CN109651247A - A kind of green high-efficient synthetic method of carbostyril compound - Google Patents

A kind of green high-efficient synthetic method of carbostyril compound Download PDF

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CN109651247A
CN109651247A CN201811565999.9A CN201811565999A CN109651247A CN 109651247 A CN109651247 A CN 109651247A CN 201811565999 A CN201811565999 A CN 201811565999A CN 109651247 A CN109651247 A CN 109651247A
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黄超
白海瑞
袁明龙
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Yunnan Minzu University
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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
    • C07D215/233—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 4
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
    • C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
    • C07D221/04—Ortho- or peri-condensed ring systems
    • C07D221/06—Ring systems of three rings
    • C07D221/10—Aza-phenanthrenes
    • 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

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  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

The invention discloses a kind of green high-efficient synthetic methods of carbostyril compound.Method is as follows: step 1, and dicarbonyl compound, triethyl orthoformate react to obtain enamine ester intermediate under solvent-free and catalysts conditions with three component raw material of amino benzenes compounds；Step 2, the enamine ester intermediate issue raw intramolecular cyclisation in the effect of cyclization reagent diphenyl ether again and obtain quinolone female ring compound, and the purity of product is up to 98.8% or more.Synthetic method beneficial effect of the present invention is mainly reflected in: efficiently, no catalyst solvent use avoids the three wastes from generating high income to the reaction of 1. step 1；2. step 2 process green, cyclization reagent can recycle reuse；3. simple process, step 1 and two can carry out in same reactor, and reaction terminates filtering and obtains quinolone compounds.

Description

A kind of green high-efficient synthetic method of carbostyril compound
Technical field
The invention belongs to chemical technology fields, and in particular to a kind of method of efficient green synthesis carbostyril compound.
Background technique
Carbostyril compound is by it with antimitotic, anticancer, antimalarial, antibacterial, antiviral, anti-diabetic, AntiHIV1 RT activity It can be used as the nucleus module of a variety of drugs with bioactivity such as anti-inflammatories.For example, it is to be used as clinical treatment drug to have sand Draw Sha Xing, Norfloxacin, Pazufloxacin, An Tuosha star, Pu Lusha star, De Lasha star and angstrom for lattice Wei etc..
Quinolone drugs structure represents
Document report, industrial production quinolone medicine are based primarily upon the methods of Conrad Limpach, Gould Jacobs.Although This method provides effective route of synthesis in the past few decades for production quinolone family drug, but due to synthetic route Complicated raw material, not enough green reaction medium are needed, acid or alkali make catalyst, and long processing route is to a certain degree Above so that quinolone drugs cost remains high and is most importantly irreversible to the persecution of environment.Therefore application is opened The green syt approach that more modern synthesis model is sent out new has great importance.
Conrad Limpach reaction
Above-mentioned reaction needs to use strong acid as catalyst there are first step schiff base reaction, by-product when second step decarboxylation is coupled More, the disadvantages of product separating difficulty is big, Atom economy is poor.
Gould Jacobs reaction
Above-mentioned technique is used there are diethyl ethoxymethylenemalonate so that high production cost, whole process, which has, uses solvent Catalyst use causes three wastes discharge capacity big, and operation difficulty is high, requires the disadvantages of high to synthetic environment.
Summary of the invention
The purpose of the present invention is to provide a kind of methods of green high-efficient synthesis carbostyril compound.
The object of the present invention is achieved like this, is to be with dicarbonyl compound, triethyl orthoformate and aminated compounds Raw material, while Condensation reaction, Substitution reaction are undergone, then be prepared by Friedel-Craft reaction It arrives, reaction principle is as follows:
The method first step of efficient green synthesis carbostyril compound of the present invention is with dicarbapentaborane simple and easy to get Object, triethyl orthoformate and three component composition of aminated compounds is closed to feed intake together.Second step is tried using diphenyl ether as cyclisation Agent is heated to reflux cyclization.Except diphenyl ether can recycle and reuse reaction process without any solvent and catalysis in whole process The use of agent fundamentally solves the problems such as former route pollution is larger, operation difficulty is high.
The invention has the advantages that
1. the simple market of raw material can buy cheap；
2. three component raw materials feed intake one pot together and operate, intermediate does not need lock out operation, reaction process high-effective and labour-saving；
3. entire transition process is high-efficient, final product does not need chromatography and simply washs that neat compounds just can be obtained；
4. the reaction process of safety, post-processing does not need column separation and only needs ethyl acetate and methanol washing and eluant, eluent Can recycle can Pollution protection；
5. the reaction process of green, by-product only have ethyl alcohol, Atom economy high；
6. quinolone compounds practical value is high, the composed structure of important antibacterials.
Detailed description of the invention
Fig. 1 is No. 1 compound hydrogen nuclear magnetic resonance spectrogram spectrum in the embodiment of the present invention 1；
Fig. 2 is No. 1 compound carbon-13 nmr spectra map in the embodiment of the present invention 1；
Fig. 3 is No. 1 compound hydrogen nuclear magnetic resonance spectrogram spectrum in the embodiment of the present invention 2；
Fig. 4 is No. 1 compound carbon-13 nmr spectra map in the embodiment of the present invention 1；
Fig. 5 is No. 1 compound hydrogen nuclear magnetic resonance spectrogram spectrum in the embodiment of the present invention 3；
Fig. 6 is No. 1 compound carbon-13 nmr spectra map in the embodiment of the present invention 1；
Fig. 7 is No. 1 compound hydrogen nuclear magnetic resonance spectrogram spectrum in the embodiment of the present invention 4；
Fig. 8 is No. 1 compound carbon-13 nmr spectra map in the embodiment of the present invention 1.
Specific embodiment
Below with reference to embodiment and attached drawing, the present invention is further illustrated, but is not subject in any way to the present invention Limitation, based on present invention teach that it is made it is any transform or replace, all belong to the scope of protection of the present invention.
The method of green high-efficient synthesis carbostyril compound of the present invention, is that the invention discloses quinolones Close one pot of green synthesis method that feeds intake of object and its novel three component.Method is as follows: step 1, dicarbonyl compound, orthoformic acid Triethyl reacts to obtain enamine ester intermediate under solvent-free and catalysts conditions with three component raw material of amino benzenes compounds；Step Two, the enamine ester intermediate occurs under cyclization reagent (diphenyl ether, polyphosphoric acids, Eton reagent or sulfuric acid) effect again Intramolecular cyclisation obtains main cyclic quinoline compound, and the purity of product is up to 98.8% or more；
Its reaction principle is as follows:
The pure of quinolone compounds product is prepared in the method for efficient green synthesis carbostyril compound of the present invention Degree can reach 98.9% or more.
Object carbostyril compound general structure of the present invention are as follows:
Wherein, R1For benzene, tert-butyl, cyclopropyl, ethyoxyl；R2For hydrogen, methyl, trifluoromethyl, cyano, nitro, halogen, first The alkyl or aryls such as base, methoxyl group, tert-butyl, ethyl.
The technology path of efficient green synthesis quinolone compounds of the present invention is as follows:
Case is embodied, the present invention will be further described below:
The specification and detecting instrument of material used in the embodiment of the present invention or reagent are unless otherwise instructed commercially available.
Nuclear magnetic resonance spectrometer: Bruker Avance III 400MHz nuclear magnetic resonance spectrometer
Infrared waves spectrometer: Thermo Nicolet S10 FT-IR infrared waves spectrometer
Mass spectrograph: Agilent LC/MSD TOF instrument mass spectrometer
Melt point instalment: Beijing Tyke Tech X-5 melt point instalment
Embodiment 1
Embodiment reaction equation is as follows:
The preparation method the following steps are included:
The first step, under stirring, using ethyl benzoylacetate, triethyl orthoformate, aniline as raw material, three components put into reaction together In device, it is warming up to 130 DEG C of insulation reactions for 24 hours, continuously adds diphenyl ether reflux, stop reacting after there are a large amount of solids to be precipitated To quinolone compounds.Decompression filters, and is washed with petroleum ether, ethyl acetate and methanol washs, be dried to obtain quinolone compounds.
In embodiment aminated compounds variation be prepared carbostyril compound yield situation it is as follows:
Above compound data are as follows:
3-benzoylquinolin-4(1H)-one (1a): White solid; yield 86%; m.p. 260-262oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.47 (br s, 1H), 8.36 (s, 1H), 8.16 (dd, 1H, J = 1.32, 1.28 Hz), 7.76-7.72 (m, 3H), 7.68 (d, 1H, J = 7.12 Hz), 7.60-7.56 (m, 1H) 7.48-7.41 (m, 3H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 194.8, 174.9, 143.7, 139.9, 139.0, 132.9, 132.6, 129.5, 128.5, 127.5, 126.0, 125.0, 119.9, 119.3; IR (KBr): v max (cm-1) 3445, 2330, 1644, 1554, 1473, 1440, 1371, 1295, 1068, 857, 758, 624; HRMS (ESI-TOF+): m/z Calcd for C16H12NO2 + [(M+H)+] 250.0863; found, 250.0862.
3-benzoyl-6-fluoroquinolin-4(1H)-one (1b): White solid; yield 74%; m.p. > 300 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.61 (br s, 1H), 8.39 (s, 1H), 7.80-7.72 (m, 4H), 7.68-7.63 (m, 1H), 7.60-7.56 (m, 1H), 7.48-7.44 (m, 2H);13C NMR (100 MHz, DMSO-d 6 , ppm): δ 194.6, 174.0, 173.9, 160.7, 158.3, 143.7, 138.8, 136.6, 132.7, 129.5, 128.9, 128.8, 128.5, 122.2, 122.1, 121.7, 121.5, 119.1, 110.3, 110.1.
3-benzoyl-6-chloroquinolin-4(1H)-one (1c): White solid; yield 71%; m.p. > 300 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.64 (br s, 1H), 8.40 (s, 1H), 8.05 (d, 1H, J = 2.24 Hz), 7.79 (m, 1H), 7.72 (t, 3H, J = 8.36 Hz), 7.59 (t, 1H, J = 7.28 Hz), 7.46 (t, 2H, J = 7.60 Hz); 13C NMR (100 MHz, F3COOD, ppm): δ 201.9, 176.9, 150.0, 141.2, 140.0, 139.6, 137.0, 136.1, 131.4, 131.1, 126.3, 123.7, 123.7.
3-benzoyl-6-bromoquinolin-4(1H)-one (1d): White solid; yield 67%; m.p. > 300 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.60 (br s, 1H), 8.39 (d, 1H, J = 5.32 Hz), 8.19 (s, 1H), 7.91 (d, 1H, J = 8.68 Hz), 7.74-7.44 (m, 6H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 194.5, 173.6, 143.9, 138.9, 138.6, 135.6, 132.8, 129.5, 128.9, 128.5, 128.1, 121.9, 120.2, 117.7.
3-benzoyl-6-iodoquinolin-4(1H)-one (1e): Pale yellow solid; m.p. >300 oC; yield 66%; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.53 (br s, 1H), 8.39 (dd, 2H, J = 2.00, 4.88 Hz), 8.03 (dd, 1H, J = 2.04, 2.04 Hz), 7.71 (t, 2H, J = 7.04 Hz), 7.59-7.56 (m, 1H), 7.49-7.43 (m, 3H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 194.5, 173.4, 143.9, 141.0, 139.2, 138.6, 134.4, 132.8, 129.5, 129.1, 128.5, 121.7, 120.4, 89.8.
3-benzoyl-6-nitroquinolin-4(1H)-one (1f): Brown solid; yield 82%; m.p. 235-238 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ12.90 (br d, 1H, J = 4.00 Hz), 8.85 (d, 1H, J = 2.64 Hz), 8.52 (dd, 1H, J = 2.68, 2.72 Hz), 8.47 (s, 1H), 7.86 (d, 1H, J = 9.12 Hz), 7.78-7.76 (m, 2H), 7.64-7.59 (m, 1H), 7.50-7.46 (m, 2H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ194.0, 174.4, 144.6, 144.0, 143.8, 138.2, 133.1, 129.6, 128.6, 127.0, 126.7, 122.3, 121.3, 121.2; IR (KBr): v max (cm-1) 3444, 2338, 1662, 1585, 1510, 1474. 1345, 1203, 1080, 905, 843, 746, 563; HRMS (ESI-TOF+): m/z Calcd for C16H11N2O4 + [(M+H)+] 295.0713; found, 295.0716.
3-benzoyl-6-(trifluoromethyl)quinolin-4(1H)-one (1g): White solid; yield 78%; m.p. >300 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.75 (br s, 1H), 8.45 (s, 1H), 8.37 (d, 1H, J = 1.04 Hz), 8.05 (dd, 1H, J = 2.08, 2.08 Hz), 7.87 (d, 1H, J = 8.68 Hz), 7.77-7.74 (m, 2H), 7.61-7.57 (m, 1H), 7.48-7.44(m, 2H);13C NMR (100 MHz, DMSO-d 6 , ppm): δ 194.3, 174.3, 144.5, 142.2, 138.4, 132.9, 129.6, 128.9, 128.6, 126.8, 123.5, 123.4, 121.0; IR (KBr): v max (cm-1) 3446, 1645, 1584, 1526, 1444, 1368, 1332, 1294, 1254, 1112, 1008, 842, 783, 699; HRMS (ESI-TOF+): m/z Calcd for C17H11F3NO2 + [(M+H)+] 318.0736; found, 318.0739.
6-acetyl-3-benzoylquinolin-4(1H)-one (1h): Pale-brown solid; yield 80%; m.p. >300 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ12.67 (br s, 1H), 8.68 (d, 1H,J = 1.92 Hz), 8.40 (s, 1H), 8.24 (dd, 1H, J = 2.00, 2.00 Hz), 7.76-7.72 (m, 3H), 7.61-7.57 (m, 1H), 7.47 (t, 2H, J = 15.2 Hz), 2.65 (s, 3H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 197.2, 194.5, 174.9, 144.1, 142.8, 138.5, 133.0, 132.9, 131.5, 129.5, 128.6, 127.4, 126.7, 121.0, 119.8, 27.1; IR (KBr): v max (cm-1) 3445, 2360, 1675, 1644, 1521, 1359, 1294, 1069, 1008, 854, 780, 696; HRMS (ESI-TOF+): m/z Calcd for C18H14NO3 + [(M+H)+] 292.0968; found, 292.0969.
3-benzoyl-6-methylquinolin-4(1H)-one (1i): White solid; yield 64%; m.p. > 300 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.37 (br s, 1H), 8.29 (s, 1H), 7.91 (d, 1H, J = 0.76Hz), 7.72-7.70 (m, 2H), 7.58-7.54 (m, 3H), 7.46-7.42 (m, 2H), 2.42 (s, 3H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 194.9, 174.7, 143.2, 138.9, 137.8, 134.5, 134.2, 132.6, 129.5, 128.4, 127.4, 125.3, 119.6, 119.2, 21.2.
3-benzoyl-6-ethylquinolin-4(1H)-one (1j): White solid; yield 56%; m.p. 282-284 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ12.40 (br s, 1H), 8.30 (s, 1H), 7.93 (d, 1H, J = 0.84 Hz), 7.73-7.70 (m, 2H), 7.62-7.54 (m, 3H), 7.46-7.42 (m, 2H), 2.75 (dd, 2H, J = 7.52, 7.56 Hz), 1.22 (t, 3H, J = 15.2 Hz); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 194.9, 174.7, 143.2, 140.7, 139.0, 138.1, 133.2, 132.5, 130.5, 129.5, 128.4, 127.5, 123.9, 119.6, 119.3, 119.0, 28.3, 15.9.
3-benzoyl-6-isopropylquinolin-4(1H)-one (1k): White solid; yield 69%; m.p. 265-267 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.41 (br s, 1H), 8.31 (s, 1H), 7.96 (d, 1H, J = 1.96 Hz), 7.73-7.70 (m, 2H), 7.66 (dd, 1H, J = 2.04, 2.04 Hz), 7.61-7.54 (m, 2H), 7.46-7.42 (m, 2H), 3.05-2.98 (m, 1H), 1.25 (dd, 6H, J = 6.92 Hz); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 194.9, 174.8, 145.3, 143.3, 139.0, 138.2, 132.5, 131.9, 130.4, 129.5, 128.4, 127.4, 122.3, 119.6, 119.4, 119.0, 33.6, 24.2.
3-benzoyl-6-(tert-butyl)quinolin-4(1H)-one (1l): White solid; yield 73%; m.p. >300 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.43 (br s, 1H), 8.32 (s, 1H), 8.10 (d, 1H, J = 2.24 Hz), 7.86 (dd, 1H, J = 2.32, 2.32 Hz), 7.74-7.71 (m, 2H), 7.63 (d, 1H, J = 8.72 Hz), 7.59-7.55 (m, 1H), 7.47-7.43 (m, 2H), 1.34 (s, 9H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 195.0, 174.9, 147.6, 143.2, 139.1, 137.9, 132.5, 131.0, 129.4, 128.4, 127.0, 121.0, 119.7, 119.2, 34.9, 31.4; IR (KBr): v max (cm-1) 3444, 3071, 2961, 1649, 1558, 1489, 1357, 1322, 1068, 838, 700, 601; HRMS (ESI-TOF+): m/z Calcd for C20H20NO2 + [(M+H)+] 306.1489; found, 306.1486.
3-benzoyl-6-methoxyquinolin-4(1H)-one (1m): White solid; yield 47%; m.p. >300 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.44 (br s, 1H), 8.28 (s, 1H), 7.72 (d, 2H, J = 8.04 Hz), 7.63 (d, 1H, J = 8.96 Hz), 7.58-7.52 (m, 2H), 7.44 (t, 2H, J = 7.56 Hz), 7.38 (dd, 1H, J = 2.76, 2.84 Hz), 3.84 (s, 3H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 195.0, 174.2, 157.0, 142.5, 139.1, 134.3, 132.5, 129.5, 128.7, 128.4, 123.0, 121.0, 118.8, 105.6, 55.9.
3-benzoyl-8-bromoquinolin-4(1H)-one (1n): White solid; yield 76%; m.p. 248-250 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 11.76 (br s, 1H), 8.19-8.14 (m, 2H), 8.10 (dd, 1H, J = 1.28, 1.32 Hz), 7.75-7.73 (m, 2H), 7.62-7.57 (m,1H), 7.49-7.45 (m, 2H), 7.37 (t, 1H, J = 7.84 Hz); 13C NMR (100 MHz, DMSO-d 6 , ppm):δ 194.2, 174.4, 144.2, 138.5, 137.5, 136.5, 132.9, 129.5, 129.0, 128.6, 126.0, 125.8, 120.4, 112.3; IR (KBr): v max (cm-1) 3445, 2360, 1646, 1523, 1432, 1328, 1278, 1069, 1009, 162, 699, 547; HRMS (ESI-TOF+): m/z Calcd for C16H11BrNO2 + [(M+H)+] 327.9968; found, 327.9968.
3-benzoyl-8-methylquinolin-4(1H)-one (1o): White solid; yield 70%; m.p. 270-272 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm):δ 11.77 (br s, 1H), 8.18 (s, 1H), 8.02 (d, 1H, J = 8.00 Hz), 7.73 (t, 2H, J = 15.28 Hz), 7.59-7.56 (m, 2H), 7.46 (t, 2H, J = 7.68 Hz), 7.32 (t, 1H, J = 7.72 Hz); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 194.7, 175.1, 143.5, 138.8, 138.4, 133.7, 132.6, 129.5, 128.5, 127.6, 127.5, 124.6, 123.9, 119.8, 17.5; IR (KBr): v max (cm-1) 3447, 2360, 1645, 1538, 1450, 1423, 1345, 1229, 1073, 1015, 793, 768, 553; HRMS (ESI-TOF+): m/z Calcd for C17H14NO2 + [(M+H)+] 264.1019; found, 264.1017.
3-benzoyl-8-isopropylquinolin-4(1H)-one (1p): White solid; yield 66%; m.p. 201-203oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ11.80 (br d, 1H, J = 6.44 Hz), 8.19 (d, 1H, J = 6.76 Hz), 8.05 (dd, 1H, J = 1.04, 1.08 Hz), 7.75-7.68 (m, 3H), 7.60-7.56 (m, 1H), 7.48-7.37 (m, 3H), 3.52 (m, 1H), 1.33 (d, 6H, J = 6.72 Hz); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 194.6, 175.1, 143.5, 138.8, 137.7, 137.0, 132.6, 130.4, 129.5, 129.1, 128.4, 127.9, 124.9, 123.8, 119.5, 119.0, 26.9, 23.4; IR (KBr): v max (cm-1) 3448, 1646, 1540, 1431, 1388, 1323, 1233, 1196, 1072, 863, 770, 712, 586; HRMS (ESI-TOF+): m/z Calcd for C19H18NO2 + [(M+H)+] 292.1332; found, 292.1329.
3-benzoyl-8-methoxyquinolin-4(1H)-one (1q): Brown solid; yield 62%; m.p. 238-240 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.06 (br s, 1H), 8.11 (s, 1H), 7.74-7.68 (m, 3H), 7.59-7.56 (m, 1H), 7.46 (t, 2H, J = 7.72 Hz), 7.38-7.34 (m, 2H), 4.03 (s, 3H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 194.7, 174.6, 149.2, 142.9, 138.9, 132.6, 130.3, 129.5, 128.5, 128.4, 124.9, 120.1, 117.1, 112.7, 56.8.
3-benzoyl-7-bromoquinolin-4(1H)-one (1r): White solid; yield 64%; m.p. > 300 oC; 1H NMR (400 MHz, F3CCOOD, ppm): δ 9.15 (s, 1H), 8.50 (d, 1H, J = 8.84 Hz), 8.28 (s, 1H), 8.02 (d, 1H, J = 8.20 Hz), 7.71-7.54 (m, 5H); 13C NMR (100 MHz, F3CCOOD, ppm): δ 220.2, 178.0, 151.0, 141.7, 137.3, 137.1, 136.6, 136.3, 131.6, 131.2, 128.5, 125.2, 121.6; IR (KBr): v max (cm-1) 3444, 1643, 1524, 1370, 1070, 1013, 847, 695, 547; HRMS (ESI-TOF+): m/z Calcd for C16H11BrNO2 + [(M+H)+] 327.9968; found, 327.9967.
3-benzoyl-7-methylquinolin-4(1H)-one (1s): White solid; yield 58%; m.p. > 300 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.34 (br t, 1H, J = 3.36 Hz), 8.29 (d, 1H, J = 8.24 Hz), 8.02 (d, 1H, J = 8.24 Hz), 7.72-7.70 (m, 2H), 7.59-7.55 (m, 1H), 7.47-7.42 (m, 3H), 7.25 (dd, 1H, J = 1.61, 1.12 Hz), 2.45(s, 3H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 194.8, 174.7, 143.5, 143.3, 140.0, 139.0, 132.6, 129.5, 129.3, 128.5, 128.4, 126.6, 125.9, 125.4, 119.8, 118.5, 21.7; IR (KBr): v max (cm-1) 3448, 3067, 1644, 1578, 1532, 1477, 1324, 1203, 1075, 1014, 848, 770, 693; HRMS (ESI-TOF+): m/z Calcd for C17H14NO2 + [(M+H)+] 264.1019; found, 264.1016.
3-benzoyl-7-methoxyquinolin-4(1H)-one (1t): Pale-Brown solid; yield 67%; m.p. >300 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.23 (br s, 1H), 8.27 (s, 1H), 8.03 (d, 1H, J = 8.92 Hz), 7.72-7.70 (m, 2H), 7.59-7.54(m, 1H), 7.47- 7.43 (m, 2H), 7.05-7.00 (m, 2H), 3.88 (s, 3H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 194.8, 174.3, 162.8, 143.5, 141.7, 139.0, 132.6, 129.5, 128.4, 127.8, 121.5, 119.9, 114.6, 100.5, 56.0; IR (KBr): v max (cm-1) 3446, 1643, 1549, 1475, 1367, 1270, 1068, 1015, 950, 866, 775, 725, 634; HRMS (ESI-TOF+): m/z Calcd for C17H14NO3 + [(M+H)+] 280.0968; found, 280.0962.
3-benzoyl-6,7-dichloroquinolin-4(1H)-one (1u): White solid; yield 84%; m.p. >300 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ12.53 (br s, 1H), 8.30 (s, 1H), 7.92 (d, 1H, J = 8.96 Hz), 7.76-7.74 (m, 2H), 7.64-7.57 (m, 2H), 7.49-7.45 (m, 2H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 194.6, 173.9, 142.2, 141.1, 138.5, 133.4, 132.8, 130.5, 129.5, 129.3, 128.6, 124.7, 122.2, 119.8; IR (KBr): v max (cm-1) 3444, 1642, 1576, 1544, 1446, 1367, 1290, 1204, 1070, 1009, 801, 777, 700, 634; HRMS (ESI-TOF+): m/z Calcd for C16H10Cl2NO2+ [(M+H)+] 318.0083; found, 318.0082.
3-benzoyl-6,7-dimethylquinolin-4(1H)-one (1v): Pale-gray solid; yield 77%; m.p. 230-232 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 11.36 (br d, 1H, J = 3.76 Hz), 8.06 (d, 1H, J = 8.96 Hz), 7.72 (t, 2H, J = 7.00 Hz), 7.58-7.55(m, 1H), 7.45 (t, 2H, J = 7.72 Hz), 7.40 (d, 1H, J = 7.48 Hz), 7.01 (d, 1H, J = 7.48 Hz), 2.68 (s, 3H), 2.46 (s, 3H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 195.0, 178.1, 141.9, 139.8, 138.9, 137.9, 132.8, 132.5, 129.3, 128.5, 127.0, 125.8, 124.8, 121.5, 23.6, 17.6; IR (KBr): v max (cm-1) 3446; 1653, 1625, 1544, 1450, 1406, 1325, 1206, 1069, 999, 854, 789, 689, 557; HRMS (ESI-TOF+): m/z Calcd for C18H16NO2 + [(M+H)+] 278.1176; found, 278.1172.
3-benzoyl-6-benzylquinolin-4(1H)-one (1w): White solid; yield 83%; m.p. 284-286 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.43 (br s, 1H), 8.31 (s, 1H), 7.95 (d, 1H, J = 0.92 Hz), 7.71 (t, 2H, J = 7.08 Hz), 7.64-7.54 (m, 3H), 7.44 (t, 2H, J = 7.72 Hz), 7.32-7.25 (m, 4H), 7.22-7.18 (m, 1H), 4.08 (s, 2H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 194.8, 174.7, 143.3, 141.3, 138.9, 138.4, 138.3, 133.8, 132.6, 129.5, 129.2, 129.0, 128.4, 127.5, 126.5, 125.2, 119.8, 119.5; IR (KBr): v max (cm-1) 3445, 1639, 1578, 1522, 1487, 1358, 1328, 1291, 1199, 1069, 862, 749, 696, 574; HRMS (ESI-TOF+): m/z Calcd for C23H17NO2 + [(M+ H)+] 340.1332; found, 340.1328.
3-benzoyl-6-(4-chlorophenoxy)quinolin-4(1H)-one (1x): White solid; yield 80%; m.p. 291-293 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.57 (br s, 1H), 8.36 (s, 1H), 7.76-7.70 (m, 3H), 7.58-7.51 (m, 3H), 7.49-7.42 (m, 4H), 7.14-7.10 (m, 2H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 194.7, 174.0, 155.6, 154.2, 143.4, 138.9, 136.1, 132.6, 130.5, 129.4, 128.7, 128.4, 128.4, 125.0, 121.8, 121.4, 119.1, 112.5; IR (KBr): v max (cm-1) 3448, 2326, 1641, 1525, 1477, 1368, 1330, 1294, 1236, 1088, 1009, 833, 698; HRMS (ESI-TOF+): m/z Calcd for C22H15ClNO3 + [(M+H)+] 376.0735; found, 376.0733.
3-benzoylbenzo[h]quinolin-4(1H)-one (1y): White solid; yield 73%; m.p. 276-278 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.75 (br s, 1H), 8.74 (t, 1H, J = 3.12 Hz), 8.29 (s, 1H), 8.16-8.10 (m, 2H), 7.88 (d, 1H, J = 8.84 Hz), 7.84- 7.79 (m, 4H), 7.61 (t, 1H, J = 7.36 Hz), 7.49 (t, 2H, J = 7.76 Hz); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 194.8, 174.5, 141.9, 138.5, 135.0, 133.0, 129.6, 129.3, 128.6, 127.7, 125.2, 122.5, 122.3, 122.1; IR (KBr): v max (cm-1) 3442, 1644, 1599, 1550, 1420, 1328, 1270, 1183, 1067, 1009, 863, 801, 763, 695, 534; HRMS (ESI-TOF+): m/z Calcd for C20H15NO2 + [(M+H)+] 300.1019; found, 300.1016.
3-benzoylpyrido[2,3-g]quinolin-4(1H)-one (1za): White solid; yield 81%; m.p. >300 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.85 (br s, 1H), 10.40 (d, 1H, J = 8.28 Hz), 8.93 (dd, 1H, J = 1.40, 1.40 Hz), 8.39 (s, 1H), 8.28 (d, 1H, J = 9.16 Hz), 7.99 (d, 1H, J = 9.20 Hz), 7.82 (d, 2H, J = 7.32 Hz), 7.66- 7.58 (m, 2H), 7.47 (t, 2H, J = 7.64 Hz); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 195.4, 177.2, 149.8, 145.6, 140.6, 140.0, 138.5, 135.2, 134.5, 133.0, 129.5, 128.7, 126.9, 124.7, 123.4, 122.5, 119.3; IR (KBr): v max (cm-1) 3449, 1654, 1597, 1559, 1528, 1368, 1310, 1284, 1206, 1075, 1014, 848, 553; HRMS (ESI-TOF+): m/z Calcd for C19H13N2O2 + [(M+H)+] 301.0972; found, 301.0971.
3-benzoylbenzo[b][1,5]naphthyridin-4(1H)-one (1zb): Yellow solid; yield 75%; m.p. >300 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 13.13 (br s, 1H), 9.92 (dd, 1H, J = 1.04, 1.16 Hz), 9.31 (s, 1H), 8.49 (s, 1H), 8.46 (dd, 1H, J = 0.96, 0.84 Hz), 7.84-7.79 (m, 2H), 7.76-7.72 (m, 2H), 7.50 (t, 2H, J = 7.76 Hz); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 195.1, 176.6, 145.6, 144.1, 140.7, 138.2, 134.7, 133.1, 129.7, 129.5, 129.1, 128.8, 126.4, 126.0, 124.4, 123.0; IR (KBr): v max (cm-1) 3446, 2329, 1643, 1495, 1417, 1272. 1068, 998, 816, 543; HRMS (ESI-TOF+): m/z Calcd for C19H13N2O2 + [(M+H)+] 301.0972; found, 301.0970.
Embodiment 2
Embodiment reaction equation is as follows:
The preparation method the following steps are included:
The first step, under stirring, with 4,4- dimethyl -3- oxopentanoic acid methyl ester, triethyl orthoformate, aniline for raw material, three components It puts into reactor together, is warming up to 130 DEG C of insulation reactions for 24 hours, diphenyl ether reflux is continuously added, wait there is a large amount of solids to be precipitated Stop reaction afterwards and obtains quinolone compounds.Decompression filters, and is washed with petroleum ether, ethyl acetate and methanol washs, be dried to obtain Quinolone compounds.
In embodiment aminated compounds variation be prepared carbostyril compound yield situation it is as follows:
Above compound data are as follows:
3-pivaloylquinolin-4(1H)-one (2a): White solid; yield 70%; m.p. 198-201oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.21 (br d, 1H, J = 4.76 Hz), 8.17 (dd, 1H, J = 1.24, 1.24 Hz), 7.04 (d, 1H, J = 6.32 Hz), 7.70-7.66 (m, 1H), 7.60 (d, 1H, J = 7.88 Hz), 7.40-7.36 (m, 1H ), 1.23 (s, 9H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 210.3, 174.5, 140.7, 139.7, 132.6, 126.9, 125.8, 124.5, 123.1, 119.0, 118.9, 44.3, 26.7; IR (KBr): v max (cm-1) 3444, 2327, 1655, 1622, 1559, 1468, 1437, 1351, 1300, 1068, 845, 791, 763, 545; HRMS (ESI-TOF+): m/z Calcd for C14H16NO2 + [(M+H)+] 230.1176; found, 230.1172.
6-fluoro-3-pivaloylquinolin-4(1H)-one (2b): White solid; yield 81%; m.p. 209-211 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.38 (br s, 1H), 8.09 (s,1H), 7.83 (dd, 1H, J = 2.92, 2.92 Hz), 7.71-7.67 (m, 1H), 7.63-7.58 (m, 1H), 1.23 (s, 9H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 210.1, 173.6, 173.5, 160.5, 158.1, 140.9, 136.4, 128.2, 128.1, 122.2, 121.8, 121.7, 121.5, 121.3, 110.1, 109.9, 44.3, 26.6; IR (KBr): v max (cm-1) 3127, 2970, 1658, 1588, 1563, 1531, 1482, 1401, 1361, 1300, 1188, 1103, 1010, 920, 801, 565; HRMS (ESI-TOF+): m/z Calcd for C14H15FNO2 + [(M+H)+] 248.1081; found, 248.1079.
6-chloro-3-pivaloylquinolin-4(1H)-one (2c): White solid; yield 75%; m.p. 260-262 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.38 (br s, 1H), 8.03 (s,1H), 8.02 (s,1H), 7.68 (dd, 1H, J = 2.44, 2.40 Hz), 7.59 (d, 1H, J = 8.84 Hz), 1.17 (s, 9H); 13C NMR (100 MHz, DMSO-d 6 , ppm): 210.0, 173.2, 141.0, 138.4, 132.7, 130.4, 129.2, 127.8, 124.8, 123.2, 121.4, 119.0, 44.3, 26.7; HRMS (ESI-TOF+): m/z Calcd for C14H15ClNO2 + [(M+H)+] 264.0876; found, 264.0873.
6-bromo-3-pivaloylquinolin-4(1H)-one (2d): White solid; yield 78%; m.p. 279-281 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.37 (br d, 1H, J = 5.4Hz), 8.25 (d, 1H, J = 2.32Hz), 8.10 (d, 1H, J = 6.28Hz), 7.86 (dd, 1H, J = 2.36, 2.36 Hz), 7.60 (d, 1H, J = 8.80 Hz), 1.24 (s, 9H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 210.0, 173.2, 140.9, 138.7, 135.3, 128.2, 128.0, 123.3, 121.6, 117.2, 44.3, 26.7; IR (KBr): v max (cm-1) 3445, 1665, 1578, 1518, 1466, 1393, 1299, 1068, 1006, 894, 823, 648, 559; HRMS (ESI-TOF+): m/z Calcd for C14H15BrNO2 + [(M +H)+] 308.0281; found, 308.0280.
6-nitro-3-pivaloylquinolin-4(1H)-one (2e): White solid; yield 80%; m.p. 260-262 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.61 (br s, 1H), 8.82 (d, 1H, J = 2.60 Hz), 8.14-8.10 (m, 2H), 7.73 (d, 1H, J = 9.12 Hz), 1.17 (s, 9H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 209.7, 174.1, 143.7, 143.6, 141.3, 126.7, 125.8, 125.5, 124.3, 122.3, 120.9, 112.8, 44.5, 26.6; IR (KBr): v max (cm-1) 3447, 1664, 1614, 1518, 1469, 1360, 1300, 1076, 1007, 825, 654, 561; HRMS (ESI-TOF+): m/z Calcd for C14H15N2O4 + [(M+H)+] 264.0786; found, 264.0784.
3-pivaloyl-6-(trifluoromethyl)quinolin-4(1H)-one (2f): White solid; yield 83%; m.p. 274-276 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.53 (br s, 1H), 8.41 (d, 1H, J = 0.92 Hz), 8.15 (s, 1H), 8.01 (dd, 1H, J = 2.61, 2.12 Hz), 7.81 (d, 1H, J = 8.68 Hz), 1.23 (s, 9H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 209.9, 173.9, 142.0, 141.3, 128.6, 128.5, 126.1, 125.9, 124.9, 124.5, 124.1, 123.4, 123.4, 123.3, 123.2, 120.7, 44.4, 26.6; IR (KBr): v max (cm-1) 3168, 1669, 1616, 1566, 1472, 1408, 1327, 1203, 1120, 844, 605; HRMS (ESI-TOF+): m/z Calcd for C15H15F3NO2 + [(M+H)+] 298.1049; found, 298.1043.
6-acetyl-3-pivaloylquinolin-4(1H)-one (2g): Yellow solid; yield 66%; m.p. 244-246 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm):δ 12.47 (br d, 1H, J = 8.68 Hz), 8.73 (d, 1H, J = 1.88 Hz), 8.20 (dd, 1H, J = 2.04, 2.04 Hz), 8.10 (d, 1H, J = 6.16 Hz), 7.68 (d, 1H, J = 8.72 Hz), 2.66 (s, 3H), 1.24 (s, 9H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 210.2, 197.2, 174.6, 142.6, 140.9, 132.6, 131.1, 127.5, 125.9, 124.1, 119.5, 44.4, 27.0, 26.7; IR (KBr): v max (cm-1) 3446, 1660, 1584, 1516, 1473, 1363, 1070, 831, 554; HRMS (ESI-TOF+): m/z Calcd for C16H18NO3 + [(M +H)+] 272.1281; found, 272.1281.
6-methyl-3-pivaloylquinolin-4(1H)-one (2h): White solid; yield 52%; m.p. 243-246 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.14 (br d, 1H, J = 5.52 Hz), 7.99 (d, 1H, J = 2.36 Hz), 7.95 (s, 1H), 7.51-7.50 (m, 2H), 2.41 (s,3H), 1.23 (s, 9H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 210.4, 174.3, 140.3, 137.7, 133.9, 126.8, 125.1, 122.8, 118.8, 44.3, 26.7, 21.2; IR (KBr): v max (cm-1) 3445, 1644, 1551, 1485, 1388, 1296, 1069, 804, 573; HRMS (ESI-TOF+): m/z Calcd for C15H18NO2 + [(M+H)+] 224.1332; found, 224.1327.
6-ethyl-3-pivaloylquinolin-4(1H)-one (2i): White solid; yield 43%; m.p. 170-173 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.19 (br d, 1H, J = 6.04 Hz), 8.02 (d, 1H, J = 6.36 Hz), 7.98 (s, 1H), 7.57-7.51 (m, 2H), 2.74 (dd, 2H, J = 7.56, 7.56 Hz), 1.24 (s, 9H), 1.21 (m, 3H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 210.4, 174.3, 140.4, 140.2, 137.9, 132.9, 126.9, 123.8, 122.8, 118.9, 44.2, 28.3, 26.7, 15.9; IR (KBr): v max (cm-1) 3442, 2961, 1659, 1567, 1486, 1385, 1296, 1066, 831, 568; HRMS (ESI-TOF+): m/z Calcd for C16H20NO2 + [(M+H)+] 258.1489; found, 258.1487.
6-(tert-butyl)-3-pivaloylquinolin-4(1H)-one (2j): White solid; yield 49%; m.p. 255-257 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ12.19 (br d, 1H, J = 6.16 Hz), 8.13 (d, 1H, J = 2.24 Hz), 8.02 (d, 1H, J = 6.4 Hz), 7.80 (dd, 1H, J = 2.20, 2.24 Hz), 7.57 (d, 1H, J = 7.56 Hz), 1.32 (s, 9H), 1.24 (s, 9H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 210.4, 174.5, 147.1, 140.5, 137.7, 130.7, 126.4, 122.9, 120.9, 118.8, 44.2, 34.9, 31.4, 26.7; IR (KBr): v max (cm-1) 3446, 3085, 2969, 1689, 1551, 1488, 1358, 1202, 1071, 1009, 839, 697; HRMS (ESI-TOF+): m/ z Calcd for C18H24NO2 + [(M+H)+] 286.1802; found, 286.1797.
6-methoxy-3-pivaloylquinolin-4(1H)-one (2k): White solid; yield 56%; m.p. 198-200 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.21 (br d, 1H, J = 5.60 Hz), 8.00 (d, 1H, J = 6.40 Hz), 7.58-7.55 (m, 2H), 7.34 (dd, 1H, J = 2.92, 2.96 Hz), 3.84 (s, 3H), 1.24 (s, 9H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 210.4, 173.7, 156.6, 139.9, 134.2, 128.1, 122.9, 121.9, 120.7, 105.4, 55.8, 44.2, 26.7; IR (KBr): v max (cm-1) 3445, 1664, 1548, 1514, 1364, 1307, 1071, 1006, 861, 570; HRMS (ESI-TOF+): m/z Calcd for C15H18NO3 + [(M+H)+] 260.1281; found, 260.1283.
8-bromo-3-pivaloylquinolin-4(1H)-one (2l): White solid; yield 72%; m.p. 211-213 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ11.56 (br s, 1H), 8.20 (dd, 1H, J = 1.24, 1.28 Hz), 8.05-8.02 (m, 1H), 7.91 (s, 1H), 7.36-7.31 (m, 1H), 1.23 (s, 9H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 209.7, 174.1, 141.3, 137.3, 136.2, 128.3, 125.9, 125.4, 123.4, 111.9, 44.4, 26.6; IR (KBr): v max (cm-1) 3446, 1611, 1544, 1438, 1333, 1300, 1071, 1001, 868, 748, 543; HRMS (ESI-TOF+): m/z Calcd for C14H15BrNO2 + [(M+H)+] 308.0281; found, 308.0281.
8-methyl-3-pivaloylquinolin-4(1H)-one (2m): White solid; yield 68%; m.p. 231-233 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 11.57 (br s, 1H), 8.05 (d, 1H, J = 8.08 Hz), 7.09 (d, 1H, J = 4.32 Hz), 7.55 (d, 1H, J = 7.04 Hz), 7.29 (t, 1H, J = 7.72 Hz), 2.50 (s, 1H), 1.24 (s, 9H); 13C NMR (100 MHz, DMSO-d 6 , ppm):δ 210.2, 174.7, 140.6, 138.3, 133.4, 127.1, 127.1, 124.2, 123.8, 123.0, 44.3, 26.7, 17.5; IR (KBr): v max (cm-1) 3448, 1621, 1552, 1445, 1363, 1280, 1070, 1003, 886, 545; HRMS (ESI-TOF+): m/z Calcd for C15H18NO2 + [(M+H)+] 224.1332; found, 224.1329.
8-methoxy-3-pivaloylquinolin-4(1H)-one (2n): White solid; yield 64%; m.p. 227-230 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 11.84 (br d, 1H, J = 5.64 Hz), 7.83 (d, 1H, J = 6.44 Hz), 7.73 (dd, 1H, J = 1.80, 1.80 Hz), 7.34-7.27 (m, 2H), 4.00 (s, 3H), 1.23 (s, 9H); 13C NMR (100 MHz, DMSO-d 6 , ppm):δ 210.2, 174.2, 149.0, 140.1, 130.3, 127.8, 124.4, 123.3, 117.0, 112.1, 56.7, 44.3, 26.6; IR (KBr): v max (cm-1) 3445, 2960, 2338, 1668, 1549, 1454, 1304, 1270, 1080, 862, 773, 673; HRMS (ESI-TOF+): m/z Calcd for C15H18NO3 + [(M+H)+] 260.1281; found, 260.1278.
7-methyl-3-pivaloylquinolin-4(1H)-one (2o): White solid; yield 50%; m.p. 246-248 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ12.08 (br s, 1H), 8.07 (dd, 2H, J = 8.24, 5.64 Hz), 7.36 (s, 1H), 7.22 (dd, 1H, J = 1.16, 1.12 Hz), 2.43 (s, 3H), 1.25 (s, 9H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 210.3, 174.3, 142.9, 140.5, 139.9, 126.1, 125.8, 124.9, 123.0, 118.7, 44.2, 27.0, 26.7; IR (KBr):v max (cm-1) 3445, 3228, 3095, 2874, 1692, 1630, 1558, 1524, 1475, 1363, 1307, 1070,999,889,775,698,560;HRMS(ESI-TOF+):m/zCalcdforC15H18NO2 +[(M+H)+] 224.1332; found, 224.1330.
7-methoxy-3-pivaloylquinolin-4(1H)-one (2p): White solid; yield 40%; m.p. 245-246 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.00 (br d, 1H, J = 5.64Hz), 8.07 (d, 1H, J = 9.60 Hz), 7.97 (d, 1H, J = 6.24 Hz), 7.00-6.97 (m, 2H), 3.86 (s, 3H), 1.23 (s, 9H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 210.4, 174.0, 162.6, 141.5, 140.4, 127.7, 123.0, 121.0, 114.4, 99.9, 55.9, 44.3, 26.7; IR (KBr):v max (cm-1) 3445, 2979, 1633, 1528, 1478, 1355, 1268, 1096, 1021, 568; HRMS (ESI-TOF+): m/z Calcd for C15H18NO3 + [(M+H)+] 260.1281; found, 260.1279.
6-benzyl-3-pivaloylquinolin-4(1H)-one (2q): White solid; yield 57%; m.p. 239-240 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.17 (br s, 1H), 8.00 (d, 2H, J = 2.16 Hz), 7.59-7.52 (m, 2H), 7.32-7.17 (m, 5H), 4.07 (s, 2H), 1.23 (s, 9H);13C NMR (100 MHz, DMSO-d 6 , ppm): δ 210.3, 174.3, 141.4, 140.4, 138.1, 137.8, 133.5, 129.2, 128.9, 126.9, 126.5, 125.0, 122.9, 119.1, 41.1, 26.7; IR (KBr):v max (cm-1) 3488, 2970, 1689, 1620, 1551, 1488, 1413, 1358, 1202, 1073, 1010, 839, 791, 616; HRMS (ESI-TOF+): m/z Calcd for C21H22NO2 + [(M+H)+] 320.1645; found, 320.1640.
3-pivaloylbenzo[g]quinolin-4(1H)-one (2r): White solid; yield 51%; m.p. 222-224 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm):δ 12.40 (br s, 1H), 10.24 (d, 1H, J = 8.44 Hz), 8.17 (d, 1H, J = 8.88 Hz), 7.99 (t, 2H, J = 7.96 Hz), 7.72-7.59 (m, 3H), 1.27 (s, 9H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 211.9, 177.0, 140.8, 135.3, 134.1, 131.3, 130.2, 128.7, 128.6, 128.1, 126.7, 126.3, 118.8, 118.6, 44.5, 27.0; IR (KBr): v max (cm-1) 3445, 1688, 1634, 1600, 1492, 1357, 1260, 1204, 1069, 865, 825, 574; HRMS (ESI-TOF+): m/z Calcd for C18H18NO2 + [(M+H)+] 280.1332; found, 280.1331.
3-pivaloylbenzo[h]quinolin-4(1H)-one (2s): White solid; yield 74%; m.p. 247-249 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.55 (br d, 1H, J = 4.80 Hz), 8.70 (t, 1H, J = 3.24 Hz), 8.19-8.00 (m, 3H), 7.84-7.77 (m, 3H), 1.27 (s, 9H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 210.4, 174.2, 138.8, 136.9, 134.8, 129.2, 129.2, 127.5, 125.4, 124.8, 123.8, 122.5, 122.1, 44.4, 26.7; IR (KBr):v max (cm-1) 3444, 1664, 1634, 1548, 1425, 1425, 1386, 1272, 1076, 1006, 861, 829, 829, 570; HRMS (ESI-TOF+): m/z Calcd for C18H18NO2 + [(M+H)+] 280.1332; found, 280.1331.
Embodiment 3
Embodiment reaction equation is as follows:
The preparation method the following steps are included:
The first step, under stirring, using 3- cyclopropyl -3- carbonyl-ethyl propionate, triethyl orthoformate, aniline as raw material, three components one It rises in investment reactor, is warming up to 130 DEG C of insulation reactions for 24 hours, diphenyl ether reflux is continuously added, after thering are a large amount of solids to be precipitated Stop reaction and obtains quinolone compounds.Decompression filters, and is washed with petroleum ether, ethyl acetate and methanol washs, be dried to obtain quinoline Promise ketone compound.
In embodiment aminated compounds variation be prepared carbostyril compound yield situation it is as follows:
Above compound data are as follows:
3-(cyclopropanecarbonyl)quinolin-4(1H)-one (3a): Brown solid; yield 75%; m.p. 276-278 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.49 (br s, 1H), 8.46 (s, 1H), 8.26 (dd, 1H, J = 1.28, 1.28 Hz), 7.74-7.70 (m, 1H), 7.63 (d, 1H, J = 8.00 Hz), 7.46-7.42 (m, 1H), 3.69-3.63 (m, 1H ), 1.00-0.91 (m, 4H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 199.6, 175.9, 144.4, 139.4, 132.9, 128.4, 126.2, 125.3, 119.3, 118.1, 19.4, 11.7; IR (KBr): v max (cm-1) 3441, 1646, 1559, 1523, 1474, 1441, 1354, 1274, 1067, 1009, 910, 850, 772, 586; HRMS (ESI-TOF+): m/z Calcd for C13H12NO2 + [(M+H)+] 214.0863; found, 214.0865.
3-(cyclopropanecarbonyl)quinolin-4(1H)-one (3b): Gray-white solid; yield 76%; m.p. 275-277 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.61 (br s, 1H), 8.47 (s, 1H), 7.88 (dd, 1H, J = 2.92, 2.92 Hz), 7.72-7.59 (m, 2H), 3.65-3.59 (m, 1H), 1.00-0.97 (m, 4H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 199.4, 175.0, 174.9, 160.9, 158.5, 144.4, 136.1, 130.0, 129.9, 122.2, 121.7, 121.4, 117.3, 110.7, 110.5, 19.4, 11.8; IR (KBr): v max (cm-1) 3445, 1652, 1572, 1520, 1384, 1362, 1293, 1270, 1091, 1016, 866, 822, 772, 577; HRMS (ESI-TOF+): m/z Calcd for C13H11FNO2 + [(M+H)+] 232.0768; found, 232.0763.
6-chloro-3-(cyclopropanecarbonyl)quinolin-4(1H)-one (3c): White solid; yield 74%; m.p. >300 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.63 (br s, 1H), 8.48 (s, 1H), 8.15 (d, 1H, J = 2.40 Hz), 7.77-7.65 (m, 2H), 3.62-3.56 (m, 1H), 1.00-0.97 (m, 4H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 199.3, 174.6, 144.7, 138.1, 113.0, 130.0, 129.6, 125.2, 121.7, 118.2, 19.5, 11.9; IR (KBr):v max (cm-1) 3445, 2338, 1649, 1552, 1399, 1350, 1299, 1076, 1014, 845, 637, 557; HRMS (ESI-TOF+): m/z Calcd for C13H11ClNO2 + [(M+H)+] 248.0473; found, 248.0467.
6-bromo-3-(cyclopropanecarbonyl)quinolin-4(1H)-one (3d): White solid; yield 70%; m.p. 258-260 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.56 (br s, 1H), 8.43 (s, 1H), 8.24 (d, 1H, J = 2.32 Hz), 7.81 (dd, 1H, J = 2.36, 2.32 Hz), 7.54 (d, 1H, J = 8.76 Hz), 3.56-3.50 (m, 1H), 0.96-0.86 (m,4H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 199.3, 174.5, 144.7, 138.4, 135.6, 129.9, 128.4, 121.9, 118.3, 118.1, 19.2, 11.9; IR (KBr): v max (cm-1) 3445, 2338, 1648, 1616, 1551, 1464, 1400, 1364, 1298, 1068, 1014, 920, 841, 585; HRMS (ESI-TOF+): m/z Calcd for C13H11BrNO2 + [(M+H)+] 291.9968; found, 291.9966.
3-(cyclopropanecarbonyl)-6-iodoquinolin-4(1H)-one (3e): White solid; yield 71%; m.p. >300 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.58 (br s, 1H), 8.51 (d, 1H, J = 1.96 Hz), 8.47 (s, 1H), 8.01 (dd, 1H, J = 2.04, 2.04 Hz), 7.45 (d, 1H, J = 8.64 Hz), 3.61-3.55 (m, 1H), 1.00-0.96 (m, 4H); 13C NMR(100 MHz, DMSO-d 6 , ppm): δ 199.3, 174.4, 144.7, 141.0, 138.8, 134.7, 130.1, 121.7, 118.4, 90.3, 19.5, 11.9; IR (KBr): v max (cm-1) 3446, 2329, 1646, 1616, 1550, 1460, 1401, 1343, 1299, 1080,1014, 550; HRMS (ESI-TOF+): m/z Calcd for C13H11INO2 + [(M+H)+] 339.9829; found, 339.9822.
3-(cyclopropanecarbonyl)-6-nitroquinolin-4(1H)-one (3f): Gray-white solid; yield 82%; m.p. >300 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.90 (br s, 1H), 8.91 (d, 1H, J = 2.64 Hz), 8.52 (s, 1H), 8.47 (dd, 1H, J = 2.68, 2.68 Hz), 7.81 (d, 1H, J = 9.08 Hz), 3.54-3.48 (m, 1H), 1.03-0.98 (m, 4H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 199.1, 175.1, 145.7, 144.2, 143.3, 127.8, 127.1, 122.4, 121.2, 119.1, 19.7, 12.1; IR (KBr): v max (cm-1) 3445, 1648, 1556, 1505, 1401, 1342, 1301, 1068, 931, 859, 794, 545; HRMS (ESI-TOF+): m/z Calcd for C13H11N2O4 + [(M+H)+] 259.0713; found, 259.0713.
3-(cyclopropanecarbonyl)-6-(trifluoromethyl)quinolin-4(1H)-one (3g): White solid; yield 80%; m.p. >300 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.77 (br s, 1H), 8.54 (s, 1H), 8.47 (s, 1H) 8.03 (dd, 1H, J = 1.60, 1.84 Hz), 7.83 (d, 1H, J = 8.64 Hz), 3.59-3.53 (m, 1H), 1.00-0.94 (m, 4H); 13C NMR (100 MHz, DOMSO-d 6 , ppm): δ 199.3, 175.1, 145.5, 141.8, 129.0, 127.9, 125.8, 125.6, 125.2, 123.7, 123.1, 121.0, 119.0, 19.6, 12.0; IR (KBr): v max (cm-1) 3445, 1650, 1561, 1525, 1407, 1332, 1297, 1070, 1013, 546; HRMS (ESI-TOF+): m/z Calcd for C14H11F3NO2 + [(M+H)+] 282.0736; found, 282.0731.
6-acetyl-3-(cyclopropanecarbonyl)quinolin-4(1H)-one (3h): Brown solid; yield 76%; m.p. >300 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ12.70 (br s, 1H), 8.79 (d, 1H, J = 2.00 Hz), 8.50 (s, 1H), 8.23 (dd, 1H, J = 2.04, 2.08 Hz), 7.72 (d, 1H, J = 8.60 Hz), 3.62-3.56 (m, 1H), 2.66 (s, 3H) 1.02-0.99 (m, 4H);13C NMR (100 MHz, DMSO-d 6 , ppm): δ 199.4, 197.2, 175.8, 145.1, 142.4, 133.3, 131.7, 127.7, 127.5, 119.9, 119.0, 27.1, 19.6, 11.9; IR (KBr): v max (cm-1) 3446, 3071, 1684, 1649, 1557, 1526, 1481, 1391, 1356, 1297, 1046, 1018, 980, 916, 829, 781, 608, 515; HRMS (ESI-TOF+): m/z Calcd for C15H14NO3 + [(M+H)+] 256.0968; found, 256.0963.
3-(cyclopropanecarbonyl)-6-methylquinolin-4(1H)-one (3i): Gray-white solid; yield 65%; m.p. 277-279 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.43 (br d, 1H, J = 5.66 Hz), 8.43 (d, 1H, J = 6.76 Hz), 8.03 (s, 1H), 7.55-7.51 (m, 2H), 3.70-3.64 (m, 1H), 3.34 (s, 3H) 0.99-0.90 (m, 4H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 199.6, 175.7, 143.9, 137.4, 134.8, 134.2, 128.4, 125.6, 119.2, 117.8, 21.2, 19.3, 11.7; IR (KBr): v max (cm-1) 3437, 2360, 1651, 1556, 1523, 1489, 1359, 1259, 1194, 1049, 1015, 580; HRMS (ESI-TOF+): m/z Calcd for C14H14NO2 + [(M+H)+] 228.1019; found, 228.1017.
3-(cyclopropanecarbonyl)-6-ethylquinolin-4(1H)-one (3j): White solid; yield 69%; m.p. 162-164 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.44 (br s, 1H), 8.43 (d, 1H, J = 5.32 Hz), 8.06 (d, 1H, J = 1.24 Hz), 7.60-7.54 (m, 2H), 3.70-3.64 (m, 1H), 3.33 (s, 1H) 2.76-2.71 (m, 2H), 1.23 (t, 3H, J = 7.56 Hz), 1.00-0.90 (m, 4H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 199.6, 175.8, 143.9, 141.1, 137.6, 133.2, 128.4, 124.3, 119.3, 117.8, 28.3, 19.3, 15.9, 11.7; IR (KBr): v max (cm-1) 3447, 1651, 1555, 1524, 1490, 1358, 1292, 1213, 1065, 1014, 828, 783, 595; HRMS (ESI-TOF+): m/z Calcd for C15H16NO2 + [(M+H)+] 242.1176; found, 242.1174.
6-(tert-butyl)-3-(cyclopropanecarbonyl)quinolin-4(1H)-one (3k): White solid; yield 54%; m.p. 239-241 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.44 (br s, 1H), 8.43 (s, 1H), 8.23 (d, 1H, J = 2.96 Hz), 7.83 (dd, 1H, J = 2.28, 2.28 Hz), 7.59 (d, 1H, J = 8.64 Hz), 3.70-3.64 (m, 1H), 1.34 (s, 9H), 1.00-0.90 (m, 4H); 13C NMR (100 MHz, DMSO-d 6 , ppm):δ 199.6, 175.9, 147.9, 143.9, 137.4, 131.0, 127.9, 121.4, 119.1, 117.9, 35.0, 31.4, 19.4, 11.6; IR (KBr): v max (cm-1) 3445, 3205, 3078, 2961, 2361, 1655, 1565, 1522, 1388, 1358, 1265, 1088, 1043, 1012, 924, 831, 598, 571; HRMS (ESI-TOF+): m/z Calcd for C17H20NO2 + [(M+ H)+] 270.1489; found, 270.1489.
3-(cyclopropanecarbonyl)-6-methoxyquinolin-4(1H)-one (3l): White solid; yield 62%; m.p. 254-256 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.47 (br d, 1H,J = 5.64 Hz), 8.41 (d, 1H, J = 6.80 Hz), 7.66 (dd, 2H, J = 2.88, 8.96 Hz), 7.38-7.32 (m, 1H), 3.85 (s, 3H), 3.72-3.66 (m, 1H), 0.99-0.90 (m, 4H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 199.6, 175.2, 157.1, 143.1, 133.8, 129.7, 122.7, 121.0, 117.1, 106.2, 55.9, 19.3, 11.6; IR (KBr): v max (cm-1) 3445, 2326, 1651, 1584, 1532, 1491, 1384, 1303, 1071, 1013, 817, 567; HRMS (ESI-TOF+): m/z Calcd for C14H14NO3 + [(M+H)+] 244.0968; found, 244.0965.
8-bromo-3-(cyclopropanecarbonyl)quinolin-4(1H)-one (3m): White solid; yield 78%; m.p. 261-263 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 11.80 (br s, 1H), 8.38 (s, 1H), 8.27 (dd, 1H, J =1.36, 1.32Hz), 8.07 (dd, 1H, J = 1.32, 1.32 Hz), 7.38 (t, 1H, J = 7.84 Hz), 3.62-3.56 (m, 1H), 1.02-0.94 (m, 4H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 199.2, 175.3, 145.1, 137.1, 136.5, 130.1, 126.2, 126.2, 118.3, 112.3, 19.5, 12.0; IR (KBr): v max (cm-1) 3447, 1657, 1601, 1543, 1436, 1389, 1328, 1273, 1206, 1068, 1008, 907, 788, 756, 545; HRMS (ESI-TOF+): m/z Calcd for C13H11BrNO2 + [(M+H)+] 291.9968; found, 291.9965.
3-(cyclopropanecarbonyl)-8-methylquinolin-4(1H)-one (3n): White solid; yield 64%; m.p. 242-244 oC; 1HNMR (400 MHz, DMSO-d 6 , ppm): δ 11.80 (br d, 1H,J = 5.64 Hz), 8.34 (d, 1H, J = 6.96 Hz), 8.12 (d, 1H, J = 7.80 Hz), 7.58-7.56 (m, 1H) 7.33 (t, 1H, J = 7.64 Hz), 3.71-3.64 (m, 1H), 2.51 (s, 3H) 1.01-0.92 (m, 4H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ199.5, 176.1, 144.0, 137.9, 133.8, 128.6, 127.5, 124.9, 124.2, 117.8, 19.4, 17.3, 11.8; IR (KBr): v max (cm-1) 3446, 2324, 1652, 1553, 1453, 1388, 1282, 1213, 1052, 905, 766, 558; HRMS (ESI-TOF+): m/z Calcd for C14H14NO2 + [(M+H)+] 228.1019; found, 228.1016.
3-(cyclopropanecarbonyl)-8-isopropylquinolin-4(1H)-one (3o): White solid; yield 52%; m.p. 235-237 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 11.81 (br s, 1H), 8.35 (d, 1H, J = 5.28 Hz), 8.16 (dd, 1H, J = 1.20, 1.20 Hz), 7.66 (dd, 1H, J = 0.96, 1.00 Hz), 7.40 (t, 1H, J = 7.67 Hz), 3.71-3.65 (m, 1H), 3.48- 3.42 (m, 1H), 1.29 (d, 6H, J = 6.76 Hz) 1.01-0.92 (m, 4H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 199.5, 176.1, 144.1, 137.7, 136.5, 129.1, 128.9, 125.2, 124.1, 117.5, 26.8, 23.3, 19.4, 11.8; IR (KBr): vmax (cm-1) 3444, 1659, 1611, 1547, 1447, 1390, 1357, 1269, 1208, 1045, 1014, 905, 853, 760, 583; HRMS (ESI-TOF+): m/z Calcd for C16H18NO2 + [(M+H)+] 256.1332; found, 256.1324.
3-(cyclopropanecarbonyl)-8-methoxyquinolin-4(1H)-one (3p): White solid; yield 58%; m.p. 245-247 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.07 (br s, 1H), 8.28 (s, 1H), 7.80 (dd, 1H, J = 1.44, 1.48 Hz), 7.38-7.31 (m, 2H), 4.00 (s, 3H), 3.70-3.63 (m, 1H), 1.00-0.91 (m, 4H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 199.6, 175.7, 149.2, 143.5, 129.8, 129.4, 125.2, 118.2, 117.4, 112.8, 56.8, 19.4, 11.8; IR (KBr): v max (cm-1) 3444, 3190, 1654, 1573, 1533, 1466, 1392, 1287, 1264, 1219, 1077, 1008, 932, 806, 755, 587, 529; HRMS (ESI-TOF+):m/z Calcd for C14H14NO3 + [(M+H)+] 244.0968; found, 244.0966.
7-bromo-3-(cyclopropanecarbonyl)quinolin-4(1H)-one (3q): White solid; yield 67%; m.p. 289-291 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.41 (br s, 1H), 8.42 (s, 1H), 8.08 (d, 1H, J = 8.64 Hz), 7.76 (d, 1H, J = 1.76 Hz), 7.53 (dd, 1H, J = 1.84, 1.80 Hz), 3.55-3.49 (m, 1H), 0.94-0.86 (m, 4H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 199.4, 175.3, 145.0, 140.4, 128.5, 128.3, 127.3, 126.3, 121.6, 118.6, 19.4, 11.9; IR (KBr): v max (cm-1) 3448, 1650, 1524, 1457, 1393, 1295, 1077, 1013, 778, 548; HRMS (ESI-TOF+): m/z Calcd for C13H11BrNO2 + [(M+H)+] 293.9947; found, 293.9941.
3-(cyclopropanecarbonyl)-7-methylquinolin-4(1H)-one (3r): Pale-yellow solid; yield 44%; m.p. 261-263 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ12.37 (br s, 1H), 8.41 (s, 1H), 8.13 (d, 1H, J = 8.24 Hz), 7.38 (s, 1H), 7.27 (dd, 1H,J = 1.08, 1.08 Hz), 3.70-3.63 (m, 1H), 2.43 (s, 3H), 0.99-0.90 (m, 4H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 199.6, 175.7, 144.2, 143.3, 139.5, 126.9, 126.3, 126.2, 118.6, 118.0, 21.6, 19.4, 11.7; IR (KBr): v max (cm-1) 3445, 1648, 1559, 1528, 1477, 1385, 1355, 1284, 1226, 1046, 1011, 909, 849, 788, 592, 513; HRMS (ESI-TOF+): m/z Calcd for C14H14NO2 + [(M+H)+] 228.1019; found, 228.1015.
3-(cyclopropanecarbonyl)-7-methoxyquinolin-4(1H)-one (3s): Pale-brown solid; yield 49%; m.p. 271-273 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.26 (br s, 1H), 8.40 (s, 1H), 8.15 (dd, 1H, J = 1.16, 1.20 Hz), 7.03-7.01 (m, 2H), 3.86 (s, 3H), 3.68-3.63 (m, 1H), 0.99-0.89 (m, 4H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 199.6, 175.4, 162.8, 144.3, 141.2, 128.1, 122.4, 118.0, 114.7, 100.6, 56.0, 19.3, 11.7; IR (KBr): v max (cm-1) ; 3442, 1648, 1573, 1532, 1481, 1386, 1267, 1179, 1024, 853, 783, 591, 512; HRMS (ESI-TOF+): m/z Calcd for C14H14NO3 + [(M+H)+] 244.0968; found, 244.0964.
7,8-dichloro-3-(cyclopropanecarbonyl)quinolin-4(1H)-one (3t): White solid; yield 67%; m.p. >300 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.16 (br s, 1H), 8.34 (d, 1H, J = 3.12 Hz), 8.19 (d, 1H, J = 8.72 Hz), 7.66 (d, 1H, J = 8.76 Hz), 3.58-3.51 (m, 1H), 1.01-0.96 (m, 4H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 199.1, 174.9, 145.3, 137.4, 136.3, 128.3, 126.4, 126.2, 121.0, 118.7, 19.6, 12.2; IR (KBr): v max (cm-1) 3445, 2390, 1658, 1604, 1520, 1437, 1386, 1295, 1179, 1067, 1037, 1007, 842, 778, 538; HRMS (ESI-TOF+): m/z Calcd for C13H10Cl2NO2 + [(M+H)+] 282.0080; found, 282.0078.
6-benzyl-3-(cyclopropanecarbonyl)quinolin-4(1H)-one (3u): White solid; yield 78%; m.p. 228-230 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.49 (br d, 1H,J = 6.12 Hz), 8.44 (d, 1H, J = 6.68 Hz), 8.08 (s, 1H), 7.61-7.55 (m, 2H), 7.32-7.24 (m, 4H), 7.20 (t, 1H, J = 7.04 Hz), 4.08 (s, 2H), 3.68-3.64 (m, 1H), 1.00-0.90 (m, 4H); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 199.6, 175.8, 144.0, 141.3, 138.7, 137.8, 133.8, 129.2, 128.9, 128.4, 126.5, 125.5, 119.5, 117.9, 19.4, 11.7; IR (KBr): v max (cm-1) 3421, 1645, 1571, 1512, 1488, 1391, 1357, 1292, 1216, 1072, 1015, 959, 853, 796, 619, 562; HRMS (ESI-TOF+): m/z Calcd for C20H18NO2 + [(M+H)+] 304.1332; found, 304.1331.
6-(4-chlorophenoxy)-3-(cyclopropanecarbonyl)quinolin-4(1H)-one (3v): Pale-brown solid; yield 73%; m.p. 286-288 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm):δ 12.62 (br s, 1H), 8.47 (s, 1H), 7.73-7.65 (m, 2H), 7.53-7.48 (m, 3H), 7.14 (d, 2H, J = 7.63 Hz), 3.61 (s, 1H), 0.97-0.92 (m, 4H), 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 199.8, 175.5, 142.9, 136.5, 135.0, 129.3, 129.2, 127.7, 125.7, 125.5, 123.8, 122.4, 122.3, 119.9, 19.6, 12.0; IR (KBr): v max (cm-1) 3447, 2025, 1652, 1563, 1478, 1390, 1273, 1238, 1086, 1013, 830, 569; HRMS (ESI-TOF+): m/z Calcd for C19H15ClNO3 + [(M+H)+] 340.0735; found, 340.0734.
3-(cyclopropanecarbonyl)benzo[h]quinolin-4(1H)-one (3w): Pale-brown solid; yield 69%; m.p. >300 oC; 1H NMR (400 MHz, F3CCOOD, ppm): δ 9.41 (s, 1H), 8.57 (d, 1H, J = 8.20 Hz), 8.26 (d, 1H, J = 9.04 Hz), 8.02 (t, 2H, J = 9.84 Hz), 7.87-7.78 (m, 2H), 2.67-2.68 (m, 1H), 1.48-1.33 (m, 4H); 13C NMR (100 MHz, DMSO-d6, ppm): δ 207.4, 175.3, 145.4, 141.1, 139.0, 134.9, 133.5, 131.9, 124.0, 123.3, 121.5, 120.3, 114.7, 19.4, 16.9; IR (KBr): v max (cm-1) 3446, 2327, 1656, 1574, 1524, 1435, 1389, 1272, 1072, 1010, 756, 536; HRMS (ESI-TOF+): m/z Calcd for C17H14NO2 + [(M+H)+] 264.0109; found, 264.0107.
Embodiment 4
Embodiment reaction equation is as follows:
The preparation method the following steps are included:
The first step, under stirring, using diethyl malonate, triethyl orthoformate, aniline as raw material, three components put into reactor together In, it is warming up to 130 DEG C of insulation reactions for 24 hours, continuously adds diphenyl ether reflux, stop reaction after thering are a large amount of solids to be precipitated and obtain Quinolone compounds.Decompression filters, and is washed with petroleum ether, ethyl acetate and methanol washs, be dried to obtain quinolone compounds.
In embodiment aminated compounds variation be prepared carbostyril compound yield situation it is as follows:
Above compound data are as follows:
Ethyl 4-oxo-1,4-dihydroquinoline-3-carboxylate (4a): White solid; yield 69%; m.p. 279-281 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 12.32 (br d, 1H, J = 4.92 Hz), 8.55 (d, 1H, J = 6.64 Hz), 8.16 (dd, 1H, J = 0.88, 0.84 Hz), 7.70- 7.68 (m, 1H), 7.62 (d, 1H, J = 8.00 Hz), 7.43-7.39 (m, 1H), 4.23 (q, 2H, J = 7.20 Hz), 1.27 (t, 3H, J = 7.12 Hz); 13C NMR (100 MHz, DMSO-d 6 , ppm): δ 173.9, 165.2, 145.3, 139.4, 132.8, 127.7, 126.0, 125.1, 119.2, 110.2, 60.0, 14.7; HRMS (ESI-TOF+): m/z Calcd for C12H12NO3 + [(M+H)+] 218.0812; found, 218.0808.
Ethyl 6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate (4b): White solid; yield 76%; m.p. 217-219 oC; 1H NMR (400 MHz, F3CCOOD, ppm): δ 9.11 (s, 1H), 8.07-8.00 (m, 2H), 7.78-7.73 (m, 1H), 4.51 (q, 2H, J = 7.20 Hz), 1.33 (t, 3H, J = 7.16 Hz); 13C NMR (100 MHz, F3CCOOD, ppm): δ 175.4, 175.3, 169.8, 147.1, 138.7, 130.1, 129.8, 125.4, 125.3, 67.2, 14.5.
Ethyl 6-chloro-4-oxo-1,4-dihydroquinoline-3-carboxylate (4c): Pale-yellow solid; yield 74%; m.p. >300 oC; 1H NMR (400 MHz, F3CCOOD, ppm): δ 9.15 (s, 1H), 8.45 (d, 1H, J = 1.76 Hz), 8.00-7.96 (m, 2H), 4.54 (q, 2H ), 1.36 (t, 3H, J = 7.16 Hz); 13C NMR (100 MHz, F3CCOOD, ppm): δ 174.9, 169.6, 147.4, 140.7, 140.0, 140.0, 126.0, 123.8, 123.2, 107.7, 67.1, 14.4.
Ethyl 6-bromo-4-oxo-1,4-dihydroquinoline-3-carboxylate (4d): White solid; yield 72%; m.p. >300 oC; 1H NMR (400 MHz, F3CCOOD, ppm): δ9.19 (s, 1H), 8.67 (s, 1H), 8.17 (d, 1H, J = 8.88 Hz), 7.92 (d, 1H, J = 8.84 Hz), 4.56 (t, 2H, J = 4.80 Hz), 1.40 (t, 3H, J = 5.44 Hz); 13C NMR (100 MHz, F3CCOOD, ppm): δ 174.6, 169.4, 147.2, 143.3, 140.1, 129.2, 127.1, 123.4, 123.2, 107.5, 66.9, 14.2.
Ethyl 6-iodo-4-oxo-1,4-dihydroquinoline-3-carboxylate (4e): Pale-yellow solid; yield 70%; m.p. >300 oC; 1H NMR (400 MHz, F3CCOOD, ppm): δ 9.16 (s, 1H), 8.88 (s, 1H), 8.32 (d, 1H, J = 8.88 Hz), 7.72 (d, 1H, J = 8.92 Hz), 4.55 (q, 2H, J = 7.20 Hz), 1.37 (t, 3H, J = 7.12 Hz); 13C NMR (100 MHz, F3CCOOD, ppm): δ 174.6, 169.6, 149.1, 147.5, 140.8, 136.1, 123.5, 123.1, 107.8, 97.2, 67.1, 14.4.
Ethyl 4-oxo-6-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylate (4f): White solid; yield 76%; m.p. >300 oC; 1H NMR (400 MHz, F3CCOOD, ppm): δ 9.24 (s, 1H), 8.76 (s, 1H), 8.20-8.21 (m, 2H), 4.51 (q, 2H, J = 7.20 Hz), 1.32 (t, 3H, J = 7.61 Hz); 13C NMR (100 MHz, F3CCOOD, ppm): δ 176.4, 169.5, 149.3, 143.0, 135.9, 135.5, 135.2, 125.0, 125.0, 123.9, 122.1, 108.3, 67.3, 14.4.
Ethyl 6-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylate (4g): Pale-yellow solid; yield 55%; m.p. 289-291 oC; 1H NMR (400 MHz, F3CCOOD, ppm): δ9.08 (s, 1H), 8.31 (s, 1H), 7.93-7.86 (m, 2H), 4.55 (q, 2H, J = 6.40 Hz), 2.54 (s, 3H), 1.40 (t, 3H, J = 5.36 Hz); 13C NMR (100 MHz, F3CCOOD, ppm): δ175.1, 169.8, 146.0, 144.7, 142.0, 139.9, 125.7, 122.3, 121.7, 106.8, 66.7, 22.0, 14.3.
Ethyl 6-ethyl-4-oxo-1,4-dihydroquinoline-3-carboxylate (4h): White solid; yield 56%; m.p. 271-273 oC; 1H NMR (400 MHz, F3CCOOD, ppm): δ 9.04 (s, 1H), 8.29 (s, 1H), 7.93 (dd, 2H, J = 8.76, 8.68 Hz), 4.51 (q, 2H, J = 6.80 Hz), 2.84 (q, 2H, J = 7.60 Hz), 1.36-1.20 (m, 6H); 13C NMR (100 MHz, F3CCOOD, ppm):δ 175.3, 169.9, 150.9, 146.1, 141.2, 140.1, 124.5, 122.5, 121.9, 106.9, 66.8, 30.5, 15.3, 14.3.
Ethyl 6-isopropyl-4-oxo-1,4-dihydroquinoline-3-carboxylate (4i): White solid; yield 64%; m.p. 247-249 oC; 1H NMR (400 MHz, F3CCOOD, ppm): δ 9.07 (s, 1H), 8.35 (d, 1H, J = 1.52 Hz), 8.02 (dd, 2H, J = 1.80, 1.80 Hz), 7.91 (d, 1H, J = 8.80 Hz), 4.54 (q, 2H, J = 7.20 Hz), 3.14-3.07 (m, 1H), 1.37 (t, 3H,J = 7.16 Hz), 1.27 (d, 6H, J = 6.92 Hz); 13C NMR (100 MHz, F3CCOOD, ppm): δ 175.1, 169.8, 155.3, 145.9, 140.0, 139.9, 106.7, 66.6, 36.4, 23.8, 14.1.
Ethyl 6-(tert-butyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate (4j): White solid; yield 71%; m.p. 271-273 oC; 1H NMR (400 MHz, F3CCOOD, ppm): δ 9.08 (s, 1H), 8.51 (d, 1H, J = 1.92 Hz), 8.23 (dd, 1H, J = 2.04, 2.04 Hz), 7.92 (d, 1H, J = 9.00 Hz), 4.54 (q, 2H, J = 5.36 Hz), 1.39-1.34 (m, 12H); 13C NMR (100MHz, F3CCOOD, ppm); δ 175.3, 169.8, 157.8, 146.0, 139.8, 139.1, 122.0, 121.9, 121.5, 106.7, 66.6, 37.3, 31.3, 14.2.
Ethyl 6-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate (4k): Brown solid; yield 69%; m.p. 282-284 oC; 1H NMR (400 MHz, F3CCOOD, ppm): δ8.94 (s, 1H), 7.85 (d, 1H, J = 9.28 Hz), 7.70-7.62 (m, 1H), 4.49 (q, 2H, J = 7.20 Hz), 3.87 (s, 3H), 1.34 (t, 3H, J = 7.16 Hz); 13C NMR (100 MHz, F3CCOOD, ppm): δ 174.2, 170.1, 144.4, 137.2, 132.5, 124.3, 123.8, 107.1, 104.7, 66.9, 57.7, 14.5.
Ethyl 8-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylate (4l): Brown solid; yield 70%; m.p. 255-257 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 11.92 (br s, 1H), 8.34 (s, 1H), 7.72 (dd, 1H, J = 1.24, 1.36 Hz), 7.37-7.31(m, 2H), 4.24 (q, 2H, J = 7.20 Hz), 4.00 (s, 1H), 1.27 (t, 3H, J = 7.08 Hz); 13C NMR (100 MHz, F3CCOOD, ppm): δ 173.6, 165.1, 149.1, 144.4, 129.8, 128.6, 125.0, 117.2, 112.6, 110.4, 60.0, 56.8, 14.7.
Ethyl 7-bromo-4-oxo-1,4-dihydroquinoline-3-carboxylate (4m): Pale-pink solid; yield 62%; m.p. >300 oC; 1H NMR (400 MHz, F3CCOOD, ppm): δ 9.12 (s, 1H), 8.33 (d, 1H, J = 8.80 Hz), 8.18 (s, 1H), 7.91 (d, 1H, J = 8.80 Hz), 4.52 (q, 2H, J = 7.20 Hz), 1.37 (t, 3H, J = 7.20 Hz); 13C NMR (100 MHz, F3CCOOD, ppm): δ 175.8, 169.6, 148.0, 142.0, 136.4, 136.3, 127.9, 125.0, 120.9, 107.4, 67.0, 14.3.
Ethyl 7-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate (4n): Yellow solid; yield 66%; m.p. >300 oC; 1H NMR (400 MHz, F3CCOOD, ppm): δ 9.45 (s, 1H), 9.03 (s, 1H), 8.81 (d, 1H, J = 9.20 Hz), 8.62 (t, 1H, J = 1.60 Hz), 4.64 (q, 2H, J = 7.20 Hz), 1.46 (q, 3H, J = 3.20 Hz); 13C NMR (100 MHz, F3CCOOD, ppm): δ 175.7, 169.8, 151.4, 145.9, 132.9, 132.8, 123.1, 117.6, 107.5, 66.9, 58.2, 14.3.
Ethyl 7-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylate (4o): Pale-brown solid; yield 50%; m.p. 281-282 oC; 1H NMR (400 MHz, F3CCOOD, ppm): δ 8.98 (s, 1H), 8.30 (d, 1H, J = 8.48 Hz), 7.80-7.48 (m, 2H), 4.44 (q, 2H, J = 6.40 Hz), 2.46 (s, 3H), 1.27 (t, 3H, J = 6.96 Hz); 13C NMR (100 MHz, F3CCOOD, ppm): δ 175.5, 170.1, 154.3, 147.1, 142.2, 134.6, 126.9, 121.4, 121.1, 120.3, 106.9, 67.1, 66.9, 23.2, 14.6.
Ethyl 7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate (4p): White solid; yield 41%; m.p. 290-292 oC; 1H NMR (400 MHz, F3CCOOD, ppm): δ 8.93 (s, 1H), 8.28 (d, 1H, J = 9.24Hz), 7.28 (t, 2H, J = 9.12Hz), 4.43 (q, 2H, J = 6.80 Hz), 3.84 (s, 3H), 1.28 (t, 3H, J = 6.88 Hz) ; 13C NMR (100 MHz, F3CCOOD, ppm): δ 174.4, 170.4, 170.1, 147.0, 144.9, 128.8, 124.4, 116.5, 106.3, 101.7, 66.7, 57.9, 14.5.
Ethyl 6,7-dichloro-4-oxo-1,4-dihydroquinoline-3-carboxylate (4q): Pale- yellow solid; yield 76%; m.p. >300 oC; 1H NMR (400 MHz, F3CCOOD, ppm): δ 9.17 (s, 1H), 8.56 (s, 1H), 8.17 (s, 1H), 4.53 (d, 2H, J = 7.20 Hz), 1.39 (d, 3H,J = 6.88 Hz); 13C NMR (100 MHz, F3CCOOD, ppm): δ 174.9, 169.6, 148.3, 146.9, 140.6, 140.2, 139.2, 127.8, 123.8, 121.5, 121.4, 107.8, 67.3, 14.4.
Ethyl 6,7-dimethyl-4-oxo-1,4-dihydroquinoline-3-carboxylate (4r): Pale- yellow solid; yield 63%; m.p. 199-201 oC; 1H NMR (400 MHz, DMSO-d 6 , ppm): δ 11.21 (br d, 1H, J = 6.44 Hz), 8.27 (d, 1H, J = 6.88 Hz), 7.36 (d, 1H, J = 7.52 Hz), 7.00 (d, 1H, J = 7.48 Hz), 4.21 (q, 2H, J = 6.80 Hz), 2.74 (s, 3H), 2.41 (s, 3H), 1.27 (t, 3H, J = 7.08 Hz); 13CNMR (100 MHz, F3CCOOD, ppm): δ 176.7, 165.3, 143.7, 139.2, 138.0, 132.8, 127.3, 126.0, 124.7, 111.7, 59.9, 23.8, 17.5, 14.7.
Ethyl 6-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxylate (4s): White solid; yield 79%; m.p. 264-265 oC; 1H NMR (400 MHz, F3CCOOD, ppm): δ 9.09 (s, 1H), 8.31 (s, 1H), 7.89 (s, 1H), 7.16 (d, 5H, J = 32.80 Hz), 4.52 (d, 2H, J = 2.60 Hz), 4.13 (d, 2H, J = 33.2 Hz), 1.38 (s, 3H); 13C NMR (100 MHz, F3CCOOD, ppm): δ 175.3, 169.8, 148.0, 146.4, 141.6, 140.4, 140.3, 130.8, 130.8, 128.9, 125.7, 122.4, 122.1, 107.0, 66.8, 43.3, 14.3.
Ethyl 6-(4-chlorophenoxy)-4-oxo-1,4-dihydroquinoline-3-carboxylate (4t): White solid; yield 81%; m.p. 289-290 oC; 1H NMR (400 MHz, F3CCOOD, ppm): δ 8.66 (s, 1H), 7.61-7.25 (m, 3H), 6.89-6.57 (m, 4H), 4.12 (d, 2H, J = 4.40 Hz), 0.97 (s, 3H); 13C NMR (100 MHz, F3CCOOD, ppm): 175.2, 170.5, 155.9, 146.2, 138.3, 134.4, 133.3, 132.7, 125.2, 124.7, 67.6, 15.2; IR (KBr): v max (cm-1) 3452, 1692, 1619, 1559, 1478, 1381, 1298, 1237, 800, 746, 609, 547; HRMS (ESI-TOF+): m/z Calcd for C12H11NO3 + [(M+H)+] 344.0684; found, 344.0677.
Ethyl 4-oxo-1,4-dihydrobenzo[h]quinoline-3-carboxylate (4w): Pale-brown solid; yield 68%; m.p. 267-270 oC; 1H NMR (400 MHz, F3CCOOD, ppm): δ 8.83 (s, 1H), 8.20 (d, 1H, J = 8.24 Hz), 7.92 (d, 1H, J = 9.12 Hz), 7.73 (q, 2H, J = 5.36 Hz), 7.53-7.45 (m, 2H), 4.21 (q, 2H, J = 7.20 Hz), 1.02 (t, 3H, J = 7.16 Hz); 13C NMR (100 MHz, F3CCOOD, ppm): δ 174.2, 169.5, 144.9, 141.3, 138.7, 134.8, 133.6, 131.8, 131.8, 123.8, 123.0, 120.6, 108.8, 66.9, 14.2, 14.1。

Claims (10)

1. a kind of method of green high-efficient synthesis carbostyril compound, it is characterised in that be with dicarbonyl compound, orthoformic acid Triethyl and aminated compounds are raw material, while undergoing Condensation reaction, Substitution reaction and Friedel- Carbostyril compound is prepared in Craft intramolecular cyclisation.
2. the method for green high-efficient synthesis carbostyril compound according to claim 1, it is characterised in that described two The molar ratio of carbonyls, triethyl orthoformate and aminated compounds is (0.5 ~ 1.5): (0.5 ~ 1.5): (0.5 ~ 1.5).
3. the method for green high-efficient synthesis carbostyril compound according to claim 2, it is characterised in that described two The molar ratio of carbonyls, triethyl orthoformate and aminated compounds is 1:1:1.
4. the method for any green high-efficient synthesis carbostyril compound according to claim 1 ~ 3, it is characterised in that institute The molar ratio of dicarbonyl compound, triethyl orthoformate and the aminated compounds stated is 1:1.25:1.
5. the method for green high-efficient synthesis carbostyril compound according to claim 1, it is characterised in that described two Carbonyls is ethyl benzoylacetate, 4,4- dimethyl -3- oxopentanoic acid methyl ester, 3- cyclopropyl -3- carbonyl-propionic acid second Ester or diethyl malonate.
6. the method for green high-efficient synthesis carbostyril compound according to claim 1, it is characterised in that the amine Class compound is aniline, pyridine amine or aromatic amine.
7. the method for green high-efficient synthesis carbostyril compound according to claim 1, it is characterised in that efficiently convenient The first step for preparing carbostyril compound is by three raw material investment reactors under the conditions of solvent-free catalysis-free agent in temperature 6 ~ 48h is reacted at 90 ~ 150 DEG C obtains the intermediate of object carbostyril compound.
8. preparation process as described in claim 1, which is characterized in that the preparation method further comprises:
It is at least one of diphenyl ether, polyphosphoric acids, Eton reagent or sulfuric acid, reaction temperature that second step, which reacts cyclization reagent, It is 90-180 DEG C.
9. the method for green high-efficient synthesis carbostyril compound according to claim 1, it is characterised in that reaction is completed After further include decompression filtering and washing step.
10. the method for green high-efficient synthesis carbostyril compound according to claim 9, it is characterised in that described subtracts Pressure filtering and washing is to carry out decompression filtering and washing using ethyl acetate, petroleum ether and methanol.
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* Cited by examiner, † Cited by third party
Title
HAIRUI BAI ET AL.: "Three-Component One-Pot Approach to Highly Efficient and Sustainable Synthesis of the Functionalized Quinolones via Linear/Branched Domino Protocols, Key Synthetic Methods for the Floxacin of Quinolone Drugs", 《ACS OMEGA》 *

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