- phenyl -7,8- dihydroquinoline
6) 4- hydroxyl -1- (4- tolyl) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
7) 4- hydroxyl -1- (4- anisyl) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
8) -2,5 (1H, 6H)-diketone of 1- (2- fluoro-phenyl) -4- hydroxyl -7,8- dihydroquinoline
9) -2,5 (1H, 6H)-diketone of 1- (3- fluoro-phenyl) -4- hydroxyl -7,8- dihydroquinoline
10) -2,5 (1H, 6H)-diketone of 1- (the chloro- phenyl of 3-) -4- hydroxyl -7,8- dihydroquinoline
11) -2,5 (1H, 6H)-diketone of 1- (the chloro- phenyl of 2-) -4- hydroxyl -7,8- dihydroquinoline
12) -2,5 (1H, 6H)-diketone of 1- (the bromo- phenyl of 3-) -4- hydroxyl -7,8- dihydroquinoline
13) 4- hydroxyl -1- (3- tolyl) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
14) -2,5 (1H, 6H)-diketone of 1- (the chloro- 5- tolyl of 3-) -4- hydroxyl -7,8- dihydroquinoline
15) -2,5 (1H, 6H)-diketone of 1- (furans -2- base) -4- hydroxyl -7,8- dihydroquinoline
16) 4- hydroxyl -1- (thiophene -2- base) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
17) 4- hydroxyl -1- (1H- indol-3-yl) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
18) -2,5 (1H, 6H)-diketone of 1- benzyl -4- hydroxyl -7,8- dihydroquinoline
19) 4- hydroxyl -7,7- dimethyl -1- (4- nitrobenzophenone) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
20) -2,5 (1H, 6H)-diketone of 1- (4- fluorophenyl) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
21) -2,5 (1H, 6H)-diketone of 1- (4- chlorphenyl) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
22) -2,5 (1H, 6H)-diketone of 1- (4- bromophenyl) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
23) -2,5 (1H, 6H)-diketone of 4- hydroxyl -7,7- dimethyl -1- phenyl -7,8- dihydroquinoline
24) 4- hydroxyl -7,7- dimethyl -1- (4- tolyl) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
25) -2,5 (1H, 6H)-diketone of 4- hydroxyl -1- (4- anisyl) -7,7- dimethyl -7,8- dihydroquinoline
26) -2,5 (1H, 6H)-diketone of 1- (2- fluorophenyl) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
27) -2,5 (1H, 6H)-diketone of 1- (3- fluorophenyl) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
28) -2,5 (1H, 6H)-diketone of 1- (3- chlorphenyl) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
29) -2,5 (1H, 6H)-diketone of 1- (3- bromophenyl) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
30) 4- hydroxyl -7,7- dimethyl -1- (3- tolyl) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
31) -2,5 (1H, 6H)-diketone of 1- (the chloro- 5- tolyl of 2-) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
32) -2,5 (1H, 6H)-diketone of 1- (furans -2- base) -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
33) 4- hydroxyl -7,7- dimethyl -1- (thiophene -2- base) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone
34) -2,5 (1H, 6H)-diketone of 4- hydroxyl -1- (1H- indol-3-yl) -7,7- dimethyl -7,8- dihydroquinoline
35) -2,5 (1H, 6H)-diketone of 1- benzyl -4- hydroxyl -7,7- dimethyl -7,8- dihydroquinoline
3. the preparation method of 2- quinolinone compounds as claimed in claim 1 or 2, which is characterized in that preparation 2- quinolinones
The reaction equation of compound is as follows:
Preparation method is to take β-ketones with Enamino-esters 1 and malonic acid 2 to be dissolved in acetic anhydride at 50 DEG C, and thin-layer chromatography monitoring reaction is completed
Afterwards, saturated sodium bicarbonate solution neutralization reaction liquid is added；Reaction solution, dry concentration organic phase, silicagel column is extracted with ethyl acetate
Chromatography obtains the 2- quinolinone compounds (1).
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