Process for producing a compound as a PI3K inhibitor and intermediate compounds therefor

Abstract

The present invention provides a method for producing a compound as a PI3K inhibitor, which includes a step having a shortened reaction time, can perform the reaction under mild conditions, and reduces the number of process steps. Thus, compared to conventionally known production methods, the present invention provides a method for producing a compound as a PI3K inhibitor, which can realize simplified processes and facilitate process control and industrial mass production.

Description

Technical Field

[0001] The present invention relates to a method for producing a compound as a PI3K inhibitor and an intermediate compound for its production.

Background Art

[0002] Phosphatidylinositol 3-kinase (PI3 kinase; PI3K) is a lipid kinase that phosphorylates lipid molecules instead of proteins, and plays an important role in cell survival, signal transduction, control of membrane trafficking, etc. When problems occur in these regulations, cancers, inflammatory diseases, autoimmune diseases, etc. occur.

[0003] In recent years, results of research on developing compounds showing a selective inhibitory effect on PI3 kinase have been reported. These compounds as PI3K inhibitors are effectively used for the treatment of cancers, autoimmune diseases, respiratory diseases, etc. Therefore, in the production of a compound as a PI3K inhibitor, simplification of the process has emerged as an important issue.

Summary of the Invention

Problems to be Solved by the Invention

[0004] One object of the present invention is to provide a new method for producing a compound as a PI3K inhibitor capable of simplifying the process.

[0005] One object of the present invention is to provide a method for producing an intermediate compound for producing a compound as a PI3K inhibitor capable of simplifying the process.

[0006] One object of the present invention is to provide an intermediate compound for producing a compound as a PI3K inhibitor capable of simplifying the process.

Means for Solving the Problems

[0007] In order to solve the above problems, the present invention provides a method for producing a compound of Chemical Formula 7.

[0008] The method for producing a compound of Chemical Formula 7 may include (S1) a step of producing a compound of Chemical Formula 5 with a compound of Chemical Formula 4; (S2) a step of reacting the compound of Chemical Formula 5 with dimethylformamide-dimethylacetal to produce a compound of Chemical Formula 6; and (S3) a step of subjecting the compound of Chemical Formula 6 to a cyclization reaction to produce a compound of Chemical Formula 7. [Chemical Formula 4] TIFF0007683005000001.tif5247[Chemical Formula 5] TIFF0007683005000002.tif5147[Chemical Formula 6] TIFF0007683005000003.tif6547[Chemical Formula 7] TIFF0007683005000004.tif5751

[0009] In Chemical Formulas 4 to 7, X 1 , X 2 and X 4 are each independently a halogen atom.

[0010] The X 1 , X 2 and X 4 may be the same as or different from each other. X 1 , X 2 and X 4 may each independently be F, Cl, Br or I. More specifically, the X 1 , X 2 and X 4 may each independently be Br or Cl. For example, X 1 , X 2 and X 4 may all be Cl. The X 1 and the X 4 may be Cl.

[0011] In the above Chemical Formula 6, R 1 and R 2 any one of them is a hydrogen atom, and the remaining one is dimethylamine.

[0012] The method for producing the compound of Chemical Formula 7 may further include the step of (S1-1) subjecting the compound of Chemical Formula 3 to a halogenation reaction to produce the compound of Chemical Formula 4. [Chemical Formula 3] TIFF0007683005000005.tif5147

[0013] In the above Chemical Formula 3, X 1 and X 2 may be the same as those defined in the above Chemical Formulas 4 to 7.

[0014] The method for producing the compound of Chemical Formula 7 may further include the step of (S1-2) reacting the compound of Chemical Formula 1 with the compound of Chemical Formula 2 to produce the compound of the above Chemical Formula 3. [Chemical Formula 1] TIFF0007683005000006.tif3441[Chemical Formula 2] TIFF0007683005000007.tif2929

[0015] In the above Chemical Formulas 1 and 2, X 1 and X 2 may each independently be the same as those defined in the above Chemical Formulas 4 to 7. In the above Chemical Formula 2, X 3 may be a halogen atom.

[0016] Unless otherwise specified in this specification, the halogen atom may be any one selected from F, Cl, Br or I. For example, it may be any one selected from Cl and Br.

[0017] The method for producing the compound as the PI3K inhibitor may include the following steps (S1) to (S3). (S1) Step of aminating the compound of Chemical Formula 4 to produce the compound of Chemical Formula 5; (S2) Step of reacting the compound of Chemical Formula 5 with dimethylformamide-dimethylacetal to produce the compound of Chemical Formula 6; and (S3) Step of subjecting the compound of Chemical Formula 6 to a cyclization reaction to produce the compound of Chemical Formula 7.

[0018] The method for producing the compound as the PI3K inhibitor may further include the following step (S1-1). (S1-1) Step of subjecting the compound of Chemical Formula 3 to a halogenation reaction to produce the compound of Chemical Formula 4.

[0019] The method for producing the compound as the PI3K inhibitor may further include the following step (S1-2). (S1-2) Step of reacting the compound of Chemical Formula 1 with the compound of Chemical Formula 2 to produce the compound of Chemical Formula 3.

[0020] The method for producing the compound of Chemical Formula 7 according to one embodiment is (S1-2) Step of reacting the compound of Chemical Formula 1 with the compound of Chemical Formula 2 to produce the compound of Chemical Formula 3; (S1-1) Step of subjecting the compound of Chemical Formula 3 to a halogenation reaction to produce the compound of Chemical Formula 4; (S1) Step of producing the compound of Chemical Formula 5 with the compound of Chemical Formula 4; (S2) Step of reacting the compound of Chemical Formula 5 with dimethylformamide-dimethylacetal to produce the compound of Chemical Formula 6; and (S3) Step of subjecting the compound of Chemical Formula 6 to a cyclization reaction to produce the compound of Chemical Formula 7 may be included, and for the compounds of Chemical Formulas 1 to 7, the same content may be applied as long as there is no contradiction.

[0021] Also, the method for producing the compound of Chemical Formula 7 according to one embodiment is (S1-2) Step of reacting the compound of Chemical Formula 1 with the compound of Chemical Formula 2 to produce the compound of Chemical Formula 3; (S1-1) Step of subjecting the compound of Chemical Formula 3 to a halogenation reaction to produce the compound of Chemical Formula 4; (S1) Step of aminating the compound of Chemical Formula 4 to produce the compound of Chemical Formula 5; (S2) Step of reacting the compound of Chemical Formula 5 with dimethylformamide-dimethylacetal to produce the compound of Chemical Formula 6; and (S3) It may include the step of subjecting the compound of Chemical Formula 6 to a cyclization reaction to produce the compound of Chemical Formula 7. Regarding the compounds of Chemical Formulas 1 to 7, the same content may be applied as long as there is no contradiction.

[0022] The step (S1) may be carried out in an aprotic polar solvent. For example, the solvent in the step (S1) may contain dimethyl sulfoxide. The step (S1) may be carried out under basic conditions. For example, in the step (S1), a basic compound such as ammonium hydroxide may be used in the reaction.

[0023] The step (S1-2) may be carried out in an aprotic polar solvent. For example, the solvent in the step (S1-2) may contain acetonitrile. The step (S1-2) may be carried out under basic conditions. For example, in the step (S1-2), a basic compound may be used in the reaction. The basic compound may be, for example, a tertiary amine such as triethylamine.

[0024] In this specification, the aprotic polar solvent may contain at least one of dichloromethane, tetrahydrofuran, ethyl acetate, dimethyl sulfoxide, dimethylformamide, and acetonitrile, but is not limited thereto.

[0025] In the step (S1-2), the equivalent ratio of the compound of Chemical Formula 1, the compound of Chemical Formula 2, and triethylamine may be 1:1.1:1.5.

[0026] The said X1 and X 2 may be Cl. More specifically, the step (S1-2) may include the steps of adding the compound of Chemical Formula 1 and the compound of Chemical Formula 2 to an organic solvent (for example, a mixed solvent of acetonitrile and triethylamine), refluxing and stirring for about 1 to 3 hours, cooling to room temperature, adding purified water and stirring at room temperature, filtering and washing (for example, the washing solvent may be purified water), and drying.

[0027] The step (S1-1) may be a step of reacting the compound of Chemical Formula 3 with N-chlorosuccinimide to carry out the chlorination reaction. In step (S1-1), the equivalent ratio of the compound of Chemical Formula 3 to N-chlorosuccinimide may be 1:1.13.

[0028] The step (S1-1) may be carried out in an aprotic polar solvent. More specifically, the step (S1-1) may be carried out in at least one solvent selected from dichloromethane and acetonitrile.

[0029] More specifically, the step (S1-1) may include the steps of adding the compound of Chemical Formula 3 and N-chlorosuccinimide to an organic solvent (for example, dichloromethane), refluxing and stirring for about 3 hours, concentrating after cooling to room temperature, adding an organic solvent (for example, acetonitrile) and concentrating again, adding acetonitrile and cooling and stirring at about 0°C or more and 5°C or less, filtering and washing (an organic solvent may be used as the washing solvent, for example, acetonitrile may be used), and drying.

[0030] The step (S1) may include a step of reacting the compound of Chemical Formula 4 with ammonium hydroxide (NH 4 OH) to produce a crude product of Chemical Formula 5. The step (S1) may include a step of purifying the crude product.

[0031] The step of purifying the crude product may include at least one selected from ethanol, isopropyl alcohol, and acetone as the purification solvent. The step of purifying the crude product may use isopropyl alcohol as the purification solvent.

[0032] In the step (S1), the equivalent ratio of the compound of Chemical Formula 4 to ammonium hydroxide (NH 4 OH) may be 1:5 to 1:15.

[0033] More specifically, the step of generating the crude product in the step (S1) involves adding the compound of Chemical Formula 4 and the ammonium hydroxide (NH 4 OH) into an organic solvent (for example, dimethyl sulfoxide), heating (about 70°C to 90°C, for example, about 80°C) and stirring for about 3 hours, stirring at room temperature for about 1 to 2 hours (or for about 2 hours or more until a solid is formed), adding purified water and stirring again at room temperature, filtering and washing (purified water may be used as the washing solvent), and drying.

[0034] More specifically, the step of purifying the crude product in the step (S1) includes adding an organic solvent (for example, isopropyl alcohol) to the crude product and refluxing and stirring for about 30 minutes, stirring at room temperature for about 1 to 2 hours, filtering and washing (an organic solvent may be used as the washing solvent, for example, isopropyl alcohol), and drying.

[0035] In the step (S2), the equivalent ratio of the compound of Chemical Formula 5 to dimethylformamide-dimethylacetal may be 1:2.

[0036] More specifically, the step (S2) may include a step of refluxing and stirring a compound of Chemical Formula 5 and dimethylformamide-dimethylacetal in an organic solvent (e.g., dichloromethane) for about 1 hour, a step of cooling and concentrating to room temperature, a step of adding an organic solvent (e.g., isopropyl alcohol) and refluxing and stirring, a step of cooling and stirring to room temperature, a step of filtering and washing (an organic solvent may be used as the washing solvent, e.g., isopropyl alcohol may also be used), and a step of drying.

[0037] In the step (S3), the cyclization reaction may include a step of reacting the compound of Chemical Formula 6 with a base and a step of adding an acid. The step of adding the acid may be performed after the step of reacting the compound of Chemical Formula 6 with the base. The base may be a tert-butoxide salt. For example, the base may be potassium tert-butoxide or sodium tert-butoxide. The acid may be an organic acid or an inorganic acid, and for example, acetic acid or hydrochloric acid may also be used.

[0038] In the step (S3), the equivalent ratio of the compound of Chemical Formula 6 to the base may be 1:1.5. The equivalent ratio of the compound of Chemical Formula 6 to the acid may be 1:3.

[0039] More specifically, the step (S3) may include a step of charging the compound of Chemical Formula 6 into an organic solvent (e.g., a mixed solvent of tetrahydrofuran and acetonitrile), cooling and stirring to about -5°C, charging the base separately (e.g., about 2 to 3 times), cooling and stirring for about 30 minutes to 2 hours, adding purified water and dropwise adding an acid (e.g., acetic acid) to form a solid, then stirring at room temperature for about 1 to 2 hours, a step of filtering and washing (purified water may be used as the washing solvent, for example), and a step of drying.

[0040] In one embodiment, the method for producing the compound of Chemical Formula 7 may further include a step of purifying the crude product of the compound of Chemical Formula 7.

[0041] In addition, the present invention can provide a method for producing a compound of Chemical Formula 6. The method for producing a compound of Chemical Formula 6 according to one embodiment may include a step of reacting a compound of Chemical Formula 5 with dimethylformamide-dimethylacetal. [Chemical Formula 5] TIFF0007683005000008.tif5047[Chemical Formula 6] TIFF0007683005000009.tif6749

[0042] In Chemical Formulas 5 and 6, X 1 and X 4 may each independently be a halogen atom. In Chemical Formula 6, either one of R 1 and R 2 is a hydrogen atom, and the other may be dimethylamine.

[0043] By providing the compound of Chemical Formula 6, which is an intermediate compound used in the production process of the compound of Chemical Formula 7 of the present invention, the production process of the compound of Chemical Formula 7 can be simplified and the process time can be reduced.

[0044] The method for producing a compound of Chemical Formula 7 according to one embodiment may include a step of subjecting the aforementioned compound of Chemical Formula 6 to a cyclization reaction.

[0045] According to one embodiment of the present invention, a compound represented by the following Chemical Formula 6 can be provided. [Chemical Formula 6] TIFF0007683005000010.tif6749

[0046] In Chemical Formula 6, X 1 and X 4 may each independently be a halogen atom. Either one of R 1 and R 2 is a hydrogen atom, and the other may be dimethylamine.

[0047] The compound represented by the chemical formula 6 is used as an intermediate compound in the manufacturing process of the compound as a PI3K inhibitor in one embodiment, and can reduce the process steps and process costs.

[0048] According to the present invention, different from the conventional method for manufacturing a compound as a PI3K inhibitor, the process steps required for manufacturing a compound as a PI3K inhibitor can be reduced, and a compound as a PI3K inhibitor can be synthesized without performing a long reflux and stirring reaction that takes several days or more. In addition, since the reaction can be carried out under mild reaction conditions, the risk factors that may occur during synthesis can be significantly reduced, and the manufacturing process can be easily managed.

[0049] Therefore, the process can be simplified, the time required for the process can be shortened, the process costs can be reduced, and the process management becomes easier. Thus, the method for manufacturing a compound as a PI3K inhibitor according to one embodiment is suitable for the industrial production of a compound as a PI3K inhibitor.

Effects of the Invention

[0050] According to the method for manufacturing a compound as a PI3K inhibitor of the present invention, it is possible to simplify the manufacturing process of the compound as a PI3K inhibitor and reduce the manufacturing steps and manufacturing costs. In addition, the intermediate compound for manufacturing a compound as a PI3K inhibitor according to the present invention can reduce the manufacturing steps and manufacturing costs by being used in the manufacturing process of the compound as a PI3K inhibitor. Thereby, the productivity of the compound as a PI3K inhibitor can be improved.

Modes for Carrying Out the Invention

[0051] Hereinafter, the advantages and features of the present invention and the methods for achieving them will be described in detail with reference to the following examples. However, the present invention is not limited by the examples disclosed below and may be embodied in various different forms. These examples are provided only to make the disclosure of the present invention complete and to fully convey the scope of the present invention to those skilled in the art. The present invention should be defined by the claims.

[0052] Example 1: Synthesis of (S)-4-((1-(4,8-dichloro-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrido[2,3-d]pyrimidin-5(8H)-one

[0053] 1. Reaction Scheme TIFF0007683005000011.tif78144

[0054] 2. Step (1) - Synthesis of Intermediate Compound QHK According to the above reaction scheme, to intermediate compound IQA ((S)-3-(1-aminoethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one) (10 g, 33.5 mmol) were added acetonitrile (AN) (80 ml), DCK (1-(4,6-dichloropyrimidin-5-yl)ethanone) (7.0 g, 36.8 mmol) and triethylamine (Et 3-N) (7.0 ml, 50.2 mmol) was added, and the mixture was refluxed and stirred for 3 hours. After cooling to room temperature (25 °C), purified water (20 ml) was added and the mixture was stirred at room temperature (25 °C). The solid was filtered, washed with purified water (25 ml), and then dried with hot air at 40 °C to obtain the intermediate compound QHK ((S)-3-(1-((5-acetyl-6-chloropyrimidin-4-yl)amino)ethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one) (13.8 g, yield: 91%). 1 H-NMR(400MHz,CDCl 3 ): δ1.43 (d, 3H), δ2.78 (s, 3H), δ4.92 (t, 1H) δ6.48 (s, 1H), δ7.26 - 7.46 (m, 8H), δ8.18 (s, 1H), δ8.97 (d, 1H).

[0055] 3. Step (2) - Synthesis of intermediate compound IQCK To the intermediate compound QHK (6.0 g, 13 mmol) obtained in the above step (1), dichloromethane (MC) (35 ml) and N-chlorosuccinimide (NCS) (2.0 g, 15 mmol) were added, and the mixture was refluxed and stirred for 3 hours. After cooling to room temperature (25 °C), the reaction mixture was concentrated under reduced pressure. Acetonitrile (18 ml) was added to the concentrated residue, and the mixture was cooled and stirred at 0 - 5 °C for 1 hour. Then the solid was filtered, washed with acetonitrile (6 ml), and dried with hot air at 40 °C to obtain the intermediate compound IQCK ((S)-3-(1-((5-acetyl-6-chloropyrimidin-4-yl)amino)ethyl)-4,8-dichloro-2-phenylisoquinolin-1(2H)-one) (5.7 g, yield: 89%). 1 H-NMR(400MHz,CDCl 3 ): δ1.62 (d, 3H), δ2.74 (s, 3H), δ4.98 (t, 1H), δ7.17 - 7.95 (m, 8H), δ8.26 (s, 1H), δ9.37 (broad, 1H)

[0056] 4. Step (3) - Synthesis of Intermediate Compound IQNK To the intermediate compound IQCK (30.4 g, 62 mmol) obtained in the above step (2), dimethyl sulfoxide (DMSO) (304 ml) and ammonium hydroxide (48.6 ml, 642 mmol) were added, and the mixture was heated and stirred at 80°C for 5 hours, then cooled to room temperature and stirred overnight. Purified water (304 ml) was added to the reaction mixture in which a solid had formed, and the mixture was further stirred at room temperature for 1.5 hours. The solid of the reaction mixture was filtered, washed with purified water (610 ml), and dried with hot air at 40°C to obtain a crude product of IQCK (29.8 g). The crude product of IQNK (29.8 g) was put into isopropyl alcohol (300 ml), refluxed and stirred for 10 minutes, then cooled to room temperature and further stirred for 2 hours. The solid was filtered, washed with isopropyl alcohol (75 ml), and dried with hot air at 40°C to obtain purified IQNK ((S)-3-(1-((5-acetyl-6-aminopyrimidin-4-yl)amino)ethyl)-4,8-dichloro-2-phenylisoquinolin-1(2H)-one) (26.9 g, yield 92%). 1 H-NMR(400MHz,CDCl 3 ):δ1.60(d,3H),δ2.56(s,3H),δ5.03(t,1H),δ5.77(br,2H),δ7.15-7.97(m,9H)

[0057] In step (3), isopropyl alcohol was used as the purification solvent for the crude product of IQNK, but the examples are not limited to this, and various organic solvents may be used. For example, any one or more organic solvents selected from ethanol, isopropyl alcohol and acetone may be used. Preferably, an isopropyl alcohol solvent may be used.

[0058] 5. Step (4) - Synthesis of Intermediate Compound IQVK To the intermediate compound IQNK (26.8 g, 57.2 mmol) obtained in the step (3), dichloromethane (130 ml) and dimethylformamide-dimethylacetal (DMF-DMA) (15.2 ml, 114.4 mmol) were added, and the mixture was refluxed and stirred for 1 hour. Then, it was cooled to room temperature (25 °C) and concentrated under reduced pressure. Isopropyl alcohol (190 ml) was added to the concentrated residue, and the mixture was refluxed and stirred. After cooling to room temperature, the solid was filtered. The filtered solid was washed with isopropyl alcohol (80 ml) and dried with hot air at 40 °C to obtain the intermediate compound IQVK ((S)-N’-(5-acetyl-6-((1-(4,8-dichloro-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidin-4-yl)-N,N-dimethylformimidamide) (26.2 g, yield: 88%). 1 H-NMR(400MHz,CDCl 3 ):δ1.60(d,3H),δ2.75(s,3H),δ3.11(s,3H),δ3.14(s,3H),δ4.99(t,1H),δ7.26-7.96(m,8H),δ8.10(s,1H),δ8.55(s,1H)

[0059] 6. Step (5) - Synthesis of the final product Tetrahydrofuran (6 ml) was added to the intermediate compound IQVK (1 g, 1.9 mmol) obtained in the step (4) above, and the mixture was cooled to -5°C and stirred. Potassium tert-butoxide (0.32 g, 2.9 mmol) was added in three portions, and the mixture was stirred for 0.5 hour while maintaining the temperature at -5°C. Then, purified water (12 ml) was added, acetic acid (0.33 ml, 5.7 mmol) was added, and the mixture was stirred at room temperature for 2 hours. The resulting solid was filtered, washed with purified water (10 ml), and dried with hot air at 40°C to obtain the final product ((S)-4-((1-(4,8-dichloro-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrido[2,3-d]pyrimidin-5(8H)-one) (0.85 g, yield: 77%). 1 H-NMR(400MHz,CDCl 3 ):δ1.67(d,3H),δ5.03(t,1H),δ6.31(d,1H),δ7.20-7.95(m,9H),δ8.25(s,1H)

[0060] Referring to Example 1, according to one embodiment, the method for producing a compound as a PI3K inhibitor can synthesize the compound as a PI3K inhibitor only through five steps of step (1) to step (5). Also, since the reaction time in each step is short, the process time can be shortened. More specifically, steps (1) to (5) do not require harsh reaction conditions such as refluxing and stirring for several days or more. In particular, steps (1) to (5) include a refluxing and stirring step of about 1 to 5 hours, and do not include a refluxing and stirring step that requires more time. Therefore, according to the method for producing a compound as a PI3K inhibitor of one embodiment, the total number of working days can be shortened by several days or more. Also, since strong acids such as TFA (Trifluoroacetic acid) or MsOH (Methane Sulfonic Acid) are not used, the reaction can be carried out under mild reaction conditions. Thus, the risk factors that may occur during synthesis can be significantly reduced, and the manufacturing process can be easily managed.

[0061] According to one embodiment, the PI3K inhibitor can simplify the process by manufacturing the PI3K inhibitor by a manufacturing method including steps (S1) to (S5), and can reduce the manufacturing steps and manufacturing costs. In addition, by manufacturing the PI3K inhibitor under mild reaction conditions, the manufacturing process can be easily managed.

Claims

1. (S1) A step of producing a compound of Formula 5 with a compound of Formula 4; (S2) A step of reacting the compound of Formula 5 with dimethylformamide-dimethylacetal to produce a compound of Formula 6; and (S3) A method for producing a compound of Formula 7, comprising a step of subjecting the compound of Formula 6 to a cyclization reaction to produce a compound of Formula 7: [Formula 4] [Formula 5] [Formula 6] [Formula 7] In Chemical Formulas 4 to 7, X １ , X ２ and X ４ are each independently a halogen atom, In the chemical formula 6, R １ and R ２ either one of them is a hydrogen atom, and the remaining one is dimethylamine.

2. The production method further includes (S1-1) a step of subjecting the compound of Formula 3 to a halogenation reaction to produce the compound of Formula 4, the method for producing the compound of Formula 7 according to Claim 1: [Formula 3] In the above Chemical Formula 3, X １ and X ２ are each independently the same as those defined by the above Chemical Formula 4 to Chemical Formula 7.

3. The production method further includes (S1-2) a step of reacting the compound of Formula 1 with the compound of Formula 2 to produce the compound of Formula 3, the method for producing the compound of Formula 7 according to Claim 2: [Formula 1] [Formula 2] In the above Chemical Formula 1 and Chemical Formula 2, X １ and X ２ are each independently the same as those defined in the above Chemical Formula 4 to Chemical Formula 7, In the above chemical formula 2, X ３ is a halogen atom.

4. The step (S1) is carried out under basic conditions, the method for producing the compound of Formula 7 according to Claim 1.

5. The step (S1) is carried out in an aprotic polar solvent, the method for producing the compound of Formula 7 according to Claim 1.

6. The step (S1-1) is a step of subjecting the compound of Formula 3 to a chlorination reaction by reacting it with N-chlorosuccinimide, the method for producing the compound of Formula 7 according to Claim 2.

7. The step (S1) includes a step of reacting the compound of Formula 4 with ammonium hydroxide to produce a crude product of Formula 5, the method for producing the compound of Formula 7 according to Claim 1.

8. The step (S1) includes a step of purifying the crude product, the method for producing the compound of Formula 7 according to Claim 7.

9. The step of purifying the crude product includes at least one selected from ethanol, isopropyl alcohol, and acetone as a purification solvent, the method for producing the compound of Formula 7 according to Claim 8.

10. The step of purifying the crude product uses isopropyl alcohol as a purification solvent, the method for producing the compound of Formula 7 according to Claim 8.

11. In the step (S3), the cyclization reaction includes a step of reacting the compound of Formula 6 with a base and a step of adding an acid, the method for producing the compound of Formula 7 according to Claim 1.

12. The method for producing the compound of Chemical Formula 7 according to claim 11, wherein the base is a tert-butoxide salt.

13. The method for producing the compound of Chemical Formula 7 according to claim 11, wherein the acid is acetic acid or hydrochloric acid.

14. A method for producing a compound of Chemical Formula 6, comprising a step of reacting a compound of Chemical Formula 5 with dimethylformamide-dimethylacetal: [Chemical Formula 5] [Chemical Formula 6] In the chemical formula 5 and the chemical formula 6, X １ and X ４ are each independently a halogen atom, In the chemical formula 6, R １ and R ２ One of them is a hydrogen atom, and the other one is dimethylamine.

15. A method for producing a compound of Chemical Formula 7, comprising a step of subjecting the compound of Chemical Formula 6 to a cyclization reaction: [Chemical Formula 6] [Chemical Formula 7] In the above Chemical Formula 6 and Chemical Formula 7, X １ and X ４ are each independently a halogen atom, In the chemical formula 6, R １ and R ２ One of them is a hydrogen atom, and the other one is dimethylamine.

16. A compound represented by the following Chemical Formula 6: [Chemical Formula 6] In the above Chemical Formula 6, X １ and X ４ are each independently a halogen atom, R １ and R ２ One of them is a hydrogen atom and the other is dimethylamine.

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