CN106083716B - A kind of preparation method of 3- aryl isoquinolines compound - Google Patents
A kind of preparation method of 3- aryl isoquinolines compound Download PDFInfo
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- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
- C07D217/16—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals substituted by oxygen atoms
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Abstract
The invention discloses a kind of preparation methods of 3- aryl isoquinolines compound, include the following steps：2- quinoline formyls benzyl amine derivative, alpha-brominated fragrant ethyl ketone, catalyst and additive are added in halogenated hydrocarbon solvent, 80~90 DEG C is heated to and is reacted, after the reaction was complete, post-processing purifying obtains intermediate；Then, intermediate, acid are added in ether solvent, are heated to 110~120 DEG C and are reacted, after the reaction was complete, vacuum distillation removes solvent；Alcohol and alkali are added into mixture, being heated to 60~70 DEG C, the reaction was continued, and after the reaction was complete, post-processing obtains the 3- aryl isoquinolines compounds；The preparation method is easy to operate, and reaction need not carry out under the conditions of anhydrous and oxygen-free, and raw material is commercially available, is simply obtained.
Description
Technical field
The invention belongs to organic synthesis field more particularly to a kind of preparation methods of 3- aryl isoquinolines compound.
Background technology
3- aryl isoquinolines compound is widely present in as a kind of important nitrogen heterocyclic ring structural unit with a variety of lifes
The active two classes quaternary ammonium type morphinane alkaloid of object --- protoberberine (organic chemistry, 2012,32,677-685) and benzo coffee
Pyridine Alkaloid (organic chemistry, 2012,32,1605-1619).Such as with antibacterial (Proc.Natl.Acad.Sci.USA
2000,97,1433-1437), anti-inflammatory (Cancer Lett.2004,203,127-137), anti-diabetic (Metabolism
2010,59,285-292), the jamaicin of the physiological activity such as anti-malarial (Eur.J.Med.Chem.1998,33,65-69)；Have
The fibrauretine of antibacterial activity (Proc.Natl.Acad.Sci.USA 2000,97,1433-1437) bends the red alkali of dish and sanguinarine
(Heterocycles 2006,68,2403-2422)。
Currently, the 3- aryl isoquinolines that document is reported synthesize there are mainly four types of methods used, the first synthetic method
Mainly use Bischler-Napieralski (Chem Ber 1893,26,1903-1908.), Pictet-Spengler
(Chem Ber 1911,44,2030-2036) and Pomeranz-Fritsch (Chem Ber 1893,26,419-422) react.
However, these reaction conditions are violent, substrate applicability is limited, has bigger limitation.Second of synthetic method is urged for palladium
The adjacent iodine imine derivative of change reacts (J.Org.Chem.2002,67,86-94) with terminal aromatic alkynes.However, this method must
Must use the imines of advance halogenation and expensive terminal alkyne substrate, substrate there are larger limitation, limit this method into
One step application.The third synthetic method is the coupling reaction of palladium chtalyst neighbour's bromine acetal derivant and fragrant ethyl ketone.Then, coupling production
Object and ammonia realized by azepine cyclization 3- aryl isoquinolines derivatives synthesis (Angew.Chem.Int.Ed.2014,
53,14555-14558).However, this method using advance halogenation adjacent bromine acetal and need additional step introduce nitrogen-atoms make
Synthesis strategy is cumbersome.Moreover, the fragrant ethyl ketone substrate that α-must be used unsubstituted limits the application of this method.4th kind of synthesis
Method is reacting (Chem.Commun.2015,51,13327-13329) for rhodium catalysis oxime and acetic acid enester.However, this method makes
With expensive rhodium catalyst, and synthesized 3- aryl isoquinolines 1 must be connected with substituent group, and there are larger limitations.
Invention content
The present invention provides a kind of preparation methods of 3- aryl isoquinolines, and the preparation method is easy to operate, and reaction does not need
It carries out, and raw material is commercially available, is simply obtained under the conditions of anhydrous and oxygen-free.
A kind of preparation method of 3- aryl isoquinolines compound, includes the following steps：
(1) 2- quinoline formyls benzyl amine derivative, alpha-brominated fragrant ethyl ketone, catalyst and additive are added to halogenated hydrocarbons
It in class solvent, is heated to 80~90 DEG C and is reacted, after the reaction was complete, post-processing purifying obtains intermediate；
(2) intermediate, acid that step (1) obtains are added in ether solvent, are heated to 110~120 DEG C and are reacted,
After the reaction was complete, vacuum distillation removes solvent, obtains mixture；
(3) alcohol and alkali are added in the mixture obtained to step (2), being heated to 60~70 DEG C, the reaction was continued, and the reaction was complete
Afterwards, post-processing obtains the 3- aryl isoquinolines compounds；
Shown in the structure such as formula (II) of the 2- quinoline formyl benzyl amine derivatives：
Shown in the structure such as formula (III) of the alpha-brominated fragrant ethyl ketone：
Shown in the structure such as formula (IV) of the alpha-brominated fragrant ethyl ketone：
Shown in the structure such as formula (I) of the 3- aryl isoquinolines：
In formula (I)~(IV), R C1~C5Alkyl, C1~C5Alkoxy, halogen；
R1For hydrogen, C1~C5Alkoxy；
The molar ratio of the catalyst and additive is 0.1：1.0~2.0.
Reaction equation is as follows：
It may be N of the catalyst in 2- quinoline formyls benzyl amine derivative (II) in reaction, be catalyzed under the action of N bidentates chelating
Activate the C-H bond at ortho position.And then, activated intermediate obtains alkylate with alpha-brominated fragrant ethyl ketone by coupling reaction
(Ⅳ).Then, imines cyclization/oxygen then occurs under alkaline condition for alkylate (IV) amide hydrolysis in acid condition
Change aromatisation and forms final 3- aryl isoquinolines compounds.Wherein, accelerating agent of the additive as reaction.
In the present invention, available last handling process includes：Filtering, silica gel mixed sample finally purify to obtain by column chromatography
Corresponding 3- aryl isoquinolines compounds use column chromatography purifying for technological means commonly used in the art.
Preferably, R is methyl, methoxyl group, fluorine, at this point, the 2- quinoline formyl benzyl amine derivatives are easy to get, and
And the regioselectivity of reaction is good, reaction yield is higher.
Preferably, R1For hydrogen, methoxyl group, at this point, the production that the alpha-brominated fragrant ethyl ketone is easy to get, and reacts
Rate is higher.
The price of the alpha-brominated fragrant ethyl ketone is relatively inexpensive, commercially available, relative to the 2- quinoline formyl benzylamines
The dosage of derivative is excessive, preferably, with molar amount, alpha-brominated fragrance ethyl ketone：2- quinoline formyl benzyl amine derivatives：It urges
Agent：Additive=2:1:0.1:2.
In the reaction of synthesis key intermediate (IV), additive plays a crucial role reaction, as
It is preferred that the additive is Potassium Benzoate or sodium carbonate.
Preferably, the reaction time is 12 hours, reaction time long increase reaction cost is then difficult to protect on the contrary
Card reacts complete.
In the present invention, the organic solvent that raw material fully dissolves can be made reaction, but reaction efficiency difference is larger；
In the reaction of synthesizing alkylated product (IV), preferably, the halogenated hydrocarbon solvent is 1,2- dichloroethanes；In acidity
In the reaction of hydrolysis, preferably, the ether solvent is Isosorbide-5-Nitrae-dioxane；In synthesis 3- aryl isoquinolines compounds
In reaction, preferably, the alcoholic solvent is methanol.
The dosage of the organic solvent can preferably dissolve raw material, and the 2- quinoline formyl benzylamines of 1.0mmol spread out
The amount for the organic solvent that biology uses is about 8mL.
Preferably, the catalyst is palladium.
Preferably, the acid is hydrochloric acid.
Preferably, the alkali is potassium carbonate.
As a further preference, the 2- quinoline formyl benzylamine intermediates are formula (IV -1)-formula (IV -4) shownization
Close one kind in object：
As a further preference, the 3- aryl isoquinolines are one in compound shown in formula (I-1)-formula (I-4)
Kind：
In formula (I-1)-(I-4) compound represented, (I-1) is known compound.
In above-mentioned preparation method, the alpha-brominated fragrant ethyl ketone and metal salt generally use commercial product, Dou Nengcong
It readily obtains in the market, the 2- quinoline formyls benzyl amine derivative can be simple and efficient by corresponding benzylamine and 2- quinolinecarboxylic acids
Be prepared.
Compared with the existing technology, beneficial effects of the present invention are embodied in：
(1) present invention is that 3- aryl is prepared in raw material by the 2- quinoline formyls benzylamine being easy to get and alpha-brominated fragrant ethyl ketone
Isoquinoline compound, reaction raw materials are easy to get, and substrate designability is strong, can be designed according to actual needs and be synthesized required knot
The compound of structure, application value are higher；
(2) preparation method of the present invention is not necessarily to anhydrous and oxygen-free condition, easily operated, and post-processing is easy；
(3) the invention preparation method reaction condition is mild, and the reaction time is short, and reaction yield is high, after simple
Processing can obtain product.
Specific implementation mode
With reference to specific embodiment, the present invention will be further described.
Catalyst, additive, 2- quinoline formyl benzylamines are added in the Schlenk pipes of 35ml according to the raw material proportioning of table 1
Derivative (II), alpha-brominated fragrant ethyl ketone (III) and halogenated hydrocarbon solvent 8ml, are mixed evenly, according to the reaction item of table 1
After the completion of part reaction, filtering, silica gel mixed sample, by column chromatography, (eluant, eluent is petroleum ether and ethyl acetate, volume ratio=6: 1) pure
Change obtains being alkylated intermediate product (IV) accordingly.Then, it is added in the Schlenk pipes of 35ml according to the raw material proportioning of table 2
It is alkylated intermediate product (IV), acid and ether solvent 9ml, is mixed evenly, reacts and completes according to the reaction condition one of table 2
Afterwards, vacuum distillation removes ether solvent.Then, alcoholic solvent 25mL and alkali are added in the residue of post-processing, according to the anti-of table 2
Answer condition two react after the completion of, filtering, silica gel mixed sample, by column chromatography (eluant, eluent be petroleum ether and ethyl acetate, volume ratio=
20: 1) purifying obtains corresponding 3- aryl isoquinolines compound.Reaction process is shown below：
The reaction condition and result of 1 step of table (1)
The reaction condition and result of 2 step of table (2) and step (3)
In Tables 1 and 2, T is reaction temperature, and t is the reaction time, and Me is methyl, and OMe is methoxyl group.
The structure confirmation data of compound is prepared in Examples 1 to 4：
The 2- quinoline formyl benzylamine intermediates being prepared by embodiment 1 be formula (IV -1) nuclear magnetic resonance (1H NMR、13C
NMR and HRMS) detection data is：
1H NMR(500MHz,CDCl3) δ 8.33 (s, 1H), 8.11 (d, J=8.5Hz, 1H), 8.09 (d, J=8.5Hz,
1H), 8.01 (d, J=8.5Hz, 1H), 7.89 (d, J=8.0Hz, 2H), 7.71 (d, J=8.0Hz, 1H), 7.62 (t, J=
7.5Hz, 1H), 7.47 (t, J=7.5Hz, 1H), 7.39 (t, J=7.5Hz, 1H), 7.26 (t, J=7.5Hz, 2H), 7.10 (m,
2H), 6.96 (d, J=7.0Hz, 1H), 4.59 (d, J=5.5Hz, 2H), 4.45 (s, 2H), 2.38 (s, 3H)；13C NMR
(125MHz,CDCl3)δ198.0,164.2,149.6,146.5,138.3,137.3,136.7,134.8,134.7,133.2,
130.0,129.9,129.2,129.1,128.6,128.5,128.4,128.1,127.9,127.6,118.8,43.5,38.5,
20.1；HRMS(APCI)Calcd for C26H22N2O2[M+H]+395.1754,found395.1744.
The 2- quinoline formyl benzylamine intermediates being prepared by embodiment 2 be formula (IV -2) nuclear magnetic resonance (1H NMR、13C
NMR and HRMS) detection data is：
1H NMR(500MHz,CDCl3) δ 8.70 (s, 1H), 8.22 (t, J=8.5Hz, 1H), 8.20 (t, J=8.5Hz,
1H), 8.08 (m, 3H), 7.83 (d, J=8.0Hz, 1H), 7.73 (t, J=8.0Hz, 1H), 7.58 (t, J=7.5Hz, 1H),
7.52 (t, J=7.5Hz, 1H), 7.41 (t, J=8.0Hz, 2H), 7.24 (t, J=7.5Hz, 1H), 6.88 (d, J=8.5Hz,
1H), 6.79 (t, J=7.5Hz, 1H), 4.72 (s, 2H), 4.69 (d, J=6.5Hz, 2H), 3.96 (s, 3H)；13C NMR
(125MHz,CDCl3)δ198.0,164.2,158.6,150.0,146.5,137.2,136.9,135.4,133.1,129.9,
129.8,129.2,128.7,128.6,128.4,127.7,127.6,125.9,123.4,118.8,109.6,55.7,43.3,
35.7；HRMS(APCI)Calcd for C26H22N2O3[M+H]+411.1703,found411.1691.
The 2- quinoline formyl benzylamine intermediates being prepared by embodiment 3 be formula (IV -3) nuclear magnetic resonance (1H NMR、13C
NMR and HRMS) detection data is：
1H NMR(600MHz,CDCl3) δ 8.64 (s, 1H), 8.23 (d, J=8.4Hz, 1H), 8.15 (d, J=8.4Hz,
1H), 8.13 (d, J=7.8Hz, 1H), 8.02 (d, J=8.4Hz, 2H), 7.85 (d, J=7.8Hz, 1H), 7.76 (t, J=
7.8Hz, 1H), 7.61 (t, J=7.8Hz, 1H), 7.53 (t, J=7.8Hz, 1H), 7.40 (t, J=7.8Hz, 2H), 7.27 (m,
1H), 7.07 (t, J=7.8Hz, 1H), 6.99 (d, J=7.8Hz, 1H), 4.73 (d, J=6.0Hz, 2H), 4.72 (s, 2H)；13C
NMR(150MHz,CDCl3)δ197.6,164.3,163.2,161.6,149.5,146.5,137.6,136.7,133.4,
130.3,129.9,129.4,129.3,129.2,128.8,128.5,128.1,127.8,127.1,124.9,124.8,
118.9,114.6,114.5,43.1,34.9,34.8；HRMS(APCI)calcd forC25H19FN2O2[M+H]+399.1503,
found 399.1495.
The 2- quinoline formyl benzylamine intermediates being prepared by embodiment 4 be formula (IV -4) nuclear magnetic resonance (1H NMR、13C
NMR and HRMS) detection data is：
1H NMR(600MHz,CDCl3) δ 8.51 (s, 1H), 8.30 (d, J=9.0Hz, 1H), 8.27 (d, J=9.0Hz,
1H), 8.18 (d, J=8.4Hz, 1H), 7.86 (d, J=7.2Hz, 1H), 7.74 (t, J=7.8Hz, 1H), 7.66 (d, J=
7.8Hz, 1H), 7.60 (t, J=7.2Hz, 1H), 7.40 (t, J=7.2Hz, 1H), 7.22 (t, J=7.8Hz, 1H), 7.18 (d,
J=7.2Hz, 1H), 7.09 (d, J=7.8Hz, 1H), 6.95 (d, J=8.4Hz, 1H), 6.84 (t, J=7.2Hz, 1H), 4.70
(d, J=5.4Hz, 2H), 4.57 (s, 2H), 3.93 (s, 3H), 2.47 (s, 3H)13C NMR(150MHz,CDCl3)δ200.4,
163.9,158.8,149.6,146.2,138.5,137.8,135.5,134.8,133.7,130.7,130.3,129.9,
129.7,129.4,129.3,128.3,128.1,128.0,127.7,120.8,119.1,111.7,55.7,48.8,38.8,
20.2；HRMS(ESI)calcd for C27H24N2O3[M+H]+425.1860,found 425.1859.
The 3- aryl isoquinolines products being prepared by embodiment 1 be formula (I-1) nuclear magnetic resonance (1HNMR、13C NMR and
HRMS) detection data is：
1H NMR(500MHz,CDCl3) δ 8.33 (s, 1H), 8.11 (d, J=8.5Hz, 1H), 8.09 (d, J=8.5Hz,
1H), 8.01 (d, J=8.5Hz, 1H), 7.89 (d, J=8.0Hz, 2H), 7.71 (d, J=8.0Hz, 1H), 7.62 (t, J=
7.5Hz, 1H), 7.47 (t, J=7.5Hz, 1H), 7.39 (t, J=7.5Hz, 1H), 7.26 (t, J=7.5Hz, 2H), 7.10 (m,
2H), 6.96 (d, J=7.0Hz, 1H), 4.59 (d, J=5.5Hz, 2H), 4.45 (s, 2H), 2.38 (s, 3H)；13C NMR
(125MHz,CDCl3)δ198.0,164.2,149.6,146.5,138.3,137.3,136.7,134.8,134.7,133.2,
130.0,129.9,129.2,129.1,128.6,128.5,128.4,128.1,127.9,127.6,118.8,43.5,38.5,
20.1；HRMS(APCI)Calcd for C26H22N2O2[M+H]+395.1754,found 395.1744.
The 3- aryl isoquinolines products being prepared by embodiment 2 be formula (I-2) nuclear magnetic resonance (1HNMR、13C NMR and
HRMS) detection data is：
1H NMR(500MHz,CDCl3) δ 8.70 (s, 1H), 8.22 (t, J=8.5Hz, 1H), 8.20 (t, J=8.5Hz,
1H), 8.08 (m, 3H), 7.83 (d, J=8.0Hz, 1H), 7.73 (t, J=8.0Hz, 1H), 7.58 (t, J=7.5Hz, 1H),
7.52 (t, J=7.5Hz, 1H), 7.41 (t, J=8.0Hz, 2H), 7.24 (t, J=7.5Hz, 1H), 6.88 (d, J=8.5Hz,
1H), 6.79 (t, J=7.5Hz, 1H), 4.72 (s, 2H), 4.69 (d, J=6.5Hz, 2H), 3.96 (s, 3H)；13C NMR
(125MHz,CDCl3)δ198.0,164.2,158.6,150.0,146.5,137.2,136.9,135.4,133.1,129.9,
129.8,129.2,128.7,128.6,128.4,127.7,127.6,125.9,123.4,118.8,109.6,55.7,43.3,
35.7；HRMS(APCI)Calcd for C26H22N2O3[M+H]+411.1703,found411.1691.
The 3- aryl isoquinolines products being prepared by embodiment 3 be formula (I-3) nuclear magnetic resonance (1HNMR、13C NMR and
HRMS) detection data is：
1H NMR(600MHz,CDCl3) δ 8.64 (s, 1H), 8.23 (d, J=8.4Hz, 1H), 8.15 (d, J=8.4Hz,
1H), 8.13 (d, J=7.8Hz, 1H), 8.02 (d, J=8.4Hz, 2H), 7.85 (d, J=7.8Hz, 1H), 7.76 (t, J=
7.8Hz, 1H), 7.61 (t, J=7.8Hz, 1H), 7.53 (t, J=7.8Hz, 1H), 7.40 (t, J=7.8Hz, 2H), 7.27 (m,
1H), 7.07 (t, J=7.8Hz, 1H), 6.99 (d, J=7.8Hz, 1H), 4.73 (d, J=6.0Hz, 2H), 4.72 (s, 2H)；13C
NMR(150MHz,CDCl3)δ197.6,164.3,163.2,161.6,149.5,146.5,137.6,136.7,133.4,
130.3,129.9,129.4,129.3,129.2,128.8,128.5,128.1,127.8,127.1,124.9,124.8,
118.9,114.6,114.5,43.1,34.9,34.8；HRMS(APCI)calcd for C25H19FN2O2[M+H]+399.1503,
found 399.1495.
The 3- aryl isoquinolines products being prepared by embodiment 4 be formula (I-4) nuclear magnetic resonance (1HNMR、13C NMR and
HRMS) detection data is：
1H NMR(600MHz,CDCl3) δ 8.51 (s, 1H), 8.30 (d, J=9.0Hz, 1H), 8.27 (d, J=9.0Hz,
1H), 8.18 (d, J=8.4Hz, 1H), 7.86 (d, J=7.2Hz, 1H), 7.74 (t, J=7.8Hz, 1H), 7.66 (d, J=
7.8Hz, 1H), 7.60 (t, J=7.2Hz, 1H), 7.40 (t, J=7.2Hz, 1H), 7.22 (t, J=7.8Hz, 1H), 7.18 (d,
J=7.2Hz, 1H), 7.09 (d, J=7.8Hz, 1H), 6.95 (d, J=8.4Hz, 1H), 6.84 (t, J=7.2Hz, 1H), 4.70
(d, J=5.4Hz, 2H), 4.57 (s, 2H), 3.93 (s, 3H), 2.47 (s, 3H)13C NMR(150MHz,CDCl3)δ200.4,
163.9,158.8,149.6,146.2,138.5,137.8,135.5,134.8,133.7,130.7,130.3,129.9,
129.7,129.4,129.3,128.3,128.1,128.0,127.7,120.8,119.1,111.7,55.7,48.8,38.8,
20.2；HRMS(ESI)calcd for C27H24N2O3[M+H]+425.1860,found 425.1859。
Claims (10)
1. a kind of preparation method of 3- aryl isoquinolines compound, which is characterized in that include the following steps：
(1) that 2- quinoline formyls benzyl amine derivative, alpha-brominated fragrant ethyl ketone, catalyst and additive are added to halogenated hydrocarbon is molten
It in agent, is heated to 80~90 DEG C and is reacted, after the reaction was complete, post-processing purifying obtains intermediate；
(2) intermediate, acid that step (1) obtains are added in ether solvent, are heated to 110~120 DEG C and are reacted, reacted
After completely, vacuum distillation removes solvent, obtains mixture；
(3) alcohol and alkali are added in the mixture obtained to step (2), being heated to 60~70 DEG C, the reaction was continued, after the reaction was complete, after
Processing obtains the 3- aryl isoquinolines compounds；
Shown in the structure such as formula (II) of the 2- quinoline formyl benzyl amine derivatives：
Shown in the structure such as formula (III) of the alpha-brominated fragrant ethyl ketone：
Shown in the structure of the intermediate such as formula (IV)：
Shown in the structure such as formula (I) of the 3- aryl isoquinolines compounds：
In formula (I)~(IV), R C1~C5Alkyl, C1~C5Alkoxy, halogen；
R1For hydrogen, C1~C5Alkoxy；
The molar ratio of the catalyst and additive is 0.1：1.0~2.0.
2. the preparation method of 3- aryl isoquinolines compound according to claim 1, which is characterized in that R is methyl, methoxy
Base or fluorine.
3. the preparation method of 3- aryl isoquinolines compound according to claim 1 or 2, which is characterized in that R1For hydrogen, first
Oxygroup.
4. the preparation method of 3- aryl isoquinolines compound according to claim 1, which is characterized in that in step (1), with
Molar amount, alpha-brominated fragrance ethyl ketone：2- quinoline formyl benzyl amine derivatives：Catalyst：Additive=2:1:0.1:2.
5. the preparation method of 3- aryl isoquinolines compound according to claim 1, which is characterized in that in step (1), institute
The additive stated is Potassium Benzoate or sodium carbonate.
6. the preparation method of 3- aryl isoquinolines compound according to claim 1, which is characterized in that step (1)~(3)
In, the halogenated hydrocarbon solvent is 1,2- dichloroethanes, and the ether solvent is Isosorbide-5-Nitrae-dioxane, and the alcohol is first
Alcohol.
7. the preparation method of 3- aryl isoquinolines compound according to claim 1, which is characterized in that in step (1), institute
The catalyst stated is palladium.
8. the preparation method of 3- aryl isoquinolines compound according to claim 1, which is characterized in that in step (2), institute
The acid stated is hydrochloric acid.
9. the preparation method of 3- aryl isoquinolines compound according to claim 1, which is characterized in that in step (3), institute
The alkali stated is potassium carbonate.
10. the preparation method of 3- aryl isoquinolines compound according to claim 1, which is characterized in that the 3- virtues
Base isoquinoline compound is one kind in compound shown in formula (I-1)-formula (I-4)：
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