CN103724344A - Method for synthesizing nitrogen-containing heterocyclic compound - Google Patents

Method for synthesizing nitrogen-containing heterocyclic compound Download PDF

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CN103724344A
CN103724344A CN201310337282.XA CN201310337282A CN103724344A CN 103724344 A CN103724344 A CN 103724344A CN 201310337282 A CN201310337282 A CN 201310337282A CN 103724344 A CN103724344 A CN 103724344A
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phenyl
trifluoromethyl
nitrogen
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synthetic method
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CN103724344B (en
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鄢明
陈艳艳
张学景
位文涛
孙翔
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Sun Yat Sen University
National Sun Yat Sen University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D455/00—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
    • C07D455/03—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
    • 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
    • C07D215/04—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
    • C07D215/06—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms having only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond

Abstract

The invention provides a novel method for synthesizing a nitrogen-containing heterocyclic compound. The method comprises the following steps of adding alkali into 2-aminophenyl olefin which serves as a raw material under the protection of nitrogen, and heating the mixture in a solvent to obtain the high-yield nitrogen-containing heterocyclic compound. The method is convenient to operate and high in reaction yield, and has high practical value for the industrial preparation of the nitrogen-containing heterocyclic compound, and the use of a transition metal catalyst in reaction is avoided.

Description

A kind of method of synthetic nitrogen-containing heterocycle compound
Technical field
The present invention relates to a kind of method of synthetic nitrogen-containing heterocycle compound, belong to organic synthesis field.
Background technology
Nitrogen-containing heterocycle compound is extensively present in natural product and synthetic drugs, and it efficiently, synthetic method has important industrial application value cheaply.The cyclization of tertiary amine and alkene is a class important method of preparing nitrogen-containing heterocycle compound, and the exemplary process of development comprises at present: (1) adopts n-Bu 3snH/AIBN free radical initiator system, the free radical cyclization (J.Chem.Soc., Perkin Trans.1999,427) that alpha-halogen tertiary amine or α-trimethyl silicon based tertiary amine and alkene occur; (2) there is 1,5-hydrogen migration in tertiary amine α-hydrogen atom under Louis acid catalysis, and intramolecular cyclization reaction (J.Am.Chem.Soc.2009,131,13226) then occurs; (3) under the effect of photocatalyst, by photoresponse, form amine alkyl diradical, then there is free radical cyclization (J.Am.Chem.Soc.2012,134,3338); (4) adopt transition-metal catalyst, the C-H by amine alpha-position activates, and cyclization (Angew.Chem.Int.Ed.2013,52,1) then occurs.Aforesaid method exists substrate narrow range, uses high toxicity reagent, or need to use the shortcomings such as noble metal catalyst, and the application in industrial production is very restricted, and therefore developing efficient and oligosaprobic new synthetic method has necessity.
The invention provides a kind of novel method of synthetic nitrogen-containing heterocycle compound.It is raw material that the method adopts 2-aminocarbonyl phenyl alkene, under nitrogen protection, adds a kind of alkali, in solvent, heats, and can obtain nitrogen-containing heterocycle compound by good productive rate.The method is easy and simple to handle, reaction yield is high, in reaction without using transition-metal catalyst, for the industry preparation of nitrogen-containing heterocycle compound, there is very high practical value.
Summary of the invention
A kind of method that the object of this invention is to provide synthetic nitrogen-containing heterocycle compound.
Concrete technical scheme is as follows:
A kind of synthesis type (I) and (II) shown in the method for nitrogen-containing heterocycle compound, it is characterized in that, 2-aminocarbonyl phenyl alkene shown in employing formula (III) is raw material, under nitrogen protection, add a kind of alkali, in solvent, heat, obtain formula (I) and (II) shown in nitrogen-containing heterocycle compound; Described alkali is potassium tert.-butoxide, sodium tert-butoxide, potassium methylate, sodium methylate; Described solvent is dimethyl sulfoxide (DMSO), DMF, N,N-dimethylacetamide; The compound of described formula (I), formula (II) and formula (III) structure is as follows:
Figure BSA0000093499030000021
In 25mL round-bottomed flask, add potassium tert.-butoxide (168mg, 1.5mmol), 2-(2-ethenylphenyl)-1; 2,3,4-tetrahydroisoquinoline (235mg, 1mmol); DMF (12mL) reacts 4 hours under nitrogen protection.After having reacted, add methylene dichloride (20mL) and water (20mL), isolate organic phase, removal of solvent under reduced pressure, resistates is eluent with the mixed solvent of sherwood oil and ethyl acetate, by silica gel column chromatography separating purification, obtains 7,11b, 12,13-tetrahydrochysene-6H-isoquinoline 99.9 [2,1-a] quinoline (179mg, 0.76mmol, productive rate 76%); 1h NMR (400MHz, CDCl 3): δ 7.53 (d, J=7.5Hz, 1H), 7.28-7.24 (br, 1H), 7.18-7.16 (br, 3H), 7.13-7.05 (m, 4H), 5.71 (d, J=17.8Hz, 1H), 5.23 (d, J=11.0Hz, 1H), 4.16 (s, 2H), 3.28 (t, J=5.8Hz, 2H), 3.01 (t, J=5.6Hz, 2H); 13cNMR (100MHz, CDCl 3): δ 150.6,135.2, and 134.6,134.4,132.5,128.9,128.5,126.8,126.4,126.3,125.8,123.0,118.9,113.6,54.5,50.7,29.5; HRMS (ESI) C 17h 18n (M+H) +calculated value be: 236.1434, measured value is: 236.1440.
Embodiment 2
Adopt the method identical with embodiment 1, with sodium tert-butoxide (288mg, 3mmol), substitute potassium tert.-butoxide, obtain 7,11b, 12,13-tetrahydrochysene-6H-isoquinoline 99.9 [2,1-a] quinoline (129mg, 0.55mmol, productive rate 55%).
Embodiment 3
Adopt the method identical with embodiment 1, it is solvent that the dimethyl sulfoxide (DMSO) of take substitutes DMF, obtains 7,11b, 12,13-tetrahydrochysene-6H-isoquinoline 99.9 [2,1-a] quinoline (146mg, 0.62mmol, productive rate 62%).
Embodiment 4
Adopt the method identical with embodiment 1, with 2-(the chloro-2-ethenylphenyl of 5-)-1,2,3,4-tetrahydroisoquinoline (269mg, 1mmol) be reaction raw materials, obtain 3-chloro-7,11b, 12,13-tetrahydrochysene-6H-isoquinoline 99.9 [2,1-a] quinoline (202mg, 0.75mmol, productive rate 75%); 1hNMR (400MHz, CDCl 3): δ 7.42 (d, J=8.2Hz, 1H), 7.22-7.15 (m, 3H), 7.09-7.02 (m, 3H), 6.97 (dd, J=17.8,11.0Hz, 1H), 5.69 (d, J=17.7Hz, 1H), 5.25 (d, J=11.0Hz, 1H), 4.14 (s, 2H), 3.26 (t, J=5.8Hz, 2H), 3.01 (t, J=5.8Hz, 2H); 13c NMR (100MHz, CDCl 3): δ 151.5,134.6, and 134.3,133.9,133.5,130.8,128.9,127.9,126.4,126.4,125.9,122.9,119.2,114.0,54.1,50.6,29.4; HRMS (ESI) C 17h 17clN (M+H) +calculated value be: 270.1044, measured value is: 270.1035.
Embodiment 5
Wherein:
R 1represent C 1～C 10alkyl, phenyl, aminomethyl phenyl, trifluoromethyl, p-methoxy-phenyl, chlorophenyl, bromo phenyl;
R 2represent phenyl, aminomethyl phenyl, trifluoromethyl, p-methoxy-phenyl, chlorophenyl, bromo phenyl, naphthyl, thienyl, furyl, pyridyl, pyrimidyl, quinolyl, benzofuryl;
R 1and R 2also can form tetrahydroisoquinoline ring together with nitrogen-atoms with the carbon atom that they connect, the carbon atom on the phenyl ring in this ring optionally has monosubstituted and two replacements, and substituting group is methoxyl group, methyl, chlorine, bromine, trifluoromethyl;
R 3represent hydrogen, C 1～C 10alkyl, phenyl, aminomethyl phenyl, trifluoromethyl, p-methoxy-phenyl, chlorophenyl, bromo phenyl, vinyl;
R 4represent hydrogen, C 1～C 10alkyl, phenyl, aminomethyl phenyl, trifluoromethyl, p-methoxy-phenyl, chlorophenyl, bromo phenyl;
R 5represent monosubstituted on phenyl ring, substituting group is hydrogen, methyl, trifluoromethyl, methoxyl group, chlorine, bromine, nitro, trifluoromethyl.
Preferably, described alkali is potassium tert.-butoxide.
Preferably, described alkali is 0.5: 1～5: 1 with respect to the mol ratio of the consumption of the 2-aminocarbonyl phenyl alkene shown in formula (III),
More preferably 1.5: 1.
Preferably, described solvent is DMF.
Preferably, the temperature of reaction that described method adopts is 40～140 ℃, more preferably 90 ℃.
Preferably, the reaction times of described method is 0.5～24 hour, more preferably 4 hours.
The method of synthetic nitrogen-containing heterocycle compound of the present invention, have advantages of easy and simple to handle, reaction yield is high, in reaction without using transition-metal catalyst, for the industry preparation of nitrogen-containing heterocycle compound, there is very high practical value.
Embodiment
Below in conjunction with embodiment, the present invention is further elaborated, but these embodiment are not limitations of the present invention.
Embodiment 1
Figure BSA0000093499030000041
Adopt the method identical with embodiment 1, with 2-(5-methoxyl group-2-ethenylphenyl)-1,2,3,4-tetrahydroquinoline (265mg, 1mmol) is reaction raw materials, obtains 3-methoxyl group-7,11b, 12,13-tetrahydrochysene-6H-isoquinoline 99.9 [2,1-a] quinoline (138mg, 0.52mmol, productive rate 52%); 1h NMR (400MHz, CDCl 3): δ 7.46 (d, J=8.5Hz, 1H), 7.17 (m, 3H), 7.09-7.07 (br, 1H), 6.99 (dd, J=17.7,11.1Hz, 1H), 6.66-6.61 (m, 2H), 5.60 (d, J=17.7Hz, 1H), 5.13 (d, J=11.0Hz, 1H), 4.15 (s, 2H), 3.81 (s, 3H), 3.28 (t, J=5.7Hz, 2H), 3.01 (t, J=5.6Hz, 2H); 13c NMR (100MHz, CDCl 3): δ 160.1,151.9, and 135.0,134.5,133.9,128.9,127.7,126.4,126.3,125.8,125.3,111.6,107.5,105.5,55.3,54.3,50.6,29.5; HRMS (ESI) C 18h 20nO (M+H) +calculated value be: 266.1539, measured value is: 266.1532.
Embodiment 6
Figure BSA0000093499030000042
Adopt the method identical with embodiment 1, with 2-(2-(2-methyl-prop-1-alkene-1-yl) phenyl)-1,2,3,4-tetrahydroisoquinoline (263mg, 1mmol) is reaction raw materials, obtain 12,12-dimethyl-7,11b, 12,13-tetrahydrochysene-6H-isoquinoline 99.9 [2,1-a] quinoline (221mg, 0.84mmol, productive rate 84%); 1h NMR (400MHz, CDCl 3): δ ppm7.22-7.15 (m, 4H), 7.11 (t, J=8.0Hz, 1H), 7.01 (d, J=7.4Hz, 1H), 6.69-6.64 (m, 2H), 4.24 (s, 1H), 3.91-3.87 (m, 1H), 3.15-3.09 (m, 1H), 3.07-2.99 (m, 1H), 2.94 (d, J=16.7Hz, 1H), 2.74-2.70 (m, 1H), 2.59-2.55 (d, J=16.7Hz, 1H), 1.04 (s, 3H), 0.71 (s, 3H); 13c NMR (100MHz, CDCl 3): δ 146.4,137.3, and 134.4,129.6,129.5,128.2,126.6,126.4,124.9,121.9,116.4,111.4,65.3,44.5,43.0,34.4,31.4,29.0,21.4; HRMS (ESI) C 19h 22n (M+H) +calculated value be: 264.1747, measured value is: 264.1755.
Embodiment 7
Adopt the method identical with embodiment 1, N-benzyl-N-methyl-2-vinyl aniline of take is reaction raw materials (223mg, 1mmol), obtain 1-methyl-2-phenyl-1,2,3, (ratio is 5: 12,187mg for 4-tetrahydroisoquinoline and 1,3-dimethyl-2-phenylindone morpholine mixture, 0.84mmol, productive rate 84%), 1h NMR (400MHz, CDCl 3): δ 7.47-7.44 (m, 1.7H), 7.40-7.28 (m, 4.9H), 7.25-7.24 (m, 0.2H), 7.22-7.20 (m, 0.2H), 7.19-7.12 (m, 2.9H), 7.07 (d, J=7.3 Hz, 0.2H), 7.04 (d, J=7.2Hz, 1H), 6.97 (d, J=6.8Hz, 0.5H), 6.77 (t, J=7.4Hz, 1H), 6.75-6.74 (m, 0.2H), 6.67 (d, J=8.1Hz, 0.5H), 6.62 (t, J=7.3Hz, 0.5H), 6.57 (m, 0.2H), 4.50-4.46 (m, 0.7H), 3.78 (d, J=10.8Hz, 1H), 3.41 (qd, J=7.8, 7.2, Hz, 0.2H), 3.10 (dq, J=13.4, 6.7Hz, 1H), 2.86 (s, 1.5H), 2.66 (s, 0.6H), 2.59 (s, 4H), 2.21-2.15 (m, 0.5H), 2.04-1.97 (m, 0.5H), 1.32 (d, J=6.7Hz, 3H), 0.74 (d, J=7.3Hz, 0.6H), 13c NMR (100MHz, CDCl 3): δ 152.8,152.7, and 146.2,144.3,141.6,138.5,134.9,133.5,128.6,128.5,128.5,128.3,128.1,127.9,127.8,127.7,127.4,127.3,126.9,126.6,123.7,122.7,122.6,118.4,115.7,110.0,107.5,107.4,81.1,75.0,63.3,45.7,40.9,37.8,34.5,34.4,30.2,24.3,17.1,16.1, HRMS (ESI) C 16h 18n (M+H) +calculated value be: 224.1434, measured value is: 224.1434.
Embodiment 8
Figure BSA0000093499030000051
Adopt the method identical with embodiment 1, N-benzyl-N-methyl-2-(1-phenyl vinyl) aniline (299mg, 1mmol) of take is reaction raw materials, obtains 1-methyl-2,4-phenylbenzene-1,2,3,4-tetrahydroquinoline (239mg, 0.80mmol, productive rate 80%); Cis-isomer/trans-isomer=1: 3, 1hNMR (400MHz, CDCl 3): δ 7.32-7.28 (m, 4.6H), 7.25-7.09 (m, 7.6H), 7.19-7.14 (m, 2H), 78-6.73 (m, 1.3H), 6.66 (d, J=7.4Hz, 1H), 6.59-6.53 (m, 1.6H), 4.49 (dd, J=11.0,4.6Hz, 0.3H), 4.42-4.39 (t, J=5.1Hz, 1H), 4.16 (dd, J=12.2,4.3Hz, 0.3H), 3.85 (dd, J=9.6,4.4Hz, 1H), 2.89 (s, 3H), 2.75 (s, 0.9H), 2.45-2.33 (m, 1.3H), 2.26-2.20 (m, 1.3H). 13c NMR (100MHz, CDCl 3): δ 147.6,146.3, and 145.0,144.2,144.0,129.0,128.7,128.6,128.5,128.4,128.1,127.9,127.7,127.5,127.2,127.0,126.9,126.6,126.3,125.4,116.5,115.8,112.3,110.4,64.9,61.8,44.2,43.0,40.1,38.9,38.0,37.8; HRMS (ESI) C 22h 22n (M+H) +calculated value be: 300.1747, measured value is: 300.1753.
Embodiment 9
Adopt the method identical with embodiment 1, N-benzyl-N-methyl-2-(2-phenyl vinyl) aniline (299mg, 1mmol) of take is reaction raw materials, obtains 3-benzyl-1-methyl-2-phenylindone quinoline (245mg, 0.82mmol, productive rate 82%); 1h NMR (400MHz, CDCl 3): δ 7.28-7.27 (m, 2H), 7.26-7.08 (m, 9H), 6.77 (d, J=7.3Hz, 1H), 6.62 (t, J=7.4Hz, 1H), 6.50 (d, J=7.8Hz, 1H), 4.01 (d, J=9.2Hz, 1H), 3.56 (dt, J=8.1,7.7Hz, 1H), 3.04 (d, J=7.2Hz, 2H), 2.58 (s, 3H); 13c NMR (100MHz, CDCl 3): δ 152.6,141.9, and 139.5,131.6,129.3,128.4,128.3,128.0,127.7,127.6,126.2,123.8,117.7,106.7,77.6,51.4,39.3,33.8; HRMS (ESI) C 22h 22n (M+H) +calculated value be: 300.1747, measured value is: 300.1754.
Embodiment 10
Figure BSA0000093499030000061
Adopt the method identical with embodiment 1, N-methyl-N (quinoline-2-methyl)-2-vinyl aniline (274mg, 1mmol) of take is reaction raw materials, obtain 1-methyl isophthalic acid, 2,3,4-tetrahydrochysene-2-2 '-2 quinoline (211mg, 0.77mmol, productive rate 77%); 1h NMR (400MHz, CDCl 3): 8.08 (d, J=8.4Hz, 2H), 7.80 (d, J=8.1Hz, 1H), 7.72 (t, J=7.6Hz, 1H), 7.52 (t, J=7.4Hz, 1H), 7.31 (d, J=8.5Hz, 1H), 7.19 (t, J=7.7Hz, 1H), 7.01 (d, J=7.3Hz, 1H), 6.74 (d, J=8.2Hz, 1H), 6.68 (t, J=7.3Hz, 1H), 4.78 (d, J=5.0Hz, 1H), 2.92 (s, 3H), 2.72 (dt, J=15.7,5.0Hz, 1H), 2.61-2.53 (m, 1H), 2.32-2.27 (m, 2H); 13c NMR (100MHz, CDCl 3): δ 164.5,147.9, and 145.7,136.8,129.7,128.8,128.6,127.6,127.5,127.4,126.2,122.9,118.9,116.2,110.5,65.9,38.0,28.8,24.8; HRMS (ESI) C 19h 18n 2(M+H) +calculated value be: 275.1543, measured value is: 275.1535.
Embodiment 11
Figure BSA0000093499030000062
Adopt the method identical with embodiment 1, N-methyl-N-(cumarone-2-methyl)-2-vinyl aniline (263mg, 1mmol) of take is reaction raw materials, obtain 2-(furans-2-yl)-1-methyl isophthalic acid, 2,3,4-tetrahydroquinoline (121mg, 0.46mmol, productive rate 46%); 1h NMR (400MHz, CDCl 3): δ 7.44 (t, J=6.8Hz, 2H), 7.24-7.10 (m, 3H), 6.97 (d, J=7.1Hz, 1H), 6.69-6.64 (m, 2H), 6.38 (s, 1H), 4.65 (t, J=4.0Hz, 1H), 3.01 (s, 3H), 2.70-2.65 (m, 2H), 2.43-2.29 (m, 1H), 2.27-2.08 (m, 1H); 13c NMR (100MHz, CDCl 3): δ 158.5,154.9, and 144.9,128.6,128.5,127.3,123.6,122.7,122.3,120.7,116.3,111.0,110.3,103.6,58.1,38.0,26.2,24.3; HRMS (ESI) C 18h 18nO (M+H) +calculated value be: 264.1383, measured value is: 264.1394.

Claims (6)

  1. A synthesis type (I) and (II) shown in the method for nitrogen-containing heterocycle compound, it is characterized in that, 2-aminocarbonyl phenyl alkene shown in employing formula (III) is raw material, under nitrogen protection, add a kind of alkali, in solvent, heat, obtain formula (I) and (II) shown in nitrogen-containing heterocycle compound; Described alkali is potassium tert.-butoxide, sodium tert-butoxide, potassium methylate, sodium methylate; Described solvent is dimethyl sulfoxide (DMSO), DMF, N,N-dimethylacetamide; The compound of described formula (I), formula (II) and formula (III) structure is as follows:
    Figure FSA0000093499020000011
    Wherein:
    R 1represent C 1～C 10alkyl, phenyl, aminomethyl phenyl, trifluoromethyl, p-methoxy-phenyl, chlorophenyl, bromo phenyl;
    R 2represent phenyl, aminomethyl phenyl, trifluoromethyl, p-methoxy-phenyl, chlorophenyl, bromo phenyl, naphthyl, thienyl, furyl, pyridyl, pyrimidyl, quinolyl, benzofuryl;
    R 1and R 2also can form tetrahydroisoquinoline ring together with nitrogen-atoms with the carbon atom that they connect, the carbon atom on the phenyl ring in this ring optionally has monosubstituted and two replacements, and substituting group is methoxyl group, methyl, chlorine, bromine, trifluoromethyl;
    R 3represent hydrogen, C 1～C 10alkyl, phenyl, aminomethyl phenyl, trifluoromethyl, p-methoxy-phenyl, chlorophenyl, bromo phenyl, vinyl;
    R 4represent hydrogen, C 1～C 10alkyl, phenyl, aminomethyl phenyl, trifluoromethyl, p-methoxy-phenyl, chlorophenyl, bromo phenyl;
    R 5represent monosubstituted on phenyl ring, substituting group is hydrogen, methyl, trifluoromethyl, methoxyl group, chlorine, bromine, nitro, trifluoromethyl.
  2. 2. synthetic method according to claim 1, is characterized in that described alkali is potassium tert.-butoxide.
  3. 3. synthetic method according to claim 1, is characterized in that described alkali is 0.5: 1～5: 1 with respect to the mol ratio of the consumption of the 2-aminocarbonyl phenyl alkene shown in formula (III), is preferably 1.5: 1.
  4. 4. synthetic method according to claim 1, is characterized in that described solvent is DMF.
  5. 5. synthetic method according to claim 1, is characterized in that temperature of reaction is 40～140 ℃, is preferably 90 ℃.
  6. 6. synthetic method according to claim 1, is characterized in that the reaction times is 0.5～24 hour, is preferably 4 hours.
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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008031750A2 (en) * 2006-09-15 2008-03-20 F. Hoffmann-La Roche Ag Process for the preparation of pyrido[2,1-a]isoquinoline derivatives by catalytic asymmetric hydrogenation of an enamine

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008031750A2 (en) * 2006-09-15 2008-03-20 F. Hoffmann-La Roche Ag Process for the preparation of pyrido[2,1-a]isoquinoline derivatives by catalytic asymmetric hydrogenation of an enamine

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
DANIEL SEIDEL ET AL: ""Catalytic Enantioselective Intramolecular Redox Reactions: Ring-Fused Tetrahydroquinolines"", 《J. AM. CHEM. SOC》 *
PAUL KNOCHEL ET AL: ""Potassium tert-Butoxide Catalyzed Addition of Carbonyl Derivatives to Styrenes"", 《ORG. LETT》 *
SUNG-GON KIM ET AL: ""Asymmetric synthesis of ring-fused tetrahydroquinolines using organocatalytic enantioselective conjugate addition and cross-dehydrogenative coupling"", 《TETRAHEDRON: ASYMMETRY》 *

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