KR20190040791A - 4 Ring-fused N-heterocycles having luminescent properties and Preparation method thereof - Google Patents

Abstract

The present invention relates to a novel 4-ring junction N-heterocyclic compound having light emitting properties, and a preparing method thereof. The novel 4-ring junction N-heterocyclic compound of the present invention is represented by chemical formula 1. In the chemical formula 1, A is a 5-6 membered heterocyclic or 5-6 membered heteroaryl, including a nitrogen atom, and R_1 is selected from hydrogen, linear or branched C_(1-6)alkyl and CO_2R_a.

Description

(4) Ring-fused N-heterocycles having luminescent properties and preparation method thereof [

The present invention relates to a 4-ring junction N-heterocyclic compound having luminescent properties and a method for producing the same.

The multi-junction N-heterocyclic compound has attracted attention as a candidate candidate for its excellent physiological activity and is widely 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 ring compounds containing nitrogen atoms inside, such as azacorannulene and azafullerene, have been found to exhibit electronically and optically interesting properties in energy transfer applications.

Accordingly, various methods for synthesizing multi-junction N-heterocyclic compounds have been devised. The ideal method is to achieve stereospecific, substituent-specific, and site-specific reactions from common starting materials. There is a need for a variety of studies on methods to make atomic-economically cyclic organic materials 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 4-ring junction N-heterocyclic compound having a light emitting property.

A second object of the present invention is to provide a process for preparing the novel 4-ring junction N-heterocyclic compound.

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

[Chemical Formula 1]

In the formula,

는 단일 또는 이중결합이고,

Is a single or double bond,

A is a 5-6 membered heterocyclic or 5-6 membered heteroaryl containing 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 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 Romero naphthyl, may be optionally substituted by -COOH, -CHO, -COOR _b, phenyl, and 1 to 3 substituents selected from 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 (3).

(2)

(3)

In the formula,

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

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; Wherein said heteroaryl is 5-6 membered heteroaryl, 1H-indolyl or lH-quinolinyl having 1-2 heteroatoms selected from N, O and S, said aryl and heteroaryl being each independently unsubstituted or substituted 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 wherein 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; Wherein said heteroaryl is 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 Which 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- (naphthalene-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-hexylindolo [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.

The present invention provides a process for preparing a compound represented by the formula (1), which comprises refluxing a compound of the formula (3) in the presence of a transition metal catalyst to form an intramolecular ring bond:

 (3)

In the formula, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ and R ₆ are as shown in the formula (2) or (3).

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

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

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

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

The present invention is capable of synthesizing multi-junction N-heterocyclic compounds that are atomically-economically cyclic organic materials from an acyclic starting material. The multi-junction N-heterocyclic compound according to the present invention can exhibit luminescent characteristics, and thus can be used in a field requiring a compound exhibiting luminescent properties, for example, a dye, a DNA dye, a herbicide, an OLED, an OPV, a biosensor, Can be applied.

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

The present invention provides a compound represented by the following formula (1): < EMI ID =

[Chemical Formula 1]

In the formula,

는 단일 또는 이중결합이고,

Is a single or double bond,

A is a 5-6 membered heterocyclic or 5-6 membered heteroaryl containing 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 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 Romero naphthyl, may be optionally substituted by -COOH, -CHO, -COOR _b, phenyl, and 1 to 3 substituents selected from 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 Isohexyl, and isohexyl, but is not limited thereto.

In the present invention, the compound of Formula 1 may be a compound of Formula 2 or Formula 3.

(2)

(3)

In the formula,

R ₁ , R ₂ , R ₃ , R ₄ , R _5, and R ₆ are as shown in 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; Wherein said heteroaryl is 5-6 membered heteroaryl, 1H-indolyl or lH-quinolinyl having 1-2 heteroatoms selected from N, O and S, said aryl and heteroaryl being each independently unsubstituted or substituted 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, preferred compounds represented by the above formula (1) are those wherein R ₁ is CO ₂ Et.

According to the present invention, preferred compounds represented by the above formula (1) may be compounds represented by formula (2) or (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; Wherein said heteroaryl is 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 Which 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- (naphthalene-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-hexylindolo [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 is not limited thereto.

According to the present invention, the reaction may be one which emits 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 process for preparing a compound represented by the formula (1), which comprises refluxing a compound of the formula (3) in the presence of a transition metal catalyst to form an intramolecular ring bond:

 (3)

[Chemical Formula 1]

In the formula,

는 단일 또는 이중결합이고,

Is a single or double bond,

A is a 5-6 membered heterocyclic or 5-6 membered heteroaryl containing 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 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 Romero naphthyl, may be optionally substituted by -COOH, -CHO, -COOR _b, phenyl, and 1 to 3 substituents selected from 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 atomic-economical since it is performed in a one-pot reaction.

In the present invention, the reaction may be an intramolecular cyclization reaction. Specifically, the reaction may be an α-addition reaction (5-exo-dig cyclization) by CH bond activation or a β- 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 above 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 , an α-addition reaction (5-exo-dig cyclization) may be formed to form a compound represented by Formula 2 below.

(2)

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

(3)

In Formula 2 or Formula 3,

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

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; Wherein said heteroaryl is 5-6 membered heteroaryl, 1H-indolyl or lH-quinolinyl having 1-2 heteroatoms selected from N, O and S, said aryl and heteroaryl being each independently unsubstituted or substituted 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 , PPh ₃ is preferably contained as a ligand in the reaction, 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 , 4-dioxane, N, N-dimethylformamide, and dimethylsulfoxide, and toluene is preferable because of less side reaction and excellent reaction yield.

According to the present invention, the reaction can be carried out under reflux conditions, preferably at 70 to 120 ° C.

According to the present invention, the? -Adding reaction can be completed within a few minutes, and the? -Adding reaction can be completed within several minutes to several hours.

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

According to the present invention, the compound represented by Formula 2 may be prepared as a Z-isomer and converted to an E-isomer by acid treatment. The acid treatment is not particularly limited as long as it is usually used for isomerization. For example, the acid treatment may be carried out in an aqueous solution of HCl, and the reaction may be further carried out by heating.

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

Examples of the use of the compound according to the present invention as an intermediate include the following reactions, but the following reactions are illustrative and not intended to be limiting.

Example

Hereinafter, the present invention will be described in more detail with reference to preferred embodiments. It will be apparent to those skilled in the art, however, that these examples are for the purpose of describing the present invention more specifically and 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

Indole-3-carboxylate (73.1 mg, 0.2 mmol), Pd (OAc) ₂ (2.3 mg, 0.01 mmol), PPh ₃ mg, 0.02 mmol) and toluene (1 mL) were placed in a capped vial. The reaction mixture was stirred (at 80 < 0 > C) in an aluminum block and allowed to react (10-60 min) until the starting material was confirmed to be complete by ¹ H NMR. After cooling to room temperature, the reaction mixture was immediately added to a silica gel column loaded with 2-3 drops of ammonia water as a base, added with hexane: ether = 9: 1, and then purified with the same solvent to obtain the desired compound. To avoid isomer formation, the reaction was refined immediately after the reaction was terminated, and was stored at a temperature below -20 캜 because it tends to be isomerized slowly at room temperature.

Reaction time 5 min, yield 99%, yellow solid

Mp = 157-158 DEG 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 &} gt ;; _{HRMS (ESI) calcd for C 25} H 19 NO 2 [M + H] + 366.1489, found 366.1490.

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

Reaction time 10 min, yield 92%, yellow solid

Mp = 143-148 DEG 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 min, yield 93%, yellow solid

Mp = 121-123 DEG 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 min, yield 96%, yellow solid

Mp = 132-134 [deg.] 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 6.77 (m, 1H), 6.04 (d, J = 7.9 Hz, 1H), 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 &} gt ;; 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 min, yield 96%, yellow solid

Mp = 152-154 DEG 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 min, yield 92%, yellow solid

Mp = 121-125 DEG 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 &} gt ;; _{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, and 30 minutes after the reaction, 5 mol% Pd (OAc) ₂ and 10 mol% PPh ₃ were further added.

Reaction time 60 min, yield 89%, brown solid

Mp = 113-115 DEG 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 &} gt ;; 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 min, yield 99%, brown solid

Mp = 120-124 DEG 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 min, yield 83%, yellow solid

Mp = 134-135 < 0 >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, IH), 6.92-6.83 (m, IH), 6.82 (s, IH), 6.01 (d, J = 8.3 Hz, ), 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 &} gt ;; _{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 min, yield 98%, pale yellow solid

Mp = 68-71 DEG 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 &} gt ;; 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 min, yield 95%, brown solid

Mp = 142-144 DEG 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, IH), 7.10-7.02 (m, IH), 6.96 (d, J = 8.1 Hz, 2H), 6.86 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 &} gt ;; 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- (naphthalene-2-ylmethylene) -6H-isoindolo [2,1-a] indole-11-carboxylate

Reaction time 15 min, yield 90%, yellow solid

Mp = 162-164 DEG 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 &} gt ;; 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-

Reaction time 15 min, yield 94%, yellow solid

Mp = 131-133 [deg.] 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.

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

Reaction time 15 min, yield 98%, pale yellow solid

Mp = 157-159 DEG 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-

Reaction time 10 min, yield 98%, yellow solid

Mp = 120-127 DEG 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 &} gt ;; 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-

The procedure of Example 1 was repeated except that 10 mol% Pd (OAc) ₂ and 20 mol% PPh ₃ were used.

Reaction time 30 min, yield 92%, yellow solid

Mp = 134-140 DEG 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 J = 7.6 Hz, 1 H), 6.82 (t, J = 7.7 Hz, 1 H), 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 &} gt ;; _{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

(73.1 mg, 0.2 mmol), PtCl ₂ (5.3 mg, 0.02 mmol) and toluene (1 mL) were added to a solution of ethyl 2-phenyl-1- (phenylethynyl) I put it in a capped vial. The reaction mixture was stirred in an aluminum block at 110 < 0 > C until reaction was confirmed to be complete (~ 16 hours) by ¹ H NMR. After cooling to room temperature, the reaction mixture was washed with diatomaceous earth with CH ₂ Cl ₂ , then filtered and concentrated in vacuo. And purified by silica gel column chromatography. The non-separable α-chloroenamine was removed by decantation on a centrifuge using hexane and then decanted. The combined supernatant was concentrated and dried in vacuo. The residue was crystallized from hexane to give further purified compound which was summed to yield.

Yield 59%, pale yellow solid

Mp = 177-178 [deg.] 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, 3 H); ^{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 &} gt ;; _{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 DEG 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 [deg.] 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 DEG 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, 3 H); ^{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 DEG 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 DEG 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, 3 H); ^{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 DEG 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 &} gt ;; 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%, pale yellow solid

Mp = 142-145 [deg.] 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 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 &} gt ;; 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 DEG 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 &} gt ;; _{HRMS (ESI) calcd for C 25} H 18 ClNO 2 [M + H] + 400.1099, found 400.1099.

Example 26. Synthesis of ethyl 5-hexylindolo [2,1-a] isoquinoline-12-carboxylate

Yield 54%, pale yellow solid

Mp = 89-91 DEG C; ¹ H NMR (300 MHz, CDCl ₃ )? 9.89-9.77 (m, 1 H), 8.36 (d, J = 7.9 Hz, 1 H), 7.97 J = 7.1 Hz, 2H), 2.91-2.74 (m, 2H), 1.72 (m, 2H), 7.44 (t, J = 7.5 Hz, 1H), 7.40-7.30 (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 &} gt ;; 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 DEG 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 &} gt ;; 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 [deg.] C; ¹ H NMR (300 MHz, CDCl ₃ )? 9.92 (d, J = 8.3 Hz, IH), 8.40 (t, J = 10.7 Hz, IH), 8.20 (s, IH), 8.04-7.86 , 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 &} gt ;; 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 [deg.] 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 &} gt ;; 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 < 0 >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 占 폚; ^{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 )? 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 , ≪ / RTI > 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 [deg.] 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 &} gt ;; _{HRMS (ESI) calcd for C 25} H 18 BrNO 2 [M + H] + 444.0594, found 444.0598.

Test Example 1. Kinetic isotope effect (KIE) evaluation

To confirm the reaction mechanism, the compounds of Example 1 and Example 17 were prepared to evaluate the intramolecular dynamic isotopic effect.

There was sufficient hydrogen / deuterium KIE ( K _H / K _D = 2.86) to confirm that the compound of Example 1 proceeded via CH activation in the 5-exo-dig cyclization under palladium catalyst. Based on the formation of strong KIE and Z-isomers, it is expected that alkane direct ortho-palladium and protopyridylation by cis-migrator insertion into the triple bond will form the compound of Example 1.

On the other hand, KIE ( K _H / K _D = 0.50) appeared on the 6-endo-dig cyclization under platinum catalyst, which is consistent with the mechanism of the electrophilic aromatic substitution reaction. This fact was confirmed by the protodymetallation process coupled with the electrophilic route for 6-endo-dig cyclization involving an intramolecular attack by a neighboring aromatic ring on the platinum catalyzed alkynyl unit, Lt; / RTI >

Claims (11)

A compound represented by the following formula (1):
[Chemical Formula 1]

In the formula,

Is a single or double bond,
A is a 5-6 membered heterocyclic or 5-6 membered heteroaryl containing 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 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 Romero naphthyl, may be optionally substituted by -COOH, -CHO, -COOR _b, phenyl, and 1 to 3 substituents selected from 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. The method according to claim 1,
A compound represented by the following formula (2) or (3):
(2)

(3)

In the formula,
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 Oxy, trihalomethyl, phenyl and benzyl,
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; Wherein said heteroaryl is 5-6 membered heteroaryl, 1H-indolyl or lH-quinolinyl having 1-2 heteroatoms selected from N, O and S, said aryl and heteroaryl being each independently unsubstituted or substituted 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 _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. The method according to claim 1,
R ₁ is CO ₂ Et Compounds. 3. The method of claim 2,
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; Wherein said heteroaryl is 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 Which may be substituted with 1 to 3 substituents,
R _b is a straight or branched C _{1 - 6} alkyl, compound. The method according to 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- (naphthalene-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-hexylindolo [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 process for producing a compound represented by the following formula (1), which comprises refluxing a compound of the following formula (3) under a transition metal catalyst to form an intramolecular ring bond:
(3)

[Chemical Formula 1]

In the formula,

Is a single or double bond,
A is a 5-6 membered heterocyclic or 5-6 membered heteroaryl containing 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 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 Romero naphthyl, may be optionally substituted by -COOH, -CHO, -COOR _b, phenyl, and 1 to 3 substituents selected from 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. The method according to claim 6,
Wherein the transition metal catalyst is selected from Pd (OAc) ₂ , PtCl ₄ and AuCl ₃ . 8. The method of claim 7,
(5-exo-dig cyclization) is formed when the transition metal catalyst is Pd (OAc) ₂ , thereby forming a compound represented by the following general formula (2): ????????
(2)

In the formula,
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 Oxy, trihalomethyl, phenyl and benzyl,
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; Wherein said heteroaryl is 5-6 membered heteroaryl, 1H-indolyl or lH-quinolinyl having 1-2 heteroatoms selected from N, O and S, said aryl and heteroaryl being each independently unsubstituted or substituted 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 _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. 8. The method of claim 7,
Wherein when the transition metal catalyst is Pd (OAc) _2, it further comprises PPh ₃ as a ligand during the reaction. 8. The method of claim 7,
Wherein the transition metal catalyst is PtCl ₄ or AuCl ₃ , a β-addition reaction (6-endo-dig cyclization) is formed to form a compound represented by the following formula (3)
(3)

In the formula,
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 Oxy, trihalomethyl, phenyl and benzyl,
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; Wherein said heteroaryl is 5-6 membered heteroaryl, 1H-indolyl or lH-quinolinyl having 1-2 heteroatoms selected from N, O and S, said aryl and heteroaryl being each independently unsubstituted or substituted 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 _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. The method according to claim 6,
Wherein the transition metal catalyst is added in an amount of 2 to 20 mol%.