A method for synthesizing alkylated nitrogen heterocycles induced by persulfate

Abstract

The application discloses a synthesis method of a peroxysulfate-induced alkylated modified nitrogen heterocyclic compound, which comprises the following steps: adding N-long chain alkyl sulfonamide shown in formula (I), nitrogen heterocyclic shown in formula (II), an oxidizing agent and an acidic additive into a reaction solvent, stirring the reaction under the condition of light source irradiation under nitrogen protection, and obtaining the target compound shown in formula (III) after post-treatment of the reaction liquid. 3 The method has the advantages of simple operation, wide substrate universality and mild reaction condition, and the generation of nitrogen radicals is induced by ET / PT triggered by peroxysulfate, and the heteroarylation of inert C(sp 3 )‑H bond is realized through long-distance hydrogen migration driven by the nitrogen radicals, the method can be directly applied to the alkylated modification of the drug isoniazid, and has certain application value.

Description

Technical Field

[0001] The invention relates to a method for synthesizing a nitrogen heterocyclic compound induced by persulfate and alkylated. Background Art

[0002] Nitrogen heterocycles are valuable structural scaffolds, widely used in a variety of fields, including pharmaceutical molecules, materials, and organic synthesis intermediates. For example, quinine is a rapid blood schizonticide and a common antimalarial drug, primarily used to treat malignant malaria caused by chloroquine-resistant and multidrug-resistant strains of parasites, and can also be used to treat Plasmodium vivax malaria. Camptothecin, an alkaloid isolated from Camptotheca acuminata, is one of the natural antitumor drugs currently widely used in clinical practice, with excellent therapeutic effects on a variety of human malignancies, including ovarian and colorectal cancer. Isoniazid is a synthetic antibacterial drug with bactericidal properties, often used in combination with other anti-tuberculosis drugs for the treatment of various types of tuberculosis, including tuberculous meningitis and other mycobacterial infections. Given the important application value of nitrogen heterocyclic nuclei in organic synthesis and pharmaceuticals, it is of great significance to improve the physicochemical properties and biological activity of drugs by functionalizing nitrogen heterocyclic nuclei. Among them, the alkylation modification of nitrogen heterocyclic nuclei has been rapidly developed in recent years, because it can significantly enhance lipid solubility, thereby improving membrane permeability, enabling better absorption of drugs and improving drug efficacy. Minici reaction is the most direct and effective method for alkylation modification of nitrogen heterocyclic nuclei. However, due to the multiple C (sp 3 )-H bond dissociation energy leads to inherent inertness and regioselectivity. Currently, alkylation modification of nitrogen heterocyclic core mainly occurs at the more active benzyl position and the α-carbon adjacent to heteroatoms (such as oxygen and nitrogen atoms). For the less active inert C(sp 3 Selective heteroarylation of the )-H site still faces great challenges.

[0003]

[0004] This patent application is based on the HAT strategy, through the C (sp 3 )-H bond with the C(sp 2 )-H bonds undergo dehydrogenative coupling to prepare alkylamine-substituted nitrogen heterocyclic compounds. Generally, the HAT strategy mainly relies on electrophilic heteroatom radicals such as chlorine radicals, bromine radicals, nitrogen and alkoxy radicals to aliphatic C (sp 3 )-H bond to realize C(sp 3) to generate an active alkyl radical species. In 2019, the group of Xinhua Duan used ruthenium as a photocatalyst and potassium phosphate as a basic additive to generate sulfonamide-based radicals through the PCET strategy, and achieved the alkylization of amine-based sulfonamide esters through the intramolecular 1,6-HAT process induced by the radicals. 3 ) to generate an active alkyl radical species. In 2019, the group of Xinhua Duan used ruthenium as a photocatalyst and potassium phosphate as a basic additive to generate sulfonamide-based radicals through the PCET strategy, and achieved the alkylization of amine-based sulfonamide esters through the intramolecular 1,6-HAT process induced by the radicals. 3 ) to generate an active alkyl radical species. In 2019, the group of Xinhua Duan used ruthenium as a photocatalyst and potassium phosphate as a basic additive to generate sulfonamide-based radicals through the PCET strategy, and achieved the alkylization of amine-based sulfonamide esters through the intramolecular 1,6-HAT process induced by the radicals.

[0005] Although there has been a great breakthrough in the initiation mode of nitrogen radicals through the PCET strategy, there are still some deficiencies, such as the use of noble metals as photocatalysts, which is high in cost and may cause metal residue in the actual production process, which is difficult to meet the strict requirements of high-quality standards in the field of food and drug production. Electron / proton transfer (ET / PT) provides another strategy for the generation of nitrogen radicals, but due to its inherent thermal chemical limitations, it has not been widely studied in the field of synthetic organic chemistry. Only a few organic electrochemical systems generate nitrogen radicals by losing one electron and one proton of the N-H substrate at the anode; and to our knowledge, the generation and further application of nitrogen radicals through the ET / PT mode induced by light are still unknown. Based on the ET / PT reaction mechanism, the present application uses inexpensive persulfate as an oxidizing agent to induce the homolysis of the sulfonamide-based N-H bond to generate sulfonamide-based nitrogen radicals, which can trigger the intramolecular 1,5-HAT process to activate the remote inert C(sp 3 ) to generate an active alkyl radical species. In 2019, the group of Xinhua Duan used ruthenium as a photocatalyst and potassium phosphate as a basic additive to generate sulfonamide-based radicals through the PCET strategy, and achieved the alkylization of amine-based sulfonamide esters through the intramolecular 1,6-HAT process induced by the radicals. 3 ) to generate an active alkyl radical species. In 2019, the group of Xinhua Duan used ruthenium as a photocatalyst and potassium phosphate as a basic additive to generate sulfonamide-based radicals through the PCET strategy, and achieved the alkylization of amine-based sulfonamide esters through the intramolecular 1,6-HAT process induced by the radicals. SUMMARY

[0006] In view of the above problems existing in the prior art, the purpose of the present application is to provide a synthesis method for alkylated modification of nitrogen heterocyclic compounds, which has novel reaction mechanism, simple operation, mild reaction conditions and high product purity.

[0007] The technical scheme adopted by the present application is as follows:

[0008] A synthesis method for alkylated modification of nitrogen heterocyclic compounds induced by persulfate, which adds N-long-chain alkyl sulfonamide represented by formula (I), nitrogen heterocycle represented by formula (II), oxidizing agent and acidic additive into a reaction solvent, protects under nitrogen, stirs under the condition of light source irradiation, and after the reaction is completed, the reaction liquid is treated to obtain the target compound represented by formula (III), and the reaction equation is as follows:

[0009]

[0010] The nitrogen heterocycle in formula (II) and formula (III) is one of benzothiazole, quinoline, isoquinoline, quinoxaline, quinazoline, phthalazine, acridine, pyrazine, thiazole, pyrimidine, or a derivative thereof, and the substituents on the derivatives are mono- or di-substituted at any C atom position on the benzene ring or other main ring, and each substituent is independently selected from halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkoxycarbonyl, C1-C4 haloalkyl, C1-C4 haloalkoxy, or amino-substituted amide;

[0011] FG in formula (I) and formula (III) is a single or double substitution at any position of the N-long chain alkyl side chain, and the substituents are independently selected from H, methyl, phenyl or methoxycarbonyl, and R 1 is selected from H, methyl, ethyl, n-propyl, n-butyl, cyclopentyl, cyclohexyl or 2-chloroethyl.

[0012] Furthermore, the oxidant is potassium persulfate, sodium persulfate, ammonium persulfate, hydrogen peroxide, tert-butyl peroxide, benzoyl peroxide or m-chloroperbenzoic acid, preferably ammonium persulfate.

[0013] Furthermore, the acidic additive is TFA, HCl or CF3SO3H, preferably CF3SO3H or TFA.

[0014] Furthermore, the reaction temperature is 20°C-50°C, preferably 25-30°C, and the reaction time is 18-35h, preferably 20-25h.

[0015] Furthermore, the reaction solvent is a mixed solvent of any one of 1,2-dichloroethane, ethyl acetate, dimethyl sulfoxide, dichloromethane or acetonitrile and water in a volume ratio of 1:0.5-2, preferably a mixed solvent of dimethyl sulfoxide or acetonitrile and water in a volume ratio of 1:1.

[0016] Furthermore, the light source is blue light, white light or purple light, preferably purple light, and the illumination power is 15 to 50 W, preferably 25 to 30 W.

[0017] Furthermore, the molar ratio of the N-long-chain alkylsulfonamide represented by formula (I) to the nitrogen heterocycle represented by formula (II) is 1:1.5.0-4.0, preferably 1:2.0-3.0; the molar ratio of the oxidant to the N-long-chain alkylsulfonamide represented by formula (I) is 1.5-3.0:1, preferably 2.0-2.5:1; and the molar ratio of the acidic additive to the N-long-chain alkylsulfonamide represented by formula (I) is 1.0-3.0:1, preferably 1.5-2.0:1.

[0018] Furthermore, the dispersion concentration of the N-long-chain alkylsulfonamide represented by formula (I) in the reaction solvent is 0.05-0.4 mol / L, preferably 0.1-0.15 mol / L.

[0019] Furthermore, the post-treatment process is as follows: the reaction solution is quenched with a saturated aqueous sodium bicarbonate solution, then extracted with ethyl acetate, separated and layered, the organic phase is washed with saturated brine, the combined organic layers are dried over anhydrous Na2SO4 and concentrated under reduced pressure to obtain a crude product, and the crude product is separated and purified by a chromatographic column to obtain the target compound represented by formula (III), which is a remote nitrogen heterocyclic substituted sulfonamide compound.

[0020] Furthermore, an N-long-chain alkyl sulfonamide represented by formula (I), a nitrogen heterocycle represented by formula (II), an oxidant, an acidic additive and a reaction solvent are added to a reaction tube equipped with a magnetic stirrer. After nitrogen replacement three times, the reaction system is placed under light source irradiation and stirred at 25-35° C. After the reaction is completed, the reaction solution is quenched with a saturated sodium bicarbonate aqueous solution, and then extracted with ethyl acetate, the layers are separated, and the organic phase is washed with saturated brine. After the organic layers are combined, they are dried over anhydrous Na2SO4 and concentrated under reduced pressure to obtain a crude product. The crude product is separated and purified by a chromatographic column to obtain the target compound, a remote nitrogen heterocycle substituted sulfonamide compound represented by formula (III).

[0021] Furthermore, the eluent used for chromatographic column separation and purification is petroleum ether / ethyl acetate with a volume ratio of 1:1 to 5:1.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] 1) The present invention involves a light-induced ET / PT reaction mechanism to achieve remote alkylation of nitrogen heterocycles. There is no similar literature report so far, and the originality is high;

[0024] 2) This invention overcomes the high dissociation free energy of the NH bond and directly generates N-centered free radicals from the NH bond. Compared with conventional technologies, this method is simple to operate and does not require pre-functionalization of the reaction substrate;

[0025] 3) The present invention has the advantages of wide substrate compatibility, simple operation, mild reaction conditions, and simple post-processing.

[0026] 4) The technology of the present invention can be used to directly perform alkylation modification on some natural compounds and nitrogen-containing heterocyclic drugs. DETAILED DESCRIPTION

[0027] The present invention will be further described below with reference to specific embodiments, but the protection scope of the present invention is not limited thereto.

[0028] Before specifically carrying out the examples, a series of conditions were optimized for the synthesis of compound (III) N-(4-(6-chlorobenzo[d]thiazol-2-yl)pentyl)-4-methoxybenzenesulfonamide using compound (I) 6-chlorobenzothiazole and compound (II) N-pentyl-4-methoxybenzenesulfonamide as template substrates. The synthesis steps were as follows: adding compound (I), compound (II), an oxidant, an acidic additive, and a reaction medium to a reaction tube equipped with a magnetic stirrer. After nitrogen substitution three times, the reaction system was placed under light irradiation, stirred for 24 hours, and the yield was calculated by chromatographic column separation. The purity was determined by high performance liquid chromatography. The specific conditions for optimization include the feed ratio of compounds (I) and (II), the type and amount of the oxidant, the acidic additive, the reaction medium and the type of light source. A series of screening of the conditions was carried out by controlling the variables, and the optimal reaction conditions were finally determined to be the feed ratio of compounds (I) and (II) of 1:2.0-3.0, the oxidant is ammonium persulfate in an amount of 2.5-3.0 equivalents, the additive is trifluoromethanesulfonic acid in an amount of 1.5-2.0 equivalents, the reaction medium is dimethyl sulfoxide or a mixed solvent composed of acetonitrile and water in a volume ratio of 1:1 as the preferred solvent, the light source is purple light, and the reaction is carried out at room temperature (25-30°C) for 24 hours. The yield of compound (III) can reach 88% and the purity is 98.8%.

[0029] Example 1 N-(4-(6-chlorobenzo[d]thiazol-2-yl)pentyl)-4-methoxybenzenesulfonamide

[0030]

[0031] In a reaction tube equipped with a magnetic stirrer, a mixture of compound (I) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), compound (II) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoromethanesulfonic acid (60.3 mg, 0.4 mmol) was added. A mixed solvent of dimethyl sulfoxide and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen substitution three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution. The mixture was extracted with ethyl acetate. The organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 4:1 to 3:1 to obtain the target product in a yield of 88% with an HPLC purity of 98.8%.

[0032] 1H NMR (400 MHz, CDC13) δ 7.83 (d, J = 8.7 Hz, 1H), 7.77 (d, J = 2.1 Hz, 1H), 7.76 - 7.72 (m, 2H), 7.38 (dd, J = 8.7, 2.1 Hz, 1H), 6.91 - 6.87 (m, 2H), 5.15 (s, 1H), 3.81 (s, 3H), 3.18 (h, J = 6.9 Hz, 1H), 2.97 - 2.86 (m, 2H), 1.88 - 1.65 (m, 2H), 1.60 - 1.40 (m, 2H), 1.36 (d, J = 6.9 Hz, 3H); 13 C NMR (101 MHz, CDC13) δ 177.74, 162.77, 151.34, 135.77, 131.44, 130.66, 129.16, 126.74, 123.33, 121.22, 114.20, 55.61, 42.90, 38.85, 33.97, 27.06, 21.20.

[0033] Example 2 N-(4-(6-Fluorobenzo[d]thiazol-2-yl)pentyl)-4-methoxybenzenesulfonamide

[0034]

[0035] In a reaction tube equipped with magnetic stirring, a mixture of compound (I) 6- fluorobenzothiazole (30.6 mg, 0.2 mmol), compound (II) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and triflic acid (60.3 mg, 0.4 mmol) was added, a mixed solvent of dimethyl sulfoxide and water (1.0 mL / 1.0 mL) was added to the mixture, the reaction system was irradiated under purple light with a power of 25 W after nitrogen replacement for three times, the reaction was stirred for 24 hours, after the reaction was completed, the reaction liquid was quenched with saturated aqueous sodium bicarbonate solution, the mixture was extracted with ethyl acetate, the organic phase was washed with saturated NaCl, then the layers were separated, dried over anhydrous Na2S04 and concentrated under reduced pressure, the crude product was purified on a silica gel column using petroleum ether / ethyl acetate with a volume ratio of 4:1 to 3:1, and the target product was obtained with a yield of 46% and an HPLC purity of 98.5%.

[0036] 1H NMR (400 MHz, CDC13) δ 7.91 (dd, J = 9.0, 4.7 Hz, 1H), 7.75 (d, J = 8.7 Hz, 2H), 7.51 (d, J = 7.9 Hz, 1H), 7.18 (t, J = 8.7 Hz, 1H), 6.91 (d, J = 8.5 Hz, 2H), 4.98 (s, 1H), 3.83 (s, 3H), 3.20 (q, J = 7.0 Hz, 1H), 2.93 (t, J = 6.8 Hz, 2H), 1.92 - 1.65 (m, 2H), 1.61 - 1.42 (m, 2H), 1.39 (d, J = 6.5 Hz, 3H); 19 F NMR (376 MHz, CDC13) δ -116.51; 13 C NMR (101 MHz, CDC13) δ 176.86, 162.79, 160.24 (d, J F-C = 245.1 Hz), 149.27 (d, J F-C = 2.0 Hz), 135.46 (d, J F-C = 1.3 Hz), 131.47, 129.17, 123.48 (d, J F-C = 9.4 Hz), 114.61 (d, J F-C = 24.6 Hz), 114.20, 107.84 (d, J F-C = 26.7 Hz), 55.60, 42.91, 38.82, 33.91, 27.05, 21.26.

[0037] Example 3 N-(4-(6-bromobenzo[d]thiazol-2-yl)pentyl)-4-methoxybenzenesulfonamide

[0038]

[0039] In a reaction tube equipped with a magnetic stirrer, a mixture of compound (I) 6-bromobenzothiazole (42.6 mg, 0.2 mmol), compound (II) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoromethanesulfonic acid (60.3 mg, 0.4 mmol) was added. A mixed solvent of dimethyl sulfoxide and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen substitution three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 4:1 to 3:1 to obtain the target product in a yield of 64% and an HPLC purity of 98.7%.

[0040] 1 H NMR (400MHz, CDCl3) δ7.95 (s, 1H), 7.79 (d, J = 8.6Hz, 1H), 7.74 (d, J = 8.5Hz, 2H), 7.53 (dt, J = 8.7, 1.8Hz, 1H), 6.90 (d, J = 8.5Hz, 2H), 5.06(s,1H),3.82(s,3H),3.20(h,J=7.1Hz,1H),2.92(t,J=6.8Hz,2H),1.90–1.66(m,2H),1.61–1.41(m,2H),1.38(d,J=6.8Hz,3H); 13 C NMR (101MHz, CDCl3) δ177.82,162.78,151.54,136.19,131.45,129.51,129.1 6,124.16,123.70,118.39,114.20,55.62,42.88,38.81,33.94,27.07,21.21.

[0041] Example 4 4-Methoxy-N-(4-(6-trifluoromethyl)benzo[d]thiazol-2-ylpentyl)benzenesulfonamide

[0042]

[0043] In a reaction tube equipped with a magnetic stirrer, compound (I) 6-trifluoromethylbenzothiazole (40.6 mg, 0.2 mmol), compound (II) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), a mixture of ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoromethanesulfonic acid (60.3 mg, 0.4 mmol) was added. A mixed solvent of dimethyl sulfoxide and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen substitution three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution. The mixture was extracted with ethyl acetate. The organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 4:1 to 3:1 to obtain the target product in a yield of 61% and an HPLC purity of 98.9%.

[0044] 1 H NMR (400MHz, CDCl3) δ8.12(s,1H),8.03(d,J=8.5Hz,1H),7.75(d,J=8.1Hz,2H),7.68(d,J=8.5Hz,1H),6.91(d,J=8.2Hz,2H),5.0 7(s,1H),3.82(s,3H),3.25(h,J=7.1Hz,1H),2.93(t,J=6.9Hz,2H),1.92–1.69(m,2H),1.61–1.45(m,2H),1.40(d,J=6.8Hz,3H); 19 F NMR (376MHz, CDCl3) δ-61.35; 13 C NMR (101MHz, CDCl3) δ180.54,162.81,154.76,134.68,131.42,129.16,127.02(q,J F-C =32.5Hz),124.18(q,J F-C =272.5Hz),123.02,(q,J F-C =3.4Hz),122.96,119.29(q,J F-C =4.1Hz),114.20,55.58,42.87,39.04,33.97,27.09,21.18.

[0045] Example 54-Methoxy-N-(4-(6-(trifluoromethoxy)benzo[d]thiazol-2-yl)pentyl)benzenesulfonamide

[0046]

[0047] In a reaction tube equipped with a magnetic stirrer, a mixture of compound (I) 6-trifluoromethoxybenzothiazole (43.8 mg, 0.2 mmol), compound (II) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoromethanesulfonic acid (60.3 mg, 0.4 mmol) was added. A mixed solvent of dimethyl sulfoxide and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen substitution three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution, the mixture was extracted with ethyl acetate, the organic phase was washed with saturated NaCl, the layers were separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 4:1 to 3:1 to obtain the target product in a yield of 52% with an HPLC purity of 99.2%.

[0048] 1 H NMR (400MHz, CDCl3) δ7.95(d,J=8.8Hz,1H),7.76(d,J=7.6Hz,2H),7.69(s,1H),7.31(d,J=8.8Hz,1H),6.91(d,J=7.6Hz,2H), 5.04(s,1H),3.82(s,3H),3.27–3.16(m,1H),2.98–2.88(m,2H),1.91–1.67(m,2H),1.60–1.42(m,2H),1.39(d,J=6.6Hz,3H); 19 FNMR (376MHz, CDCl3) δ-58.04; 13 C NMR (101MHz, CDCl3) δ178.48,162.80,151.23,146.19,135.36,131.45,129.16,123.39,1 20.52(q,J=257.4Hz),119.97,114.27,114.20,55.58,42.88,38.90,33.94,27.06,21.23.

[0049] Example 6 Ethyl 2-(5-((4-methoxyphenyl)sulfonamido)pentan-2-yl)benzo[d]thiazole-6-carboxylate

[0050]

[0051] In a reaction tube equipped with a magnetic stirrer, compound (I) benzothiazole-6-carboxylic acid ethyl ester (41.4 mg, 0.2 mmol), compound (II) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), a mixture of ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoromethanesulfonic acid (60.3 mg, 0.4 mmol) was added. A mixed solvent of dimethyl sulfoxide and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen substitution three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After completion of the reaction, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, the mixture was extracted with ethyl acetate, the organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 3:1 to 2:1 to obtain the target product in a yield of 80% and an HPLC purity of 98.3%.

[0052] 1 H NMR (400MHz, CDCl3) δ8.55(d,J=1.5Hz,1H),8.12(dd,J=8.5,1.7Hz,1H),7.97(d,J=8.5Hz,1H),7.77–7.72(m,2H),6.93–6.88(m,2H),4.99(s, 1H),4.41(q,J=7.1Hz,2H),3.82(s,3H),3.25(h,J=7.0Hz,1H),2.94(t, J=6.8Hz,2H),1.92–1.70(m,2H),1.62–1.45(m,2H),1.45–1.36(m,6H); 13 C NMR (101MHz, CDCl3) δ180.91,166.17,162.79,155.57,134.43,131.46,129.15,127.28,1 27.04,123.78,122.24,114.20,61.31,55.60,42.90,39.08,33.98,27.11,21.18,14.37.

[0053] Example 7 N-(4-(5-chlorobenzo[d]thiazol-2-yl)pentyl)-4-methoxybenzenesulfonamide

[0054]

[0055] In a reaction tube equipped with magnetic stirring, a mixture of compound (I) 5- chlorobenzothiazole (33.8 mg, 0.2 mmol), compound (II) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and triflic acid (60.3 mg, 0.4 mmol) was added, and a mixed solvent of dimethyl sulfoxide and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen replacement for three times, the reaction system was irradiated under purple light with a power of 25 W, and the stirring reaction was carried out for 24 hours. After the reaction was completed, the reaction liquid was quenched with saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. After the organic phase was washed with saturated NaCl, it was separated, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate (4:1-3:1, by volume) to obtain the target product with a yield of 67% and an HPLC purity of 98.3%.

[0056] 1 H NMR (400 MHz, CDCl3) δ 7.90 (s, 1H), 7.77-7.70 (m, 3H), 7.31 (d, J = 8.5 Hz, 1H), 6.90 (d, J = 8.4 Hz, 2H), 5.03 (s, 1H), 3.83 (s, 3H), 3.20 (h, J = 7.0 Hz, 1H), 2.95-2.89 (m, 2H), 1.88-1.67 (m, 2H), 1.60-1.41 (m, 2H), 1.38 (d, J = 6.8 Hz, 3H); 13 C NMR (101 MHz, CDCl3) δ 179.24, 162.79, 153.62, 132.80, 131.99, 131.45, 129.15, 125.29, 122.45, 122.34, 114.20, 55.61, 42.90, 38.93, 34.05, 27.12, 21.23.

[0057] Example 8 N-(4-(5-bromobenzo[d]thiazol-2-yl)pentyl)-4-methoxybenzenesulfonamide

[0058]

[0059] A mixture of compound (I) 5-bromobenzothiazole (42.6 mg, 0.2 mmol), compound (II) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoromethanesulfonic acid (60.3 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of dimethyl sulfoxide and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen substitution three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution. The mixture was extracted with ethyl acetate. The organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 4:1 to 3:1 to obtain the target product in a yield of 74% and an HPLC purity of 99.5%.

[0060] 1 H NMR (400MHz, CDCl3) δ8.05(s,1H),7.74(d,J=8.4Hz,2H),7.67(d,J=8.5Hz,1H),7.43(d,J=8.4Hz,1H),6.90(d,J=8.4Hz,2H),5 .09(s,1H),3.82(s,3H),3.20(h,J=7.0Hz,1H),2.95–2.88(m,2H),1.87–1.66(m,2H),1.59–1.40(m,2H),1.37(d,J=6.9Hz,3H); 13 C NMR (101MHz, CDCl3) δ179.07,162.79,153.93,133.35,131.44,129.14,127.9 0,125.47,122.70,119.56,114.21,55.62,42.90,38.90,34.06,27.11,21.22.

[0061] Example 9 N-(4-(5,6-dimethylbenzo[d]thiazol-2-yl)pentyl)-4-methoxybenzenesulfonamide

[0062]

[0063] In a reaction tube equipped with a magnetic stirrer, a mixture of compound (I) 5,6-dimethylbenzothiazole (32.6 mg, 0.2 mmol), compound (II) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoromethanesulfonic acid (60.3 mg, 0.4 mmol) was added. A mixed solvent of dimethyl sulfoxide and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen replacement three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After the reaction, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 4:1 to 3:1 to obtain the target product in a yield of 43% and an HPLC purity of 99.8%.

[0064] 1 H NMR (400MHz, CDCl3) δ7.76(s,1H),7.73(d,J=5.9Hz,2H),7.57(s,1H),6.90(d,J=8.5Hz,2H),4.98(t,J=6.1Hz,1H),3.83( s,3H),3.18(h,J=6.9Hz,1H),2.97–2.88(m,2H),2.36(s,6H),1.87–1.66(m,2H),1.58–1.40(m,2H),1.37(d,J=6.8Hz,3H); 13 C NMR (101MHz, CDCl3) δ175.91,162.74,151.49,135.19,134.21,131.86,131.55,129. 17,122.80,121.52,114.16,55.57,42.95,38.72,34.06,27.03,21.43,20.19,20.11.

[0065] Example 10 N-(4-(Benzo[d]thiazol-2-yl)pentyl)-4-methoxybenzenesulfonamide

[0066]

[0067] A mixture of compound (I) benzothiazole (27.0 mg, 0.2 mmol), compound (II) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoromethanesulfonic acid (60.3 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of dimethyl sulfoxide and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen substitution three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution. The mixture was extracted with ethyl acetate. The organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 4:1 to 3:1 to obtain the target product in a yield of 61% and an HPLC purity of 99.2%.

[0068] 1 H NMR (400MHz, CDCl3) δ7.95(d,J=8.1Hz,1H),7.82(d,J=8.0Hz,1H),7.75(d,J=8.1Hz,2H),7.44(t,J=7.6Hz,1H),7.34(t,J=7.6Hz,1H),6.89(d,J=8.2 Hz,2H),5.15(t,J=5.8Hz,1H),3.81(s,3H),3.21(h,J=7.1Hz,1H),2.92(q, J=6.6Hz,2H),1.89–1.66(m,2H),1.60–1.42(m,2H),1.38(d,J=6.8Hz,3H); 13 C NMR (101MHz, CDCl3) δ177.20,162.75,152.69,134.50,131.50,129.16,126.0 2,124.83,122.58,121.63,114.19,55.60,42.93,38.83,34.04,27.07,21.37.

[0069] Example 11 N-(4-(Isoquinolin-1-yl)pentyl)-4-methoxybenzenesulfonamide

[0070]

[0071] In a reaction tube equipped with magnetic stirring, a mixture of compound (I) isoquinoline (25.8 mg, 0.2 mmol), compound (II) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoromethanesulfonic acid (60.3 mg, 0.4 mmol) was added, and a mixed solvent of dimethyl sulfoxide and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen replacement for three times, the reaction system was irradiated under purple light with a power of 25 W, and the stirring reaction was carried out for 24 hours. After the reaction was completed, the reaction liquid was quenched with saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. After the organic phase was washed with saturated NaCl, it was separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate (3:1-2:1, by volume) to obtain the target product with a yield of 67% and an HPLC purity of 99.5%.

[0072] 1 H NMR (400 MHz, CDC13) δ 8.46 (d, J = 5.5 Hz, 1H), 8.14 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 8.1 Hz, 1H), 7.73 (d, J = 8.6 Hz, 2H), 7.62 (dt, J = 32.6, 7.2 Hz, 2H), 7.49 (d, J = 5.4 Hz, 1H), 6.89 (d, J = 8.6 Hz, 2H), 5.09 (t, J = 5.9 Hz, 1H), 3.83 (s, 3H), 3.72 (h, J = 6.9 Hz, 1H), 2.88 (q, J = 6.3 Hz, 2H), 2.11 - 1.95 (m, 1H), 1.75 - 1.64 (m, 1H), 1.57 - 1.44 (m, 1H), 1.38 - 1.27 (m, 4H); 13 C NMR (101 MHz, CDC13) δ 164.77, 162.68, 141.62, 136.43, 131.57, 129.86, 129.17, 127.62, 127.18, 126.74, 124.59, 119.28, 114.11, 55.58, 43.19, 35.75, 32.46, 27.44, 21.40.

[0073] Example 12 4-Methoxy-N-(4-(quinazolin-4-yl)pentyl)benzenesulfonamide

[0074]

[0075] A mixture of compound (I) quinazoline (26.0 mg, 0.2 mmol), compound (II) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoromethanesulfonic acid (60.3 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of dimethyl sulfoxide and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen substitution three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution. The mixture was extracted with ethyl acetate. The organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 3:1 to 1:1 to obtain the target product in a yield of 53% and an HPLC purity of 98.8%.

[0076] 1 H NMR (400MHz, CDCl3) δ9.20(s,1H),8.11(d,J=8.4Hz,1H),8.03(d,J=8.4Hz,1H),7.87( ddd,J=8.3,7.0,1.2Hz,1H),7.74–7.70(m,2H),7.62(ddd,J=8.2,7.0,1.1Hz,1H),6.9 1–6.87(m,2H),4.95(t,J=6.0Hz,1H),3.83(s,3H),3.72(h,J=6.8Hz,1H),2.89(q,J=6 .7Hz,2H),2.06–1.95(m,1H),1.75–1.65(m,1H),1.56–1.42(m,1H),1.40–1.30(m,4H); 13 C NMR (101MHz, CDCl3) δ174.66,162.79,154.53,150.07,133.59,131.47,129.33,12 9.13,127.68,124.03,123.64,114.18,55.60,43.08,35.58,32.28,27.54,20.72.

[0077] Example 13 N-(4-(3-chloroquinoxalin-2-yl)pentyl)-4-methoxybenzenesulfonamide

[0078]

[0079] In a reaction tube equipped with a magnetic stirrer, a mixture of compound (I) 2-chloroquinoxaline (32.8 mg, 0.2 mmol), compound (II) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoromethanesulfonic acid (60.3 mg, 0.4 mmol) was added. A mixed solvent of dimethyl sulfoxide and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen substitution three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution. The mixture was extracted with ethyl acetate. The organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 3:1 to 1:1 to obtain the target product in a yield of 80% and an HPLC purity of 98.6%.

[0080] 1 H NMR(400MHz, CDCl3)δ8.03(dd,J=7.0,2.9Hz,1H),7.95(dt,J=9.2,2.0Hz,1H),7.77–7.67(m,4H),6.88(d,J=7.9Hz,2H),4.95(s,1H),3.80(s,3 H),3.47(h,J=7.2Hz,1H),2.96–2.88(m,2H),2.00–1.91(m,1H),1.68–1 .57(m,1H),1.56–1.46(m,1H),1.43–1.32(m,1H),1.28(d,J=6.5Hz,3H); 13 C NMR (101MHz, CDCl3) δ162.75,158.54,147.44,140.96,140.65,131.45,130.18,13 0.10,129.15,128.75,128.03,114.17,55.59,43.13,37.25,31.90,27.36,19.67.

[0081] Example 14 4-Methoxy-N-(4-(4-methylquinolin-2-yl)pentyl)benzenesulfonamide

[0082]

[0083] In a reaction tube equipped with a magnetic stirrer, a mixture of compound (I) 4-methylquinoline (28.6 mg, 0.2 mmol), compound (II) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoromethanesulfonic acid (60.3 mg, 0.4 mmol) was added. A mixed solvent of dimethyl sulfoxide and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen substitution three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution, the mixture was extracted with ethyl acetate, the organic phase was washed with saturated NaCl, the layers were separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 4:1 to 2:1 to obtain the target product in a yield of 59% and an HPLC purity of 98.4%.

[0084] 1 H NMR (600MHz, CDCl3) δ8.08 (dd, J=8.4, 1.2Hz, 1H), 7.93 (dd, J=8.3, 1.4Hz, 1H), 7.74–7.70 (m, 2H), 7.67 (ddd, J=8.3, 6.8,1.4Hz,1H),7.50(ddd,J=8.2,6.8,1.2Hz,1H),7.07(s,1H),6.88–6.84(m,2H),5.62(t,J=4.7Hz,1H),3.80(s,3 H),2.95(ddt,J=18.9,12.9,6.7Hz,2H),2.86(dq,J=12.3,6.5Hz,1H),2.65(s,3H),1.81(dtd,J=14.1,9.1,5.2Hz,1 H),1.63(ddt,J=13.7,9.3,6.3Hz,1H),1.44(ddq,J=13.5,9.0,6.7Hz,1H),1.40–1.32(m,1H),1.27(d,J=7.0Hz,3H); 13 C NMR (151MHz, CDCl3) δ165.61,162.61,147.21,144.92,131.69,129.33,129.25,129.14,1 27.02,125.71,123.61,120.27,114.08,55.56,43.11,41.71,33.74,27.11,21.08,18.86.

[0085] Example 15 N-(4-chloroquinolin-2-yl)pentyl)-4-methoxybenzenesulfonamide

[0086]

[0087] A mixture of compound (I) 4-chloroquinoline (32.6 mg, 0.2 mmol), compound (II) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoromethanesulfonic acid (60.3 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of dimethyl sulfoxide and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen substitution three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution. The mixture was extracted with ethyl acetate. The organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 5:1 to 3:1 to obtain the target product in a yield of 44% and an HPLC purity of 98.9%.

[0088] 1 H NMR (400MHz, CDCl3) δ8.17(d,J=8.3Hz,1H),8.09(d,J=8.4Hz,1H),7.78–7.70(m,3H),7.59(t,J=7.5Hz,1H),7.33(s,1H),6.88(d,J=8.3H z,2H),5.28–5.23(m,1H),3.81(s,3H),3.02–2.83(m,3H),1.87–1.76(m,1H),1.72–1.58(m,1H),1.54–1.32(m,2H),1.29(d,J=6.8Hz,3H); 13 CNMR(101MHz,CDCl3)δ165.98,162.69,148.36,143.05,131.56,130.51,129.24,129.1 4,126.95,125.14,123.93,119.84,114.12,55.58,43.05,41.81,33.53,27.16,20.92.

[0089] Example 16 N-(4-bromoquinolin-2-yl)pentyl)-4-methoxybenzenesulfonamide

[0090]

[0091] In a reaction tube equipped with a magnetic stirrer, a mixture of compound (I) 4-bromoquinoline (41.4 mg, 0.2 mmol), compound (II) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoromethanesulfonic acid (60.3 mg, 0.4 mmol) was added. A mixed solvent of dimethyl sulfoxide and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen substitution three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution. The mixture was extracted with ethyl acetate. The organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 5:1 to 2:1 to obtain the target product in a yield of 53% and an HPLC purity of 98.8%.

[0092] 1 H NMR (400MHz, CDCl3) δ8.11(d,J=8.3Hz,1H),8.05(d,J=8.4Hz,1H),7.77–7.66(m,3H),7.57(t,J=7.4Hz,1H),7.52(s,1H),6.90–6.83(m,2 H),5.37(t,J=6.0Hz,1H),3.79(s,3H),3.02–2.81(m,3H),1.86–1.75(m,1H),1.69–1.56(m,1H),1.53–1.31(m,2H),1.28(d,J=6.8Hz,3H); 13 C NMR (101MHz, CDCl3) δ165.97,162.67,148.09,134.65,131.55,130.50,129.26,129.1 4,127.20,126.57,126.48,123.73,114.12,55.58,43.04,41.67,33.51,27.20,20.88.

[0093] Example 17 N-(4,7-dichloroquinolin-2-yl)pentyl)-4-methoxybenzenesulfonamide

[0094]

[0095] In a reaction tube equipped with a magnetic stirrer, a mixture of compound (I) 4,7-dichloroquinoline (39.4 mg, 0.2 mmol), compound (II) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoromethanesulfonic acid (60.3 mg, 0.4 mmol) was added. A mixed solvent of dimethyl sulfoxide and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen replacement three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After the reaction, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 4:1 to 2:1 to obtain the target product in a yield of 32% and an HPLC purity of 98.2%.

[0096] 1 H NMR(400MHz, CDCl3)δ8.10(d,J=8.9Hz,1H),8.07(s,1H),7.77–7.71(m,2H),7.53(dd,J=8.9,2.1Hz,1H),7.32(s,1H),6.94–6.87(m,2H) ,4.95(t,J=6.0Hz,1H),3.83(s,3H),3.02–2.85(m,3H),1.86–1.75(m,1H),1.70–1.58(m,1H),1.51–1.33(m,2H),1.29(d,J=6.7Hz,3H); 13 C NMR (101MHz, CDCl3) δ167.38,162.75,148.77,142.97,136.53,131.52,129.14,128.2 3,127.88,125.37,123.65,120.18,114.15,55.59,43.05,41.90,33.42,27.30,20.75.

[0097] Example 18 4-Methoxy-N-(4-(phthalazin-1-yl)pentyl)benzenesulfonamide

[0098]

[0099] A mixture of compound (I) phthalazine (26.0 mg, 0.2 mmol), compound (II) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoromethanesulfonic acid (60.3 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of dimethyl sulfoxide and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen substitution three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution. The mixture was extracted with ethyl acetate. The organic phase was washed with saturated NaCl, separated into layers, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using dichloromethane / methanol in a volume ratio of 40:1-20 to obtain the target product in a yield of 51% and an HPLC purity of 98.3%.

[0100] 1 H NMR(400MHz, CDCl3)δ9.38(s,1H),8.14(d,J=8.0Hz,1H),8.00–7.86(m,3H),7.79–7.75(m,2H),6.96–6.87(m,2H),5.22(t,J=5.9Hz,1H) ,3.85(s,3H),3.78–3.65(m,1H),2.93(q,J=6.7Hz,2H),2.25–2.11(m,1H),1.87–1.74(m,1H),1.63–1.45(m,2H),1.42(d,J=6.9Hz,3H); 13 C NMR (101MHz, CDCl3) δ163.11,162.69,150.22,132.66,131.96,131.63,129.17,12 7.28,126.59,125.36,123.40,114.14,55.59,43.19,35.11,32.45,27.54,20.86.

[0101] Example 19 N-(4-(acridin-9-yl)pentyl)-4-methoxybenzenesulfonamide

[0102]

[0103] A mixture of compound (I) acridine (35.8 mg, 0.2 mmol), compound (II) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoromethanesulfonic acid (60.3 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of dimethyl sulfoxide and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen substitution three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution. The mixture was extracted with ethyl acetate. The organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 2:1 to 1:1 to obtain the target product in a yield of 47% and an HPLC purity of 98.6%.

[0104] 1 H NMR (400MHz, CDCl3) δ8.33(d,J=28.8Hz,2H),8.21(d,J=8.7Hz,2H),7.72(t, J=7.7Hz,2H),7.67–7.63(m,2H),7.54–7.43(m,2H),6.87–6.80(m,2H),4.65( t,J=6.3Hz,1H),4.25(h,J=7.2Hz,1H),3.81(s,3H),2.83(q,J=6.7Hz,2H),2. 26–2.09(m,2H),1.67(d,J=7.3Hz,3H),1.54–1.42(m,1H),1.22–1.10(m,1H); 13 C NMR (101MHz, CDCl3) δ162.75,150.19,148.88,148.53,131.36,130.88,130.45,129.67,129.47,129.0 4,125.98,125.82,125.70,125.37,124.73,123.51,114.14,55.60,43.00,34.07,33.71,28.76,21.27.

[0105] Example 20 4-methoxy-N-(4-(3,5,6-trimethylpyrazin-2-yl)pentyl)benzenesulfonamide

[0106]

[0107] In a reaction tube equipped with magnetic stirring, a mixture of compound (I) 2,3,5-trimethylpyrazine (24.4 mg, 0.2 mmol), compound (II) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and triflic acid (60.3 mg, 0.4 mmol) was added, and a mixed solvent of dimethyl sulfoxide and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen replacement for three times, the reaction system was irradiated under purple light with a power of 25 W, and the stirring reaction was carried out for 24 hours. After the reaction was completed, the reaction liquid was quenched with saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. After the organic phase was washed with saturated NaCl, it was separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate (4:1-2:1, by volume) to obtain the target product with a yield of 66% and an HPLC purity of 98.8%.

[0108] 1 H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.4 Hz, 2H), 6.92 (d, J = 8.3 Hz, 2H), 4.87 (t, J = 6.1 Hz, 1H), 3.83 (s, 3H), 2.94-2.86 (m, 1H), 2.83 (q, J = 6.7 Hz, 2H), 2.44-2.39 (m, 9H), 1.82-1.72 (m, 1H), 1.55-1.34 (m, 2H), 1.27-1.17 (m, 1H), 1.10 (d, J = 6.8 Hz, 3H); 13 C NMR (101 MHz, CDCl3) δ 162.75, 154.57, 148.81, 147.89, 147.08, 131.55, 129.14, 114.15, 55.60, 43.17, 35.73, 32.22, 27.47, 21.57, 21.35, 20.76, 20.30.

[0109] Example 21 N-(4-(4,6-dimethylpyrimidin-2-yl)pentyl)-4-methoxybenzenesulfonamide

[0110]

[0111] A mixture of compound (I) 4,6-dimethylpyrimidine (21.6 mg, 0.2 mmol), compound (II) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoromethanesulfonic acid (60.3 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of dimethyl sulfoxide and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen substitution three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution. The mixture was extracted with ethyl acetate. The organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 3:1 to 2:1 to obtain the target product in a yield of 61% and an HPLC purity of 98.9%.

[0112] 1 H NMR (400MHz, CDCl3) δ7.76(d,J=8.2Hz,2H),6.94(d,J=8.3Hz,2H),6.83(s,1H),5.21(t,J=5.9Hz,1H),3.85(s,3H ),2.94–2.83(m,3H),2.43(s,6H),1.84–1.73(m,1H),1.57–1.40(m,2H),1.37–1.27(m,1H),1.21(d,J=6.7Hz,3H); 13 C NMR (101MHz, CDCl3) δ173.28,166.61,162.70,131.71,129.17,117.64,114.14,55.59,43.09,42.17,32.86,27.09,23.95,20.34.

[0113] Example 22 Ethyl 2-(5-((4-methoxyphenyl)sulfonamido)pentan-2-yl)-4-methylthiazole-5-carboxylate

[0114]

[0115] In a reaction tube equipped with a magnetic stirrer, compound (I) ethyl 4-methylthiazole-5-carboxylate (34.2 mg, 0.2 mmol), compound (II) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), a mixture of ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoromethanesulfonic acid (60.3 mg, 0.4 mmol) was added. A mixed solvent of dimethyl sulfoxide and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen substitution three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution. The mixture was extracted with ethyl acetate. The organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 4:1 to 2:1 to obtain the target product in a yield of 64% with an HPLC purity of 99.0%.

[0116] 1 H NMR (400MHz, CDCl3) δ7.76(d,J=8.2Hz,2H),6.94(d,J=8.2Hz,2H),5.01(t,J=6.1Hz,1H),4.29(q,J=7.2Hz,2H),3.84(s,3H),3.04(h, J=7.2Hz,1H),2.90(q,J=7.0Hz,2H),2.65(s,3H),1.76–1.57(m,2H),1.54–1.39(m,2H),1.34(t,J=7.2Hz,3H),1.29(d,J=7.0Hz,3H); 13 C NMR (101MHz, CDCl3) δ179.26,162.80,162.22,159.55,131.47,129.15,121. 01,114.21,61.17,55.61,42.88,38.22,34.27,27.03,21.20,17.30,14.33.

[0117] Example 23 N-(4-(4-(hydrazinecarbonyl)pyridin-2-yl)pentyl)-4-methoxybenzenesulfonamide

[0118]

[0119] In a reaction tube equipped with a magnetic stirrer, a mixture of compound (I) isoniazid (27.4 mg, 0.2 mmol), compound (II) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoromethanesulfonic acid (60.3 mg, 0.4 mmol) was added. A mixed solvent of dimethyl sulfoxide and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen substitution three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution. The mixture was extracted with ethyl acetate, the organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using dichloromethane and methanol in a volume ratio of 20:1 to 10:1 to obtain the target product in a yield of 32% and an HPLC purity of 99.1%.

[0120] 1 H NMR(400MHz, CDCl3)δ8.99(d,J=4.8Hz,1H),8.20(t,J=4.2Hz,1H),7.64–7.60(m,2H),7.47–7.45(m,1H),7.42(dd,J=4.9,2.2Hz,1H),7.09–7.04( m,2H),5.03(t,J=7.0Hz,1H),4.00(d,J=4.0Hz,2H),3.82(s,3H),3.20–3 .09(m,3H),1.90–1.81(m,1H),1.51–1.42(m,3H),1.40(d,J=7.0Hz,3H).

[0121] 13 C NMR (101MHz, CDCl3) δ167.01,166.63,163.62,149.49,135.97,131.81,12 8.31,119.21,118.82,113.51,55.35,43.64,39.56,33.21,26.68,17.82.

[0122] Example 24 N-(4-(6-chlorobenzo[d]thiazol-2-yl)hexyl)-4-methoxybenzenesulfonamide

[0123]

[0124] In a reaction tube equipped with a magnetic stirrer, a mixture of compound (I) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), compound (II) N-hexyl-4-methoxybenzenesulfonamide (108.4 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoroacetic acid (34.2 mg, 0.3 mmol) was added. A mixed solvent of acetonitrile and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen substitution three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution. The mixture was extracted with ethyl acetate. The organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 4:1 to 3:1 to obtain the target product in a yield of 70% and an HPLC purity of 98.8%.

[0125] 1 H NMR (400MHz, CDCl3) δ7.82(d,J=8.7Hz,1H),7.76(s,1H),7.72(d,J=8.6Hz,2H),7.37(d,J=8.6Hz,1H),6.88(d,J=8.6Hz,2H),5.17(t,J=6.4 Hz,1H),3.81(s,3H),2.99–2.92(m,1H),2.91–2,85(m,2H),1.79–1.67(m,4H),1.51–1.42(m,1H),1.41–1.33(m,1H),0.84(t,J=7.2Hz,3H); 13 CNMR(101MHz,CDCl3)δ176.75,162.75,151.34,135.82,131.48,130.66,129.13,1 26.66,123.33,121.21,114.17,55.59,46.28,42.90,32.33,29.30,27.16,11.73.

[0126] Example 25 N-(4-(6-chlorobenzo[d]thiazol-2-yl)heptyl)-4-methoxybenzenesulfonamide

[0127]

[0128] In a reaction tube equipped with magnetic stirring, a mixture of compound (I) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), compound (II) N-heptyl-4-methoxybenzenesulfonamide (114.1 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoroacetic acid (34.2 mg, 0.3 mmol) was added, and a mixed solvent of acetonitrile and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen replacement for three times, the reaction system was irradiated under purple light with a power of 25 W, and the stirring reaction was carried out for 24 hours. After the reaction was completed, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. After the organic phase was washed with saturated NaCl, it was separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate (4:1-3:1, by volume) to obtain the target product with a yield of 69% and an HPLC purity of 98.9%.

[0129] 1 H NMR (400 MHz, CDC13) δ 7.85 (d, J = 8.7 Hz, 1H), 7.79 (s, 1H), 7.73 (d, J = 8.5 Hz, 2H), 7.40 (d, J = 8.8 Hz, 1H), 6.90 (d, J = 8.6 Hz, 2H), 4.90 (s, 1H), 3.83 (s, 3H), 3.11 - 3.01 (m, 1H), 2.90 (t, J = 7.0 Hz, 2H), 1.79 - 1.63 (m, 4H), 1.53 - 1.33 (m, 2H), 1.31 - 1.19 (m, 2H), 0.86 (t, J = 7.1 Hz, 3H); 13 C NMR (101 MHz, CDC13) δ 176.95, 162.78, 151.24, 135.75, 131.47, 130.75, 129.14, 126.74, 123.35, 121.23, 114.18, 55.60, 44.47, 42.90, 38.49, 32.73, 27.17, 20.42, 13.94.

[0130] Example 26 N-(4-(6-chlorobenzo[d]thiazol-2-yl)octyl)-4-methoxybenzenesulfonamide

[0131]

[0132] In a reaction tube equipped with magnetic stirring, a mixture of compound (I) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), compound (II) 4-methoxy-N-octylbenzenesulfonamide (119.7 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoroacetic acid (34.2 mg, 0.3 mmol) was added, and a mixed solvent of acetonitrile and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen replacement for three times, the reaction system was irradiated under purple light with a power of 25 W, and the stirring reaction was carried out for 24 hours. After the reaction was completed, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. After the organic phase was washed with saturated NaCl, it was separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate (4:1-3:1, by volume) to obtain the target product with a yield of 62% and an HPLC purity of 98.6%.

[0133] 1 H NMR (400 MHz, CDC13) δ 7.84 (d, J = 8.7 Hz, 1H), 7.78 (s, 1H), 7.73 (d, J = 8.3 Hz, 2H), 7.39 (d, J = 8.6 Hz, 1H), 6.89 (d, J = 8.5 Hz, 2H), 4.97 (t, J = 6.2 Hz, 1H), 3.82 (s, 3H), 3.09 - 2.99 (m, 1H), 2.93 - 2.85 (m, 2H), 1.82 - 1.62 (m, 4H), 1.53 - 1.33 (m, 2H), 1.30 - 1.14 (m, 4H), 0.82 (t, J = 6.9 Hz, 3H), 13 CNMR (101 MHz, CDC13) δ 176.95, 162.77, 151.33, 135.80, 131.50, 130.70, 129.14, 126.69, 123.37, 121.22, 114.17, 55.58, 44.72, 42.91, 36.08, 32.77, 29.35, 27.17, 22.55, 13.87.

[0134] Example 27 N-(4-(6-chlorobenzo[d]thiazol-2-yl)-2,2-dimethylhexyl)-4- methoxybenzenesulfonamide

[0135]

[0136] In a reaction tube equipped with a magnetic stirrer, compound (I) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), compound (II) N-(2,2-dimethylhexyl)-4-methoxybenzenesulfonamide (119.7 mg, 0.4 mmol), a mixture of ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoroacetic acid (34.2 mg, 0.3 mmol) were added. A mixed solvent of acetonitrile and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen replacement three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After the reaction, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 4:1 to 3:1 to obtain the target product in a yield of 33% and an HPLC purity of 98.5%.

[0137] 1 H NMR (400MHz, CDCl3) δ7.90(d,J=8.6Hz,1H),7.78(s,1H),7.47–7.41(m,3H),6.74(d,J=8.1Hz,2H),5.43(t,J=5.0Hz,1H),3.81(s,3H),3.03(q, J=7.8Hz,1H),2.62–2.54(m,1H),2.27–2.15(m,2H),1.79–1.67(m,2H), 1.51(d,J=14.7Hz,1H),0.94(s,3H),0.86(t,J=7.3Hz,3H),0.83(s,3H); 13 C NMR (101MHz, CDCl3) δ178.04,162.42,151.12,151.09,135.80,131.67,130.93,128.71,126. 94,123.51,121.24,113.90,55.54,51.90,43.41,42.06,34.50,32.03,26.81,25.04,11.50.

[0138] Example 28 N-(5-(6-chlorobenzo[d]thiazol-2-yl)-5-methylhexyl)-4-methoxybenzenesulfonamide

[0139]

[0140] In a reaction tube equipped with a magnetic stirrer, compound (I) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), compound (II) 4-methoxy-N-(5-methylhexyl)benzenesulfonamide (114.1 mg, 0.4 mmol), a mixture of ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoroacetic acid (34.2 mg, 0.3 mmol) were added. A mixed solvent of acetonitrile and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen replacement three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After the reaction, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 4:1 to 3:1 to obtain the target product in a yield of 55% and an HPLC purity of 99.8%.

[0141] 1 H NMR (400MHz, CDCl3) δ7.90(d,J=8.7Hz,1H),7.84(d,J=8.6Hz,0.45H),7.80–7.69(m,3H+1.36H),7.37(d,J=8.6Hz,1H+0.4 5H),6.91(d,J=8.4Hz,2H),6.87(d,J=9.5Hz,0.9H),5.14(s,0.45H),5.07(t,J=6.4Hz,1H),3.82(s,3H),3.81(s,1.36H),2 .87(q,J=6.7Hz,2H+0.9H),2.83–2.77(m,0.45H),1.95(h,J=6.8Hz,0.45H),1.87–1.78(m,0.45H),1.75–1.65(m,2H+0.45H ),1.44–1.37(m,8H),1.35–1.27(m,0.45H),1.26–1.14(m,2H+0.45H),0.94(d,J=6.5Hz,1.36H),0.84(d,J=6.6Hz,1.36H); 13C NMR (101MHz, CDCl3) δ181.59,175.83,162.74,151.55,151.20,136.05,135.82,131.56,131.49,130.70,130.50,129.15,129.12,126.66,126.5 9,123.51,123.38,121.14,121.05,114.19,114.16,55.60,51.46,42.95 ,42.69,42.52,41.51,33.82,29.41,28.67,27.54,21.52,20.52,20.24.

[0142] Example 29 N-(4-(6-chlorobenzo[d]thiazol-2-yl)-1-phenylpentyl)-4-methoxybenzenesulfonamide

[0143]

[0144] In a reaction tube equipped with a magnetic stirrer, compound (I) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), compound (II) 4-methoxy-N-(1-phenylpentyl)benzenesulfonamide (113.3 mg, 0.4 mmol), a mixture of ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoroacetic acid (34.2 mg, 0.3 mmol) were added. A mixed solvent of acetonitrile and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen substitution three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution, the mixture was extracted with ethyl acetate, the organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 4:1 to 3:1 to obtain the target product in a yield of 49% with an HPLC purity of 99.1%.

[0145] 1H NMR (400MHz, CDCl3) δ7.91(t,J=7.3Hz,1H),7.78(s,1H),7.56(t,J=8.1Hz,2H) ,7.41(dd,J=8.7,2.2Hz,1H),7.15–7.08(m,3H),7.04–6.97(m,2H),6.77–6.67 (m,2H),5.85(d,J=6.4Hz,0.5H),5.79(d,J=6.6Hz,0.5H),4.24(t,J=7.1Hz,1H ),3.76(s,3H),3.17(h,J=7.4Hz,1H),1.87–1.58(m,4H),1.33(d,J=6.3Hz,3H); 13 C NMR (101MHz, CDCl3) δ177.61,177.57,162.50,162.49,151.32,151.29,140.93,1 40.77,135.83,132.24,132.22,130.74,130.70,129.13,129.10,128.46,127.39 ,127.36,126.81,126.77,126.44,126.39,123.46,121.21,121.19,113.81,58.25,58.12,55.55,55.54,38.86,38.82,35.13,34.73,32.98,32.92,21.57,21.08.

[0146] Example 30 Methyl (2R)-5-(6-chlorobenzo[d]thiazol-2-yl)-2-(4-methoxyphenylsulfonamido)hexanoate

[0147]

[0148] In a reaction tube equipped with a magnetic stirrer, compound (I) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), compound (II) (R)-2-((4-methoxyphenyl)sulfonamido)hexanoic acid methyl ester (126.0 mg, 0.4 mmol), a mixture of ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoroacetic acid (34.2 mg, 0.3 mmol) was added. A mixed solvent of acetonitrile and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen substitution three times, the reaction system was irradiated under violet light at a power of 25 W and stirred for 24 hours. After completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution, the mixture was extracted with ethyl acetate, the organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 3:1 to 2:1 to obtain the target product in a yield of 58% and an HPLC purity of 98.6%.

[0149] 1 H NMR (400MHz, CDCl3) δ7.86(d,J=8.6Hz,1H),7.81(s,1H),7.77–7.70(m,2H),7.40(d,J=8.7Hz,1H),6.95–6.87(m,2H),5.41(d,J=8.7Hz ,1H),3.93–3.86(m,1H),3.83(s,3H),3.47(s,3H),3.23(p,J=6.2Hz,1H),1.93–1.75(m,3H),1.68–1.52(m,1H),1.40(d,J=6.4Hz,3H); 13 C NMR (101MHz, CDCl3) δ177.16,177.13,171.97,163.03,151.45,151.43,135.84,131.13,130.74,129.41,126.76 ,123.44,121.24,114.16,114.14,55.63,55.62,55.43,52.59,38.76,32.49,32.45,30.77,30.72,21.43,20.92.

[0150] Example 31 N-(4-(6-chlorobenzo[d]thiazol-2-yl)-2-methylpentyl)-4-methoxybenzenesulfonamide

[0151]

[0152] In a reaction tube equipped with a magnetic stirrer, compound (I) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), compound (II) 4-methoxy-N-(2-methylpentyl)benzenesulfonamide (108.4 mg, 0.4 mmol), a mixture of ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoroacetic acid (34.2 mg, 0.3 mmol) were added. A mixed solvent of acetonitrile and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen substitution three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution, the mixture was extracted with ethyl acetate, the organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 4:1 to 3:1 to obtain the target product in a yield of 77% with an HPLC purity of 99.9%.

[0153] 1 H NMR(400MHz, CDCl3)δ7.90(d,J=8.6Hz,0.5H),7.84(d,J=8.7Hz,0.5H),7.80–7.69(m,3H), 7.39(d,J=8.1Hz,1H),6.88(dd,J=14.8,8.5Hz,2H),5.57(t,J=6.0Hz,0.5H),5.46(d,J=6.4 Hz,0.5H),3.81(d,J=3.6Hz,3H),3.33–3.23(m,1H),2.86–2.68(m,2H),2.14–1.91(m,1H), 1.76–1.48(m,2H),1.35(t,J=7.1Hz,3H),0.91(d,J=6.5Hz,1.5H),0.86(d,J=4.7Hz,1.5H); 13 C NMR (101MHz, CDCl3) δ178.31,177.83,162.72,162.66,151.32,151.20,13 5.80,135.75,131.61,131.54,130.76,130.66,129.11,129.09,126.81,1 26.75,123.45,123.35,121.21,114.18,114.12,55.59,55.58,48.96,48. 73,41.35,41.17,37.22,36.63,31.32,30.83,22.92,21.04,17.96,17.90.

[0154] Example 32 N-(4-(6-chlorobenzo[d]thiazol-2-yl)-3-methylpentyl)-4- methoxybenzenesulfonamide

[0155]

[0156] In a reaction tube equipped with magnetic stirring, a mixture of compound (I) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), compound (II) 4-methoxy-N-(2-methylpentyl)benzenesulfonamide (108.4 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoroacetic acid (34.2 mg, 0.3 mmol) was added, and a mixed solvent of acetonitrile and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen replacement for three times, the reaction system was irradiated under purple light with a power of 25 W, and the stirring reaction was carried out for 24 hours. After the reaction was completed, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. After the organic phase was washed with saturated NaCl, it was separated, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate (4:1-3:1, by volume) to obtain the target product with a yield of 75% and an HPLC purity of 98.8%.

[0157] 1 H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 8.6 Hz, 0.43H), 7.86 (d, J = 8.6 Hz, 0.57H), 7.79 (s, 1H), 7.75 (d, J = 7.8 Hz, 2H), 7.43-7.37 (m, 1H), 6.91 (d, J = 8.0 Hz, 2H), 5.47 (s, 0.43H), 5.10 (s, 0.57H), 3.83 (s, 3H), 3.11 (dt, J = 32.4, 6.7 Hz, 1H), 3.04-2.87 (m, 2H), 2.17-1.96 (m, 1H), 1.67-1.48 (m, 1H), 1.38-1.28 (m, 4H), 0.89 (d, J = 6.3 Hz, 3H); 13C NMR (101MHz, CDCl3) δ177.44,176.90,162.77,162.73,151.28,151.19,135.77,135.73,131.45,131.43,130.77,130.73,129.17,126.83,126.7 7,123.48,123.39,121.16,121.09,114.18,114.16,55.61,43.91,43.55 ,41.29,41.10,35.97,35.22,34.48,32.50,17.31,17.07,16.48,15.99.

[0158] Example 33 N-(2-(1-(6-chlorobenzo[d]thiazol-2-yl)ethoxy)ethyl)-4-methoxybenzenesulfonamide

[0159]

[0160] In a reaction tube equipped with a magnetic stirrer, compound (I) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), compound (II) N-(2-ethoxyethyl)-4-methoxybenzenesulfonamide (103.6 mg, 0.4 mmol), a mixture of ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoroacetic acid (34.2 mg, 0.3 mmol) was added. A mixed solvent of acetonitrile and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen replacement three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After the reaction, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 3:1 to 2:1 to obtain the target product in a yield of 60% and an HPLC purity of 98.6%.

[0161] 1 H NMR (400MHz, CDCl3) δ7.89(d,J=8.7Hz,1H),7.82(d,J=2.0Hz,1H),7.79–7.75(m,2H),7.41(dd,J=8.7,2.1Hz,1H),6.93–6.88(m,2H),5.43(s,1H), 4.75(q,J=6.6Hz,1H),3.82(s,3H),3.62(ddd,J=9.8,5.9,4.0Hz,1H),3. 53(ddd,J=9.7,6.2,4.2Hz,1H),3.22–3.10(m,2H),1.56(d,J=6.6Hz,3H);13 C NMR (101MHz, CDCl3) δ175.28,162.86,151.36,135.94,131.49,131.23,12 9.18,127.01,123.86,121.50,114.23,76.37,68.13,55.62,43.05,22.19.

[0162] Example 34 N-(6-chloro-4-(6-chlorobenzo[d]thiazol-2-yl)hexyl)-4-methoxybenzenesulfonamide

[0163]

[0164] In a reaction tube equipped with a magnetic stirrer, compound (I) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), compound (II) N-(6-chlorohexyl)-4-methoxybenzenesulfonamide (122.0 mg, 0.4 mmol), a mixture of ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoroacetic acid (34.2 mg, 0.3 mmol) was added. A mixed solvent of 1.0 mL / 1.0 mL of acetonitrile and water was added to the mixture. After nitrogen substitution three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution. The mixture was extracted with ethyl acetate. The organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 4:1 to 3:1 to obtain the target product in a yield of 35% with an HPLC purity of 99.7%.

[0165] 1 H NMR (400MHz, CDCl3) δ7.86(d,J=8.7Hz,1H),7.81(s,1H),7.73(d,J=8.2Hz,2H),7.42(d,J=8.7Hz,1H),6.91(d,J=8.3Hz,2H),4.89(s,1H),3 .83(s,3H),3.53(dt,J=10.7,5.4Hz,1H),3.44–3.31(m,2H),2.90(t,J =7.0Hz,2H),2.34–2.06(m,2H),1.90–1.74(m,2H),1.55–1.36(m,2H); 13CNMR(101MHz,CDCl3)δ174.41,162.83,151.46,135.70,131.40,131.06,129.14,1 26.97,123.54,121.28,114.23,55.62,42.76,42.24,41.50,38.23,32.37,27.08.

[0166] Example 35 Ethyl 5-(6-chlorobenzo[d]thiazol-2-yl)-8-((4-methoxyphenyl)sulfonamido)octanoate

[0167]

[0168] In a reaction tube equipped with a magnetic stirrer, compound (I) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), compound (II) ethyl 8-((4-methoxyphenyl)sulfonamido)octanoate (142.9 mg, 0.4 mmol), a mixture of ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoroacetic acid (34.2 mg, 0.3 mmol) was added. A mixed solvent of acetonitrile and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen substitution three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution, the mixture was extracted with ethyl acetate, the organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 3:1 to 2:1 to obtain the target product in a yield of 43% and an HPLC purity of 98.7%.

[0169] 1 H NMR (400MHz, CDCl3) δ7.84(d,J=8.7Hz,1H),7.80–7.77(m,1H),7.72(d,J=8. 7Hz,2H),7.42–7.36(m,1H),6.89(d,J=8.8Hz,2H),4.97(s,1H),4.07(q,J=7 .1Hz,2H),3.82(s,3H),3.07(p,J=7.7Hz,1H),2.88(t,J=6.8Hz,2H),2.26(t ,J=7.4Hz,2H),1.82–1.70(m,4H),1.65–1.33(m,4H),1.20(t,J=7.1Hz,3H); 13C NMR (101MHz, CDCl3) δ176.20,173.20,162.77,151.22,135.74,131.44,130.85,129.14,126.81, 123.40,121.26,114.19,60.39,55.60,44.41,42.83,35.49,33.91,32.64,27.08,22.53,14.23.

[0170] Example 36 N-(3-(6-chlorobenzo[d]thiazol-2-yl)cyclohexyl)methyl)-4-methoxybenzenesulfonamide

[0171]

[0172] In a reaction tube equipped with a magnetic stirrer, a mixture of compound (I) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), compound (II) N-cyclohexylmethyl-4-methoxybenzenesulfonamide (113.2 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoroacetic acid (34.2 mg, 0.3 mmol) was added. A mixed solvent of acetonitrile and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen substitution three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution, the mixture was extracted with ethyl acetate, the organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 4:1 to 3:1 to obtain the target product in a yield of 63% and an HPLC purity of 98.5%.

[0173] 1 H NMR (400MHz, CDCl3) δ7.84–7.76(m,4H),7.38(d,J=8.6Hz,1H),6.94(d,J=8.0 Hz,2H),4.93(t,J=6.6Hz,1H),3.82(s,3H),3.02(t,J=11.1Hz,1H),2.88–2.78 (m,2H),2.17(t,J=10.9Hz,2H),1.90(d,J=12.5Hz,1H),1.79(d,J=12.7Hz,1H ),1.72–1.59(m,1H),1.55–1.33(m,2H),1.29–1.19(m,1H),1.01–0.85(m,1H); 13C NMR (101MHz, CDCl3) δ177.07,162.83,151.50,135.65,131.52,130.56,129.17,126. 70,123.29,121.21,114.24,55.59,49.00,42.69,37.73,36.75,32.99,29.69,25.28.

[0174] Example 37 N-(2-(2-(6-chlorobenzo[d]thiazol-2-yl)cyclopentyl)ethyl)-4-methoxybenzenesulfonamide

[0175]

[0176] In a reaction tube equipped with a magnetic stirrer, compound (I) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), compound (II) N-(2-cyclopentylethyl)-4-methoxybenzenesulfonamide (113.2 mg, 0.4 mmol), a mixture of ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoroacetic acid (34.2 mg, 0.3 mmol) was added. A mixed solvent of acetonitrile and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen replacement three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After the reaction, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 4:1 to 3:1 to obtain the target product in a yield of 71% and an HPLC purity of 99.8%.

[0177] 1 H NMR (400MHz, CDCl3) δ7.83(d,J=8.6Hz,1H),7.74(s,1H),7.65(d,J=8.2Hz,2 H),7.37(d,J=8.6Hz,1H),6.81(d,J=8.2Hz,2H),5.76(t,J=6.2Hz,1H),3.78( s,3H),3.02(q,J=8.5Hz,1H),2.89(tq,J=12.5,6.0Hz,2H),2.35–2.13(m,2H) ,1.99–1.90(m,1H),1.89–1.78(m,1H),1.78–1.54(m,4H),1.33–1.19(m,1H); 13C NMR (101MHz, CDCl3) δ177.00,162.62,151.30,135.86,131.58,130.66,129.04,126. 79,123.27,121.17,114.07,55.58,50.20,44.18,41.87,34.94,34.54,32.79,24.50.

[0178] Example 38 N-(2-(6-chlorobenzo[d]thiazol-2-yl)cyclohexyl)ethyl)-4-methoxybenzenesulfonamide

[0179]

[0180] In a reaction tube equipped with a magnetic stirrer, compound (I) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), compound (II) N-(2-cyclohexylethyl)-4-methoxybenzenesulfonamide (118.9 mg, 0.4 mmol), a mixture of ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoroacetic acid (34.2 mg, 0.3 mmol) was added. A mixed solvent of acetonitrile and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen replacement three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After the reaction, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 4:1 to 3:1 to obtain the target product in a yield of 74% and an HPLC purity of 98.9%.

[0181] 1 H NMR (400MHz, CDCl3) δ7.90(d,J=8.6Hz,1H),7.78(s,1H),7.70(d,J=7.9Hz,2H),7.41(d,J=8.6Hz,1H),6.86(d,J=7.9Hz,2H),5.47(s,1 H),3.82(s,3H),2.98–2.72(m,3H),2.04(d,J=11.5Hz,1H),1.88–1.64(m,4H),1.58–1.35(m,2H),1.33–1.17(m,3H),1.08–0.93(m,1H); 13C NMR (101 MHz, CDC13) δ 177.06, 162.66, 151.04, 135.62, 131.45, 130.85, 129.14, 126.89, 123.42, 121.24, 114.07, 55.60, 48.76, 40.68, 39.36, 35.49, 33.82, 31.99, 25.94, 25.62.

[0182] Example 39 N-(3-(1-(6-chlorobenzo[d]thiazol-2-yl)cyclopentyl)propyl)-4- methoxybenzenesulfonamide

[0183]

[0184] In a reaction tube equipped with magnetic stirring, a mixture of compound (I) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), compound (II) N-(3-cyclopentylpropyl)-4- methoxybenzenesulfonamide (118.9 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoroacetic acid (34.2 mg, 0.3 mmol) was added, and a mixed solvent of acetonitrile and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen replacement for three times, the reaction system was irradiated under purple light with a power of 25 W, and the stirring reaction was carried out for 24 hours. After the reaction was completed, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. After the organic phase was washed with saturated NaCl, it was separated, dried over anhydrous Na2S04, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate (4:1-3:1, by volume) to obtain the target product with a yield of 67% and an HPLC purity of 99.8%.

[0185] 1 H NMR (400 MHz, CDC13) δ 7.87 (dd, J = 8.7, 2.4 Hz, 1H), 7.77 (s, 1H), 7.71 (d, J = 8.1 Hz, 2H), 7.38 (dt, J = 7.3, 1.9 Hz, 1H), 6.92 - 6.82 (m, 2H), 5.10 (t, J = 5.9 Hz, 1H), 3.82 (s, 3H), 2.84 (q, J = 6.0 Hz, 2H), 2.22 - 2.13 (m, 2H), 1.91 - 1.65 (m, 8H), 1.47 - 1.29 (m, 2H); 13 C{ 1H}NMR (101MHz, CDCl3) δ180.86,162.74,151.42,136.19,131.48,130.58,129.14, 126.63,123.45,121.05,114.14,55.60,53.31,43.28,39.53,38.17,25.52,24.38.

[0186] Example 40 N-(3-(6-chlorobenzo[d]thiazol-2-yl)cyclohexyl)propyl)-4-methoxybenzenesulfonamide

[0187]

[0188] In a reaction tube equipped with a magnetic stirrer, compound (I) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), compound (II) N-(3-cyclohexylpropyl)-4-methoxybenzenesulfonamide (124.5 mg, 0.4 mmol), a mixture of ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoroacetic acid (34.2 mg, 0.3 mmol) were added. A mixed solvent of acetonitrile and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen replacement three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After the reaction, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 4:1 to 3:1 to obtain the target product in a yield of 70% and an HPLC purity of 98.4%.

[0189] 1 H NMR (400MHz, CDCl3) δ7.86(d,J=8.6Hz,1H),7.78(s,1H),7.70(d,J=8.1Hz,2H),7.38(dt,J=8.8,2.1Hz,1H),6.88(d,J=8.1Hz,2H),4.92(t,J= 5.9Hz,1H),3.82(s,3H),2.80(q,J=6.1Hz,2H),2.15–2.05(m,2H),1.72 –1.64(m,2H),1.65–1.51(m,4H),1.51–1.35(m,4H),1.31–1.22(m,2H); 13C NMR (101MHz, CDCl3) δ180.28,162.75,151.41,136.12,131.45,130.56,129.13,126. 49,123.50,121.10,114.15,55.60,45.11,43.37,39.09,36.94,25.74,23.76,22.31.

[0190] Example 41 N-(4-(6-chlorobenzo[d]thiazol-2-yl)-4-methylpentyl)-4-methoxybenzenesulfonamide

[0191]

[0192] In a reaction tube equipped with a magnetic stirrer, compound (I) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), compound (II) 4-methoxy-N-(4-methylpentyl)benzenesulfonamide (108.4 mg, 0.4 mmol), a mixture of ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoroacetic acid (34.2 mg, 0.3 mmol) were added. A mixed solvent of acetonitrile and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen substitution three times, the reaction system was irradiated under 25 W violet light and stirred for 24 hours. After completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution, the mixture was extracted with ethyl acetate, the organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate in a volume ratio of 4:1 to 3:1 to obtain the target product in a yield of 82% with an HPLC purity of 98.7%.

[0193] 1 H NMR (400MHz, CDCl3) δ7.89(d,J=8.7Hz,1H),7.78(s,1H),7.73(dd,J=8.9,2.3Hz,2H),7.38(dt,J=8.8,2.2Hz,1H), 6.88(dd,J=8.9,2.4Hz,2H),5.27(s,1H),3.82(s,3H),2.86(t,J=6.8Hz,2H),1.86–1.64(m,2H),1.43–1.35(m,8H); 13 C NMR (101MHz, CDCl3) δ181.22,162.74,151.38,136.03,131.46,130.62,129.1 5,126.70,123.51,121.08,114.15,55.60,43.28,41.37,39.83,28.75,24.69.

[0194] Example 42 N-(4-(6-chlorobenzo[d]thiazol-2-yl)butyl)-4-methoxybenzenesulfonamide

[0195]

[0196] In a reaction tube equipped with magnetic stirring, a mixture of compound (I) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), compound (II) N-butyl-4-methoxybenzenesulfonamide (97.2 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoroacetic acid (34.2 mg, 0.3 mmol) was added, and a mixed solvent of acetonitrile and water (1.0 mL / 1.0 mL) was added to the mixture. After nitrogen replacement for three times, the reaction system was irradiated under purple light with a power of 25 W, and the stirring reaction was carried out for 24 hours. After the reaction was completed, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. After the organic phase was washed with saturated NaCl, it was separated, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate (4:1-3:1, by volume) to obtain the target product with a yield of 24% and an HPLC purity of 98.8%.

[0197] 1 H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 8.6 Hz, 1H), 7.83-7.72 (m, 3H), 7.41 (d, J = 8.7 Hz, 1H), 6.94 (d, J = 7.8 Hz, 2H), 4.78 (s, 1H), 3.84 (s, 3H), 3.05 (t, J = 7.2 Hz, 2H), 2.97 (t, J = 7.0 Hz, 2H), 1.88 (p, J = 7.3 Hz, 2H), 1.60 (p, J = 7.3 Hz, 2H); 13 C NMR (101 MHz, CDCl3) δ 171.84, 162.84, 151.57, 136.20, 131.45, 130.80, 129.18, 126.84, 123.29, 121.15, 114.23, 55.61, 42.68, 33.39, 28.77, 25.94.

[0198] Example 43 (2S,5R)-2-isopropyl-5-methylcyclohexyl 4-(6-chlorobenzo[d]thiazol-2-yl)-7-(4-methoxyphenylsulfonamidyl)heptanoate

[0199]

[0200] In a reaction tube equipped with magnetic stirring, a mixture of compound (I) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), compound (II) (2S, 5R)-2-isopropyl-5-methylcyclohexyl 7-((4-methoxyphenyl)sulfonamido)heptanoate (181.3 mg, 0.4 mmol), ammonium persulfate (114.1 mg, 0.5 mmol) and trifluoroacetic acid (34.2 mg, 0.3 mmol) was added, and a mixed solvent of acetonitrile and water ( 1.0mL / 1.0mL), after nitrogen replacement three times, the reaction system was irradiated under purple light with a power of 25W, and the reaction was stirred for 24 hours. After the reaction, the reaction solution was quenched with a saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated NaCl, separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate with a volume ratio of 4:1 to 3:1 to obtain the target product in a yield of 31% and an HPLC purity of 99.8%.

[0201] 1 H NMR(400MHz, CDCl3)δ7.86(dd,J=8.7,2.2Hz,1H),7.81(t,J=2.0Hz,1H),7.76–7.70(m,2H),7.42(ddd,J=8.6,2.1,1 .0Hz,1H),6.96–6.86(m,2H),4.75(td,J=6.2,2.3Hz,1H),4.64(tdd,J=10.9,4.4,1.5Hz,1H),3.83(s,3H),3.16–3. 07(m,1H),2.91(q,J=6.6Hz,2H),2.25(t,J=7.3Hz,2H),2.12–2.00(m,2H),1.96–1.85(m,1H),1.84–1.75(m,2H),1. 70–1.60(m,2H),1.55–1.38(m,3H),1.35–1.24(m,2H),1.08–0.95(m,1H),0.90–0.83(m,8H),0.72(t,J=7.1Hz,3H); 13C NMR (101 MHz, CDC13) δ 175.21, 172.37, 162.80, 151.49, 135.81, 131.44, 130.94, 129.15, 126.86, 123.54, 121.26, 114.19, 74.38, 55.60, 46.92, 43.83, 43.81, 42.82, 42.80, 40.90, 40.87, 34.19, 32.59, 32.52, 32.02, 31.37, 31.36, 31.08, 31.01, 27.18, 26.23, 23.36, 22.03, 22.01, 20.78, 20.76, 16.32, 16.28.

[0202] Example 44 Anti-tumor activity test

[0203] The effects of the corresponding compounds in Examples 4, 5, 17, 19 and 23 on the proliferation of MCF-7 cells were investigated:

[0204] The cell survival rate was determined by MTT method. MCF-7 cell culture: MCF-7 cells were inoculated in DMEM medium containing 10% FBS, 1% penicillin mixed solution, 10% serum, 1% Glutamx, 1% Sodium Pyruvate 100 mM Solution, 1% Non-essential Amino Acids, and cultured in a 37°C constant temperature incubator containing 5% CO2.

[0205] Logarithmic growth phase MCF-7 cells were inoculated into 96-well plates (100 μL, 8 x 10 4 cells / mL), and incubated in a 5% CO2 incubator at 37°C for 24 h. Then, the MCF-7 cells were treated with different compounds at a concentration of 40 μL for 48 h (3 parallel groups for each concentration), and the experimental group without drug was used as a blank control. Then 10 μL of MTT solution at a concentration of 5 mg / mL was added to each well, and incubated in a 5% CO2 incubator at 37°C for 4 h. The supernatant was discarded, 100 μL of DMSO was added to each well, and shaken at 500 rpm for 10 min. The absorbance at 492 nm was measured. The detection formula for cell survival rate was:

[0206] Cell survival rate (%) = OD drug-treated group average / OD control group average x 100%.

[0207] Experimental results: Compared with the blank control group, the changes in the proliferation of MCF-7 cells in the experimental groups treated with different compounds for 48 h are shown in the table:

[0208]

[0209] The above test results show that at a concentration of 40 μM, compound III-ax has a certain inhibitory effect on MCF-7 tumor cells, and its structure can be further modified or transformed to further enhance its anti-tumor activity.

[0210] The contents described in this specification are merely an enumeration of implementation forms of the inventive concept, and the protection scope of the present invention should not be considered as being limited to the specific forms described in the embodiments.

Claims

1. A method for synthesizing a nitrogen heterocyclic compound induced by persulfate alkylation, characterized in that The N-long-chain alkylsulfonamide represented by formula (I), the nitrogen heterocycle represented by formula (II), an oxidant and an acidic additive are added to a reaction solvent, and the mixture is stirred under nitrogen protection and irradiated with a light source. After the reaction is completed, the reaction solution is post-treated to obtain the target compound represented by formula (III). The reaction equation is as follows: The oxidant is potassium persulfate, sodium persulfate or ammonium persulfate; the light source is blue light, white light or purple light; the light power is 15 to 50W; The target compound represented by formula (III) has a structure selected from the following:

2. The method for synthesizing a persulfate-induced alkylation-modified nitrogen heterocyclic compound according to claim 1, characterized in that The oxidizing agent is ammonium persulfate.

3. The method for synthesizing a persulfate-induced alkylation-modified nitrogen heterocyclic compound according to claim 1, characterized in that The acidic additive is TFA, HCl or CF3SO3H.

4. The method for synthesizing a persulfate-induced alkylation-modified nitrogen heterocyclic compound according to claim 3, characterized in that The acidic additive is CF3SO3H or TFA.

5. The method for synthesizing a persulfate-induced alkylation-modified nitrogen heterocyclic compound according to claim 1, characterized in that The reaction temperature is 20°C-50°C, and the reaction time is 18-35h.

6. The method for synthesizing a persulfate-induced alkylation-modified nitrogen heterocyclic compound according to claim 5, characterized in that The reaction temperature is 25-30°C and the reaction time is 20-25h.

7. The method for synthesizing a persulfate-induced alkylation-modified nitrogen heterocyclic compound according to claim 1, characterized in that The reaction solvent is a mixed solvent consisting of any one of 1,2-dichloroethane, ethyl acetate, dimethyl sulfoxide, dichloromethane or acetonitrile and water in a volume ratio of 1:0.5-2.

8. The method for synthesizing a persulfate-induced alkylation-modified nitrogen heterocyclic compound according to claim 7, characterized in that The reaction solvent is a mixed solvent consisting of dimethyl sulfoxide or acetonitrile and water in a volume ratio of 1:

1.

9. The method for synthesizing a persulfate-induced alkylation-modified nitrogen heterocyclic compound according to claim 1, characterized in that The light source is purple light; the lighting power is 25~30W.

10. The method for synthesizing a persulfate-induced alkylation-modified nitrogen heterocyclic compound according to claim 1, characterized in that The molar ratio of the N-long-chain alkylsulfonamide represented by formula (I) to the nitrogen heterocycle represented by formula (II) is 1:1.5.0-4.0, the molar ratio of the oxidant to the N-long-chain alkylsulfonamide represented by formula (I) is 1.5-3.0:1, and the molar ratio of the acidic additive to the N-long-chain alkylsulfonamide represented by formula (I) is 1.0-3.0:1; The dispersion concentration of the N-long-chain alkylsulfonamide represented by formula (I) in the reaction solvent is 0.05-0.4 mol / L.

11. The method for synthesizing a persulfate-induced alkylation-modified nitrogen heterocyclic compound according to claim 10, characterized in that The molar ratio of the N-long-chain alkylsulfonamide represented by formula (I) to the nitrogen heterocycle represented by formula (II) is 1:2.0-3.0; the molar ratio of the oxidant to the N-long-chain alkylsulfonamide represented by formula (I) is 2.0-2.5:1; and the molar ratio of the acidic additive to the N-long-chain alkylsulfonamide represented by formula (I) is 1.5-2.0:

1. The dispersion concentration of the N-long-chain alkylsulfonamide represented by formula (I) in the reaction solvent is 0.1-0.15 mol / L.

12. The method for synthesizing a persulfate-induced alkylation-modified nitrogen heterocyclic compound according to claim 1, characterized in that The post-treatment process is as follows: the reaction solution is quenched with a saturated aqueous sodium bicarbonate solution, then extracted with ethyl acetate, separated into layers, the organic phase is washed with saturated brine, the combined organic layers are dried over anhydrous Na2SO4 and concentrated under reduced pressure to obtain a crude product, and the crude product is separated and purified by a chromatographic column to obtain the target compound, a remote nitrogen heterocyclic substituted sulfonamide compound represented by formula (III).

13. The method for synthesizing a persulfate-induced alkylation-modified nitrogen heterocyclic compound according to claim 1, characterized in that In a reaction tube equipped with a magnetic stirrer, an N-long-chain alkylsulfonamide represented by formula (I), a nitrogen heterocycle represented by formula (II), an oxidant, an acidic additive and a reaction solvent are added. After nitrogen replacement three times, the reaction system is placed under light source irradiation and stirred at 25-35° C. for reaction. After the reaction is completed, the reaction solution is quenched with a saturated sodium bicarbonate aqueous solution, then extracted with ethyl acetate, separated, and the organic phase is washed with saturated brine. After the organic layers are combined, they are dried over anhydrous Na2SO4 and concentrated under reduced pressure to obtain a crude product. The crude product is separated and purified by a chromatographic column to obtain the target compound, a remote nitrogen heterocycle substituted sulfonamide compound represented by formula (III).

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