A series of functionalization synthetic methods of photocatalytic inert c(sp3)-h bond

Abstract

The application discloses a series of functional group synthesis method of photocatalytic inert C(sp 3 )-H bond, which adds N-long chain alkyl sulfonamide shown in formula (I), nitrogen heterocycle shown in formula (II) or functional group reagent shown in formula (III) into a reaction medium, irradiates under a photocatalytic reaction system, stirs and reacts at room temperature, and after the reaction is completed, the reaction liquid is treated to obtain remote inert C(sp 3 )-H heteroarylation product shown in formula (IV) or remote inert C(sp 3 )-H series of functional group product shown in formula (V), and the reaction equation is as follows: The synthesis method has the characteristics of simple operation, mild reaction condition, good substrate universality, wide functional group generalization and novel reaction mechanism, and provides a new idea for the synthesis method of the series of functional group of inert C(sp 3 )-H bond; in addition, the method can modify a series of drug derivatives, and has certain industrialization popularization and application value.

Description

Technical Field

[0001] This invention relates to a photocatalytic inert C(sp) 3 A series of functionalization synthesis methods for H-bonds. Background Technology

[0002] Inert C(sp) 3 Direct functionalization of C-H bonds is one of the most powerful techniques in synthetic chemistry, providing a rapid, convenient, and highly atom-economical strategy for the rapid construction of carbon-carbon and carbon-heteroatom bonds in natural products and active pharmaceutical ingredients. Over the past few decades, the synergistic catalytic mode of transition metals combined with directing groups has made significant progress in the activation of aliphatic CH bonds, but significant challenges remain in terms of reactivity and selectivity. In recent years, radical-mediated photoredox catalysis has provided a very attractive route for the direct functionalization of aliphatic CH bonds. However, due to the high bond dissociation energy of aliphatic CH bonds, current methods involving the photoinduced cleavage of aliphatic CH bonds to generate alkyl radicals mainly rely on hydrogen-snap radicals with certain electrophilicity, such as chlorine radicals, (sulfonamide)nitrogen radicals, or alkoxy radicals. Typically, hydrogen-snap radicals are electrophilic for C(sp...)... 3 Extraction of )-H occurs at the ortho or benzylic and allylic positions of highly reactive heteroatoms, while for distal inert C(sp) 3 Activation of the -H bond still faces significant challenges.

[0003] Hofmann- Intramolecular hydrogen atom transfer established by the -Freytag (HLF) reaction, such as 1,5-hydrogen migration, is a long-range inert C(sp) atom. 3 Functionalization of the NH-H bond offers a promising strategy with excellent regioselectivity and chemoselectivity. The key to the HLF reaction is the generation of a nitrogen radical with hydrogen-snap-forming ability. This is achieved by converting the free NH bond into an N-halogen, NN, NO, or NS precursor, thereby generating a nitrogen-centered radical intermediate to achieve inert C(sp) bonds. 3Significant progress has been made in the functionalization of NH bonds. However, the prefunctionalization of NH bonds to form nitrogen-centered radical intermediates inevitably has certain limitations, such as cumbersome multi-step procedures, low atom economy, and the possibility of introducing prefunctionalized groups into the final product. In contrast, homolytic cleavage of the NH bond in free amines to generate nitrogen radicals is the most direct and ideal strategy. However, this is often proven challenging because the NH bond is highly stable, and breaking it requires overcoming a significant energy barrier. Proton-coupled electron transfer (PCET) catalysis, through the co-transfer of protons and electrons, has recently become an effective strategy for activating NH bonds to generate nitrogen radicals. For example, the Knowles and Rovis group independently achieved distal δ-selectivity of C(sp) radicals between amides and electron-deficient alkenes. 3 )-H alkylation (Nature 2016, 539, 268-271; Nature 2016, 539, 272-275). Subsequently, Rovis and Tambar's group reported a cascade process that uses alkyl halides as alkylating agents and alkyl Ni(II) complexes to intercept the distal alkyl radical following 1,5-HAT, in order to provide C(sp... 3 )-C(sp 3 Cross-coupling products (J. Am. Chem. Soc. 2019, 141, 14062-14067; ACS Catal. 2019, 9, 4627-4631). Despite these impressive achievements, the PCET strategy in inert C(sp) 3 The functionalization of )-H is limited to C(sp) 3 )-C(sp 3 ) bond and C(sp 3 )-C(sp 2 The construction of NH bonds. Therefore, there is an urgent need to develop a new and more general photo-redox catalytic strategy that can directly generate nitrogen radicals from non-prefunctionalized NH bonds, thereby achieving a series of functionalizations of inert aliphatic CH bonds in a site-selective manner.

[0004] Electron / proton transfer (ET / PT) events offer an alternative strategy for nitrogen radical generation, but due to their inherent thermochemical limitations, they have not been widely studied in synthetic organic chemistry. Only a few organic electrochemical systems generate nitrogen radicals by losing an electron and a proton from an NH substrate at the anode; and to our knowledge, the generation and further applications of nitrogen radicals via photoredox catalysis in the ET / PT mode remain unknown. Considering the ubiquity and relevance of nitrogen in organic molecules, the use of the more challenging ET / PT photocatalytic mode to generate corresponding nitrogen radicals from highly acidified sulfonamide NH bonds is of profound significance. On the other hand, the Minisci reaction, involving the coupling of nitrogen-containing heteroaromatics with nucleophilic alkyl radicals, is an effective method for achieving heteroaromatic diversification. However, previous methods involving the Minisci reaction have been limited by the use of expensive catalysts, excess oxidants, or high-temperature conditions due to the strong aliphatic CH bonds and net oxidation properties.

[0005] In this patent, to further supplement the photocatalytic nitrogen radical generation strategy and overcome the many unfavorable conditions involved in the traditional Minisci reaction, we propose combining photoinduced ET / PT catalysis with cobalt catalysis to achieve inert C(sp) through hydrogen evolution. 3 We successfully implemented the Minisci reaction of α-H and applied this method to the modification of drug derivatives. Furthermore, based on a photoinduced ET / PT catalytic mode, we successfully achieved remote bromination, fluorination, alkylation, amination, cyanation, azidation, and deuteration of N-alkylsulfonamides, further demonstrating the versatility and strong application value of this strategy in synthetic chemistry. Finally, compounds prepared using this patented technology exhibited certain antitumor activity and can serve as key intermediates in drug synthesis. Summary of the Invention

[0006] To address the aforementioned technical problems in the existing technology, the purpose of this invention is to provide a photocatalytic inert C(sp) reaction mechanism that is novel, versatile, widely applicable, has mild reaction conditions, and produces high-purity products. 3 A series of functionalization methods for )-H bonds were developed, and drug fragments could be selectively modified using this method.

[0007] This invention defines a photocatalytic inert C(sp) 3 The series of functionalization synthesis methods for the )-H bond are as follows: N-long-chain alkyl sulfonamides (I), nitrogen heterocycles (II), or functionalizing agents (III) are added to the reaction medium. Under a specific photocatalytic reaction system, the mixture is irradiated with a light source and stirred at room temperature. After the reaction is complete, the reaction solution is post-treated to obtain the target compound, represented by formula (IV), a long-range inert C(sp) group. 3)-H heteroarylated products or long-range inert C(sp) as shown in formula (V) 3 The reaction equations for the )-H series functionalized products are as follows:

[0008]

[0009] FG in equations (I), (IV) and (V) 1 It is a mono- or di-substituted N-long-chain alkyl side chain at any position, with the substituent independently selected from H, methyl, ethyl, phenyl, or methoxycarbonyl, R 1 Selected from hydrogen, methyl, ethyl, n-propyl, n-butyl, cyclopentyl, cyclohexyl, or 2-chloroethyl;

[0010] The nitrogen heterocycle in formulas (II) and (IV) is one of benzothiazole, quinoline, isoquinoline, quinazoline, phthalazine, pyrazine, pyridine, pyrimidine, pyridazine, thiazole, acridine or its derivatives. The substituents on the derivatives can be mono- or di-substituted at any C atom position on the benzene ring or other host ring. The substituents are independently selected from halogen, phenyl, C1-C4 alkyl, C1-C4 alkyl carbonyl, cyano, aldehyde or C1-C4 alkoxy carbonyl.

[0011] The functionalizing reagent in formula (III) is selected from N-bromosuccinimide, fluorinated reagent, 2-benzylmalonium, ethyl 2-cyano-3-phenylacrylate, diethyl ethylene malonate, di-tert-butyl azodicarbonate, p-acetaminobenzenesulfonyl azide, 4-toluenesulfonyl cyanide, or deuterium water, respectively corresponding to the long-range C(sp) shown in formula (V). 3 The target products of )-H bromination, fluorination, alkylation, amination, azidation, cyanation and deuteration.

[0012] Furthermore, the present invention specifies that the photocatalyst in the photocatalytic system is 9-trismetyl-10-methylacridine perchlorate, 9-trismetyl-10-phenylacridine tetrafluoroborate, 2,4,5,6-tetra(carbazole-9-yl)-1,3-dicyanobenzene, tris(2-phenylpyridine)iridium or (4,4'-di-tert-butyl-2,2'-bipyridine)bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridyl]phenyl]iridium(III) hexafluorophosphate, preferably 9-trismetyl-10-methylacridine perchlorate. The amount of the photocatalyst is 0.5-3% of the molar amount of the N-long-chain alkyl sulfonamide shown in formula (I), preferably 1-3%.

[0013] Furthermore, the present invention also specifies the preparation of long-range C(sp) 3The cooperating catalyst required for the photocatalytic system of the )-H heteroarylation product is chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III), and the amount of chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) is 2 to 5% of the molar amount of the N-long-chain alkyl sulfonamide shown in formula (I).

[0014] Furthermore, the preparation of long-range C(sp) 3 The photocatalyst required for the photocatalytic system of the )-H deuterated product is diphenyl disulfide, and the amount of diphenyl disulfide used is 10-25% of the molar amount of the N-long-chain alkyl sulfonamide shown in formula (I), preferably 20%. Meanwhile, the preparation of long-range C(sp... 3 The photocatalytic system for )-H brominated, fluorinated, alkylated, amination-azidated, and cyaninated products does not require a co-catalyst.

[0015] Furthermore, the present invention also specifies the preparation of the long-range C(sp) of formula (III) by reacting compounds of formula (I) and formula (II). 3 The photocatalytic system for the )-H heteroarylation product requires the use of an acidic additive, which is concentrated hydrochloric acid, trifluoroacetic acid, or trifluoromethanesulfonic acid, preferably trifluoroacetic acid. The molar ratio of the acidic additive to the N-long-chain alkyl sulfonamide shown in formula (I) is 1:0.8 to 1.2. The preparation of the product of formula (IV) from compounds of formula (I) and formula (III) does not require an acidic additive.

[0016] Furthermore, the present invention specifies that the light source is blue light, white light, or violet light, preferably blue light. The illumination power is 15-50W, preferably 20-25W.

[0017] Furthermore, the present invention further specifies that the reaction medium is a mixed solvent of one or any combination of acetonitrile, hexafluoroisopropanol, dichloromethane, dimethyl sulfoxide or 1,2-dichloroethane, preferably a mixed solvent composed of acetonitrile and hexafluoroisopropanol in a volume ratio of 3 to 9:1.

[0018] Furthermore, the N-long-chain alkyl sulfonamide shown in formula (I) is dispersed at a concentration of 0.1-0.4 mol / L in the reaction medium.

[0019] Furthermore, the present invention also defines remote C(sp) 3 In the )-H heteroarylation reaction, the molar ratio of the N-long-chain alkyl sulfonamide shown in formula (I) to the nitrogen heterocycle shown in formula (II) is 1.5-3:1, preferably 2-2.2:1.

[0020] Furthermore, in the preparation of long-range C(sp) 3In the reaction of the )-H functionalized product, when the functionalizing agent in formula (III) is selected from N-bromosuccinimide, fluorinated reagent, 2-benzylmalonium, ethyl 2-cyano-3-phenylacrylate, diethyl ethylene malonate, di-tert-butyl azodicarbonate, p-acetaminobenzenesulfonyl azide, or 4-toluenesulfonyl cyanide, the molar ratio of the N-long-chain alkyl sulfonamide shown in formula (I) to the functionalizing agent shown in formula (III) is 1:2.0-3.0; when the functionalizing agent in formula (III) is selected from deuterium water, the feed ratio of the N-long-chain alkyl sulfonamide shown in formula (I) to deuterium water is 0.8-1.2 mol:1 L.

[0021] Furthermore, the present invention also defines a remote C(sp) 3 The post-processing of the )-H heteroarylation was as follows: the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, then extracted with ethyl acetate. The organic phase was washed with saturated NaCl, separated into layers, and the combined organic layers were dried with anhydrous Na2SO4 and concentrated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain the long-range C(sp) of the target compound, represented by formula (Ⅳ). 3 )-H heteroarylized products; preparation of long-range C(sp 3 The post-treatment process of the reaction of the )-H functionalized product is as follows: quench the reaction with saturated Na2S2O3 or saturated NaCl solution and wash, then extract with ethyl acetate, combine the organic layers, dry with anhydrous Na2SO4 and concentrate under reduced pressure to obtain the crude product, and purify the crude product by column chromatography to obtain the long-range inert C(sp) of the target compound (V). 3 )-H series functionalized products.

[0022] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0023] 1) This invention innovatively proposes a photocatalytic ET / PT mode for the generation of nitrogen radical intermediates, thereby achieving inert C(sp) 3 The series of functionalizations of )-H are highly original, and their unique reaction mechanisms have attracted widespread attention in academia and industry.

[0024] 2) Based on the photocatalytic ET / PT mode, this invention achieves remote inert C(sp) at room temperature by utilizing relatively inexpensive and readily available photocatalysts and cobalt catalysts. 3 Heteroarylation of )-H avoids the use of noble metal catalysts, excess oxidants and high temperature conditions in the traditional Minisci reaction, and the reaction conditions are mild and controllable with broad substrate versatility.

[0025] 3) Based on the photocatalytic ET / PT mode, this invention utilizes the synergistic catalysis of a photocatalyst and diphenyl disulfide to precisely achieve remote inert C(sp) 3The deuteration of )-H further promoted the development of deuteration technology; in addition, remote inert C(sp) deuteration was achieved through photo-oxidation-reduction catalysis. 3 The bromination, fluorination, alkylation, amination, azidation, and cyanation of )-H are widely applicable.

[0026] 4) The technology of this invention can be used to directly functionalize some drug fragments. Detailed Implementation

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

[0028] Example 1: N-(4-(6-chlorobenzo[d]thiazolyl-2-yl)pentyl)-4-methoxybenzenesulfonamide (IV-a)

[0029]

[0030] A mixture of compound (I) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), compound (II) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), 9-trimethyl-10-methylacridine perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol), and trifluoroacetic acid (45.6 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL) was added to the compound. After purging with nitrogen three times, the reaction system was irradiated under a 25 W blue light and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with a saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate, and the organic phase was washed with saturated NaCl. After separation, the phases were dried with anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 4:1 to 3:1 to obtain the target product with a yield of 66% and an HPLC purity of 99.0%.

[0031] 1H NMR (400MHz, CDCl3) δ7.83(d,J=8.7Hz,1H),7.77(d,J=2.1Hz,1H),7.76–7.72(m,2H),7.38(dd,J=8.7,2.1Hz,1H),6.91–6.87(m,2H ),5.15(br,1H),3.81(s,3H),3.18(h,J=6.9Hz,1H),2.97–2.86(m,2H),1.88–1.65(m,2H),1.60–1.40(m,2H),1.36(d,J=6.9Hz,3H). 13 C NMR (101MHz, CDCl3) δ177.74,162.77,151.34,135.77,131.44,130.66,129.1 6,126.74,123.33,121.22,114.20,55.61,42.90,38.85,33.97,27.06,21.20.

[0032] Example 2 4-Methoxy-N-(4-(2-phenylquinoline-4-yl)pentyl)benzenesulfonamide (IV-b)

[0033]

[0034] A mixture of compound (I) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), compound (II) 2-phenylquinoline (41.0 mg, 0.2 mmol), 9-trimethyl-10-methylacridine perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol), and trifluoroacetic acid (45.6 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL) was added to the compound. After purging with nitrogen three times, the reaction system was irradiated under a 25 W blue light and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with a saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate, and the organic phase was washed with saturated NaCl. After separation, the phases were dried with anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 4:1 to 3:1 to obtain the target product with a yield of 86% and an HPLC purity of 99.2%.

[0035] 1H NMR (400MHz, CDCl3) δ8.21(d,J=8.3Hz,1H),8.11(d,J=7.5Hz,2H),8.01(d,J=8.4Hz,1H),7.73–7.66(m,4H),7.55–7.42(m,4H),6.86(d,J=8.4Hz, 2H),4.83(t,J=5.7Hz,1H),3.79(s,3H),3.56(h,J=7.4Hz,1H),2.89(q,J =6.9Hz,2H),1.87–1.67(m,2H),1.57–1.40(m,2H),1.36(d,J=6.6Hz,3H). 13 C NMR (101MHz, CDCl3) δ162.77,157.14,153.74,148.41,139.81,131.39,130.54,129.35,129.33,129.1 1,128.84,127.66,126.22,126.04,122.75,115.58,114.18,55.58,43.11,34.03,33.21,27.53,21.29.

[0036] Example 3 N-(4-(isoquinoline-1-yl)pentyl)-4-methoxybenzenesulfonamide (IV-c)

[0037]

[0038] A mixture of compound (I) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), compound (II) isoquinoline (25.8 mg, 0.2 mmol), 9-trimethyl-10-methylacridine perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol), and trifluoroacetic acid (45.6 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL) was added to the mixture. After purging with nitrogen three times, the reaction system was irradiated under a 25 W blue light and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with a saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate, and the organic phase was washed with saturated NaCl. The layers were separated, dried with anhydrous Na₂SO₄, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 4:1 to 3:1 to obtain the target product in 52% yield with an HPLC purity of 99.1%.

[0039] 1H NMR (400MHz, CDCl3) δ8.46(d,J=5.5Hz,1H),8.14(d,J=8.4Hz,1H),7.81(d,J=8.1Hz,1 H),7.73(d,J=8.6Hz,2H),7.62(dt,J=32.6,7.2Hz,2H),7.49(d,J=5.4Hz,1H),6.89(d ,J=8.6Hz,2H),5.09(t,J=5.9Hz,1H),3.83(s,3H),3.72(h,J=6.9Hz,1H),2.88(q,J=6 .3Hz,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 (101MHz, CDCl3) δ164.77,162.68,141.62,136.43,131.57,129.86,129.17,127.6 2,127.18,126.74,124.59,119.28,114.11,55.58,43.19,35.75,32.46,27.44,21.40.

[0040] Example 4: 4-Methoxy-N-(4-(quinazolin-4-yl)pentyl)benzenesulfonamide (IV-d)

[0041]

[0042] A mixture of compound (I) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), compound (II) quinazoline (26.0 mg, 0.2 mmol), 9-trimethyl-10-methylacridine perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol), and trifluoroacetic acid (45.6 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL) was added to the mixture. After purging with nitrogen three times, the reaction system was irradiated with blue light at a power of 25 W and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate, and the organic phase was washed with saturated NaCl. The phases were separated, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 4:1 to 3:1 to obtain the target product with a yield of 31% and an HPLC purity of 98.8%.

[0043] 1H 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 CNMR(101MHz,CDCl3)δ174.66,162.79,154.53,150.07,133.59,131.47,129.33,1 29.13,127.68,124.03,123.64,114.18,55.60,43.08,35.58,32.28,27.54,20.72.

[0044] Example 5: 4-Methoxy-N-(4-(phthalazin-1-yl)pentyl)benzenesulfonamide (IV-e)

[0045]

[0046] A mixture of compound (I) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), compound (II) phthalazine (26.0 mg, 0.2 mmol), 9-trimethyl-10-methylacridine perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol), and trifluoroacetic acid (45.6 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL) was added to the mixture. After purging with nitrogen three times, the reaction system was irradiated with blue light at a power of 25 W and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate, and the organic phase was washed with saturated NaCl. The phases were separated, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 4:1 to 3:1 to obtain the target product with a yield of 53% and an HPLC purity of 98.8%.

[0047] 1H 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) δ163.09,162.67,150.21,132.65,131.95,131.61,129.16,12 7.27,126.58,125.34,123.39,114.13,55.58,43.18,35.11,32.45,27.54,20.85.

[0048] Example 6 N-(4-(5-acetyl-6-methylpyrazine-2-yl)pentyl)-4-methoxybenzenesulfonamide (IV-f)

[0049]

[0050] Compound (I) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), compound (II) 1-(3-methylpyrazin-2-yl)ethyl-1-one (27.2 mg, 0.2 mmol), 9-trimethylmethyl-10-methylacridine perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol), and trifluoroacetic acid (45.6 mg, 0.4 mmol) were added to a reaction tube equipped with a magnetic stirrer. The mixture was then purged with a mixed solvent of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL). After three nitrogen purgings, the reaction system was irradiated under a 25 W blue light and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with a saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate, and the organic phase was washed with saturated NaCl. The phases were separated, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using a petroleum ether / ethyl acetate volume ratio of 4:1 to 2:1 to obtain the target product with a yield of 41% and an HPLC purity of 98.9%.

[0051] 1H NMR(400MHz, CDCl3)δ8.25(s,1H),7.76(d,J=8.3Hz,2H),6.94(d,J=8.3Hz,2H),4.77(br,1H),3.85(s,3H),2.94–2.85(m,3H) ,2.77(s,3H),2.67(s,3H),1.81–1.70(m,1H),1.66–1.56(m,1H),1.52–1.40(m,1H),1.38–1.28(m,1H),1.25(d,J=6.8Hz,3H). 13 CNMR(101MHz, CDCl3)δ201.24,162.83,162.47,153.47,144.65,139.43,131. 44,129.15,114.22,55.63,43.00,39.00,33.12,27.88,27.45,23.65,20.28.

[0052] Example 7 N-(4-(4-cyanopyridin-2-yl)pentyl)-4-methoxybenzenesulfonamide (IV-g)

[0053]

[0054] A mixture of compound (I) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), compound (II) 4-cyanopyridine (20.8 mg, 0.2 mmol), 9-trimethyl-10-methylacridine perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol), and trifluoroacetic acid (45.6 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL) was added to the compound. After purging with nitrogen three times, the reaction system was irradiated under a 25 W blue light and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with a saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate, and the organic phase was washed with saturated NaCl. The phases were separated, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 4:1 to 2:1 to obtain the target product with a yield of 45% and an HPLC purity of 98.9%.

[0055] 1H NMR (400MHz, CDCl3) δ8.69(d,J=4.9Hz,1H),7.78–7.74(m,2H),7.33(dd,J=5.0,1.3Hz,1H),7.30(s,1H),6.98–6.93(m,2H),4.68(t,J=6.1 Hz,1H),3.86(s,3H),2.93–2.82(m,3H),1.75–1.67(m,1H),1.64–1.53(m,1H),1.49–1.37(m,1H),1.35–1.27(m,1H),1.24(d,J=6.9Hz,3H). 13 C NMR (101MHz, CDCl3) δ167.39,162.84,150.24,131.46,129.18,123.41,12 2.73,120.73,116.71,114.22,55.64,43.02,41.35,33.41,27.43,20.59.

[0056] Example 8 N-(4-(4,6-dimethylpyrimidin-2-yl)pentyl)-4-methoxybenzenesulfonamide (IV-h)

[0057]

[0058] A mixture of compound (I) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), compound (II) 4,6-dimethylpyrimidine (21.6 mg, 0.2 mmol), 9-trimethyl-10-methylacridine perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol), and trifluoroacetic acid (45.6 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL) was added to the mixture. After purging with nitrogen three times, the reaction system was irradiated under a 25 W blue light and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with a saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate, and the organic phase was washed with saturated NaCl. The phases were separated, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 4:1 to 3:1 to obtain the target product with a yield of 79% and an HPLC purity of 99.2%.

[0059] 1H 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.

[0060] Example 9 4-Methoxy-N-(4-(pyridazin-3-yl)pentyl)benzenesulfonamide (IV-i)

[0061]

[0062] A mixture of compound (I) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), compound (II) pyridazine (16.0 mg, 0.2 mmol), 9-trimethyl-10-methylacridine perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol), and trifluoroacetic acid (45.6 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL) was added to the mixture. After purging with nitrogen three times, the reaction system was irradiated with blue light at a power of 25 W and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate, and the organic phase was washed with saturated NaCl. The phases were separated, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 4:1 to 3:1 to obtain the target product with a yield of 63% and an HPLC purity of 99.0%.

[0063] 1H NMR (400MHz, CDCl3) δ9.04(d,J=5.3Hz,1H),8.99(s,1H),7.80–7.74(m,2H),7.25(dd,J=5.3,2.3Hz,1H),6.98–6.93(m,2H),5.35(t,J=6.1Hz,1H ),3.87(s,3H),2.92(q,J=6.6Hz,2H),2.69(h,J=7.0Hz,1H),1.63(q,J= 7.5Hz,2H),1.52–1.41(m,1H),1.39–1.30(m,1H),1.25(d,J=7.0Hz,3H). 13 C NMR (101MHz, CDCl3) δ162.83,151.85,151.13,146.12,131.49,129.11,124.62,114.24,55.65,42.84,36.76,33.88,27.35,20.82.

[0064] Example 10 N-(4-(5-formylthiazolyl-2-yl)pentyl)-4-methoxybenzenesulfonamide (IV-j)

[0065]

[0066] A mixture of compound (I) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), compound (II) thiazolium-5-carboxaldehyde (22.6 mg, 0.2 mmol), 9-trimethyl-10-methylacridine perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol), and trifluoroacetic acid (45.6 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL) was added to the compound. After purging with nitrogen three times, the reaction system was irradiated under a 25 W blue light and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with a saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate, and the organic phase was washed with saturated NaCl. The phases were separated, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using a petroleum ether / ethyl acetate volume ratio of 4:1 to 3:1 to obtain the target product with a yield of 50% and an HPLC purity of 99.1%.

[0067] 1H NMR(400MHz, CDCl3)δ9.98(s,1H),8.26(s,1H),7.79–7.75(m,2H),6.98–6.93(m,2H),4.69(br,1H),3.86(s,3 H),3.18(h,J=7.0Hz,1H),2.93(t,J=7.0Hz,2H),1.83–1.64(m,2H),1.57–1.41(m,2H),1.36(d,J=6.8Hz,3H). 13 C NMR (101MHz, CDCl3) δ184.99,182.07,162.87,151.14,138.57,131.45,129.18,114.26,55.64,42.86,38.81,34.16,27.10,21.10.

[0068] Example 11: Ethyl 2-(5-((4-methoxyphenyl)sulfonamido)pent-2-yl)-4-methylthiazolyl-5-carboxylate (IV-k)

[0069]

[0070] A mixture of compound (I) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), compound (II) ethyl 4-methylthiazolium-5-carboxylate (34.2 mg, 0.2 mmol), 9-trimethylmethyl-10-methylacridine perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol), and trifluoroacetic acid (45.6 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL) was added to the mixture. After purging with nitrogen three times, the reaction system was irradiated under a 25 W blue light and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with a saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate, and the organic phase was washed with saturated NaCl. After separation, the phases were dried with anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 4:1 to 3:1 to obtain the target product with a yield of 62% and an HPLC purity of 98.7%.

[0071] 1H 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.

[0072] Example 12 N-(4-(acridin-9-yl)pentyl)-4-methoxybenzenesulfonamide (IV-l)

[0073]

[0074] A mixture of compound (I) N-pentyl-4-methoxybenzenesulfonamide (102.8 mg, 0.4 mmol), compound (II) acridine (35.8 mg, 0.2 mmol), 9-trimethyl-10-methylacridinium perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol), and trifluoroacetic acid (45.6 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL) was added to the mixture. After purging with nitrogen three times, the reaction system was irradiated with blue light at a power of 25 W and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate, and the organic phase was washed with saturated NaCl. The phases were separated, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 4:1 to 2:1 to obtain the target product with a yield of 76% and an HPLC purity of 98.9%.

[0075] 1H 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.

[0076] Example 13 4-Methoxy-N-(2-methyl-4-(2-phenylquinolin-4-yl)pentyl)benzenesulfonamide (IV-m)

[0077]

[0078] A mixture of compound (I) 4-methoxy-N-(2-methylpentyl)benzenesulfonamide (108.4 mg, 0.4 mmol), compound (II) 2-phenylquinoline (41.0 mg, 0.2 mmol), 9-trimethyl-10-methylacridine perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol), and trifluoroacetic acid (45.6 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL) was added to the mixture. After purging with nitrogen three times, the reaction system was irradiated under a 25 W blue light and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with a saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate, and the organic phase was washed with saturated NaCl. The phases were separated, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 4:1 to 2:1 to obtain the target product with a yield of 77% and an HPLC purity of 99.1%.

[0079] 1 H NMR (600MHz, CDCl3) δ8.24–8.21(m,1H),8.19–7.99(m,3H),7.75–7.66(m,4H),7.56– 7.49(m,3H),7.45(td,J=7.1,1.5Hz,1H),6.86–6.82(m,2H),5.25(t,J=6.5Hz,0.67H ),5.14(t,J=6.5Hz,0.33H),3.77–3.75(m,3H),3.73–3.63(m,1H),2.87–2.71(m,2H) ,1.77–1.47(m,3H),1.36–1.30(m,3H),0.95(d,J=6.5Hz,2H),0.83(d,J=6.4Hz,1H). 13 C NMR (151MHz, CDCl3) δ162.74,162.73,154.13,153.70,148.59,148.56,139.95,139.86 ,131.57,131.53,130.67,130.63,129.30,129.26,129.07,129.06,128.87,128.82,12 7.69,127.65,126.24,126.22,126.15,125.84,122.74,122.59,115.73,115.66,114.19,55.56,49.14,49.10,41.51,41.22,31.11,31.08,30.79,22.76,20.92,17.95,17.54.

[0080] Example 14 N-(4-(6-chlorobenzo[d]thiazo-2-yl)-2-ethylhexyl)-4-methoxybenzenesulfonamide (IV-n)

[0081]

[0082] A mixture of compound (I) N-(2-ethylhexyl)-4-methoxybenzenesulfonamide (119.7 mg, 0.4 mmol), compound (II) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), 9-trimethyl-10-methylacridine perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol), and trifluoroacetic acid (45.6 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL) was added to the mixture. After purging with nitrogen three times, the reaction system was irradiated under a 25 W blue light and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with a saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate, and the organic phase was washed with saturated NaCl. The phases were separated, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 4:1 to 2:1 to obtain the target product with a yield of 65% and an HPLC purity of 99.0%.

[0083] 1 H NMR (400MHz, CDCl3) δ8.03(d,J=8.8Hz,0.55H),7.89(d,J=8.8Hz,0.45H),7.82(d,J=2.2Hz,1H),7 .75(dd,J=19.1,8.4Hz,2H),7.44(dd,J=10.8,8.4Hz,1H),6.90(dd,J=19.3,8.4Hz,2H),5.92(br, 0.55H),5.33(br,0.45H),3.84(d,J=6.2Hz,3H),3.08(dt,J=11.4,5.9Hz,1H),2.99–2.69(m,2H), 1.76(dt,J=14.6,7.2Hz,3H),1.58–1.17(m,4H),0.91–0.85(m,3H),0.77(dt,J=26.0,7.2Hz,3H). 13C NMR (101MHz, CDCl3) δ177.25,177.06,162.72,162.60,151.17,151.00,135.83,135 .81,131.59,131.46,130.92,130.76,129.13,129.11,126.93,126.74,123.61,123 .40,121.27,121.17,114.16,114.05,55.60,55.57,46.27,45.36,44.46,44.05,37.77,37.65,37.00,36.24,30.57,29.98,25.02,24.87,11.84,11.21,10.84,10.81.

[0084] Example 15 N-(4-(6-chlorobenzo[d]thiazo-2-yl)-1-phenylpentyl)-4-methoxybenzenesulfonamide (IV-o)

[0085]

[0086] A mixture of compound (I) 4-methoxy-N-(1-phenylpentyl)benzenesulfonamide (133.3 mg, 0.4 mmol), compound (II) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), 9-trimethyl-10-methylacridine perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol), and trifluoroacetic acid (45.6 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL) was added to the mixture. After purging with nitrogen three times, the reaction system was irradiated under a 25 W blue light and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with a saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate, and the organic phase was washed with saturated NaCl. The phases were separated, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 4:1 to 2:1 to obtain the target product with a yield of 49% and an HPLC purity of 99.3%.

[0087] 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.

[0088] Example 16 (2R)-2-((4-methoxyphenyl)sulfonamido)-5-(2-phenylquinoline-4-yl)hexanoate (IV-p)

[0089]

[0090] In a reaction tube equipped with a magnetic stirrer, a mixture of compound (I) (R)-2-((4-methoxyphenyl)sulfonamido)hexanoate methyl ester (126.0 mg, 0.4 mmol), compound (II) 2-phenylquinoline (41.0 mg, 0.2 mmol), 9-trimethylmethyl-10-methylacridine perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol) and trifluoroacetic acid (45.6 mg, 0.4 mmol) was added. The mixture was prepared by adding a mixed solvent of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL), purging with nitrogen three times, irradiating the reaction system under 25 W blue light, and stirring for 24 hours. After the reaction was completed, 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 into layers, dried with anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 4:1 to 2:1 to obtain the target product with a yield of 66% and an HPLC purity of 99.0%.

[0091] 1 H NMR(400MHz, CDCl3)δ8.21(d,J=8.4Hz,1H),8.18–8.13(m,2H),8.04(dd,J=8.2,4.1Hz,1H), 7.71(td,J=7.2,2.0Hz,4H),7.57–7.51(m,3H),7.49–7.42(m,1H),6.90–6.83(m,2H),5.34( dd,J=9.1,3.4Hz,1H),3.92–3.84(m,1H),3.79(s,2H),3.77(s,1H),3.60(h,J=7.5Hz,1H),3 .41(s,1H),3.39(s,2H),1.96–1.70(m,3H),1.66–1.49(m,1H),1.39(dd,J=6.8,3.3Hz,3H). 13C NMR (101MHz, CDCl3) δ172.01,171.96,163.03,163.00,157.21,157.18,153.14,153.07,148. 60,148.55,139.90,139.85,131.02,130.68,130.63,129.39,129.36,129.32,128.86,128.85 ,127.66,127.61,126.25,126.22,126.09,125.98,122.75,122.69,115.55,115.50,114.15,114.12,55.66,55.62,55.60,55.57,52.55,33.18,32.34,32.14,31.21,31.19,21.69,21.21.

[0092] Example 17 N-(2,2-dimethyl-4-(2-phenylquinolin-4-yl)hexyl)-4-methoxybenzenesulfonamide (IV-q)

[0093]

[0094] A mixture of compound (I) N-(2,2-dimethylhexyl)-4-methoxybenzenesulfonamide (119.7 mg, 0.4 mmol), compound (II) 2-phenylquinoline (41.0 mg, 0.2 mmol), 9-trimethylmethyl-10-methylacridine perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol), and trifluoroacetic acid (45.6 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. The mixture was treated with a mixed solvent of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL). After purging with nitrogen three times, the reaction system was irradiated with blue light at a power of 25 W and stirred for 24 hours. After the reaction was completed, 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, the layers were separated, dried with anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 4:1 to 2:1 to obtain the target product with a yield of 89% and an HPLC purity of 99.4%.

[0095] 1H NMR (600MHz, CDCl3) δ8.24–8.21(m,1H),8.18–8.04(m,3H),7.80–7.57(m,4H ),7.56–7.50(m,3H),7.48–7.43(m,1H),6.91–6.82(m,2H),5.16(t,J=6.9Hz, 0.28H),4.99(t,J=7.2Hz,0.72H),3.82–3.77(m,3H),3.60–3.47(m,1H),2.6 8–2.37(m,2H),2.03–1.57(m,3.6H),1.41–1.16(m,1.4H),0.87–0.66(m,8H). 13 C NMR (101MHz, CDCl3) δ162.74,162.65,157.21,156.82,154.45,154.35,148.57,140.05,139.88,1 31.50,131.32,130.76,130.60,129.36,129.32,129.24,129.15,128.91,128.86,127.66,127.62, 126.74,126.35,126.19,126.16,122.94,122.69,116.24,115.48,114.24,55.58,53.50,52.75,45.63,37.37,35.65,34.91,34.31,33.76,33.01,31.34,25.79,25.64,25.07,24.90,21.37,12.01.

[0096] Example 18 N-(4-(6-chlorobenzo[d]thiazolyl-2-yl)butyl)-4-methoxybenzenesulfonamide (IV-r)

[0097]

[0098] A mixture of compound (I) N-n-butyl-4-methoxybenzenesulfonamide (97.2 mg, 0.4 mmol), compound (II) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), 9-trimethyl-10-methylacridine perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol), and trifluoroacetic acid (45.6 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL) was added to the compound. After purging with nitrogen three times, the reaction system was irradiated under a 25 W blue light and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with a saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate, and the organic phase was washed with saturated NaCl. After separation, the phases were dried with anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 4:1 to 2:1 to obtain the target product with a yield of 22% and an HPLC purity of 99.3%.

[0099] 1 H NMR (400MHz, CDCl3) δ7.87(d,J=8.6Hz,1H),7.83–7.72(m,3H),7.41(d,J=8.7Hz,1H),6.94(d,J=7.8Hz,2H),4.78 (br,1H),3.84(s,3H),3.05(t,J=7.2Hz,2H),2.97(t,J=7.0Hz,2H),1.88(p,J=7.3Hz,2H),1.60(p,J=7.3Hz,2H). 13 C NMR (101MHz, CDCl3) δ171.84,162.84,151.57,136.20,131.45,130.80,12 9.18,126.84,123.29,121.15,114.23,55.61,42.68,33.39,28.77,25.94.

[0100] Example 19 N-(4-(6-chlorobenzo[d]thiazolyl)hexyl)-4-methoxybenzenesulfonamide (IV-s)

[0101]

[0102] A mixture of compound (I) N-hexyl-4-methoxybenzenesulfonamide (108.4 mg, 0.4 mmol), compound (II) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), 9-trimethyl-10-methylacridine perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol), and trifluoroacetic acid (45.6 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL) was added to the mixture. After purging with nitrogen three times, the reaction system was irradiated under a 25 W blue light and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with a saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate, and the organic phase was washed with saturated NaCl. The phases were separated, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 4:1 to 2:1 to obtain the target product with a yield of 48% and an HPLC purity of 99.0%.

[0103] 1 H NMR(400MHz, CDCl3)δ7.87(d,J=8.7Hz,0.3H),7.84(d,J=8.7Hz,1H),7.80–7.76(m,1H+0.6H),7 .75–7.70(m,2H+0.3H),7.38(dd,J=8.7,2.1Hz,1H+0.3H),6.95–6.86(m,2H+0.6H),5.09(br,1H) ,4.98(br,0.3H),3.83(s,0.9H),3.82(s,3H),3.19(h,J=7.0Hz,0.3H),3.01–2.93(m,1H),2.89 (t,J=6.8Hz,2H+0.6H),1.82–1.68(m,4H+0.9H),1.54–1.27(m,2H+1.8H),0.85(t,J=7.4Hz,3H). 13C NMR (101MHz, CDCl3) δ178.19,176.81,162.76,151.32,151.22,135.77,135.72,131.49,131.45,130.72,130.65,129.17,129.14,126.74,12 6.72,123.32,121.23,121.21,114.20,114.18,55.60,46.27,42.90,4 2.80,39.16,36.51,32.34,29.33,29.15,27.16,24.07,21.17,11.74.

[0104] Example 20 N-(4-(6-chlorobenzo[d]thiazolyl-2-yl)heptyl)-4-methoxybenzenesulfonamide (IV-t)

[0105]

[0106] A mixture of compound (I) N-n-heptyl-4-methoxybenzenesulfonamide (114.1 mg, 0.4 mmol), compound (II) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), 9-trimethyl-10-methylacridine perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol), and trifluoroacetic acid (45.6 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL) was added to the mixture. After purging with nitrogen three times, the reaction system was irradiated under a 25 W blue light and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with a saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate, and the organic phase was washed with saturated NaCl. The phases were separated, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 4:1 to 2:1 to obtain the target product with a yield of 57% and an HPLC purity of 99.2%.

[0107] 1H NMR(600MHz, CDCl3)δ7.86(d,J=8.7Hz,0.16H),7.82(d,J=8.6Hz,1H),7.79(s,0.16H),7.77(s,1H),7.75–7 .70(m,2H+0.32H),7.38(d,J=8.7Hz,1H+0.16H),6.94–6.91(m,0.32H),6.90–6.87(m,2H),5.08(br,1H),4. 94(br,0.16H),3.83(s,0.48H),3.81(s,3H),3.08–3.02(m,1H),2.99–2.94(m,0.16H),2.93–2.84(m,2H+0. 32H),1.80–1.61(m,4H+0.64H),1.53–1.33(m,2H+0.80H),1.31–1.17(m,2H+0.32H),0.85(t,J=7.5Hz,3H). 13 CNMR(151MHz,CDCl3)δ177.07,176.90,162.77,151.47,151.36,135.84,1 35.81,131.62,131.53,130.67,130.62,129.16,129.13,126.66,126.63, 123.39,123.36,121.20,114.21,114.17,55.58,46.66,44.48,42.90,42. 80,38.45,34.85,32.74,29.27,29.21,27.17,24.16,20.40,13.92,11.79.

[0108] Example 21 N-(4-(6-chlorobenzo[d]thiazo-2-yl)octyl)-4-methoxybenzenesulfonamide (IV-u)

[0109]

[0110] A mixture of compound (I) N-n-octyl-4-methoxybenzenesulfonamide (119.7 mg, 0.4 mmol), compound (II) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), 9-trimethyl-10-methylacridine perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol), and trifluoroacetic acid (45.6 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL) was added to the mixture. After purging with nitrogen three times, the reaction system was irradiated under a 25 W blue light and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with a saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate, and the organic phase was washed with saturated NaCl. The phases were separated, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 4:1 to 2:1 to obtain the target product with a yield of 60% and an HPLC purity of 98.7%.

[0111] 1 H NMR(400MHz, CDCl3)δ7.86(d,J=8.7Hz,0.12H),7.83(d,J=8.7Hz,1H),7.80–7.76(m,1H+0.12H),7.7 5–7.71(m,2H+0.24H),7.41–7.33(m,1H+0.12H),6.93–6.85(m,2H+0.24H),5.09(br,1H),4.94(t,J=6 .1Hz,0.12H),3.83(s,0.36H),3.81(s,3H),3.09–2.98(m,1H+0.12H),2.93–2.82(m,2H+0.24H),1.8 0–1.63(m,4H+0.48H),1.53–1.32(m,2H+0.24H),1.31–1.12(m,4H+0.48H),0.89–0.78(m,3H+0.36H). 13 C NMR (151MHz, CDCl3) δ176.98,162.76,151.31,135.80,131.54,130.68,129.13,126.67, 123.35,121.22,114.17,55.58,44.71,42.91,36.05,32.78,29.34,27.18,22.54,13.86.

[0112] Example 22 N-(3-(1-(6-chlorobenzo[d]thiazo-2-yl)cyclopentyl)propyl)-4-methoxybenzenesulfonamide (IV-v)

[0113]

[0114] A mixture of compound (I) N-(3-cyclopentylpropyl)-4-methoxybenzenesulfonamide (118.9 mg, 0.4 mmol), compound (II) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), 9-trimethylmethyl-10-methylacridine perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol), and trifluoroacetic acid (45.6 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. The mixture was treated with a mixed solvent of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL). After purging with nitrogen three times, the reaction system was irradiated with blue light at a power of 25 W and stirred for 24 hours. After the reaction was completed, 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, the layers were separated, dried with anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 4:1 to 2:1 to obtain the target product with a yield of 69% and an HPLC purity of 98.8%.

[0115] 1 H NMR (400MHz, CDCl3) δ7.87(dd,J=8.7,2.4Hz,1H),7.77(s,1H),7.71(d,J=8.1Hz,2H),7.38(dt,J=7.3,1.9Hz,1H),6.92–6.8 2(m,2H),5.10(t,J=5.9Hz,1H),3.82(s,3H),2.84(q,J=6.0Hz,2H),2.22–2.13(m,2H),1.91–1.65(m,8H),1.47–1.29(m,2H). 13 CNMR(101MHz,CDCl3)δ180.86,162.74,151.42,136.19,131.48,130.58,129.14,1 26.63,123.45,121.05,114.14,55.60,53.31,43.28,39.53,38.17,25.52,24.38.

[0116] Example 23 N-(3-(1-(6-chlorobenzo[d]thiazo-2-yl)cyclohexyl)propyl)-4-methoxybenzenesulfonamide (IV-w)

[0117]

[0118] A mixture of compound (I) N-(3-cyclohexylpropyl)-4-methoxybenzenesulfonamide (124.5 mg, 0.4 mmol), compound (II) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), 9-trimethyl-10-methylacridine perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol), and trifluoroacetic acid (45.6 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. The mixture was treated with a mixed solvent of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL). After purging with nitrogen three times, the reaction system was irradiated with blue light at a power of 25 W and stirred for 24 hours. After the reaction was completed, 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, the layers were separated, dried with anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 4:1 to 2:1 to obtain the target product with a yield of 74% and an HPLC purity of 98.9%.

[0119] 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). 13 C 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.

[0120] Example 24 N-(6-chloro-4-(6-chlorobenzo[d]thiazo-2-yl)hexyl)-4-methoxybenzenesulfonamide (IV-x)

[0121]

[0122] A mixture of compound (I) N-(6-chlorohexyl)-4-methoxybenzenesulfonamide (122.0 mg, 0.4 mmol), compound (II) 6-chlorobenzothiazole (33.8 mg, 0.2 mmol), 9-trimethyl-10-methylacridine perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol), and trifluoroacetic acid (45.6 mg, 0.4 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL) was added to the mixture. After purging with nitrogen three times, the reaction system was irradiated under a 25 W blue light and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with a saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate, and the organic phase was washed with saturated NaCl. After separation, the phases were dried with anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 4:1 to 2:1 to obtain the target product with a yield of 38% and an HPLC purity of 98.6%.

[0123] 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(br,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). 13 C NMR (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.

[0124] Example 25 6-((4-methoxyphenyl)sulfonamido)-3-(2-phenylquinoline-4-yl)hexyl 2-(4-isobutylphenyl)propionic acid (IV-y)

[0125]

[0126] In a reaction tube equipped with a magnetic stirrer, compound (I) 6-((4-methoxyphenyl)sulfonamide)hexyl 2-(4-isobutylphenyl)propionic acid (190.1 mg, 0.4 mmol), compound (II) 2-phenylquinoline (41.0 mg, 0.2 mmol), 9-trimethylmethyl-10-methylacridine perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol), and trifluoroacetic acid (45.6 mg, 0.4 mmol) were added. A mixture of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL) was added to the mixture. After purging with nitrogen three times, the reaction system was irradiated under a 25 W blue light and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with a saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate, the organic phase was washed with saturated NaCl, separated into layers, dried with anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using a 2:1 volume ratio of petroleum ether / ethyl acetate to obtain the target product with a yield of 53% and an HPLC purity of 99.4%.

[0127] 1 H NMR(400MHz, CDCl3)δ8.21(d,J=8.4Hz,1H),8.13–8.08(m,2H),7.80(dd,J=25.8,8.5Hz,1H),7.7 5–7.60(m,4H),7.56–7.37(m,4H),7.18–7.05(m,4H),6.88–6.83(m,2H),4.62–4.52(m,1H),4.15– 4.01(m,1H),3.85–3.73(m,4H),3.64–3.39(m,2H),2.80(p,J=7.1Hz,2H),2.43(d,J=7.2Hz,2H),2 .11–1.98(m,2H),1.88–1.67(m,3H),1.41(d,J=7.1Hz,3H),1.36–1.15(m,2H),0.90–0.84(m,6H). 13C NMR (101MHz, CDCl3) δ174.55,162.78,157.01,151.40,148.50,140.67,140.58,139.59,137. 94,137.57,131.38,131.37,130.62,129.53,129.42,129.35,129.06,128.88,127.64,127.17 ,127.14,126.65,126.39,126.33,122.61,115.88,114.19,62.60,62.35,55.58,45.18,45.02,45.00,43.00,42.97,35.21,35.12,32.80,32.77,30.19,27.34,22.41,22.38,18.56,18.23.

[0128] Example 26 6-((4-methoxyphenyl)sulfonamido)-3-(2-phenylquinoline-4-yl)hexyl-2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropionate (IV-z)

[0129]

[0130] Compound (I) 2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropionic acid 6-((4-methoxyphenyl)sulfonamido)hexyl ester (234.9 mg, 0.4 mmol), compound (II) 2-phenylquinoline (41.0 mg, 0.2 mmol), 9-trimethylmethyl-10-methylacridine perchlorate (1.6 mg, 0.004 mmol), chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) (4.5 mg, 0.01 mmol), and trifluoroacetic acid (45.6 mg) were added to a reaction tube equipped with a magnetic stirrer. A mixture of g (0.4 mmol) was added to the mixture, along with a mixed solvent of acetonitrile and hexafluoroisopropanol (1.5 mL / 0.5 mL). After purging with nitrogen three times, the reaction system was irradiated under a 25 W blue light and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with a saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate, and the organic phase was washed with saturated NaCl. The phases were separated, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using a 2:1 volume ratio of petroleum ether / ethyl acetate to obtain the target product with a yield of 66% and an HPLC purity of 99.3%.

[0131] 1H NMR (400MHz, CDCl3) δ8.17(d,J=8.4Hz,1H),8.11–8.07(m,2H),7.83(d,J=7.2Hz,1 H),7.74–7.62(m,8H),7.53–7.40(m,6H),6.89–6.84(m,4H),5.14(t,J=6.3Hz,1H) ,4.31–4.23(m,1H),3.83–3.78(m,4H),3.44–3.19(m,1H),2.75(q,J=6.7Hz,2H),2 .07–1.98(m,2H),1.83–1.69(m,2H),1.66(s,3H),1.60(s,3H),1.12–1.03(m,2H). 13 C NMR (101MHz, CDCl3) δ194.67,173.49,162.69,159.79,157.05,151.04,148.54 ,139.53,138.74,135.99,132.14,131.56,131.36,130.68,130.29,129.52,129 .44,129.09,128.88,128.63,127.58,126.63,126.23,122.64,116.80,115.69,114.12,79.35,63.46,55.57,43.09,35.19,34.62,32.85,27.30,26.65,24.07.

[0132] Example 27 N-(4-bromopentyl)-4-methoxybenzenesulfonamide (Va)

[0133]

[0134] A mixture of compound (I) N-pentyl-4-methoxybenzenesulfonamide (51.4 mg, 0.2 mmol), compound (III) N-bromosuccinimide (71.2 mg, 0.4 mmol), and 9-trimethylmethyl-10-methylacridine perchlorate (2.4 mg, 0.006 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.8 mL / 0.2 mL) was added to the mixture. After purging with nitrogen three times, the reaction system was irradiated under a blue light with a power of 25 W and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with saturated Na2S2O3 solution. The mixture was extracted with ethyl acetate, and the organic phase was washed with saturated NaCl. After separation, the phases were dried with anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 6:1 to 4:1 to obtain the target product with a yield of 53% and an HPLC purity of 98.9%.

[0135] 1 H NMR(400MHz, CDCl3)δ7.82–7.77(m,2H+0.22H),7.00–6.95(m,2H+0.22H),4.88(br,0.11H),4.80(br,1H),4.09–4.00(m,1H),3.86(s,3H+ 0.33H),3.02(q,J=6.3Hz,0.22H),2.94(t,J=7.6Hz,2H),2.48(s,0.33H),2.34–2.28(m,0.22H),1.92–1.83(m,0.22H),1.82–1.54(m,7H). 13 C NMR (101MHz, CDCl3) δ162.97,162.91,131.32,131.27,129.23,129.21,114.37,114 .32,67.42,55.67,50.80,49.61,42.44,42.20,41.41,37.78,28.38,27.81,26.48.

[0136] Example 28 N-(4-fluoropentyl)-4-methoxybenzenesulfonamide (Vb)

[0137]

[0138] A mixture of compound (I) N-pentyl-4-methoxybenzenesulfonamide (51.4 mg, 0.2 mmol), compound (III) Selectfluor (141.7 mg, 0.4 mmol), and 9-trimethylmethyl-10-methylacridine perchlorate (2.4 mg, 0.006 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.8 mL / 0.2 mL) was added to the mixture. After purging with nitrogen three times, the reaction system was irradiated under a blue light with a power of 25 W and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with saturated NaCl solution and washed. The mixture was extracted with ethyl acetate, separated into layers, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 6:1 to 4:1 to obtain the target product with a yield of 66% and an HPLC purity of 99.1%.

[0139] 1 H NMR (400MHz, CDCl3) δ7.82–7.75(m,2H+2H),7.01–6.93(m,2H+2H),5.01(t,J=6.4Hz,1H),4.93(t,J=6.4Hz,1H),4.69–4. 46(m,1H),3.85(s,3H+3H),2.98–2.89(m,2H+2H),1.91–1.76(m,2H),1.70–1.47(m,7H+2H),1.25(dd,J=24.0,6.2Hz,3H). 19 F NMR(376MHz, CDCl3)δ-91.06,-173.24. 13 C NMR (101MHz, CDCl3) δ162.91,162.87,131.38,131.32,129.17,123.93(t,J F-C =238.1Hz),114.31,114.28,90.45(d,J F-C =165.1Hz),55.64,42.87,42.62,34.86(t,J F-C =25.9Hz), 33.72(d,J F-C =21.3Hz), 25.28(d,J F-C =4.0Hz), 23.41(t,J F-C =27.9Hz), 22.92(t,J F-C =4.6Hz), 20.94(d,J F-C =22.4Hz).

[0140] Example 29 N-(6,6-dicyano-4-methyl-5-phenylhexyl)-4-methoxybenzenesulfonamide (Vc)

[0141]

[0142] A mixture of compound (I) N-pentyl-4-methoxybenzenesulfonamide (51.4 mg, 0.2 mmol), compound (III) 2-benzylmalonium (93.7 mg, 0.6 mmol), and 9-trimethylmethyl-10-methylacridine perchlorate (2.4 mg, 0.006 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.8 mL / 0.2 mL) was added to the mixture. After purging with nitrogen three times, the reaction system was irradiated under blue light with a power of 25 W and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with saturated NaCl solution and washed. The mixture was extracted with ethyl acetate, separated into layers, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 5:1 to 4:1 to obtain the target product with a yield of 45% and an HPLC purity of 99.0%.

[0143] 1 H NMR(400MHz, CDCl3)δ7.83–7.68(m,2H),7.44–7.39(m,3H),7.31–7.27(m,2H) ,7.01–6.96(m,2H),4.56(t,J=5.4Hz,1H),4.21(d,J=5.8Hz,1H),3.89(s,3H) ,2.90(dd,J=9.6,5.8Hz,1H),2.79(hept,J=6.1Hz,2H),2.24–2.13(m,1H),1. 58–1.44(m,1H),1.40–1.21(m,2H),1.08(d,J=6.6Hz,3H),1.00–0.91(m,1H). 13 C NMR (101MHz, CDCl3) δ162.92,136.22,131.32,129.25,129.16,128.94,128.26,1 14.31,112.15,111.85,55.66,52.04,42.95,34.50,30.21,27.72,26.58,17.42.

[0144] Example 30: Ethyl 2-cyano-7-((4-methoxyphenyl)sulfonamido)-4-methyl-3-phenylheptanoate (Vd)

[0145]

[0146] A mixture of compound (I) N-pentyl-4-methoxybenzenesulfonamide (51.4 mg, 0.2 mmol), compound (III) ethyl 2-cyano-3-phenylacrylate (120.7 mg, 0.6 mmol), and 9-trimethylmethyl-10-methylacridine perchlorate (2.4 mg, 0.006 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.8 mL / 0.2 mL) was added to the mixture. After purging with nitrogen three times, the reaction system was irradiated under blue light with a power of 25 W and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with saturated NaCl solution and washed. The mixture was extracted with ethyl acetate, separated into layers, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 5:1 to 4:1 to obtain the target product with a yield of 41% and an HPLC purity of 99.0%.

[0147] 1 H NMR (400MHz, CDCl3) δ7.87–7.79(m,1H),7.79–7.70(m,1H),7.36–7.10(m,5H),7.06–6.94(m,2H),4.95–4.75(m,0.5H),4.70–4.45(m,0.5 H),4.17–3.80(m,6H),3.30–2.87(m,2H),2.87–2.65(m,1H),2.24–2.02(m,1H),1.71–1.43(m,2H),1.41–1.11(m,2H),1.10–0.66(m,6H). 13C NMR (101MHz, CDCl3) δ165.58,165.54,165.36,162.89,162.85,162.83,138.61,137.77,137.73,137.01,131.54,131.50,131.44,129.24,12 9.20,129.17,129.14,128.73,128.68,128.58,128.56,128.47,128.4 3,128.24,128.10,127.92,127.83,127.79,116.12,116.06,115.75,11 5.47,114.32,114.28,114.26,114.24,62.80,62.74,62.54,55.64,55.63,51.49,51.27,51.03,50.49,43.25,43.12,43.07,42.43,42.36,41.90,41.75,35.02,34.80,34.75,31.67,30.94,30.80,29.92,27.15,26.89,26.50,17.48,17.27,17.03,15.41,13.74,13.72,13.69,13.67.

[0148] Example 31: Diethyl 2-(6-((4-methoxyphenyl)sulfonamido)-3-methylhexyl-2-yl)malonate (Ve)

[0149]

[0150] A mixture of compound (I) N-pentyl-4-methoxybenzenesulfonamide (51.4 mg, 0.2 mmol), compound (III) diethyl ethylene malonate (111.7 mg, 0.6 mmol), and 9-trimethylmethyl-10-methylacridine perchlorate (2.4 mg, 0.006 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.8 mL / 0.2 mL) was added to the mixture. After purging with nitrogen three times, the reaction system was irradiated under a blue light with a power of 25 W and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with saturated NaCl solution and washed. The mixture was extracted with ethyl acetate, separated into layers, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 5:1 to 4:1 to obtain the target product with a yield of 47% and an HPLC purity of 99.3%.

[0151] 1H NMR(400MHz, CDCl3) δ7.79(dq,J=8.2,3.0Hz,2H),7.01–6.93(m,2H),4.72(t,J=6.2Hz,0.52H),4.60(t,J=6.3Hz,0.48H),4.20–4.1 2(m,4H),3.86(s,3H),3.26(dd,J=13.5,10.1Hz,1H),2.96–2.79(m,2H),2.31–2.14(m,1H),1.56–1.13(m,11H),0.88–0.70(m,6H). 13 C NMR (101MHz, CDCl3) δ169.19,168.89,168.83,168.78,162.80,162.79,131.64,131.58,129.20,114.22,114.20,61.39,61.28,61. 22,56.63,56.10,55.61,43.28,43.11,38.47,36.29,34.32,33.77,32.14,27.61,27.49,27.36,17.85,14.10,13.67,12.36,11.03.

[0152] Example 32: Di-tert-butyl 1-(5-((4-methoxyphenyl)sulfonamido)pent-2-yl)hydrazine-1,2-dicarboxylic acid (Vf)

[0153]

[0154] A mixture of compound (I) N-pentyl-4-methoxybenzenesulfonamide (51.4 mg, 0.2 mmol), compound (III) di-tert-butyl azodicarbonate (138.1 mg, 0.6 mmol), and 9-trimethylmethyl-10-methylacridine perchlorate (2.4 mg, 0.006 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.8 mL / 0.2 mL) was added to the mixture. After purging with nitrogen three times, the reaction system was irradiated under a blue light with a power of 25 W and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with saturated NaCl solution and washed. The mixture was extracted with ethyl acetate, separated into layers, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 5:1 to 4:1 to obtain the target product with a yield of 52% and an HPLC purity of 99.2%.

[0155] 1H NMR(400MHz, CDCl3)δ7.83–7.70(m,2H),6.94(d,J=8.5Hz,2H),6.10(br,1H),5.28–4.85(m,1H), 4.25–2.96(m,1H),3.84(s,3H),2.90(q,J=5.8Hz,2H),1.68–1.36(m,22H),1.04(d,J=6.7Hz,3H). 13 C NMR (101MHz, CDCl3) δ162.64,156.53,155.07,131.71,129.18,114.10,81.45,81.09,55.58,51.91,42.77,31.08,28.25,28.23,25.88,18.35.

[0156] Example 33 N-(4-azidopentyl)-4-methoxybenzenesulfonamide (Vg)

[0157]

[0158] A mixture of compound (I) N-pentyl-4-methoxybenzenesulfonamide (51.4 mg, 0.2 mmol), compound (III) p-acetaminobenzenesulfonyl azide (144.1 mg, 0.6 mmol), and 9-trimethylmethyl-10-methylacridine perchlorate (2.4 mg, 0.006 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.8 mL / 0.2 mL) was added to the mixture. After purging with nitrogen three times, the reaction system was irradiated under blue light with a power of 25 W and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with saturated NaCl solution and washed. The mixture was extracted with ethyl acetate, separated into layers, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 5:1 to 3:1 to obtain the target product with a yield of 23% and an HPLC purity of 99.1%.

[0159] 1 H NMR (400MHz, CDCl3) δ7.85–7.78(m,2H),7.04–6.97(m,2H),4.73(t,J=6.2Hz,1H),3.89(s, 3H), 3.41 (h, J=6.5Hz, 1H), 2.95 (q, J=6.5Hz, 2H), 1.65–1.40 (m, 4H), 1.24 (d, J=6.5Hz, 3H). 13C NMR (101MHz, CDCl3) δ162.93,131.49,129.18,114.29,57.36,55.61,42.78,33.08,26.16,19.34.

[0160] Example 34 N-(4-cyano-4-methylpentyl)-4-methoxybenzenesulfonamide (Vh)

[0161]

[0162] A mixture of compound (I) 4-methoxy-N-(4-methylpentyl)benzenesulfonamide (54.2 mg, 0.2 mmol), compound (III) 4-toluenesulfonyl cyanide (108.7 mg, 0.6 mmol), and 9-trimethylmethyl-10-methylacridine perchlorate (2.4 mg, 0.006 mmol) was added to a reaction tube equipped with a magnetic stirrer. A mixed solvent of acetonitrile and hexafluoroisopropanol (1.8 mL / 0.2 mL) was added to the mixture. After purging with nitrogen three times, the reaction system was irradiated under a blue light with a power of 25 W and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with saturated NaCl solution and washed. The mixture was extracted with ethyl acetate, separated into layers, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 3:1 to 2:1 to obtain the target product with a yield of 76% and an HPLC purity of 99.4%.

[0163] 1 H NMR (500MHz, CDCl3) δ7.64–7.60(m,2H),7.08–7.04(m,2H),5.03(t,J=5.8Hz,1H),3.82(s,3 H),2.69(dt,J=5.7,4.4Hz,2H),1.62–1.58(m,2H),1.52(td,J=5.7,0.8Hz,2H),1.37(s,6H). 13 C NMR (125MHz, CDCl3) δ163.62,131.81,128.31,124.89,113.51,55.35,43.51,41.77,32.61,26.54,24.32.

[0164] Example 35 4-Methoxy-N-(pentyl-4-d)benzenesulfonamide (Vi)

[0165]

[0166] A mixture of compound (I) N-pentyl-4-methoxybenzenesulfonamide (51.4 mg, 0.2 mmol), compound (III) deuterium water (0.2 mL), 9-mesinetrilyl-10-methylacridine perchlorate (2.4 mg, 0.006 mmol), and diphenyl disulfide (8.7 mg, 0.04 mmol) was added to a reaction tube equipped with a magnetic stirrer. Acetonitrile (1.8 mL) was added as the reaction solvent. After purging with nitrogen three times, the reaction system was irradiated under a blue light with a power of 25 W and stirred for 24 hours. After the reaction was completed, the reaction solution was quenched with saturated NaCl solution and washed. The mixture was extracted with ethyl acetate, separated into layers, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column using petroleum ether / ethyl acetate at a volume ratio of 5:1-4:1 to obtain the target product with a yield of 80% and an HPLC purity of 85.7%.

[0167] 1 H NMR (400MHz, CDCl3) δ7.81–7.77(m,2H),6.98–6.92(m,2H),5.00(t,J=6.2Hz,1H),3.83(s,3H) ,2.86(q,J=6.8Hz,2H),1.42(tt,J=8.0,6.6Hz,2H),1.24–1.14(m,3.15H),0.84–0.76(m,3H). 13 C NMR (101MHz, CDCl3) δ162.75,131.53,129.19,114.19,55.61,43.16,29.09(t,J D-C =2.5Hz), 28.55(t,J D-C =10.6Hz), 21.73(t,J D-C =19.2Hz), 13.76(t,J) D-C =11.1Hz).

[0168] Example 35 Antitumor Activity Test

[0169] The effects of the corresponding compounds in Examples 1, 2, 4, 12, and 26 on the proliferation of MCF-7 cells were investigated:

[0170] Cell viability was determined using the MTT assay. MCF-7 cell culture: MCF-7 cells were seeded in DMEM medium containing a mixture of 10% FBS and 1% penicillin, 10% serum, 1% Glutamx, 1% Sodium Pyruvate 100mM solution, and 1% Non-essential Amino Acids, and cultured in a 37°C incubator containing 5% CO2.

[0171] MCF-7 cells in logarithmic growth phase were seeded into 96-well plates (100 μL, 8 × 10⁶ cells / well). 4 Cells were incubated at 37°C for 24 h with 5% CO2. Subsequently, MCF-7 cells were treated with 40 μL of different compounds for 48 h each (three replicates per concentration), with the untreated group serving as a blank control. Then, 10 μL of 5 mg / mL MTT solution was added to each well, and the cells were incubated at 37°C for 4 h with 5% CO2. After discarding the supernatant, 100 μL of DMSO was added to each well, and the cells were shaken at 500 rpm for 10 min. The absorbance was then measured at 492 nm. The formula for cell viability detection is:

[0172] Cell viability (%) = (average value of OD drug-treated group / average value of OD control group) × 100%.

[0173] Experimental Results: Compared with the blank control group, the proliferation changes of MCF-7 cells in the experimental groups treated with different compounds for 48 hours are shown in the table below:

[0174]

[0175] The above test results indicate that at a concentration of 40 μM, compound IV-z has a certain inhibitory effect on MCF-7 tumor cells, and its structure can be further modified or altered to further enhance its anti-tumor activity.

[0176] Example 36: Application of compound Vh in drug synthesis

[0177] The compound Vh corresponding to Example 34 can be used as a synthetic intermediate for the drug gemfibrozil. The specific synthetic route is shown below:

[0178]

[0179] The above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention.

Claims

1. A photocatalytic inert C(sp) 3 A method for synthesizing a series of functionalized H-bonds, characterized in that... The N-long-chain alkyl sulfonamide of formula (I), the nitrogen heterocycle of formula (II), or the functionalized reagent of formula (III) was added to the reaction medium. The reaction was carried out under photocatalytic reaction system with irradiation by a light source and stirring at room temperature. After the reaction was completed, the reaction solution was post-treated to obtain the target compound, formula (IV), representing a long-range inert C(sp) group. 3 )-H heteroarylated products or long-range inert C(sp) as shown in formula (V) 3 The reaction equations for the )-H series functionalized products are as follows: ； The functionalizing reagent in formula (III) is selected from N-bromosuccinimide, fluorinated reagent, 2-benzylmalonium, ethyl 2-cyano-3-phenylacrylate, diethyl ethylene malonate, di-tert-butyl azodicarbonate, p-acetaminobenzenesulfonyl azide, 4-toluenesulfonyl cyanide, or deuterium water, respectively corresponding to the long-range C(sp) shown in formula (V). 3 )-H brominated, fluorinated, alkylated, aminationated, azidated, cyaninated, and deuterated target products; The photocatalyst in the photocatalytic system is 9-trimethyl-10-methylacridinium perchlorate; The N-long-chain alkyl sulfonamide of formula (I) reacts with the nitrogen heterocycle of formula (II) to prepare the long-range inert C(sp) of formula (IV). 3 In the )-H heteroarylation product, its photocatalytic system also includes a co-catalyst and an acidic additive. The co-catalyst is chlorobis(dimethyloxime)[4-(dimethylamino)pyridine]cobalt(III), and the acidic additive is concentrated hydrochloric acid, trifluoroacetic acid, or trifluoromethanesulfonic acid. When the functionalizing agent shown in formula (III) is deuterium water, the N-long-chain alkyl sulfonamide shown in formula (I) reacts with the functionalizing agent shown in formula (III) to prepare a long-range C(sp) 3 In the )-H deuterated product, the photocatalytic system also includes the co-catalyst diphenyl disulfide, and the amount of the co-catalyst diphenyl disulfide is 10~25% of the molar amount of the N-long-chain alkyl sulfonamide shown in formula (I); Compounds of formula (IV) are selected from one of the following compounds: 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 ； The compound of formula (V) is selected from one of the following compounds: 、 、 、 、 、 、 、 、 。 2. The photocatalytic inert C(sp) according to claim 1 3 A method for synthesizing a series of functionalized H-bonds, characterized in that... The amount of the photocatalyst used is 0.5 to 3% of the molar amount of the N-long-chain alkyl sulfonamide described in formula (I).

3. A photocatalytic inert C(sp) according to claim 2 3 A method for synthesizing a series of functionalized H-bonds, characterized in that... The amount of the photocatalyst used is 1 to 3% of the molar amount of the N-long-chain alkyl sulfonamide described in formula (I).

4. The photocatalytic inert C(sp) according to claim 1 3 A method for synthesizing a series of functionalized H-bonds, characterized in that, The amount of chlorobis(dimethylglyoxime)[4-(dimethylamino)pyridine]cobalt(III) is 2-5% of the molar amount of the N-long-chain alkyl sulfonamide described in formula (I); The amount of the co-catalyst diphenyl disulfide is 20% of the molar amount of the N-long-chain alkyl sulfonamide described in formula (I).

5. A photocatalytic inert C(sp) according to claim 1 3 A method for synthesizing a series of functionalized H-bonds, characterized in that, The acidic additive is trifluoroacetic acid; the molar ratio of the acidic additive to the N-long-chain alkyl sulfonamide described in formula (I) is 1:0.8~1.

2.

6. A photocatalytic inert C(sp) according to claim 1 3 A method for synthesizing a series of functionalized H-bonds, characterized in that... The light source is blue, white, or violet light; the illumination power is 15~50W.

7. A photocatalytic inert C(sp) according to claim 6 3 A method for synthesizing a series of functionalized H-bonds, characterized in that... The light source is blue light; the illumination power is 20~25W.

8. A photocatalytic inert C(sp) according to claim 1 3 A method for synthesizing a series of functionalized H-bonds, characterized in that... The reaction medium is one or any combination of acetonitrile, hexafluoroisopropanol, dichloromethane, dimethyl sulfoxide, or 1,2-dichloroethane.

9. A photocatalytic inert C(sp) according to claim 8 3 A method for synthesizing a series of functionalized H-bonds, characterized in that... The reaction medium is a mixed solvent consisting of acetonitrile and hexafluoroisopropanol in a volume ratio of 3 to 9:

1.

10. A photocatalytic inert C(sp) according to claim 1 3 A method for synthesizing a series of functionalized H-bonds, characterized in that... The N-long-chain alkyl sulfonamide described in formula (I) is dispersed at a concentration of 0.1-0.4 mol / L in the reaction medium.

11. A photocatalytic inert C(sp) according to claim 1 3 A method for synthesizing a series of functionalized H-bonds, characterized in that... In the preparation of long-range C(sp) 3 In the reaction of the )-H heteroarylation product, the molar ratio of the N-long-chain alkyl sulfonamide of formula (I) to the nitrogen heterocycle of formula (II) is 1.5-3:1; In the preparation of long-range C(sp) 3 In the reaction of the )-H functionalized product, when the functionalizing agent in formula (III) is selected from N-bromosuccinimide, fluorinated reagent, 2-benzylmalonium, ethyl 2-cyano-3-phenylacrylate, diethyl ethylene malonate, di-tert-butyl azodicarbonate, p-acetaminobenzenesulfonyl azide, or 4-toluenesulfonyl cyanide, the molar ratio of the N-long-chain alkyl sulfonamide in formula (I) to the functionalizing agent in formula (III) is 1:2.0-3.0; when the functionalizing agent in formula (III) is selected from deuterium water, the feed ratio of the N-long-chain alkyl sulfonamide in formula (I) to deuterium water is 0.8~1.2 mol:1 L.

12. A photocatalytic inert C(sp) according to claim 11 3 A method for synthesizing a series of functionalized H-bonds, characterized in that... In the preparation of long-range C(sp) 3 In the reaction of the )-H heteroarylation product, the molar ratio of the N-long-chain alkyl sulfonamide of formula (I) to the nitrogen heterocycle of formula (II) is 2-2.2:

1.

13. A photocatalytic inert C(sp) according to claim 1 3 A method for synthesizing a series of functionalized H-bonds, characterized in that... Preparation of remote C(sp) 3 The post-processing of the reaction of the )-H heteroarylation product was as follows: the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, then extracted with ethyl acetate, the organic phase was washed with saturated NaCl, the layers were separated, the combined organic layers were dried with anhydrous Na2SO4 and concentrated under reduced pressure to obtain the crude product, the crude product was purified by column chromatography to obtain the long-range C(sp) of the target compound of formula (IV). 3 )-H heteroarylated products; Preparation of remote C(sp) 3 The post-processing of the reaction of the )-H functionalized product is as follows: quench the reaction with saturated Na2S2O3 or saturated NaCl solution and wash, then extract with ethyl acetate, combine the organic layers, dry with anhydrous Na2SO4 and concentrate under reduced pressure to obtain the crude product, and purify the crude product by column chromatography to obtain the remote inert C(sp) of the target compound formula (V). 3 )-H series functionalized products.

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