KR102060527B1 - 4 Ring-fused N-heterocycles having luminescent properties and Preparation method thereof - Google Patents

Abstract

The present invention relates to a tetracyclic conjugated N-heterocyclic compound having luminescent properties and a method for preparing the same.

Description

4 ring-fused N-heterocycles having luminescent properties and preparation method thereof

The present invention relates to a tetracyclic conjugated N-heterocyclic compound having luminescent properties and a method for preparing the same.

The multi-junction N-heterocyclic compound has attracted attention as a drug candidate because of its excellent physiological activity and is used as an important base material in electronic materials such as being used as a hole transporting material (HTM) of an organic light emitting diode. (a) J. Org. Chem. 2001, 66, 412, b) J. Med. Chem. 1995, 38, 669].

Recently, conjugated aromatic cyclic compounds containing nitrogen atoms such as azacorannulene or azafullerene have been found to have electronic and optically interesting characteristics in energy conversion applications.

Thus, various methods have been devised to synthesize multiple conjugated N-heterocyclic compounds. The ideal method is to succeed stereospecific, substituent specific and position specific reactions from ordinary starting materials. Various studies are needed on how to make cyclized organic materials atomically-economically from acyclic starting materials [a) Nat. Commun. 2015, 6, 8215, b) Angew. Chem. Int. Ed. 2010, 49, 6764; Angew. Chem. 2010, 122, 6916.

The first problem to be solved by the present invention is to provide a novel tetracyclic conjugated N-heterocyclic compound having luminescent properties.

The second problem to be solved by the present invention is to provide a method for producing the novel 4-ring conjugated N-heterocyclic compound.

In order to achieve the above object, the present invention provides a compound represented by the following formula (1):

[Formula 1]

In the formula,

는 단일 또는 이중결합이고,

Is a single or double bond,

A is 5-6 membered heterocyclic or 5-6 membered heteroaryl, including a nitrogen atom,

R ₁ is hydrogen, straight or branched C _{1 - 6} alkyl and is selected from CO ₂ R _a,

_{R 2, R 3, R 4} , R 5 and R ₆ are the same or different and each is independently hydrogen, halo, straight or branched C ₁ to each other _{- 6} alkyl, CO ₂ R _a, C _{1 - 6} alkyl Selected from oxy, trihalomethyl, phenyl and benzyl,

R ₇ is straight or branched C _{1 - 6} alkyl is selected from _6-alkyl, C _{3 - - 7} cycloalkyl, aryl, heteroaryl, aryl C _1-6 alkyl and heteroaryl C _1; And the aryl or aryl C _{1 - 6} alkyl, aryl is phenyl or naphthyl; Wherein the heteroaryl or heteroaryl C _{1 - 6} alkyl heteroaryl is N, O, and 5-6 membered having from 1 to 2 heteroatoms selected from S-heteroaryl, 1H- indolyl or quinolinyl 1H- and; Wherein the aryl, heteroaryl, aryl C _{1 - 6} alkyl and heteroaryl C _{1- 6} alkyl, each independently unsubstituted or substituted by halo, straight or branched C _1-6 alkyl, C _{1 - 6} alkyloxy, trihalomethyl May be substituted with 1 to 3 substituents selected from rommethyl, -COOH, -CHO, -COOR _b , phenyl and benzyl,

R _a and R _b are the same or different and each is independently a straight or branched C ₁ to each other _- a ₆ alkyl.

In the present invention, the compound of Formula 1 may be represented by the following formula (2) or formula (3).

[Formula 2]

[Formula 3]

In the formula,

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ and R ₆ are as previously described,

R ₈ is straight or branched C _{1 - 6} alkyl, C _{3 - 7} is selected from cycloalkyl, aryl, and heteroaryl, wherein the aryl is phenyl or naphthyl; The heteroaryl is 5-6 membered heteroaryl having 1 to 2 heteroatoms selected from N, O and S, 1H-indolyl or 1H-quinolinyl, and the aryl and heteroaryl are each independently unsubstituted or or halo, straight or branched C _{1 - 6} alkyl, C _{1 - 6} alkyl optionally substituted by oxy, methyl, -COOH, -CHO, -COOR _b, phenyl and benzyl 1 to 3 substituents selected from trihaloalkyl Can,

R _b is a straight or branched C _{1 - 6} is alkyl.

According to the present invention, the compound represented by Formula 1 may be that R ₁ is CO ₂ Et.

According to the present invention, the compound represented by Formula 2 or Formula 3

R ₁ is CO ₂ Et,

R ₈ is straight or branched C _{1 - 6} is selected from alkyl, aryl and heteroaryl, wherein the aryl is phenyl or naphthyl; The heteroaryl is a 5-6 membered heteroaryl having 1 to 2 heteroatoms selected from O and S; Wherein aryl and heteroaryl are each independently unsubstituted or substituted by halo, straight or branched C _{1 - 6} is alkyloxy, selected from methyl, -COOH, -CHO and -COOR _b trihaloalkyl _{- 6} alkyl, C ₁ May be substituted with 1 to 3 substituents,

R _b is a straight or branched C _{1 - 6} alkyl which may be one.

In the present invention, the compound of formula 1 is ethyl (Z) -6-benzylidene-6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6- (4-methylbenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6- (4- (methoxycarbonyl) benzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6- (4-formylbenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6- (4- (trifluoromethyl) benzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6- (4-fluorobenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6- (2-methylbenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6- (3-methoxybenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6- (3-chlorobenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6- (3-chlorobenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6- (thiophen-2-ylmethylene) -6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6- (naphthalen-2-ylmethylene) -6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6-benzylidene-2-methoxy-6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6-benzylidene-2- (trifluoromethyl) -6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6-benzylidene-8-methoxy-6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6-benzylidene-8-bromo-6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl 5-phenylindolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 5- (p-tolyl) indolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 5- (4- (methoxycarbonyl) phenyl) indolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 5- (4-formylphenyl) indolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 5- (4- (trifluoromethyl) phenyl) indolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 5- (4-fluorophenyl) indolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 5- (o-tolyl) indolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 5- (3-methoxyphenyl) indolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 5- (3-chlorophenyl) indolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 5-hexyl indolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 5- (thiophen-2-yl) indolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 5- (naphthalen-2-yl) indolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 10-methoxy-5-phenylindolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 5-phenyl-10- (trifluoromethyl) indolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 3-methoxy-5-phenylindolo [2,1-a] isoquinoline-12-carboxylate; And

Ethyl 3-bromo-5-phenylindolo [2,1-a] isoquinoline-12-carboxylate; may be selected from the group consisting of.

The present invention provides a method for preparing a compound represented by Chemical Formula 1, comprising refluxing a compound of Chemical Formula 3 under a transition metal catalyst to form an intramolecular ring bond:

 [Formula 3]

In formula, R <_1> , R <_2> , R <_3> , R <_4> , R <_5> and R <_6> are as having shown to Formula (2) or (3).

In the production method of the present invention, the transition metal catalyst may be selected from Pd (OAc) ₂ , PtCl ₄ and AuCl ₃ .

When the transition metal catalyst is Pd (OAc) ₂ , α-addition reaction (5-exo-dig cyclization) may be formed to form a compound represented by Chemical Formula 2.

When the transition metal catalyst is PtCl ₄ or AuCl ₃ , β-addition reaction (6-endo-dig cyclization) may be formed to form a compound represented by Chemical Formula 3.

According to the present invention, the transition metal catalyst may be added in 2 to 20 mol%.

The present invention can synthesize multiple conjugated N-heterocyclic compounds that are atom-economically cyclized organics from acyclic starting materials. Since the multi-conjugated N-heterocyclic compound according to the present invention may exhibit luminescent properties, materials requiring luminescent properties, such as dyes, DNA staining, herbicides, OLEDs, OPVs, biosensors, cell imaging probes, etc. It is possible to apply.

Hereinafter, the present invention will be described in more detail.

The present invention provides a compound represented by Formula 1:

[Formula 1]

In the formula,

는 단일 또는 이중결합이고,

Is a single or double bond,

A is 5-6 membered heterocyclic or 5-6 membered heteroaryl, including a nitrogen atom,

R ₁ is hydrogen, straight or branched C _{1 - 6} alkyl and is selected from CO ₂ R _a,

_{R 2, R 3, R 4} , R 5 and R ₆ are the same or different and each is independently hydrogen, halo, straight or branched C ₁ to each other _{- 6} alkyl, CO ₂ R _a, C _{1 - 6} alkyl Selected from oxy, trihalomethyl, phenyl and benzyl,

R ₇ is straight or branched C _{1 - 6} alkyl is selected from _6-alkyl, C _{3 - - 7} cycloalkyl, aryl, heteroaryl, aryl C _1-6 alkyl and heteroaryl C _1; And the aryl or aryl C _{1 - 6} alkyl, aryl is phenyl or naphthyl; Wherein the heteroaryl or heteroaryl C _{1 - 6} alkyl heteroaryl is N, O, and 5-6 membered having from 1 to 2 heteroatoms selected from S-heteroaryl, 1H- indolyl or quinolinyl 1H- and; Wherein the aryl, heteroaryl, aryl C _{1 - 6} alkyl and heteroaryl C _{1- 6} alkyl, each independently unsubstituted or substituted by halo, straight or branched C _1-6 alkyl, C _{1 - 6} alkyloxy, trihalomethyl May be substituted with 1 to 3 substituents selected from rommethyl, -COOH, -CHO, -COOR _b , phenyl and benzyl,

R _a and R _b are the same or different and each is independently a straight or branched C ₁ to each other _- a ₆ alkyl.

In the present invention, the straight-chain or branched C _{1 - 6} alkyl is methyl, ethyl, n- propyl, isopropyl, n- butyl, isobutyl, tert- butyl, n- pentyl, isopentyl, n- hexyl, and It may be selected from isohexyl, but is not limited thereto.

In the present invention, the compound of Formula 1 may be a compound represented by the following formula (2) or (3).

[Formula 2]

[Formula 3]

In the formula,

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ and R ₆ are the same as shown in Chemical Formula 1,

R ₈ is straight or branched C _{1 - 6} alkyl, C _{3 - 7} is selected from cycloalkyl, aryl, and heteroaryl, wherein the aryl is phenyl or naphthyl; The heteroaryl is 5-6 membered heteroaryl having 1 to 2 heteroatoms selected from N, O and S, 1H-indolyl or 1H-quinolinyl, and the aryl and heteroaryl are each independently unsubstituted or or halo, straight or branched C _{1 - 6} alkyl, C _{1 - 6} alkyl optionally substituted by oxy, methyl, -COOH, -CHO, -COOR _b, phenyl and benzyl 1 to 3 substituents selected from trihaloalkyl Can,

R _b is a straight or branched C _{1 - 6} is alkyl.

According to the present invention, a preferred compound represented by the formula (1) may be that R ₁ is CO ₂ Et.

According to the present invention, a preferred compound represented by Formula 1 may be a compound represented by Formula 2 or Formula 3, more preferably R ₁ is CO ₂ Et; R ₈ is straight or branched C _{1 - 6} is selected from alkyl, aryl and heteroaryl, wherein the aryl is phenyl or naphthyl; The heteroaryl is a 5-6 membered heteroaryl having 1 to 2 heteroatoms selected from O and S; Wherein aryl and heteroaryl are each independently unsubstituted or substituted by halo, straight or branched C _{1 - 6} is alkyloxy, selected from methyl, -COOH, -CHO and -COOR _b trihaloalkyl _{- 6} alkyl, C ₁ May be substituted with 1 to 3 substituents,

R _b is a straight or branched C _{1 - 6} may be alkyl.

In the present invention, Et means ethyl.

In the present invention, particularly preferred compounds of formula 1 are ethyl (Z) -6-benzylidene-6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6- (4-methylbenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6- (4- (methoxycarbonyl) benzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6- (4-formylbenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6- (4- (trifluoromethyl) benzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6- (4-fluorobenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6- (2-methylbenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6- (3-methoxybenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6- (3-chlorobenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6- (3-chlorobenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6- (thiophen-2-ylmethylene) -6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6- (naphthalen-2-ylmethylene) -6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6-benzylidene-2-methoxy-6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6-benzylidene-2- (trifluoromethyl) -6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6-benzylidene-8-methoxy-6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl (Z) -6-benzylidene-8-bromo-6H-isoindolo [2,1-a] indole-11-carboxylate;

Ethyl 5-phenylindolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 5- (p-tolyl) indolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 5- (4- (methoxycarbonyl) phenyl) indolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 5- (4-formylphenyl) indolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 5- (4- (trifluoromethyl) phenyl) indolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 5- (4-fluorophenyl) indolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 5- (o-tolyl) indolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 5- (3-methoxyphenyl) indolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 5- (3-chlorophenyl) indolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 5-hexyl indolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 5- (thiophen-2-yl) indolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 5- (naphthalen-2-yl) indolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 10-methoxy-5-phenylindolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 5-phenyl-10- (trifluoromethyl) indolo [2,1-a] isoquinoline-12-carboxylate;

Ethyl 3-methoxy-5-phenylindolo [2,1-a] isoquinoline-12-carboxylate; And

Ethyl 3-bromo-5-phenylindolo [2,1-a] isoquinoline-12-carboxylate; but may be selected from the group consisting of, but is not limited thereto.

According to the present invention, the reaction may be to emit fluorescence.

According to the present invention, the compound of Formula 2 may be a Z-isomer or an E-isomer.

The present invention provides a method for preparing a compound represented by Chemical Formula 1, comprising refluxing a compound of Chemical Formula 3 under a transition metal catalyst to form an intramolecular ring bond:

 [Formula 3]

[Formula 1]

In the formula,

는 단일 또는 이중결합이고,

Is a single or double bond,

A is 5-6 membered heterocyclic or 5-6 membered heteroaryl, including a nitrogen atom,

R ₁ is hydrogen, straight or branched C _{1 - 6} alkyl and is selected from CO ₂ R _a,

_{R 2, R 3, R 4} , R 5 and R ₆ are the same or different and each is independently hydrogen, halo, straight or branched C ₁ to each other _{- 6} alkyl, CO ₂ R _a, C _{1 - 6} alkyl Selected from oxy, trihalomethyl, phenyl and benzyl,

R ₇ is straight or branched C _{1 - 6} alkyl is selected from _6-alkyl, C _{3 - - 7} cycloalkyl, aryl, heteroaryl, aryl C _1-6 alkyl and heteroaryl C _1; And the aryl or aryl C _{1 - 6} alkyl, aryl is phenyl or naphthyl; Wherein the heteroaryl or heteroaryl C _{1 - 6} alkyl heteroaryl is N, O, and 5-6 membered having from 1 to 2 heteroatoms selected from S-heteroaryl, 1H- indolyl or quinolinyl 1H- and; Wherein the aryl, heteroaryl, aryl C _{1 - 6} alkyl and heteroaryl C _{1- 6} alkyl, each independently unsubstituted or substituted by halo, straight or branched C _1-6 alkyl, C _{1 - 6} alkyloxy, trihalomethyl May be substituted with 1 to 3 substituents selected from rommethyl, -COOH, -CHO, -COOR _b , phenyl and benzyl,

R _a and R _b are the same or different and each is independently a straight or branched C ₁ to each other _- a ₆ alkyl.

In the present invention, the reaction is carried out in a one-pot reaction, and thus is atomic-economic.

In the present invention, the reaction may be an intramolecular cyclization reaction, specifically, α-addition reaction (5-exo-dig cyclization) by CH bond activation or β-addition reaction by π bond activation (6- endo-dig cyclization).

In the present invention, the form of the intramolecular cyclization reaction may vary depending on the transition metal catalyst used in the reaction.

In the production method of the present invention, the transition metal catalyst may be selected from Pd (OAc) ₂ , PtCl ₄ and AuCl ₃ .

In the reaction of the present invention, when the transition metal catalyst is Pd (OAc) ₂ , α-addition reaction (5-exo-dig cyclization) may be formed to form a compound represented by the following Chemical Formula 2.

[Formula 2]

In the reaction of the present invention, when the transition metal catalyst is PtCl ₄ or AuCl ₃ , β-addition reaction (6-endo-dig cyclization) may be formed to form the compound represented by Chemical Formula 3.

[Formula 3]

In Chemical Formula 2 or Chemical Formula 3,

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ and R ₆ are as previously described,

R ₈ is straight or branched C _{1 - 6} alkyl, C _{3 - 7} is selected from cycloalkyl, aryl, and heteroaryl, wherein the aryl is phenyl or naphthyl; The heteroaryl is 5-6 membered heteroaryl having 1 to 2 heteroatoms selected from N, O and S, 1H-indolyl or 1H-quinolinyl, and the aryl and heteroaryl are each independently unsubstituted or or halo, straight or branched C _{1 - 6} alkyl, C _{1 - 6} alkyl optionally substituted by oxy, methyl, -COOH, -CHO, -COOR _b, phenyl and benzyl 1 to 3 substituents selected from trihaloalkyl Can,

R _b is a straight or branched C _{1 - 6} is alkyl.

According to the present invention, when the transition metal catalyst is Pd (OAc) ₂ , it is preferable to further include PPh ₃ as a ligand in the reaction, and more preferably 5 to 20 mol%.

According to the present invention, the reaction can take place in an organic solvent, the organic solvent is not particularly limited, C _{1 - 4} alcohols, toluene, acetonitrile, dichloromethane, dichloroethane, tetrahydrofuran, ethyl acetate, 1 It may be selected from the group consisting of, 4-dioxane, N, N- dimethylformamide and dimethyl sulfoxide, preferably toluene is less side reactions and excellent reaction yield.

According to the invention, the reaction may be carried out under reflux conditions, preferably may be carried out at 70 to 120 ℃.

According to the present invention, the α-addition reaction may be completed in minutes, and the β-addition reaction may be completed in minutes to several hours.

According to the present invention, the transition metal catalyst may be added in 2 to 20 mol%.

According to the present invention, the compound represented by Chemical Formula 2 may be prepared as Z-isomer, and may be converted to E-isomer by acid treatment. The acid treatment is not particularly limited as long as it is commonly used for isomerization, and may be, for example, reacting in an aqueous HCl solution, and may be achieved by further including heating during the reaction.

The compound represented by Chemical Formula 2 according to the present invention may be used as an intermediate for preparing various compounds by substituting a double bond.

Examples of using the compound according to the present invention as an intermediate may include the following reactions, but the following reactions are exemplary and not limited thereto.

Example

Hereinafter, the present invention will be described in more detail with reference to preferred examples. However, these examples are intended to more specifically to the present invention, it will be apparent to those skilled in the art that the scope of the present invention is not limited thereby.

Example 1 Synthesis of Ethyl (Z) -6-benzylidene-6H-isoindolo [2,1-a] indole-11-carboxylate

Ethyl 2-phenyl-1- (phenylethynyl) -1H-indole-3-carboxylate (73.1 mg, 0.2 mmol), Pd (OAc) ₂ (2.3 mg, 0.01 mmol), PPh ₃ (5.3) mg, 0.02 mmol) and toluene (1 mL) were placed in a capped vial. The reaction mixture was allowed to react (10-60 minutes) until stirring of the starting material was confirmed on ¹ H NMR with stirring at 80 ° C. in an aluminum block. After cooling to room temperature, the reaction mixture was immediately placed in a silica gel column loaded with 2-3 drops of ammonia water with hexane: ether = 9: 1 added as a base, and then purified with the same solvent to obtain a desired compound. In order to avoid the formation of isomers, the reaction product was purified immediately after the completion of the reaction, and stored at a temperature of -20 ° C. or less because it tends to be isomerized slowly at room temperature.

5 min reaction time, 99% yield, yellow solid

Mp = 157-158 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.77-8.68 (m, 1H), 8.18 (d, J = 7.9 Hz, 1H), 7.73 (d, J = 6.9 Hz, 1H), 7.55-7.33 (m, 7H), 7.14 (t, J = 7.4 Hz, 1H), 7.05 (s, 1H), 6.88-6.77 (m, 1H), 6.04 (d, J = 8.4 Hz, 1H), 4.53 (q, J = 7.1 Hz, 2H), 1.54 (t, J = 7.1 Hz, 3H); ¹³ C NMR (151 MHz, CDCl ₃ ) δ 165.1, 148.0, 140.5, 135.6, 134.0, 132.5, 131.6, 130.1, 129.2, 129.0, 128.5, 128.1, 125.4, 122.8, 122.4, 119.9, 114.9, 109.3, 102.9, 60.1 , 14.6 (two carbon peaks are overlapped); IR (ATR): 3049, 2972, 1688, 1600, 1565, 1438 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₅ H ₁₉ NO ₂ [M + H] ⁺ 366.1489, found 366.1490.

Example 2 Synthesis of Ethyl (Z) -6- (4-methylbenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate

Reaction time 10 minutes, yield 92%, yellow solid

Mp = 143-148 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.73 (d, J = 7.4 Hz, 1H), 8.20 (d, J = 8.0 Hz, 1H), 7.72 (d, J = 6.9 Hz, 1H), 7.46 (dd , J = 13.8, 7.0 Hz, 2H), 7.21 (dt, J = 17.8, 7.9 Hz, 5H), 7.01 (s, 1H), 6.87 (t, J = 7.6 Hz, 1H), 6.16 (d, J = 8.4 Hz, 1H), 4.54 (q, J = 14.2, 7.1 Hz, 2H), 2.43 (s, 3H), 1.55 (t, J = 7.1 Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 165.1, 147.9, 140.5, 138.0, 133.3, 132.4, 132.3, 131.5, 129.9, 129.1, 128.9, 128.8, 125.3, 122.6, 122.3, 119.7, 115.1, 109.6, 102.5, 60.1 21.4, 14.6 (two carbon peaks are overlapped); IR (ATR): 3053, 2956, 1666, 1562, 1443, 1407, 1383, 1154 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₆ H ₂₁ NO ₂ [M + H] ⁺ 380.1645, found 380.1646.

Example 3 Synthesis of Ethyl (Z) -6- (4- (methoxycarbonyl) benzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate

Reaction time 15 minutes, yield 93%, yellow solid

Mp = 121-123 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.72 (d, J = 7.3 Hz, 1H), 8.18 (d, J = 8.2 Hz, 1H), 8.07 (d, J = 8.3 Hz, 2H), 7.75 (d , J = 7.7 Hz, 1H), 7.54-7.39 (m, 4H), 7.15 (t, J = 7.6 Hz, 1H), 7.01 (s, 1H), 6.86 (t, J = 7.8 Hz, 1H), 6.05 (d, J = 8.4 Hz, 1H), 4.53 (q, J = 7.1 Hz, 2H), 3.96 (s, 3H), 53 (t, J = 7.1 Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 166.6, 164.9, 147.9, 140.3, 140.2, 134.7, 132.2, 131.5, 130.0, 129.9, 129.6, 129.5, 129.2, 129.1, 125.5, 123.1, 122.7, 122.6, 120.1, 114.9 , 107.7, 103.5, 60.2, 52.2, 14.6; IR (ATR): 3054, 2920, 2850, 1716, 1668, 1602, 1563, 1469, 1440 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₇ H ₂₁ NO ₄ [M + H] ⁺ 424.1543, found 424.1545.

Example 4 Synthesis of Ethyl (Z) -6- (4-formylbenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate

Reaction time 15 minutes, yield 96%, yellow solid

Mp = 132-134 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 10.04 (s, 1H), 8.72 (d, J = 7.0 Hz, 1H), 8.19 (d, J = 7.9 Hz, 1H), 7.90 (d, J = 8.0 Hz , 2H), 7.72 (dd, J = 21.3, 7.4 Hz, 2H), 7.49 (dd, J = 16.2, 7.7 Hz, 3H), 7.20-7.08 (m, 1H), 7.00 (s, 1H), 6.91- 6.77 (m, 1 H), 6.04 (d, J = 7.9 Hz, 1 H), 4.61-4.43 (m, 2H), 1.63-1.44 (m, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 191.3, 164.8, 147.9, 141.9, 140.4, 135.4, 135.3, 132.4, 131.7, 130.6, 129.8, 129.7, 129.4, 129.1, 125.6, 123.2, 122.9, 122.8, 120.1, 114.8 , 107.2, 104.0, 60.2, 14.6; IR (ATR): 3047, 2921, 2851, 1685, 1652, 1561, 1441, 1146 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₆ H ₁₉ NO ₃ [M + H] ⁺ 394.1438, found 394.1434.

Example 5 Synthesis of Ethyl (Z) -6- (4- (trifluoromethyl) benzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate

Reaction time 10 minutes, yield 96%, yellow solid

Mp = 152-154 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.68 (d, J = 7.5 Hz, 1H), 8.17 (d, J = 8.0 Hz, 1H), 7.75-7.55 (m, 3H), 7.55-7.33 (m, 4H), 7.15 (t, J = 7.6 Hz, 1H), 6.91 (s, 1H), 6.84 (t, J = 7.8 Hz, 1H), 5.90 (d, J = 8.4 Hz, 1H), 4.51 (q, J = 7.1 Hz, 2H), 1.53 (t, J = 7.1 Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 164.9, 147.9, 140.2, 139.2, 134.9, 132.2, 131.6, 130.3, 129.9 (q, J _{F -C} = 32.25 Hz), 129.6, 129.2, 129.1, 125.5, 125.3 ( q, J _{F -C} = 3.75 Hz), 124.0 (q, J _{F -C} = 270.75 Hz), 123.1, 122.7, 122.7, 120.0, 114.7, 106.9, 103.6, 60.3, 14.6; IR (ATR): 3055, 2986, 2921, 1694, 1582, 1441, 1318 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₆ H ₁₈ F ₃ NO ₂ [M + H] ⁺ 434.1362, found 434.1362.

Example 6 Synthesis of Ethyl (Z) -6- (4-fluorobenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate

Reaction time 10 minutes, yield 92%, yellow solid

Mp = 121-125 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.68 (d, J = 7.4 Hz, 1H), 8.18 (d, J = 8.0 Hz, 1H), 7.64 (d, J = 7.5 Hz, 1H), 7.50-7.34 (m, 2H), 7.35-7.23 (m, 2H), 7.16 (t, J = 7.7 Hz, 1H), 7.07 (t, J = 8.6 Hz, 2H), 6.93-6.81 (m, 2H), 6.05 ( d, J = 8.4 Hz, 1H), 4.58-4.41 (m, 2H), 1.60-1.44 (m, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 165.0, 162.2 (d, J _{F -C} = 247.5 Hz), 147.9, 140.3, 133.8, 132.2, 131.7 (d, J _{F -C} = 8.25 Hz), 131.5, 131.4 , 131.4, 129.2, 128.9, 128.9, 125.3, 122.8, 122.5 (d, J _{F -C} = 3.75 Hz), 119.8, 115.5 (d, J _{F -C} = 21.7 Hz), 114.7, 107.9, 102.8, 60.1, 14.6 ; IR (ATR): 3046, 2975, 1670, 1562, 1504, 1441 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₅ H ₁₈ FNO ₂ [M + H] ⁺ 384.1394, found 384.1399.

Example 7 Synthesis of Ethyl (Z) -6- (2-methylbenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate

The reaction was carried out in the same manner as in Example 1, but after 30 minutes, 5 mol% Pd (OAc) ₂ and 10 mol% PPh ₃ were further added.

60 min reaction time, 89% yield, brown solid

Mp = 113-115 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.75 (d, J = 7.0 Hz, 1H), 8.16 (d, J = 7.8 Hz, 1H), 7.78 (d, J = 6.8 Hz, 1H), 7.53-7.40 (m, 2H), 7.33 (s, 2H), 7.22 (d, J = 13.0 Hz, 2H), 7.11 (t, J = 7.5 Hz, 1H), 7.02 (s, 1H), 6.75 (t, J = 7.6 Hz, 1H), 5.83 (d, J = 8.3 Hz, 1H), 4.52 (dd, J = 13.8, 6.8 Hz, 2H), 2.34 (s, 3H), 1.53 (t, J = 6.9 Hz, 3H) ; ¹³ C NMR (75 MHz, CDCl ₃ ) δ 165.2, 147.8, 140.1, 137.5, 135.2, 134.8, 132.6, 131.4, 130.6, 130.2, 129.3, 129.2, 128.9, 128.5, 125.9, 125.4, 123.1, 122.4, 122.3, 120.0 , 113.9, 108.4, 102.6, 60.1, 20.2, 14.6; IR (ATR): 2963, 2925, 1686, 1554, 1510, 1444, 1379 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₆ H ₂₁ NO ₂ [M + H] ⁺ 380.1645, found 380.1644.

Example 8 Synthesis of Ethyl (Z) -6- (3-methoxybenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate

Reaction time 15 minutes, yield 99%, brown solid

Mp = 120-124 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.70 (d, J = 7.3 Hz, 1H), 8.19 (d, J = 7.9 Hz, 1H), 7.66 (d, J = 7.4 Hz, 1H), 7.50-7.33 (m, 2H), 7.29 (t, J = 7.8 Hz, 1H), 7.13 (dd, J = 18.0, 10.5 Hz, 1H), 7.01-6.80 (m, 5H), 6.11 (d, J = 8.3 Hz, 1H), 4.53 (dd, J = 14.1, 7.0 Hz, 2H), 3.68 (s, 3H), 1.54 (t, J = 7.1 Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 164.9, 159.5, 147.8, 140.4, 136.7, 134.0, 132.4, 131.5, 129.4, 129.1, 128.9, 125.4, 122.8, 122.6, 122.4, 122.4, 119.8, 115.0, 114.7, 114.4 , 109.1, 102.9, 60.0, 55.1, 14.6 (one carbon peak is overlapped); IR (ATR): 3046, 2972, 2899, 1672, 1558, 1467, 1438 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₆ H ₂₁ NO ₃ [M + H] ⁺ 396.1594, found 396.1597.

Example 9 Synthesis of Ethyl (Z) -6- (3-chlorobenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate

Reaction time 15 minutes, yield 83%, yellow solid

Mp = 134-135 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.66 (d, J = 7.4 Hz, 1H), 8.17 (d, J = 7.9 Hz, 1H), 7.62 (d, J = 7.4 Hz, 1H), 7.52-7.04 (m, 7H), 7.26-7.23 (m, 1H), 6.92-6.83 (m, 1H), 6.82 (s, 1H), 6.01 (d, J = 8.3 Hz, 1H), 4.66-4.30 (m, 3H ), 1.52 (t, J = 7.0 Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 164.9, 147.8, 140.2, 137.2, 134.4, 134.3, 132.2, 131.5, 129.7, 129.5, 129.4, 129.1, 128.9, 128.1, 128.0, 125.4, 123.0, 122.6, 122.5, 119.9 , 114.7, 107.2, 103.2, 60.2, 14.6; IR (ATR): 3043, 2922, 2853, 1670, 1559, 1468, 1444 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₅ H ₁₈ ClNO ₂ [M + H] ⁺ 400.1099, found 400.1099.

Example 10 Synthesis of Ethyl (Z) -6- (3-chlorobenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate

Reaction time 10 minutes, yield 98%, light yellow solid

Mp = 68-71 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.69 (d, J = 7.0 Hz, 1H), 8.25 (d, J = 4.8 Hz, 1H), 7.80 (d, J = 7.6 Hz, 1H), 7.56 (d , J = 7.1 Hz, 1H), 7.40 (dd, J = 15.4, 7.2 Hz, 2H), 7.27 (dd, J = 8.9, 5.1 Hz, 2H), 5.84 (t, J = 6.9 Hz, 1H), 4.51 (dd, J = 13.7, 6.7 Hz, 2H), 2.84 (dd, J = 13.8, 6.9 Hz, 2H), 1.73-1.19 (m, 11H), 0.92 (t, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 165.2, 147.5, 139.9, 133.8, 132.8, 131.5, 128.6, 128.4, 128.2, 125.1, 122.9, 122.6, 122.3, 119.2, 112.7, 112.1, 101.3, 60.0, 31.6, 30.4 , 29.9, 29.0, 22.5, 14.6, 14.0; IR (ATR): 3049, 2924, 2854, 1694, 1571, 1443 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₅ H ₂₇ NO ₂ [M + H] ⁺ 374.2115, found 374.2113.

Example 11 Synthesis of Ethyl (Z) -6- (thiophen-2-ylmethylene) -6H-isoindolo [2,1-a] indole-11-carboxylate

Reaction time 15 minutes, yield 95%, brown solid

Mp = 142-144 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.66 (d, J = 7.5 Hz, 1H), 8.19 (d, J = 8.0 Hz, 1H), 7.61 (d, J = 7.3 Hz, 1H), 7.49-7.33 (m, 3H), 7.18 (t, J = 7.6 Hz, 1H), 7.10-7.02 (m, 1H), 6.96 (d, J = 8.1 Hz, 2H), 6.86 (s, 1H), 6.20 (d, J = 8.3 Hz, 1H), 4.51 (q, J = 7.1 Hz, 2H), 1.54 (t, J = 7.1 Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 164.9, 147.8, 140.0, 137.0, 134.7, 132.2, 131.5, 129.5, 129.2, 128.9, 128.9, 127.4, 127.1, 125.3, 122.9, 122.5, 122.5, 119.9, 114.8, 103.1 , 101.3, 60.1, 14.6; IR (ATR): 3050, 2922, 2851, 1669, 1559, 1471, 1442, 1403 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₃ H ₁₇ NO ₂ S [M + H] ⁺ 372.1053, found 372.1057.

Example 12 Synthesis of Ethyl (Z) -6- (naphthalen-2-ylmethylene) -6H-isoindolo [2,1-a] indole-11-carboxylate

Reaction time 15 minutes, yield 90%, yellow solid

Mp = 162-164 ° C; ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.73 (d, J = 7.5 Hz, 1H), 8.20 (d, J = 7.9 Hz, 1H), 7.82 (dd, J = 18.3, 7.5 Hz, 3H), 7.70 (dd, J = 11.0, 8.3 Hz, 2H), 7.58-7.36 (m, 5H), 7.17-7.08 (m, J = 14.7, 7.4 Hz, 1H), 7.06 (s, 1H), 6.67 (t, J = 7.6 Hz, 1H), 6.13 (d, J = 8.3 Hz, 1H), 4.54 (q, J = 6.9 Hz, 2H), 1.55 (t, J = 7.0 Hz, 3H); ¹³ C NMR (151 MHz, CDCl ₃ ) δ 165.1, 148.0, 140.7, 133.9, 133.0, 132.9, 132.8, 132.5, 131.6, 129.2, 129.2, 129.0, 128.1, 127.9, 127.7, 127.7, 126.5, 126.5, 125.5, 122.8 , 122.4, 119.9, 115.1, 109.4, 103.1, 60.1, 14.6 (two carbon peaks are overlapped); IR (ATR): 3050, 2979, 1665, 1559, 1465, 1442 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₉ H ₂₁ NO ₂ [M + H] ⁺ 416.1645, found 416.1649.

Example 13. Synthesis of Ethyl (Z) -6-benzylidene-2-methoxy-6H-isoindolo [2,1-a] indole-11-carboxylate

Reaction time 15 minutes, yield 94%, yellow solid

Mp = 131-133 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.64 (d, J = 7.4 Hz, 1H), 7.74-7.63 (m, 2H), 7.49-7.28 (m, 7H), 6.96 (s, 1H), 6.42 ( d, J = 9.1 Hz, 1H), 5.86 (d, J = 9.1 Hz, 1H), 4.51 (q, J = 7.1 Hz, 2H), 3.84 (s, 3H), 1.54 (t, J = 7.1 Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 165.0, 155.5, 148.1, 140.2, 135.4, 133.8, 132.7, 129.9, 129.3, 129.1, 128.7, 128.5, 128.1, 127.3, 125.1, 119.8, 115.5, 111.6, 109.1, 104.5 , 102.3, 60.0, 55.4, 14.6; IR (ATR): 3051, 2980, 2928, 2828, 1687, 1580, 1472, 1435 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₆ H ₂₁ NO ₃ [M + H] ⁺ 396.1594, found 396.1599.

Example 14 Synthesis of Ethyl (Z) -6-benzylidene-2- (trifluoromethyl) -6H-isoindolo [2,1-a] indole-11-carboxylate

Reaction time 15 minutes, yield 98%, light yellow solid

Mp = 157-159 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.64 (d, J = 6.2 Hz, 1H), 8.42 (s, 1H), 7.64 (d, J = 6.0 Hz, 1H), 7.37 (t, J = 19.5 Hz , 7H), 7.00 (d, J = 11.0 Hz, 2H), 5.94 (d, J = 8.8 Hz, 1H), 4.49 (q, J = 7.0 Hz, 2H), 1.53 (t, J = 7.1 Hz, 3H ); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 164.5, 149.2, 140.2, 135.2, 133.7, 133.6, 131.1, 129.9, 129.5, 129.4, 128.7, 128.5, 128.5, 125.7, 124.8 (q, J _{F -C} = 270 Hz ), 124.4 (q, J _{F -C} = 32.25 Hz), 120.0, 119.8 (q, J _{F -C} = 4.5 Hz), 119.5 (q, J _{F -C} = 3.0 Hz), 114.8, 110.4, 102.9, 60.4 , 14.5; IR (ATR): 2986, 2926, 1683, 1614, 1562, 1447, 1422, 1325 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₆ H ₁₈ F ₃ NO ₂ [M + H] ⁺ 434.1362, found 434.1360.

Example 15 Synthesis of Ethyl (Z) -6-benzylidene-8-methoxy-6H-isoindolo [2,1-a] indole-11-carboxylate

Reaction time 10 minutes, yield 98%, yellow solid

Mp = 120-127 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.56 (d, J = 8.6 Hz, 1H), 8.15 (d, J = 7.9 Hz, 1H), 7.36 (dd, J = 13.1, 3.8 Hz, 5H), 7.18 -7.06 (m, 2H), 6.95 (d, J = 8.6 Hz, 1H), 6.88 (s, 1H), 6.80 (t, J = 7.7 Hz, 1H), 5.96 (d, J = 8.3 Hz, 1H) , 4.50 (q, J = 7.1 Hz, 2H), 3.88 (s, 3H), 1.53 (t, J = 7.1 Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 165.3, 160.7, 148.5, 142.5, 135.4, 133.8, 132.5, 131.6, 130.1, 128.4, 128.1, 126.6, 122.4, 122.3, 122.2, 115.6, 114.8, 109.2, 104.8, 101.5 , 60.0, 55.6, 14.7 (one carbon peak is overlapped); IR (ATR): 3048, 2987, 2835, 1667, 1562, 1436, 1163 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₆ H ₂₁ NO ₃ [M + H] ⁺ 396.1594, found 396.1592.

Example 16 Synthesis of Ethyl (Z) -6-benzylidene-8-bromo-6H-isoindolo [2,1-a] indole-11-carboxylate

In the same manner as in Example 1, 10 mol% Pd (OAc) ₂ and 20 mol% PPh ₃ were used.

Reaction time 30 minutes, yield 92%, yellow solid

Mp = 134-140 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 8.50 (d, J = 8.3 Hz, 1H), 8.14 (d, J = 7.9 Hz, 1H), 7.75 (s, 1H), 7.50 (t, J = 9.8 Hz , 1H), 7.42-7.27 (m, 5H), 7.14 (t, J = 7.6 Hz, 1H), 6.89 (s, 1H), 6.82 (t, J = 7.7 Hz, 1H), 5.96 (d, J = 8.3 Hz, 1H), 4.47 (q, J = 7.1 Hz, 2H), 1.51 (t, J = 7.1 Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 164.9, 146.8, 141.9, 134.9, 132.6, 132.2, 132.0, 131.3, 130.0, 128.4, 128.3, 127.7, 126.6, 123.1, 123.0, 123.0, 122.6, 122.4, 115.0, 110.2 , 103.1, 60.2, 14.6; IR (ATR): 3047, 2983, 1689, 1577, 1557, 1440 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₅ H ₁₈ BrNO ₂ [M + H] ⁺ 444.0594, found 444.0591.

Example 17 Synthesis of Ethyl 5-phenylindolo [2,1-a] isoquinoline-12-carboxylate

Ethyl 2-phenyl-1- (phenylethynyl) -1H-indole-3-carboxylate, (73.1 mg, 0.2 mmol), PtCl ₂ (5.3 mg, 0.02 mmol) and toluene (1 mL) as indole amide Placed in a vial with a cap. The reaction mixture was reacted with stirring at 110 ° C. in an aluminum block until no starting material was confirmed on ¹ H NMR (˜16 hours). After cooling to room temperature, the reaction mixture was washed with diatomaceous earth with CH ₂ Cl ₂ , filtered and concentrated in vacuo. Purification was carried out using silica gel column chromatography. Α-chloroenamine that is not separated was distributed in hexane using a centrifugal separator and then decanted. The combined supernatants were concentrated and dried in vacuo. The residue was crystallized in hexane to give further purified compound, which was combined to calculate the yield.

Yield 59%, pale yellow solid

Mp = 177-178 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 9.88 (d, J = 8.3 Hz, 1H), 8.40 (d, J = 8.1 Hz, 1H), 8.14 (s, 1H), 7.78 (d, J = 8.1 Hz , 1H), 7.65 (dd, J = 14.5, 8.0 Hz, 2H), 7.59-7.42 (m, 7H), 7.37 (t, J = 7.6 Hz, 1H), 4.59 (q, J = 7.0 Hz, 2H) , 1.59 (t, J = 7.0 Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 166.4, 137.2, 136.5, 131.0, 130.8, 130.2, 129.1, 128.9, 128.6, 128.5, 128.0, 127.3, 125.4, 125.2, 125.0, 124.2, 122.5, 122.1, 120.4, 109.6 , 100.8, 60.2, 14.6; IR (ATR): 3049, 2974, 1668, 1598, 1491, 1448, 1365 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₅ H ₁₉ NO ₂ [M + H] ⁺ 366.1489, found 366.1489.

Example 18 Synthesis of Ethyl 5- (p-tolyl) indolo [2,1-a] isoquinoline-12-carboxylate

Yield 53%, pale yellow solid

Mp = 171-172 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 9.87 (d, J = 8.3 Hz, 1H), 8.40 (d, J = 8.1 Hz, 1H), 8.15 (s, 1H), 7.80 (d, J = 8.1 Hz , 1H), 7.66 (dd, J = 20.0, 8.0 Hz, 2H), 7.59-7.28 (m, 7H), 4.59 (q, J = 13.6, 6.6 Hz, 2H), 2.49 (s, 3H), 1.59 ( t, J = 6.6 Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 166.5, 137.9, 137.3, 133.5, 131.2, 130.8, 130.0, 129.3, 129.1, 128.8, 128.5, 127.3, 125.5, 125.2, 125.0, 124.2, 122.5, 122.2, 120.3, 109.6 , 100.7, 60.3, 21.3, 14.6; IR (ATR): 3080, 3023, 2899, 1670, 1495, 1452, 1365 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₆ H ₂₁ NO ₂ [M + H] ⁺ 380.1645, found 380.1643.

Example 19 Synthesis of Ethyl 5- (4- (methoxycarbonyl) phenyl) indolo [2,1-a] isoquinoline-12-carboxylate

Yield 65%, solid

Mp = 182-187 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 9.83 (d, J = 7.7 Hz, 1H), 8.36 (d, J = 8.0 Hz, 1H), 8.19 (d, J = 8.1 Hz, 2H), 8.12 (s , 1H), 7.78 (d, J = 8.1 Hz, 1H), 7.67-7.41 (m, 6H), 7.36 (t, J = 7.5 Hz, 1H), 4.57 (q, J = 7.1 Hz, 2H), 3.98 (s, 3H), 1.57 (t, J = 7.1 Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 166.7, 166.3, 141.3, 137.1, 130.7, 130.3, 130.2, 129.9, 129.6, 129.2, 128.9, 128.5, 127.5, 125.2, 125.0, 124.3, 123.9, 122.5, 122.3, 120.6 , 109.56, 101.1, 60.3, 52.3, 14.6; IR (ATR): 3075, 2923, 2852, 1714, 1677, 1601, 1492, 1452 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₇ H ₂₁ NO ₄ [M + H] ⁺ 424.1543, found 424.1541.

Example 20 Synthesis of Ethyl 5- (4-formylphenyl) indolo [2,1-a] isoquinoline-12-carboxylate

Yield 58%, pale yellow solid

Mp = 228-231 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 10.11 (s, 1H), 9.83 (d, J = 8.1 Hz, 1H), 8.37 (d, J = 8.0 Hz, 1H), 8.14 (s, 1H), 8.03 (d, J = 7.7 Hz, 2H), 7.79 (d, J = 8.1 Hz, 1H), 7.73-7.65 (m, 2H), 7.64-7.30 (m, 5H), 4.57 (q, J = 7.0 Hz, 2H), 1.57 (t, J = 7.0 Hz, 3H); ¹³ C NMR (151 MHz, CDCl ₃ ) δ 191.6, 166.4, 143.1, 137.1, 135.9, 130.9, 130.8, 130.2, 130.0, 129.3, 129.1, 128.6, 127.7, 125.4, 125.0, 124.5, 123.9, 122.7, 122.5, 120.8 , 109.5, 101.5, 60.4, 14.6; IR (ATR): 3050, 2973, 2900, 2841, 1672, 1601, 1489, 1452 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₆ H ₁₉ NO ₃ [M + H] ⁺ 394.1438, found 394.1433.

Example 21 Synthesis of Ethyl 5- (4- (trifluoromethyl) phenyl) indolo [2,1-a] isoquinoline-12-carboxylate

Yield 62%, pale yellow solid

Mp = 196-199 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 9.84 (d, J = 8.2 Hz, 1H), 8.37 (d, J = 8.0 Hz, 1H), 8.11 (s, 1H), 7.78 (t, J = 9.8 Hz , 3H), 7.71-7.42 (m, 6H), 7.37 (t, J = 7.3 Hz, 1H), 4.57 (q, J = 7.0 Hz, 2H), 1.58 (t, J = 7.0 Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 166.4, 140.3, 137.0, 130.7, 130.5, 130.3, 130.2 (q, J _{F -C} = 32.25 Hz), 129.3, 128.9, 128.4, 127.6, 125.7 (q, J _{F -C} = 3.75 Hz), 125.2, 125.0, 124.4, 124.1 (q, J _{F -C} = 270.75 Hz), 123.6, 122.6, 122.4, 120.7, 109.5, 101.2, 60.3, 14.6; IR (ATR): 3067, 2982, 2924, 2849, 1698, 1615, 1494, 1452, 1318 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₆ H ₁₈ F ₃ NO ₂ [M + H] ⁺ 434.1362, found 434.1360.

Example 22 Synthesis of Ethyl 5- (4-fluorophenyl) indolo [2,1-a] isoquinoline-12-carboxylate

Yield 67%, yellow solid

Mp = 192-193 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 9.86 (d, J = 8.2 Hz, 1H), 8.39 (d, J = 8.1 Hz, 1H), 8.11 (s, 1H), 7.79 (d, J = 8.2 Hz , 1H), 7.69-7.42 (m, 6H), 7.38 (t, J = 7.5 Hz, 1H), 7.23 (t, J = 8.5 Hz, 2H), 4.58 (q, J = 7.1 Hz, 2H), 1.58 (t, J = 7.1 Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 166.4, 162.6 (d, J _{F -C} = 246.0 Hz), 137.2, 132.5, 132.5 (d, J _{F -C} = 3.3 Hz), 131.8 (d, J _{F -C} = 8.2 Hz), 130.9, 130.8, 129.2, 128.9, 128.5, 127.4, 125.2, 124.3, 123.9, 122.5, 122.2, 120.5, 115.7 (d, J _{F -C} = 21.75 Hz), 109.5, 100.9, 60.3, 14.6; IR (ATR): 3053, 2974, 2899, 1664, 1493, 1448, 1363 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₅ H ₁₈ FNO ₂ [M + H] ⁺ 384.1394, found 384.1392.

Example 23 Synthesis of Ethyl 5- (o-tolyl) indolo [2,1-a] isoquinoline-12-carboxylate

Yield 50%, pale yellow solid

Mp = 88-90 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 9.91 (d, J = 8.3 Hz, 1H), 8.45 (d, J = 8.1 Hz, 1H), 8.16 (s, 1H), 7.80 (d, J = 8.2 Hz , 1H), 7.66 (t, J = 7.6 Hz, 2H), 7.58-7.33 (m, 7H), 7.33-7.24 (m, 1H), 4.62 (dd, J = 14.2, 7.1 Hz, 2H), 2.16 ( s, 3H), 1.61 (t, J = 7.1 Hz, 3H); ¹³ C NMR (151 MHz, CDCl ₃ ) δ 166.5, 137.9, 137.5, 135.8, 131.2, 130.9, 130.9, 130.2, 129.3, 128.9, 128.6, 128.5, 127.3, 126.1, 125.4, 125.1, 124.3, 124.2, 122.6, 122.2 , 120.4, 109.6, 101.0, 60.2, 20.0, 14.6; IR (ATR): 3050, 2975, 1682, 1488, 1452, 1355 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₆ H ₂₁ NO ₂ [M + H] ⁺ 380.1645, found 380.1641.

Example 24 Synthesis of Ethyl 5- (3-methoxyphenyl) indolo [2,1-a] isoquinoline-12-carboxylate

Yield 57%, light yellow solid

Mp = 142-145 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 9.87 (d, J = 8.2 Hz, 1H), 8.40 (d, J = 8.0 Hz, 1H), 8.17 (s, 1H), 7.80 (d, J = 8.2 Hz , 1H), 7.71 (d, J = 8.0 Hz, 1H), 7.63 (dd, J = 11.2, 4.2 Hz, 1H), 7.59-7.51 (m, 1H), 7.50-7.33 (m, 3H), 7.16- 6.98 (m, 3H), 4.59 (q, J = 7.1 Hz, 2H), 3.88 (s, 3H), 1.58 (t, J = 7.1 Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 166.4, 159.7, 137.9, 137.3, 130.9, 130.8, 129.7, 129.2, 128.9, 128.5, 127.3, 125.4, 125.2, 124.9, 124.2, 122.6, 122.5, 122.2, 120.3, 115.8 , 113.4, 109.6, 100.9, 60.3, 55.3, 14.6; IR (ATR): 3022, 2976, 2933, 1675, 1581, 1488, 1457, 1362 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₆ H ₂₁ NO ₃ [M + H] ⁺ 396.1594, found 396.1592.

Example 25 Synthesis of Ethyl 5- (3-chlorophenyl) indolo [2,1-a] isoquinoline-12-carboxylate

Yield 58%, pale yellow solid

Mp = 179-182 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 9.84 (d, J = 8.1 Hz, 1H), 8.38 (d, J = 8.1 Hz, 1H), 8.10 (s, 1H), 7.77 (d, J = 8.2 Hz , 1H), 7.68-7.28 (m, 9H), 4.57 (q, J = 7.1 Hz, 2H), 1.58 (t, J = 7.1 Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 166.3, 138.4, 137.1, 134.5, 130.8, 130.4, 130.1, 129.9, 129.2, 128.9, 128.5, 128.4, 128.2, 127.5, 125.2, 125.1, 124.3, 123.6, 122.6, 122.3 , 120.6, 109.5, 101.1, 60.3, 14.6; IR (ATR): 3050, 2974, 1690, 1634, 1505, 1452 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₅ H ₁₈ ClNO ₂ [M + H] ⁺ 400.1099, found 400.1099.

Example 26. Synthesis of Ethyl 5-hexyl indolo [2,1-a] isoquinoline-12-carboxylate

Yield 54%, light yellow solid

Mp = 89-91 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 9.89-9.77 (m, 1H), 8.36 (d, J = 7.9 Hz, 1H), 7.97 (s, 1H), 7.84-7.69 (m, 2H), 7.68- 7.53 (m, 2H), 7.44 (t, J = 7.5 Hz, 1H), 7.40-7.30 (m, 1H), 4.56 (q, J = 7.1 Hz, 2H), 2.91-2.74 (m, 2H), 1.72 (dd, J = 14.2, 7.0 Hz, 2H), 1.62-1.50 (m, 3H), 1.51-1.21 (m, 6H), 0.91 (s, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 166.5, 137.5, 131.1, 130.6, 129.1, 129.1, 128.4, 126.9, 125.4, 124.0, 123.1, 122.5, 122.2, 121.8, 118.9, 109.5, 100.2, 60.1, 31.7, 30.3 , 29.3, 29.3, 22.6, 14.6, 14.1; IR (ATR): 3070, 2953, 2927, 2853, 1682, 1486, 1452, 1366 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₅ H ₂₇ NO ₂ [M + H] ⁺ 374.2115, found 374.2112.

Example 27 Synthesis of Ethyl 5- (thiophen-2-yl) indolo [2,1-a] isoquinoline-12-carboxylate

Yield 22%, pale yellow solid

Mp = 168-169 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 9.83 (d, J = 7.9 Hz, 1H), 8.37 (d, J = 8.0 Hz, 1H), 8.28 (s, 1H), 7.97-7.88 (m, 1H) , 7.80 (d, J = 8.1 Hz, 1H), 7.70-7.53 (m, 2H), 7.47 (t, J = 7.2 Hz, 2H), 7.38 (t, J = 7.2 Hz, 1H), 7.31-7.17 ( m, 2H), 4.57 (q, J = 7.1 Hz, 2H), 1.57 (t, J = 7.1 Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 166.4, 137.2, 137.1, 130.9, 130.8, 129.3, 128.8, 128.5, 128.4, 127.5, 127.5, 126.2, 125.2, 125.1, 124.4, 122.6, 122.4, 121.7, 117.6, 109.6 , 101.3, 60.3, 14.6; IR (ATR): 3064, 2971, 2891, 1676, 1497, 1453, 1367 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₃ H ₁₇ NO ₂ S [M + H] ⁺ 372.1053, found 372.1051.

Example 28 Synthesis of Ethyl 5- (naphthalen-2-yl) indolo [2,1-a] isoquinoline-12-carboxylate

Yield 75%, pale yellow solid

Mp = 212-213 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 9.92 (d, J = 8.3 Hz, 1H), 8.40 (t, J = 10.7 Hz, 1H), 8.20 (s, 1H), 8.04-7.86 (m, 4H) , 7.77 (d, J = 8.2 Hz, 1H), 7.73-7.43 (m, 7H), 7.37 (t, J = 7.6 Hz, 1H), 4.61 (q, J = 7.1 Hz, 2H), 1.61 (t, J = 7.1 Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 166.5, 13.3, 134.1, 133.4, 132.8, 131.1, 130.9, 129.2, 129.0, 128.9, 128.6, 128.2, 128.1, 128.0, 127.8, 127.4, 126.6, 126.5, 125.5, 125.3 , 125.0, 124.3, 122.6, 122.3, 120.7, 109.7, 101.0, 60.4, 14.7; IR (ATR): 3047, 2973, 2897, 1667, 1492, 1452 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₉ H ₂₁ NO ₂ [M + H] ⁺ 416.1645, found 416.1646.

Example 29. Synthesis of ethyl 10-methoxy-5-phenylindolo [2,1-a] isoquinoline-12-carboxylate

Yield 56%, pale yellow solid

Mp = 153-155 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 9.84 (d, J = 8.0 Hz, 1H), 8.08 (s, 1H), 7.84 (s, 1H), 7.73-7.42 (m, 9H), 7.00 (d, J = 8.1 Hz, 1H), 4.65-4.47 (q, J = 6.0 Hz, 2H), 3.93 (s, 3H), 1.58 (t, J = 6.8 Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 166.4, 157.2, 137.5, 136.5, 130.7, 130.2, 129.6, 128.9, 128.8, 128.6, 128.0, 127.2, 125.9, 125.3, 125.1, 125.0, 120.4, 112.6, 110.4, 103.5 , 100.4, 60.1, 55.4, 14.6; IR (ATR): 3047, 2967, 1680, 1612, 1490, 1450 1351 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₆ H ₂₁ NO ₃ [M + H] ⁺ 396.1594, found 396.1595.

Example 30 Synthesis of Ethyl 5-phenyl-10- (trifluoromethyl) indolo [2,1-a] isoquinoline-12-carboxylate

Yield 62%, pale yellow solid

Mp = 169-170 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 9.86 (d, J = 8.1 Hz, 1H), 8.69 (s, 1H), 8.13 (s, 1H), 7.85 (d, J = 8.6 Hz, 1H), 7.76 -7.38 (m, 9H), 4.57 (q, J = 14.1, 7.0 Hz, 2H), 1.58 (t, J = 7.0 Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 165.8, 138.6, 136.1, 131.9, 131.1, 130.1, 129.8, 129.2, 128.8, 128.3, 127.9, 127.7, 126.4 (q, J _{F -C} = 34.5 Hz), 126.0, 125.7, 125.0, 124.9 (q, J _{F -C} = 270.75 Hz), 120.4 (q, J _{F -C} = 4.5 Hz), 120.1, 118.7 (q, J _{F -C} = 3.75 Hz), 110.2, 101.4, 60.6 , 14.5; ; IR (ATR): 3073, 3024, 2983, 1682, 1582, 1502, 1492, 1452, 1325 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₆ H ₁₈ F ₃ NO ₂ [M + H] + 434.1362, found 434.1368.

Example 31 Synthesis of Ethyl 3-methoxy-5-phenylindolo [2,1-a] isoquinoline-12-carboxylate

Yield 58%, pale yellow solid

Mp = 140-142 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 9.93 (d, J = 9.2 Hz, 1H), 8.38 (d, J = 8.1 Hz, 1H), 8.12 (s, 1H), 7.76 (d, J = 8.2 Hz , 1H), 7.61-7.39 (m, 6H), 7.34 (t, J = 7.4 Hz, 1H), 7.22 (d, J = 9.2 Hz, 1H), 7.10 (s, 1H), 4.56 (q, J = 7.1 Hz, 2H), 3.80 (s, 3H), 1.58 (t, J = 7.1 Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 166.6, 160.0, 138.0, 136.6, 133.3, 131.2, 130.8, 130.1, 128.8, 128.7, 128.1, 124.7, 124.2, 122.5, 121.8, 120.9, 119.1, 115.2, 109.4, 108.1 , 99.4, 60.2, 55.3, 14.7; IR (ATR): 3096, 3000, 2970, 1699, 1606, 1465, 1354 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₆ H ₂₁ NO ₃ [M + H] ⁺ 396.1594, found 396.1591.

Example 32. Synthesis of ethyl 3-bromo-5-phenylindolo [2,1-a] isoquinoline-12-carboxylate

Yield 27%, pale yellow solid

Mp = 215-218 ° C .; ¹ H NMR (300 MHz, CDCl ₃ ) δ 9.81 (d, J = 9.0 Hz, 1H), 8.38 (d, J = 8.1 Hz, 1H), 8.15 (s, 1H), 7.78 (d, J = 8.7 Hz , 2H), 7.69 (dd, J = 9.0, 1.6 Hz, 1H), 7.52 (tt, J = 15.0, 7.3 Hz, 6H), 7.39 (t, J = 7.5 Hz, 1H), 4.56 (q, J = 7.1 Hz, 2H), 1.57 (t, J = 7.1 Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 166.4, 136.6, 135.8, 132.7, 130.8, 130.7, 130.4, 130.1, 128.9, 128.5, 128.4, 127.8, 124.5, 124.1, 124.0, 123.8, 122.7, 122.6, 121.5, 109.6 , 101.3, 60.7, 14.6; IR (ATR): 3053, 2983, 1689, 1577, 1557, 1440 cm ⁻¹ ; HRMS (ESI) calcd for C ₂₅ H ₁₈ BrNO ₂ [M + H] ⁺ 444.0594, found 444.0598.

Test Example 1 Evaluation of Kinetic Isotope Effect (KIE) in Molecules

In order to confirm the reaction mechanism, the compounds of Examples 1 and 17 were prepared to evaluate the intramolecular dynamic isotope effect.

Sufficient hydrogen / deuterium KIE ( K _H / K _D = 2.86) was found to confirm that the compound of Example 1 proceeded through CH activation in 5-exo-dig cyclization under a palladium catalyst. Based on the formation of strong KIE and Z-isomers, it is predicted that alkine direct ortho-pallation and protodepallation by cis-micrograph insertion for triple bonds form the compound of Example 1.

On the other hand, KIE ( K _H / K _D = 0.50) was observed for 6-endo-dig cyclization under platinum catalyst, which is consistent with the mechanism of electrophilic aromatic substitution. This fact was obtained by the process of Example 17 followed by an electrophilic pathway for 6-endo-dig cyclization involving molecular attack by neighboring aromatic rings on an alkynyl unit activated with a platinum catalyst followed by a proto-demetallization process. The formation of the compound was supported.

Claims (11)

Compound represented by the following formula (1):
[Formula 1]

In the formula,

Is a single or double bond,
A is 5-6 membered heterocyclic or 5-6 membered heteroaryl, including a nitrogen atom,
R ₁ is CO ₂ R _a ,
R ₂ , R ₃ , R ₄ , R ₅ and R ₆ are the same or different from each other, and are each independently hydrogen, halo, methyl, ethyl or straight or branched C _3-6 alkyl, CO ₂ R _a , C _1-6 alkyloxy, trihalomethyl, phenyl and benzyl,
R ₇ is selected from methyl, ethyl or straight or branched C _3-6 alkyl, C _3-7 cycloalkyl, aryl, heteroaryl, arylC _1-6 alkyl and heteroarylC _1-6 alkyl; Aryl of the aryl or aryl C _1-6 alkyl is phenyl or naphthyl; Heteroaryl of heteroaryl or heteroarylC _1-6 alkyl is 5-6 membered heteroaryl, 1H-indolyl or 1H-quinolinyl having 1 to 2 heteroatoms selected from N, O and S; The aryl, heteroaryl, arylC _1-6 alkyl and heteroarylC _1-6 alkyl are each independently unsubstituted or halo, methyl, ethyl or straight or branched C _3-6 alkyl, C _1-6 alkyl May be substituted with 1 to 3 substituents selected from oxy, trihalomethyl, -COOH, -CHO, -COOR _b , phenyl and benzyl,
R _a and R _b are the same as or different from each other, and are each independently methyl, ethyl or straight or branched C _3-6 alkyl. The method of claim 1,
Compound represented by the following formula (2) or formula (3):
[Formula 2]

[Formula 3]

In the formula,
R ₁ is CO ₂ R _a ,
R ₂ , R ₃ , R ₄ , R ₅ and R ₆ are the same or different from each other, and are each independently hydrogen, halo, methyl, ethyl or straight or branched C _3-6 alkyl, CO ₂ R _a , C _1-6 alkyloxy, trihalomethyl, phenyl and benzyl,
R ₈ is selected from methyl, ethyl or straight or branched C _3-6 alkyl, C _3-7 cycloalkyl, aryl and heteroaryl, wherein aryl is phenyl or naphthyl; The heteroaryl is 5-6 membered heteroaryl having 1 to 2 heteroatoms selected from N, O and S, 1H-indolyl or 1H-quinolinyl, and the aryl and heteroaryl are each independently unsubstituted or Or 1 to 3 selected from halo, methyl, ethyl or straight or branched C _3-6 alkyl, C _1-6 alkyloxy, trihalomethyl, -COOH, -CHO, -COOR _b , phenyl and benzyl May be substituted with a substituent,
R _a and R _b are the same as or different from each other, and are each independently methyl, ethyl or straight or branched C _3-6 alkyl. delete The method of claim 2,
R ₁ is CO ₂ Et,
R ₈ is selected from methyl, ethyl or straight or branched C _3-6 alkyl, aryl and heteroaryl, wherein aryl is phenyl or naphthyl; The heteroaryl is a 5-6 membered heteroaryl having 1 to 2 heteroatoms selected from O and S; The aryl and heteroaryl are each independently unsubstituted or halo, methyl, ethyl or straight or branched C _3-6 alkyl, C _1-6 alkyloxy, trihalomethyl, -COOH, -CHO and -COOR may be substituted with 1 to 3 substituents selected from _b ,
R _b is methyl, ethyl or straight or branched C _3-6 alkyl. The method of claim 1,
Ethyl (Z) -6-benzylidene-6H-isoindolo [2,1-a] indole-11-carboxylate;
Ethyl (Z) -6- (4-methylbenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;
Ethyl (Z) -6- (4- (methoxycarbonyl) benzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;
Ethyl (Z) -6- (4-formylbenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;
Ethyl (Z) -6- (4- (trifluoromethyl) benzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;
Ethyl (Z) -6- (4-fluorobenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;
Ethyl (Z) -6- (2-methylbenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;
Ethyl (Z) -6- (3-methoxybenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;
Ethyl (Z) -6- (3-chlorobenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;
Ethyl (Z) -6- (3-chlorobenzylidene) -6H-isoindolo [2,1-a] indole-11-carboxylate;
Ethyl (Z) -6- (thiophen-2-ylmethylene) -6H-isoindolo [2,1-a] indole-11-carboxylate;
Ethyl (Z) -6- (naphthalen-2-ylmethylene) -6H-isoindolo [2,1-a] indole-11-carboxylate;
Ethyl (Z) -6-benzylidene-2-methoxy-6H-isoindolo [2,1-a] indole-11-carboxylate;
Ethyl (Z) -6-benzylidene-2- (trifluoromethyl) -6H-isoindolo [2,1-a] indole-11-carboxylate;
Ethyl (Z) -6-benzylidene-8-methoxy-6H-isoindolo [2,1-a] indole-11-carboxylate;
Ethyl (Z) -6-benzylidene-8-bromo-6H-isoindolo [2,1-a] indole-11-carboxylate;
Ethyl 5-phenylindolo [2,1-a] isoquinoline-12-carboxylate;
Ethyl 5- (p-tolyl) indolo [2,1-a] isoquinoline-12-carboxylate;
Ethyl 5- (4- (methoxycarbonyl) phenyl) indolo [2,1-a] isoquinoline-12-carboxylate;
Ethyl 5- (4-formylphenyl) indolo [2,1-a] isoquinoline-12-carboxylate;
Ethyl 5- (4- (trifluoromethyl) phenyl) indolo [2,1-a] isoquinoline-12-carboxylate;
Ethyl 5- (4-fluorophenyl) indolo [2,1-a] isoquinoline-12-carboxylate;
Ethyl 5- (o-tolyl) indolo [2,1-a] isoquinoline-12-carboxylate;
Ethyl 5- (3-methoxyphenyl) indolo [2,1-a] isoquinoline-12-carboxylate;
Ethyl 5- (3-chlorophenyl) indolo [2,1-a] isoquinoline-12-carboxylate;
Ethyl 5-hexyl indolo [2,1-a] isoquinoline-12-carboxylate;
Ethyl 5- (thiophen-2-yl) indolo [2,1-a] isoquinoline-12-carboxylate;
Ethyl 5- (naphthalen-2-yl) indolo [2,1-a] isoquinoline-12-carboxylate;
Ethyl 10-methoxy-5-phenylindolo [2,1-a] isoquinoline-12-carboxylate;
Ethyl 5-phenyl-10- (trifluoromethyl) indolo [2,1-a] isoquinoline-12-carboxylate;
Ethyl 3-methoxy-5-phenylindolo [2,1-a] isoquinoline-12-carboxylate; And
Ethyl 3-bromo-5-phenylindolo [2,1-a] isoquinoline-12-carboxylate. A method for preparing a compound represented by the following Chemical Formula 1, comprising refluxing a compound of Chemical Formula 3 under a transition metal catalyst to form an intramolecular ring bond:
[Formula 3]

[Formula 1]

In the formula,

Is a single or double bond,
A is 5-6 membered heterocyclic or 5-6 membered heteroaryl, including a nitrogen atom,
R ₁ is CO ₂ R _a ,
R ₂ , R ₃ , R ₄ , R ₅ and R ₆ are the same or different from each other, and are each independently hydrogen, halo, methyl, ethyl or straight or branched C _3-6 alkyl, CO ₂ R _a , C _1-6 alkyloxy, trihalomethyl, phenyl and benzyl,
R ₇ is selected from methyl, ethyl or straight or branched C _3-6 alkyl, C _3-7 cycloalkyl, aryl, heteroaryl, arylC _1-6 alkyl and heteroarylC _1-6 alkyl; Aryl of the aryl or arylC _1-6 alkyl is phenyl or naphthyl; Heteroaryl of heteroaryl or heteroarylC _1-6 alkyl is 5-6 membered heteroaryl, 1H-indolyl or 1H-quinolinyl having 1 to 2 heteroatoms selected from N, O and S; The aryl, heteroaryl, arylC _1-6 alkyl and heteroarylC _1-6 alkyl are each independently unsubstituted or halo, methyl, ethyl or straight or branched C _3-6 alkyl, C _1-6 alkyl May be substituted with 1 to 3 substituents selected from oxy, trihalomethyl, -COOH, -CHO, -COOR _b , phenyl and benzyl,
R _a and R _b are the same as or different from each other, and are each independently methyl, ethyl or straight or branched C _3-6 alkyl. The method of claim 6,
The transition metal catalyst is selected from Pd (OAc) ₂ , PtCl ₄ and AuCl ₃ , the production method. The method of claim 7, wherein
If the transition metal catalyst is Pd (OAc) ₂ , α-addition reaction (5-exo-dig cyclization) is formed to form a compound represented by the following formula (2):
[Formula 2]

In the formula,
R ₁ is CO ₂ R _a ,
R ₂ , R ₃ , R ₄ , R ₅ and R ₆ are the same or different from each other, and are each independently hydrogen, halo, methyl, ethyl or straight or branched C _3-6 alkyl, CO ₂ R _a , C _1-6 alkyloxy, trihalomethyl, phenyl and benzyl,
R ₈ is selected from methyl, ethyl or straight or branched C _3-6 alkyl, C _3-7 cycloalkyl, aryl and heteroaryl, wherein aryl is phenyl or naphthyl; The heteroaryl is 5-6 membered heteroaryl having 1 to 2 heteroatoms selected from N, O and S, 1H-indolyl or 1H-quinolinyl, and the aryl and heteroaryl are each independently unsubstituted or Or 1 to 3 selected from halo, methyl, ethyl or straight or branched C _3-6 alkyl, C _1-6 alkyloxy, trihalomethyl, -COOH, -CHO, -COOR _b , phenyl and benzyl May be substituted with a substituent,
R _a and R _b are the same as or different from each other, and are each independently methyl, ethyl or straight or branched C _3-6 alkyl. The method of claim 7, wherein
If the transition metal catalyst is Pd (OAc) _2, it will further comprise PPh ₃ as a ligand in the reaction. The method of claim 7, wherein
If the transition metal catalyst is PtCl ₄ or AuCl ₃ , β-addition reaction (6-endo-dig cyclization) is formed to form a compound represented by the following formula (3):
[Formula 3]

In the formula,
R ₁ is CO ₂ R _a ,
R ₂ , R ₃ , R ₄ , R ₅ and R ₆ are the same or different from each other, and are each independently hydrogen, halo, methyl, ethyl or straight or branched C _3-6 alkyl, CO ₂ R _a , C _1-6 alkyloxy, trihalomethyl, phenyl and benzyl,
R ₈ is selected from methyl, ethyl or straight or branched C _3-6 alkyl, C _3-7 cycloalkyl, aryl and heteroaryl, wherein aryl is phenyl or naphthyl; The heteroaryl is 5-6 membered heteroaryl having 1 to 2 heteroatoms selected from N, O and S, 1H-indolyl or 1H-quinolinyl, and the aryl and heteroaryl are each independently unsubstituted or Or 1 to 3 selected from halo, methyl, ethyl or straight or branched C _3-6 alkyl, C _1-6 alkyloxy, trihalomethyl, -COOH, -CHO, -COOR _b , phenyl and benzyl May be substituted with a substituent,
R _a and R _b are the same as or different from each other, and are each independently methyl, ethyl or straight or branched C _3-6 alkyl. The method of claim 6,
The transition metal catalyst is added in 2 to 20 mol%, the preparation method.