CN115304545B - Copper-catalyzed selective cyclization of 2-alkynylanilines to quinolines and quinolone derivatives - Google Patents
Copper-catalyzed selective cyclization of 2-alkynylanilines to quinolines and quinolone derivatives Download PDFInfo
- Publication number
- CN115304545B CN115304545B CN202210769933.1A CN202210769933A CN115304545B CN 115304545 B CN115304545 B CN 115304545B CN 202210769933 A CN202210769933 A CN 202210769933A CN 115304545 B CN115304545 B CN 115304545B
- Authority
- CN
- China
- Prior art keywords
- added
- mmol
- ethyl acetate
- mixture
- tmscf
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Quinoline Compounds (AREA)
Abstract
The invention aims to provide a method for using 2-amino alkyneClass of compounds, TMSCF 3 And THF under nitrogen, 2-difluoromethyl ether-3-substituted quinoline and 2-quinolone compound are respectively produced through temperature control. TMSCF (TMSCF) 3 In the reaction, not only as C1 source but also as CF 2 Thus, the TMSCF is explained 3 The reagent is a multifunctional fluoridation reagent and a carbon source reagent. The cyclic ether not only plays a role of a solvent in the reaction, but also serves as an oxygen source and an alkane provider for the target product.
Description
[ field of technology ]
The invention relates to a TMSCF (TMSCF) which uses 2-amino alkyne compounds 3 And THF under nitrogen, 2-difluoromethyl ether-3-substituted quinoline and 2-quinolone compound are respectively produced through temperature control. TMSCF (TMSCF) 3 In the reaction, not only as C1 source but also as CF 2 Thus, the TMSCF is explained 3 The reagent is a multifunctional fluoridation reagent and a carbon source reagent. The cyclic ether not only plays a role of a solvent in the reaction, but also serves as an oxygen source and an alkane provider for the target product.
[ background Art ]
Quinoline and quinolone derivatives widely exist in nature as alkaloids, have good biological pharmacological activity, and have important application in the fluorescent and phosphorescent probe molecular fields; as a highly efficient catalyst or ligand, it also plays an important role in chiral molecule synthesis. Based on the application of quinoline and quinolone compounds in different fields, how to efficiently and greenly synthesize derivatives with quinoline and quinolone skeletons has been a target pursued by organic chemists. In particular, 2-alkoxyquinoline is a basic structure widely used in bioactive medicines, such as Bedaquinine (Bedaquine) which is regarded by the world guard as the first drug for treating multi-drug resistant tuberculosis, and tafenoquine (tafenoquine) is a new quinoline antimalarial drug, a local anesthetic and the like. Likewise, 2-quinolones are also core frameworks in a variety of pharmaceutical drugs, such as laquinimod (laquinimod), which is a potent immunomodulator, preventing neurodegeneration and inflammation of the central nervous system; tipirfanib (tipifarnib) is a potent anti-tumor activity that can inhibit farnesyl transferase very well. The conversion of abundant renewable biomass into value-added raw materials provides a potential sustainable solution to the growing global demand for chemicals and fuels. Cyclic ethers such as tetrahydrofuran and tetrahydropyran derivatives are important targets because they are readily available from biomass-derived intermediates such as levulinic acid and furfural. How to convert cyclic ether compounds into hydrocarbons by an efficient, highly selective route is a great challenge in biomass research, where obtaining high value-added chemicals by oxygen removal alone is a viable route in addition to the way of catalytic hydrodeoxygenation. At present, one common strategy in the conversion of the ring ether is to deoxidize the ring ether into diiodide through a samarium iodide and other ways, and also to obtain the dichloro compound through other ways. However, the process of obtaining high value-added chemicals by the deoxidized difunctional route is rare and difficult to achieve. I group realized that cyclic ether is deoxidized with organic carboxylic acid to construct iodo-alkyl ester compound in the previous work, and is the difunctional research for realizing cyclic ether deoxidization for the first time. The subject group uses 2-amino alkyne compounds to obtain double-tube-group carbostyril target products as well as cyclic ethers, and makes contribution to the deoxidation double-functional group reaction of the cyclic ethers again, and provides a brand-new synthetic approach for synthesizing 2-carbostyril derivatives.
Fluorine-containing compounds have wide application in the fields of medicines, pesticides, materials and the like because fluorine atoms have the greatest electronegativity, smaller atomic radius and special lipophilicity of fluorine-containing groups. The difluoromethoxy is taken as a bioelectrode isostere of the alcoholic hydroxyl and the thiol, so that the metabolic stability and the bioavailability of bioactive molecules can be better improved, and the development of a novel method for synthesizing 2-bit difluoromethoxy quinoline compounds is of great significance for the discovery and development of medicaments. The current method for synthesizing 2-difluoromethyl ether quinoline is rarely involved, and the current method is only realized by 2-quinolone or dihydroquinolinone and fluorinationThe alkyl reagent produces the target substance, but the substrate universality is poor, and the multi-step one-pot method is generally required, which generally results in poor compatibility of the hanging energy group, and the phenomenon of incapacity of reducing the yield caused by long-time protection or radical deprotection, and the like, so that a direct strategy is still required for constructing the compound. Here we use 2-alkynylaniline with TMSCF 3 Directly constructing diverse 2-difluoromethyl ether-3-substituted quinoline. At present, no public literature and patent application for synthesizing 2-difluoromethoxy-3-substituted quinoline and N-substituted-2-quinolone compounds exist at home and abroad.
[ invention ]
The invention develops a high-efficiency and simple method for preparing 2-difluoromethoxy-3-substituted quinoline and N-substituted-2-quinolone compounds by using low-cost copper as a catalyst. The reaction shows tolerance to various terminal alkynes, and the corresponding product has higher chemoselectivity and regioselectivity and mild reaction conditions. The catalytic scheme has the advantages of wide raw materials, no noble metal and harmful byproducts, and the like. Moreover, these products constitute multifunctional electrophiles, which find application in both organic synthesis and chemical biology.
Wherein said R is 1 Aromatic groups (phenyl, etc.); r is a substituent (halogen, methyl, etc.).
[ description of the drawings ]
FIG. 1 shows a scheme for the synthesis of 2-difluoromethoxy-3-substituted quinoline and N-substituted-2-quinolones.
[ detailed description ] of the invention
Wherein said R is 1 Aromatic groups (phenyl, etc.); r is a substituent (halogen, methyl, etc.).
Example 1:
to a 10mL Schlenk tube equipped with magnetic stirring was added 2- ((4-methoxyphenyl) ethynyl) aniline (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 50℃for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product was separated by column chromatography on silica gel to give purified 2-difluoromethoxy-3-substituted quinoline.
Purification by column chromatography (petroleum ether/ethyl acetate=250:1) afforded the title compound as a yellow solid. Yield: 75.9mg,84%. 1 H NMR(400MHz,CDCl 3 )δ8.11(s,1H),7.89(d,J＝8.4Hz,1H),7.81(s, 1H),7.79(d,J＝1.4Hz,1H),7.67(m,1H),7.61–7.53(m,2H),7.49(m,1H),7.06–6.97(m,2H), 3.87(s,3H). 13 C NMR(101MHz,CDCl 3 )δ159.7,154.7,144.4,139.2,130.7,129.9,127.5,127.4, 127.4,126.7,125.9,125.3,116.8,114.3,114.0,111.7,55.4. 19 F NMR(377MHz,CDCl 3 )δ-89.63.
Example 2:
to a 10mL Schlenk tube equipped with magnetic stirring were added 2- ((4-ethoxyphenyl) ethynyl) aniline (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 50℃for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product was separated by column chromatography on silica gel to give purified 2-difluoromethoxy-3-substituted quinoline.
Example 3:
to a 10mL Schlenk tube equipped with magnetic stirring was added 2- ((3-methoxyphenyl) ethynyl) aniline (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 50℃for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product was separated by column chromatography on silica gel to give purified 2-difluoromethoxy-3-substituted quinoline.
Example 4:
to a 10mL Schlenk tube equipped with magnetic stirring was added 2- ((2-methoxyphenyl) ethynyl) aniline (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 50℃for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product was separated by column chromatography on silica gel to give purified 2-difluoromethoxy-3-substituted quinoline.
Example 5:
2- ((4) was added to a 10mL Schlenk tube equipped with magnetic stirringMethylphenyl) ethynyl aniline (0.30 mmol,1.0 eq), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 50℃for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product was separated by column chromatography on silica gel to give purified 2-difluoromethoxy-3-substituted quinoline.
Example 6:
to a 10mL Schlenk tube equipped with magnetic stirring were added 2- ((4-ethylphenyl) ethynyl) aniline (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 50℃for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product was separated by column chromatography on silica gel to give purified 2-difluoromethoxy-3-substituted quinoline.
Example 7:
to a 10mL Schlenk tube equipped with magnetic stirring was added 2- ((3-methylphenyl) ethynyl) aniline (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) of the product, and de-ionizedSub-water (0.45 mmol,1.5 eq.). The mixture was stirred at 50℃for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product was separated by column chromatography on silica gel to give purified 2-difluoromethoxy-3-substituted quinoline.
Example 8:
to a 10mL Schlenk tube equipped with magnetic stirring was added 2- ((2-methylphenyl) ethynyl) aniline (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 50℃for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product was separated by column chromatography on silica gel to give purified 2-difluoromethoxy-3-substituted quinoline.
Example 9:
to a 10mL Schlenk tube equipped with magnetic stirring were added 2- ((4-substituted phenyl) ethynyl) aniline (substituents: fluoro, chloro, phenyl) (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 50℃for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 Dewatering and combiningIs concentrated under reduced pressure. The crude product was separated by column chromatography on silica gel to give purified 2-difluoromethoxy-3-substituted quinoline.
Example 10:
to a 10mL Schlenk tube equipped with magnetic stirring was added 2- (pent-1-yn-1-yl) aniline (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 50℃for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product was separated by column chromatography on silica gel to give purified 2-difluoromethoxy-3-substituted quinoline.
Example 11:
to a 10mL Schlenk tube equipped with magnetic stirring was added 2- ((2-naphthyl) ethynyl) aniline (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 50℃for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product was separated by column chromatography on silica gel to give purified 2-difluoromethoxy-3-substituted quinoline.
Example 12:
to a 10mL Schlenk tube equipped with magnetic stirring was added 2- ((4-carbomethoxyphenyl) ethynyl) aniline (0.30 mmol,1.0 eq.),CuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 50℃for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product was separated by column chromatography on silica gel to give purified 2-difluoromethoxy-3-substituted quinoline.
Example 13:
to a 10mL Schlenk tube equipped with magnetic stirring were added 2- (thiophene-2-ethylene) aniline (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 50℃for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product was separated by column chromatography on silica gel to give purified 2-difluoromethoxy-3-substituted quinoline.
Example 14:
to a 10mL Schlenk tube equipped with magnetic stirring were added 2- ((2-chlorophenyl) ethynyl) aniline (substituents: fluoro, chloro, phenyl) (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq). The mixture was stirred at 50℃for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product was separated by column chromatography on silica gel to give purified 2-difluoromethoxy-3-substituted quinoline.
Example 15:
to a 10mL Schlenk tube equipped with magnetic stirring were added 2- ((phenyl) ethynyl) aniline (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 50℃for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product was separated by column chromatography on silica gel to give purified 2-difluoromethoxy-3-substituted quinoline.
Example 16:
to a 10mL Schlenk tube equipped with magnetic stirring was added 2- ((4-methoxyphenyl) ethynyl) aniline (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 25 ℃ for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product was passed over silica gelAnd (3) a column chromatographic separation method to obtain the purified N-substituted-2-quinolone compound.
Purification by column chromatography (petroleum ether/ethyl acetate=250:1) afforded the title compound as a yellow liquid. Yield: 90.9mg,70%. 1 HNMR(400MHz,CDCl 3 )δ7.75(s,1H),7.70–7.65(m,2H),7.61–7.51(m,2H), 7.37(s,1H),7.22(t,J＝7.5Hz,1H),7.01–6.90(m,2H),4.37(t,J＝7.3Hz,2H),3.83(s,3H), 3.26(t,J＝6.6Hz,2H),2.04–1.89(m,4H). 13 C NMR(101MHz,CDCl 3 )δ161.5,159.6,138.4, 136.0,131.8,130.2,130.1,129.0,122.2,121.2,113.9,113.7,55.4,41.7,30.8,28.5,6.3.
Example 17:
to a 10mL Schlenk tube equipped with magnetic stirring were added 2- ((4-ethoxyphenyl) ethynyl) aniline (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 25 ℃ for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product is separated on silica gel by column chromatography to obtain purified N-substituted-2-quinolone compounds.
Example 18:
to a 10mL Schlenk tube equipped with magnetic stirring was added 2- ((3-methoxyphenyl) ethynyl) aniline (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 25 ℃ for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was treated with ethyl acetateDiluting with ethyl acetate, adding appropriate amount of water, extracting with ethyl acetate three times, collecting organic phase, and adding appropriate amount of anhydrous Na 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product is separated on silica gel by column chromatography to obtain purified N-substituted-2-quinolone compounds.
Example 19:
to a 10mL Schlenk tube equipped with magnetic stirring was added 2- ((2-methoxyphenyl) ethynyl) aniline (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 25 ℃ for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product is separated on silica gel by column chromatography to obtain purified N-substituted-2-quinolone compounds.
Example 20:
to a 10mL Schlenk tube equipped with magnetic stirring were added 2- ((4-methylphenyl) ethynyl) aniline (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 25 ℃ for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product is separated on silica gel by column chromatography to obtain purified N-substituted-2-quinolone compounds.
Example 21:
to a 10mL Schlenk tube equipped with magnetic stirring were added 2- ((4-ethylphenyl) ethynyl) aniline (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 25 ℃ for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product is separated on silica gel by column chromatography to obtain purified N-substituted-2-quinolone compounds.
Example 22:
to a 10mL Schlenk tube equipped with magnetic stirring was added 2- ((3-methylphenyl) ethynyl) aniline (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 25 ℃ for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product is separated on silica gel by column chromatography to obtain purified N-substituted-2-quinolone compounds.
Example 23:
to a 10mL Schlenk tube equipped with magnetic stirring was added 2- ((2-methylphenyl) ethynyl) aniline (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 Atmosphere of1.0mL of ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 25 ℃ for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product is separated on silica gel by column chromatography to obtain purified N-substituted-2-quinolone compounds.
Example 24:
to a 10mL Schlenk tube equipped with magnetic stirring were added 2- ((4-substituted phenyl) ethynyl) aniline (substituents: fluoro, chloro, phenyl) (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 25 ℃ for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product is separated on silica gel by column chromatography to obtain purified N-substituted-2-quinolone compounds.
Example 25:
to a 10mL Schlenk tube equipped with magnetic stirring was added 2- (pent-1-yn-1-yl) aniline (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 25 ℃ for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, and a suitable amount of water was added theretoExtracting with ethyl acetate three times, collecting organic phase, and adding appropriate amount of anhydrous Na 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product is separated on silica gel by column chromatography to obtain purified N-substituted-2-quinolone compounds.
Example 26:
to a 10mL Schlenk tube equipped with magnetic stirring was added 2- ((2-naphthyl) ethynyl) aniline (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 25 ℃ for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product is separated on silica gel by column chromatography to obtain purified N-substituted-2-quinolone compounds.
Example 27:
to a 10mL Schlenk tube equipped with magnetic stirring was added 2- ((4-carbomethoxyphenyl) ethynyl) aniline (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 25 ℃ for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product is separated on silica gel by column chromatography to obtain purified N-substituted-2-quinolone compounds.
Example 28:
to a 10mL Schlenk tube equipped with magnetic stirring were added 2- (thiophene-2-ethylene) aniline (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 25 ℃ for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product is separated on silica gel by column chromatography to obtain purified N-substituted-2-quinolone compounds.
Example 29:
to a 10mL Schlenk tube equipped with magnetic stirring were added 2- ((2-chlorophenyl) ethynyl) aniline (substituents: fluoro, chloro, phenyl) (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 25 ℃ for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product is separated on silica gel by column chromatography to obtain purified N-substituted-2-quinolone compounds.
Example 30:
to a 10mL Schlenk tube equipped with magnetic stirring were added 2- ((phenyl) ethynyl) aniline (0.30 mmol,1.0 eq.), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of ultra-dry solvent is added under the atmosphereFuran, trifluoromethyl Trimethylsilane (TMSCF) 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 25 ℃ for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product is separated on silica gel by column chromatography to obtain purified N-substituted-2-quinolone compounds.
Example 31:
to a 10mL Schlenk tube equipped with magnetic stirring was added 4-halo-2- (4-methoxyphenyl) ethynyl) aniline (0.30 mmol,1.0 eq.) with halogen: fluorine, chlorine, bromine, methyl), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 25 ℃ for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product is separated on silica gel by column chromatography to obtain purified N-substituted-2-quinolone compounds.
Example 32:
to a 10mL Schlenk tube equipped with magnetic stirring was added 2, 4-dichloro-6- (4-methoxyphenyl) acetylene aniline (0.30 mmol,1.0 eq.) with halogen: fluorine, chlorine, bromine, methyl), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 25 ℃ for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was quenched with acetic acidDiluting with ethyl ester, adding appropriate amount of water, extracting with ethyl acetate three times, collecting organic phase, and adding appropriate amount of anhydrous Na 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product is separated on silica gel by column chromatography to obtain purified N-substituted-2-quinolone compounds.
Example 33:
to a 10mL Schlenk tube equipped with magnetic stirring was added 4- (2-aminophenyl) ethynyl) -N, N-diphenylaniline (0.30 mmol,1.0 eq.) with halogen: fluorine, chlorine, bromine, methyl), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 25 ℃ for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product is separated on silica gel by column chromatography to obtain purified N-substituted-2-quinolone compounds.
Example 34
To a 10mL Schlenk tube equipped with magnetic stirring was added 2- (4- (9H-carbazol-9-yl) phenyl) ethynyl) aniline (0.30 mmol,1.0 eq.) with halogen: fluorine, chlorine, bromine, methyl), cuI (0.03 mmol,0.1 eq.) and sodium iodide (NaI, 0.60mmol,2.0 eq.). After being evacuated by a pump, nitrogen is filled three times. Then, at N 2 1.0mL of the ultra-dry solvent tetrahydrofuran, trifluoromethyl Trimethylsilane (TMSCF) was added under an atmosphere 3 0.36mmol,1.2 eq.) in deionized water (0.45 mmol,1.5 eq.). The mixture was stirred at 25 ℃ for 12 hours (thermostatted oil bath). After cooling to room temperature, the mixture was diluted with ethyl acetate, then a suitable amount of water was added, extracted three times with ethyl acetate, the organic phase was collected, and a suitable amount of anhydrous Na was added 2 SO 4 The combined organic layers were dehydrated and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gelSpectrum separation method to obtain purified N-substituted-2-quinolone compound.
The foregoing examples illustrate only a few embodiments of the invention and are described in detail herein without thereby limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.
Claims (1)
1. A preparation method of quinoline derivatives is characterized in that:
to a 10mL Schlenk tube equipped with magnetic stirring, 0.30mmol of 2-alkynylaniline, 0.1 equivalent of CuI and 2.0 equivalent of NaI were added, and after evacuation by a pump, nitrogen was filled three times, followed by N 2 1.0mL of tetrahydrofuran and 1.2 equivalents of TMSCF were added under an atmosphere 3 The mixture was stirred at 150 ℃ for 12 hours, cooled to room temperature, diluted with ethyl acetate, extracted three times with water, the organic phase was collected and anhydrous Na was added 2 SO 4 Dehydrating the combined organic layers and concentrating under reduced pressure, separating the crude product on silica gel by column chromatography to obtain purified quinoline derivative,
the reaction formula is as follows:
wherein R is 1 Is phenyl, R is halogen or methyl.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210769933.1A CN115304545B (en) | 2022-07-01 | 2022-07-01 | Copper-catalyzed selective cyclization of 2-alkynylanilines to quinolines and quinolone derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210769933.1A CN115304545B (en) | 2022-07-01 | 2022-07-01 | Copper-catalyzed selective cyclization of 2-alkynylanilines to quinolines and quinolone derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115304545A CN115304545A (en) | 2022-11-08 |
| CN115304545B true CN115304545B (en) | 2023-09-15 |
Family
ID=83854650
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210769933.1A Active CN115304545B (en) | 2022-07-01 | 2022-07-01 | Copper-catalyzed selective cyclization of 2-alkynylanilines to quinolines and quinolone derivatives |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115304545B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111960997A (en) * | 2020-09-07 | 2020-11-20 | 浙江工业大学 | Method for synthesizing hydroxyalkyl substituted quinoline derivatives |
-
2022
- 2022-07-01 CN CN202210769933.1A patent/CN115304545B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111960997A (en) * | 2020-09-07 | 2020-11-20 | 浙江工业大学 | Method for synthesizing hydroxyalkyl substituted quinoline derivatives |
Non-Patent Citations (1)
| Title |
|---|
| "Copper-Catalyzed Cyclization of 2-Alkynylanilines to Give 2‑Haloalkoxy-3-alkyl(aryl)quinolines";Dong Lu et al.;《Org. Lett.》;第25卷;第676-681页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115304545A (en) | 2022-11-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108276287B (en) | Synthesis method of 4-oxo acrylate derivative catalyzed by visible light | |
| CN110204486B (en) | Synthesis method of quinoline derivative | |
| CN113024556B (en) | Preparation method of fused ring compound containing indole skeleton | |
| WO2020114025A1 (en) | PREPARATION METHOD FOR β-LACTAM DERIVATIVES | |
| CN115304545B (en) | Copper-catalyzed selective cyclization of 2-alkynylanilines to quinolines and quinolone derivatives | |
| CN112321487A (en) | Polysubstituted isoindoline compound and preparation method thereof | |
| CN109651367B (en) | Method for preparing 1, 4-dihydroquinoline and pyrrolo [1,2-a ] quinoline compounds | |
| CN110204533B (en) | Preparation method of 4- (isochromen-1-yl) isoquinoline derivative | |
| CN113636968B (en) | Synthetic method of 3-acyl pyrrole compound | |
| CN113912609B (en) | Preparation method of natural alkaloid tryptanthrin and derivatives thereof | |
| CN109734705A (en) | A method of preparation N- heterocyclic arene derivative is alkylated through dehalogenation | |
| CN111004164B (en) | Preparation method of polysubstituted 2-aryl indole derivative | |
| CN105272918B (en) | Halogenation -1- alkyl -3- vinyl -2,4,5- triarylimidazoles and preparation method and purposes | |
| CN113651788A (en) | 3-amine alkyl chromone compound and preparation method thereof | |
| CN104072495B (en) | The preparation method of natural product alkaloid A aptamine | |
| CN112645871A (en) | N-CF2H-1, 2-dihydroSynthesis method of pyridine-2-ketone compound | |
| CN112174962A (en) | Synthesis method of benzo [ e ] pyridylimidazo [4,5-g ] isoindole-1, 3(2H) -diketone compound | |
| CN110294708A (en) | The preparation method of trifluoro second seleno phenanthridines and 3,4- dihydro-isoquinoline analog derivative | |
| CN109836384A (en) | A kind of 3- aryl methylene -2,3- dihydro -4(1H)-quinolinone preparation method | |
| CN110194760B (en) | Process for preparing 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindol-1-ones | |
| CN114277389B (en) | Method for synthesizing quinoline derivative by utilizing pyridinium photoelectrocatalysis Minisci reaction | |
| CN112552235B (en) | Synthetic method of 2, 3-diacyl quinoline compound | |
| CN109422711A (en) | A method of synthesis trifluoromethyl dihydroisobenzofuran class compound | |
| CN115197137B (en) | Isoquinolinones compound and synthesis method thereof | |
| CN107382642B (en) | α -diphenyl-1-aryl propenone compound preparation method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |