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CN108976198A - A kind of synthetic method of 3- (4- pyridine) Benzazole compounds - Google Patents

A kind of synthetic method of 3- (4- pyridine) Benzazole compounds Download PDF

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CN108976198A
CN108976198A CN201811073559.1A CN201811073559A CN108976198A CN 108976198 A CN108976198 A CN 108976198A CN 201811073559 A CN201811073559 A CN 201811073559A CN 108976198 A CN108976198 A CN 108976198A
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pyridine
compound
ethyl acetate
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CN108976198B (en
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高庆贺
刘兴霞
原焕
王亚坤
仝培源
申昊天
张志昂
张伟荣
张积霞
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Xinxiang Medical University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings

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  • Organic Chemistry (AREA)
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Abstract

本发明公开了一种3‑(4‑吡啶)吲哚类化合物的合成方法，属于有机合成技术领域。本发明的技术方案要点为：一种3‑(4‑吡啶)吲哚类化合物的合成方法，具体步骤为：将醋酸肟酯类化合物和3‑甲酰基吲哚或其衍生物溶于溶剂中，然后加入催化剂和含氮有机碱，在密封管中于100‑130℃反应制得3‑(4‑吡啶)吲哚类化合物。本发明合成过程简单高效，通过无过渡金属催化的一锅串联反应一步直接制得3‑(4‑吡啶)吲哚类化合物，避免了由于多步反应中多种试剂的使用以及对各步反应中间体的纯化处理等引起的资源浪费和环境污染，原料易于制备，反应条件温和，底物适用范围广。The invention discloses a method for synthesizing 3-(4-pyridine) indole compounds, belonging to the technical field of organic synthesis. The main points of the technical scheme of the present invention are: a kind of synthetic method of 3-(4-pyridine) indole compound, concrete steps are: acetic acid oxime ester compound and 3-formyl indole or derivative thereof are dissolved in solvent , and then add a catalyst and a nitrogen-containing organic base, and react in a sealed tube at 100-130° C. to prepare 3-(4-pyridine) indole compounds. The synthesis process of the present invention is simple and efficient, and the 3-(4-pyridine) indole compound is directly prepared in one step through a one-pot series reaction without transition metal catalysis, which avoids the use of multiple reagents in the multi-step reaction and the need for each step of the reaction Waste of resources and environmental pollution caused by the purification of intermediates, easy preparation of raw materials, mild reaction conditions, wide range of substrates.

Description

一种3-(4-吡啶)吲哚类化合物的合成方法A kind of synthetic method of 3-(4-pyridine) indole compound

技术领域technical field

本发明属于有机合成技术领域，具体涉及一种3-(4-吡啶)吲哚类化合物的合成方法。The invention belongs to the technical field of organic synthesis, and in particular relates to a synthesis method of 3-(4-pyridine) indole compounds.

背景技术Background technique

研究表明，3-(4-吡啶)吲哚衍生物具有显著的生物活性，是潜在的肌苷一磷酸脱氢酶、Rho-激酶抑制剂和抗恶性细胞增生治疗药物，在生物和医药等领域具有重要的应用价值。而目前相关文献中报道的3-(4-吡啶)吲哚类化合物的合成方法主要是通过钯催化的Suzuki偶联反应、金属催化炔烃环加成反应以及反应制得的。这些文献方法具有使用昂贵的催化剂、底物适用范围窄、反应条件苛刻和产率低等缺点，这在很大程度上限制了该类合成方法在实际生产中的应用。因此，鉴于3-(4-吡啶)吲哚类化合物的重要性和现有合成方法的不足，发展简捷、高效的此类化合物的合成方法非常必要。Studies have shown that 3-(4-pyridine) indole derivatives have significant biological activity, and are potential inosine monophosphate dehydrogenase, Rho-kinase inhibitors and anti-malignant cell proliferation therapeutic drugs, in the fields of biology and medicine It has important application value. And the synthetic method of 3-(4-pyridine) indole compounds reported in relevant literature at present is mainly by Suzuki coupling reaction catalyzed by palladium, metal-catalyzed alkyne cycloaddition reaction and produced by the reaction. These literature methods have disadvantages such as the use of expensive catalysts, narrow substrate scope, harsh reaction conditions, and low yields, which largely limit the application of this type of synthetic method in actual production. Therefore, in view of the importance of 3-(4-pyridine)indole compounds and the deficiency of existing synthetic methods, it is necessary to develop simple and efficient synthetic methods for such compounds.

发明内容Contents of the invention

本发明解决的技术问题是提供了一种起始原料简单易制备、底物适用范围广、区域选择性高、反应条件温和且操作简单的3-(4-吡啶)吲哚类化合物的合成方法。The technical problem solved by the present invention is to provide a synthetic method of 3-(4-pyridine)indole compounds with simple and easy preparation of starting materials, wide application range of substrates, high regioselectivity, mild reaction conditions and simple operation .

本发明为解决上述技术问题采用如下技术方案，一种3-(4-吡啶)吲哚类化合物的合成方法，其特征在于具体步骤为：将醋酸肟酯类化合物1和3-甲酰基吲哚类化合物2溶于溶剂中，然后加入催化剂和含氮有机碱，在密封管中于100-130℃反应制得目标产物3-(4-吡啶)吲哚类化合物3，该合成方法中的反应方程式为：The present invention adopts following technical scheme for solving above-mentioned technical problem, a kind of synthetic method of 3-(4-pyridine) indole compound is characterized in that concrete steps are: the acetic acid oxime ester compound 1 and 3-formyl indole Compound 2 is dissolved in a solvent, then catalyst and nitrogen-containing organic base are added, and the target product 3-(4-pyridine) indole compound 3 is obtained by reacting in a sealed tube at 100-130°C. The reaction in this synthetic method The equation is:

其中R1为苯基、取代苯基、2-萘基或噻吩基，该取代苯基为3,4-亚甲二氧基苯基、3,4-二氯基苯基或一元取代苯基，一元取代苯基苯环上的取代基为甲基、甲氧基、硝基、氯或溴，R2为氢、甲基、甲氧基、甲氧苄基、氟、氯、甲酯基或硝基，R3为氢或甲基，溶剂为甲苯、氯苯、乙腈、1,4-二氧六环、四氢呋喃(THF)或N,N-二甲基甲酰胺(DMF)，催化剂为碘单质、N-碘代丁二酰亚胺或碘化铵，含氮有机碱为三乙胺、二乙胺、吡啶、1,4-二氮杂二环[2.2.2]辛烷(DABCO)、1,8-二氮杂二环十一碳-7-烯(DBU)或喹啉。Wherein R is phenyl, substituted phenyl, 2 -naphthyl or thienyl, and the substituted phenyl is 3,4-methylenedioxyphenyl, 3,4-dichlorophenyl or monosubstituted phenyl , the substituent on the benzene ring of monosubstituted phenyl is methyl, methoxy, nitro, chlorine or bromine, and R2 is hydrogen , methyl, methoxy, methoxybenzyl, fluorine, chlorine, methylcarboxylate Or nitro, R 3 is hydrogen or methyl, the solvent is toluene, chlorobenzene, acetonitrile, 1,4-dioxane, tetrahydrofuran (THF) or N,N-dimethylformamide (DMF), and the catalyst is Iodine element, N-iodosuccinimide or ammonium iodide, nitrogen-containing organic bases are triethylamine, diethylamine, pyridine, 1,4-diazabicyclo[2.2.2]octane (DABCO ), 1,8-diazabicycloundec-7-ene (DBU) or quinoline.

进一步优选，所述醋酸肟酯类化合物1、3-甲酰基吲哚或其衍生物2、催化剂与含氮有机碱的投料摩尔比为2:1:1:1，醋酸肟酯类化合物1与溶剂的投料配比为1mmol:2mL。Further preferably, the molar ratio of the acetate oxime ester compound 1, 3-formyl indole or its derivative 2, catalyst and nitrogen-containing organic base is 2:1:1:1, and the acetate oxime ester compound 1 and The feeding ratio of the solvent is 1mmol:2mL.

本发明所述的3-(4-吡啶)吲哚类化合物的合成方法，其特征在于具体步骤为：将醋酸肟酯类化合物1l和3-甲酰基吲哚2a溶于溶剂1,4-二氧六环中，然后加入催化剂碘单质和含氮有机碱吡啶，在密封管中于110℃反应制得目标产物喹啉-4-甲酰胺类化合物3l，该合成方法中的反应方程式为：The synthetic method of 3-(4-pyridine) indole compounds of the present invention is characterized in that the specific steps are: dissolving acetic acid oxime ester compound 11 and 3-formyl indole 2a in solvent 1,4-di In the oxygen hexane, then add the catalyst iodine element and nitrogen-containing organic base pyridine, react in a sealed tube at 110 ° C to obtain the target product quinoline-4-carboxamide compound 31, the reaction equation in this synthesis method is:

进一步优选，所述醋酸肟酯类化合物1l、3-甲酰基吲哚2a、催化剂碘单质与含氮有机碱吡啶的投料摩尔比为2:1:1:1，醋酸肟酯类化合物1l与溶剂1,4-二氧六环的投料配比为1mmol:2mL。Further preferably, the molar ratio of the oxime acetate compound 11, 3-formyl indole 2a, catalyst iodine element and nitrogen-containing organic base pyridine is 2:1:1:1, and the oxime acetate compound 1l and the solvent The feeding ratio of 1,4-dioxane is 1mmol:2mL.

进一步优选，所述3-(4-吡啶)吲哚类化合物3为下列化合物之一：Further preferably, the 3-(4-pyridine)indole compound 3 is one of the following compounds:

本发明与现有技术相比具有以下优点：1、合成过程为无过渡金属催化的一锅串联反应，过程简单、高效，同时避免了由于多步反应中多种试剂的使用以及对各步反应中间体的纯化处理等引起的资源浪费和环境污染；2、原料易于制备；3、反应条件温和，操作简便；4、底物的适用范围广。因此，本发明为3-(4-吡啶)吲哚类化合物的合成提供了一种经济实用且绿色环保的新方法。Compared with the prior art, the present invention has the following advantages: 1. The synthesis process is a one-pot series reaction without transition metal catalysis. Waste of resources and environmental pollution caused by the purification of intermediates; 2. The raw materials are easy to prepare; 3. The reaction conditions are mild and the operation is simple; 4. The substrate has a wide range of applications. Therefore, the present invention provides an economical, practical and environmentally friendly new method for the synthesis of 3-(4-pyridine) indole compounds.

具体实施方式Detailed ways

以下通过实施例对本发明的上述内容做进一步详细说明，但不应该将此理解为本发明上述主题的范围仅限于以下的实施例，凡基于本发明上述内容实现的技术均属于本发明的范围。The above-mentioned contents of the present invention are described in further detail below through the embodiments, but this should not be interpreted as the scope of the above-mentioned themes of the present invention being limited to the following embodiments, and all technologies realized based on the above-mentioned contents of the present invention all belong to the scope of the present invention.

实施例1Example 1

在25mL密封管中加入化合物1a(1.0mmol,191mg)、化合物2a(0.5mmol,72.6mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于110℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1,v/v)得到白色固体产物3a(153.3mg,82％)。该化合物的表征数据如下：1H NMR(400MHz,DMSO-d6):δ(ppm)11.79(s,1H),8.29(d,J＝2.8Hz,1H),8.21(d,J＝8.0Hz,4H),8.15(s,2H),8.13–8.08(m,1H),7.58–7.50(m,1H),7.36(d,J＝8.0Hz,4H),7.26–7.22(m,2H),2.39(s,6H)；13C NMR(100MHz,DMSO-d6)δ(ppm)156.1,145.4,138.4,137.2,136.5,129.3,126.7,126.5,124.8,121.9,120.5,119.3,115.0,113.4,112.3,20.9；HRMS(ESI):m/z[M+Na]+calcd for C27H22N2Na:397.1675；found:397.1676。Add compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube ring (2 mL), and then placed in an oil bath at 110° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=10/1, v/v) to obtain the white solid product 3a (153.3 mg, 82%). The characterization data of this compound are as follows: 1 H NMR (400MHz, DMSO-d 6 ): δ(ppm) 11.79(s, 1H), 8.29(d, J=2.8Hz, 1H), 8.21(d, J=8.0Hz ,4H),8.15(s,2H),8.13–8.08(m,1H),7.58–7.50(m,1H),7.36(d,J＝8.0Hz,4H),7.26–7.22(m,2H), 2.39(s,6H); 13 C NMR(100MHz,DMSO-d 6 )δ(ppm)156.1,145.4,138.4,137.2,136.5,129.3,126.7,126.5,124.8,121.9,120.5,119.3,115.0,113.4, 112.3, 20.9; HRMS (ESI): m/z [M + Na] + calcd for C27H22N2Na: 397.1675 ; found: 397.1676 .

实施例2Example 2

在25mL密封管中加入化合物1a(1.0mmol,191mg)、化合物2a(0.5mmol,72.6mg)、碘单质(0.5mmol,127mg)、三乙胺(0.5mmol,50.5mg)和氯苯(2mL)，然后置于130℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1,v/v)得到白色固体产物3a(121.6mg,65％)。Add compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine (0.5mmol, 127mg), triethylamine (0.5mmol, 50.5mg) and chlorobenzene (2mL) into a 25mL sealed tube , and then placed in an oil bath at 130°C and stirred for 12h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=10/1, v/v) to obtain the white solid product 3a (121.6 mg, 65%).

实施例3Example 3

在25mL密封管中加入化合物1a(1.0mmol,191mg)、化合物2a(0.5mmol,72.6mg)、碘单质(0.5mmol,127mg)、三乙胺(0.5mmol,50.5mg)和甲苯(2mL)，然后置于130℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝5/1,v/v)得到白色固体产物3a(112.2mg,60％)。Add compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine (0.5mmol, 127mg), triethylamine (0.5mmol, 50.5mg) and toluene (2mL) into a 25mL sealed tube, Then placed in a 130°C oil bath and stirred for 12h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=5/1, v/v) to obtain the product 3a (112.2 mg, 60%) as a white solid.

实施例4Example 4

在25mL密封管中加入化合物1a(1.0mmol,191mg)、化合物2a(0.5mmol,72.6mg)、碘单质(0.5mmol,127mg)、三乙胺(0.5mmol,50.5mg)和1,4-二氧六环(2mL)，然后置于130℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝5/1,v/v)得到白色固体产物3a(142.1mg,76％)。Add compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine (0.5mmol, 127mg), triethylamine (0.5mmol, 50.5mg) and 1,4-di Oxyhexane (2 mL), then placed in an oil bath at 130° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=5/1, v/v) to obtain the product 3a (142.1 mg, 76%) as a white solid.

实施例5Example 5

在25mL密封管中加入化合物1a(1.0mmol,191mg)、化合物2a(0.5mmol,72.6mg)、碘单质(0.5mmol,127mg)、三乙胺(0.5mmol,50.5mg)和乙腈(2mL)，然后置于130℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝5/1,v/v)得到白色固体产物3a(134.6mg,72％)。Add compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine (0.5mmol, 127mg), triethylamine (0.5mmol, 50.5mg) and acetonitrile (2mL) into a 25mL sealed tube, Then placed in a 130°C oil bath and stirred for 12h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=5/1, v/v) to obtain the white solid product 3a (134.6 mg, 72%).

实施例6Example 6

在25mL密封管中加入化合物1a(1.0mmol,191mg)、化合物2a(0.5mmol,72.6mg)、碘单质(0.5mmol,127mg)、三乙胺(0.5mmol,50.5mg)和四氢呋喃(2mL)，然后置于130℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝5/1,v/v)得到白色固体产物3a(129mg,69％)。Add compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine (0.5mmol, 127mg), triethylamine (0.5mmol, 50.5mg) and tetrahydrofuran (2mL) into a 25mL sealed tube, Then placed in a 130°C oil bath and stirred for 12h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=5/1, v/v) to obtain the product 3a (129 mg, 69%) as a white solid.

实施例7Example 7

在25mL密封管中加入化合物1a(1.0mmol,191mg)、化合物2a(0.5mmol,72.6mg)、碘单质(0.5mmol,127mg)、三乙胺(0.5mmol,50.5mg)和N,N-二甲基甲酰胺(2mL)，然后置于130℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝5/1,v/v)得到白色固体产物3a(89.8mg,48％)。Add compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine element (0.5mmol, 127mg), triethylamine (0.5mmol, 50.5mg) and N,N-di Methylformamide (2 mL), then placed in an oil bath at 130°C and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=5/1, v/v) to obtain the white solid product 3a (89.8 mg, 48%).

实施例8Example 8

在25mL密封管中加入化合物1a(1.0mmol,191mg)、化合物2a(0.5mmol,72.6mg)、N-碘代丁二酰亚胺(0.5mmol,112.5mg)、三乙胺(0.5mmol,50.5mg)和1,4-二氧六环(2mL)，然后置于130℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝5/1,v/v)得到白色固体产物3a(110.3mg,59％)。Add compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), N-iodosuccinimide (0.5mmol, 112.5mg), triethylamine (0.5mmol, 50.5 mg) and 1,4-dioxane (2mL), then placed in an oil bath at 130°C and stirred for 12h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=5/1, v/v) to obtain the white solid product 3a (110.3 mg, 59%).

实施例9Example 9

在25mL密封管中加入化合物1a(1.0mmol,191mg)、化合物2a(0.5mmol,72.6mg)、碘化铵(0.5mmol,72.5mg)、三乙胺(0.5mmol,50.5mg)和1,4-二氧六环(2mL)，然后置于130℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝5/1,v/v)得到白色固体产物3a(78.5mg,42％)。Add compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), ammonium iodide (0.5mmol, 72.5mg), triethylamine (0.5mmol, 50.5mg) and 1,4 in a 25mL sealed tube - Dioxane (2 mL), then placed in an oil bath at 130° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=5/1, v/v) to obtain the white solid product 3a (78.5 mg, 42%).

实施例10Example 10

在25mL密封管中加入化合物1a(1.0mmol,191mg)、化合物2a(0.5mmol,72.6mg)、碘单质(0.5mmol,127mg)、二乙胺(0.5mmol,36.6mg)和1,4-二氧六环(2mL)，然后置于130℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝5/1,v/v)得到白色固体产物3a(127.2mg,68％)。Add compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine (0.5mmol, 127mg), diethylamine (0.5mmol, 36.6mg) and 1,4-di Oxyhexane (2 mL), then placed in an oil bath at 130° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=5/1, v/v) to obtain the white solid product 3a (127.2 mg, 68%).

实施例11Example 11

在25mL密封管中加入化合物1a(1.0mmol,191mg)、化合物2a(0.5mmol,72.6mg)、碘单质(0.5mmol,127mg)、1,4-二氮杂二环[2.2.2]辛烷(0.5mmol,56mg)和1,4-二氧六环(2mL)，然后置于130℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝5/1,v/v)得到白色固体产物3a(119.7mg,64％)。Add compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine (0.5mmol, 127mg), 1,4-diazabicyclo[2.2.2]octane into a 25mL sealed tube (0.5mmol, 56mg) and 1,4-dioxane (2mL), then placed in an oil bath at 130°C and stirred for 12h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=5/1, v/v) to obtain the white solid product 3a (119.7 mg, 64%).

实施例12Example 12

在25mL密封管中加入化合物1a(1.0mmol,191mg)、化合物2a(0.5mmol,72.6mg)、碘单质(0.5mmol,127mg)、1,8-二氮杂二环十一碳-7-烯(0.5mmol,76mg)和1,4-二氧六环(2mL)，然后置于130℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝5/1,v/v)得到白色固体产物3a(80.4mg,43％)。Add compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine (0.5mmol, 127mg), 1,8-diazabicycloundec-7-ene into a 25mL sealed tube (0.5mmol, 76mg) and 1,4-dioxane (2mL), then placed in an oil bath at 130°C and stirred for 12h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=5/1, v/v) to obtain the white solid product 3a (80.4 mg, 43%).

实施例13Example 13

在25mL密封管中加入化合物1a(1.0mmol,191mg)、化合物2a(0.5mmol,72.6mg)、碘单质(0.5mmol,127mg)、喹啉(0.5mmol,64.6mg)和1,4-二氧六环(2mL)，然后置于130℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝5/1,v/v)得到白色固体产物3a(76.7mg,41％)。Add compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine (0.5mmol, 127mg), quinoline (0.5mmol, 64.6mg) and 1,4-dioxine into a 25mL sealed tube Hexacyclic (2mL), and then placed in an oil bath at 130°C and stirred for 12h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=5/1, v/v) to obtain the white solid product 3a (76.7 mg, 41%).

实施例14Example 14

在25mL密封管中加入化合物1a(1.0mmol,191mg)、化合物2a(0.5mmol,72.6mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于130℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝5/1,v/v)得到白色固体产物3a(153.3mg,82％)。Add compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube ring (2 mL), and then placed in an oil bath at 130 °C and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=5/1, v/v) to obtain the white solid product 3a (153.3 mg, 82%).

实施例15Example 15

在25mL密封管中加入化合物1a(1.0mmol,191mg)、化合物2a(0.5mmol,72.6mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于100℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝5/1,v/v)得到白色固体产物3a(136.5mg,73％)。Add compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube ring (2 mL), and then placed in an oil bath at 100 °C and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=5/1, v/v) to obtain the product 3a (136.5 mg, 73%) as a white solid.

实施例16Example 16

在25mL密封管中加入化合物1b(1.0mmol,177mg)、化合物2a(0.5mmol,72.6mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于110℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1,v/v)得到白色固体产物3b(136.7mg,79％)。该化合物的表征数据如下：1H NMR(400MHz,DMSO-d6):δ(ppm)11.81(s,1H),8.32(d,J＝7.6Hz,5H),8.22(s,2H),8.14(d,J＝4.4Hz,1H),7.64–7.53(m,5H),7.52–7.45(m,2H),7.29–7.21(m,2H)；13CNMR(100MHz,DMSO-d6)δ(ppm)156.3,145.6,139.2,137.2,129.0,128.7,126.8,126.6,124.8,121.9,120.6,119.4,115.7,113.3,112.3；HRMS(ESI):m/z[M+H]+calcd forC25H19N2:347.1543；found:347.1545。Add compound 1b (1.0mmol, 177mg), compound 2a (0.5mmol, 72.6mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube ring (2 mL), and then placed in an oil bath at 110° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=10/1, v/v) to obtain the white solid product 3b (136.7 mg, 79%). The characterization data of this compound are as follows: 1 H NMR (400MHz, DMSO-d 6 ): δ (ppm) 11.81 (s, 1H), 8.32 (d, J=7.6Hz, 5H), 8.22 (s, 2H), 8.14 (d,J=4.4Hz,1H),7.64–7.53(m,5H),7.52–7.45(m,2H),7.29–7.21(m,2H); 13 CNMR(100MHz,DMSO-d 6 )δ( ppm) 156.3, 145.6, 139.2, 137.2, 129.0, 128.7, 126.8, 126.6, 124.8, 121.9, 120.6, 119.4, 115.7, 113.3, 112.3; HRMS(ESI): m/z[M+H] + calcd for C 25 H 19 N 2 : 347.1543; found: 347.1545.

实施例17Example 17

在25mL密封管中加入化合物1c(1.0mmol,207mg)、化合物2a(0.5mmol,72.6mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于110℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1,v/v)得到白色固体产物3c(180.6mg,89％)。该化合物的表征数据如下：1H NMR(400MHz,DMSO-d6):δ(ppm)11.78(s,1H),8.27(d,J＝7.6Hz,5H),8.16–8.02(m,3H),7.56(d,J＝5.6Hz,1H),7.25(d,J＝3.6Hz,2H),7.11(d,J＝8.4Hz,4H),3.83(s,6H)；13C NMR(100MHz,DMSO-d6)δ(ppm)160.1,155.9,145.3,137.2,131.9,128.1,126.4,124.9,121.9,120.5,119.4,114.2,114.1,113.6,112.4,55.2；HRMS(ESI):m/z[M+H]+calcdfor C27H23N2O2:407.1754；found:407.1757。Add compound 1c (1.0mmol, 207mg), compound 2a (0.5mmol, 72.6mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube ring (2 mL), and then placed in an oil bath at 110° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=10/1, v/v) to obtain the product 3c (180.6 mg, 89%) as a white solid. The characterization data of this compound are as follows: 1 H NMR (400MHz, DMSO-d 6 ): δ (ppm) 11.78 (s, 1H), 8.27 (d, J=7.6Hz, 5H), 8.16–8.02 (m, 3H) ,7.56(d,J=5.6Hz,1H),7.25(d,J=3.6Hz,2H),7.11(d,J=8.4Hz,4H),3.83(s,6H); 13 C NMR(100MHz, DMSO-d 6 ) δ (ppm) 160.1, 155.9, 145.3, 137.2, 131.9, 128.1, 126.4, 124.9, 121.9, 120.5, 119.4, 114.2, 114.1, 113.6, 112.4, 55.2; HRMS (ESI): m/z[ M+H] + calcd for C 27 H 23 N 2 O 2 : 407.1754; found: 407.1757.

实施例18Example 18

在25mL密封管中加入化合物1d(1.0mmol,221mg)、化合物2a(0.5mmol,72.6mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于110℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1,v/v)得到白色固体产物3d(188.8mg,87％)。该化合物的表征数据如下：1H NMR(400MHz,DMSO-d6):δ(ppm)11.76(s,1H),8.28(s,1H),8.10(s,1H),8.07(s,2H),7.87(s,3H),8.84(s,1H),7.53(d,J＝4.4Hz,1H),7.23(d,J＝2.8Hz,2H),7.08(d,J＝7.6Hz,2H),6.12(s,4H)；13C NMR(100MHz,DMSO-d6)δ(ppm)155.5,148.1,147.9,145.4,137.2,133.7,126.5,124.8,121.9,120.9,120.5,119.5,114.7,113.4,112.3,108.4,107.0,101.3；HRMS(ESI):m/z[M+H]+calcd for C27H19N2O4:435.1339；found:435.1338。Add compound 1d (1.0mmol, 221mg), compound 2a (0.5mmol, 72.6mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube ring (2 mL), and then placed in an oil bath at 110° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=10/1, v/v) to obtain the white solid product 3d (188.8 mg, 87%). The characterization data of this compound are as follows: 1 H NMR (400MHz, DMSO-d 6 ): δ (ppm) 11.76 (s, 1H), 8.28 (s, 1H), 8.10 (s, 1H), 8.07 (s, 2H) ,7.87(s,3H),8.84(s,1H),7.53(d,J=4.4Hz,1H),7.23(d,J=2.8Hz,2H),7.08(d,J=7.6Hz,2H) ,6.12(s,4H); 13 C NMR(100MHz,DMSO-d 6 )δ(ppm)155.5,148.1,147.9,145.4,137.2,133.7,126.5,124.8,121.9,120.9,120.5,119.5,114.7,113.4 , 112.3, 108.4, 107.0, 101.3; HRMS (ESI): m/z[M+H] + calcd for C 27 H 19 N 2 O 4 : 435.1339; found: 435.1338.

实施例19Example 19

在25mL密封管中加入化合物1e(1.0mmol,222mg)、化合物2a(0.5mmol,72.6mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于110℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1,v/v)得到白色固体产物3e(154.7mg,71％)。该化合物的表征数据如下：1H NMR(400MHz,DMSO-d6):δ(ppm)11.84(s,1H),9.03(s,2H),8.70(d,J＝7.6Hz,2H),8.36(d,J＝2.8Hz,1H),8.34(s,2H),8.31(d,J＝2.0Hz,1H),8.29(d,J＝2.0Hz,1H),8.12(d,J＝7.2Hz,1H),7.82(t,J＝8.0Hz,2H),7.55–7.50(m,1H),7.28–7.18(m,2H)；13CNMR(100MHz,DMSO-d6)δ(ppm)154.0,148.4,146.4,140.4,137.2,133.1,130.3,127.4,124.6,123.7,122.0,121.2,120.6,119.5,116.9,112.7,112.3；HRMS(ESI):m/z[M+Na]+calcd for C25H16N4NaO4:459.1064；found:459.1069。Add compound 1e (1.0mmol, 222mg), compound 2a (0.5mmol, 72.6mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube ring (2 mL), and then placed in an oil bath at 110° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=10/1, v/v) to obtain the white solid product 3e (154.7 mg, 71%). The characterization data of this compound are as follows: 1 H NMR (400MHz, DMSO-d 6 ): δ (ppm) 11.84 (s, 1H), 9.03 (s, 2H), 8.70 (d, J=7.6Hz, 2H), 8.36 (d, J=2.8Hz, 1H), 8.34(s, 2H), 8.31(d, J=2.0Hz, 1H), 8.29(d, J=2.0Hz, 1H), 8.12(d, J=7.2Hz ,1H),7.82(t,J＝8.0Hz,2H),7.55–7.50(m,1H),7.28–7.18(m,2H); 13 CNMR(100MHz,DMSO-d 6 )δ(ppm)154.0, 148.4,146.4,140.4,137.2,133.1,130.3,127.4,124.6,123.7,122.0,121.2,120.6,119.5,116.9,112.7,112.3 ; H 16 N 4 NaO 4 : 459.1064; found: 459.1069.

实施例20Example 20

在25mL密封管中加入化合物1f(1.0mmol,211mg)、化合物2a(0.5mmol,72.6mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于110℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1,v/v)得到白色固体产物3f(126.5mg,61％)。该化合物的表征数据如下：1H NMR(400MHz,DMSO-d6):δ(ppm)11.89(s,1H),8.43(s,2H),8.40(s,3H),8.31(s,2H),8.23–8.18(m,1H),7.68(d,J＝8.4Hz,4H),7.64–7.59(m,1H),7.35–7.28(m,2H)；13CNMR(100MHz,DMSO-d6)δ(ppm)155.0,145.9,137.8,137.2,133.9,128.7,128.6,126.9,124.7,122.0,120.6,119.4,115.8,113.0,112.3；HRMS(ESI):m/z[M+H]+calcd forC25H17Cl2N2:415.0763；found:415.0764。Add compound 1f (1.0mmol, 211mg), compound 2a (0.5mmol, 72.6mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube ring (2 mL), and then placed in an oil bath at 110° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=10/1, v/v) to obtain the white solid product 3f (126.5 mg, 61%). The characterization data of this compound are as follows: 1 H NMR (400MHz, DMSO-d 6 ): δ (ppm) 11.89 (s, 1H), 8.43 (s, 2H), 8.40 (s, 3H), 8.31 (s, 2H) ,8.23–8.18(m,1H),7.68(d,J＝8.4Hz,4H),7.64–7.59(m,1H),7.35–7.28(m,2H); 13 CNMR(100MHz,DMSO-d 6 ) δ(ppm)155.0,145.9,137.8,137.2,133.9,128.7,128.6,126.9,124.7,122.0,120.6,119.4,115.8,113.0,112.3; HRMS(ESI):m/z[M+H] + calcd forC 25H17Cl2N2 : 415.0763 ; found: 415.0764 .

实施例21Example 21

在25mL密封管中加入化合物1g(1.0mmol,256mg)、化合物2a(0.5mmol,72.6mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于110℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1,v/v)得到白色固体产物3g(161.3mg,64％)。该化合物的表征数据如下：1H NMR(400MHz,DMSO-d6):δ(ppm)11.81(s,1H),8.31(d,J＝2.8Hz,1H),8.28–8.20(m,6H),8.14–8.09(m,1H),7.73(d,J＝8.4Hz,4H),7.56–7.51(m,1H),7.28–7.19(m,2H)；13CNMR(100MHz,DMSO-d6)δ(ppm)155.1,145.9,138.2,137.2,131.6,128.9,126.9,124.7,122.7,122.0,120.6,119.4,115.8,113.0,112.4；HRMS(ESI):m/z[M+H]+calcd forC25H17Br2N2:502.9753；found:502.9758。Add compound 1g (1.0mmol, 256mg), compound 2a (0.5mmol, 72.6mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube ring (2 mL), and then placed in an oil bath at 110° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated through a silica gel column (petroleum ether/ethyl acetate=10/1, v/v) to obtain 3 g (161.3 mg, 64%) of a white solid product. The characterization data of this compound are as follows: 1 H NMR (400MHz, DMSO-d 6 ): δ (ppm) 11.81 (s, 1H), 8.31 (d, J=2.8Hz, 1H), 8.28–8.20 (m, 6H) ,8.14–8.09(m,1H),7.73(d,J＝8.4Hz,4H),7.56–7.51(m,1H),7.28–7.19(m,2H); 13 CNMR(100MHz,DMSO-d 6 ) δ(ppm)155.1,145.9,138.2,137.2,131.6,128.9,126.9,124.7,122.7,122.0,120.6,119.4,115.8,113.0,112.4; HRMS(ESI):m/z[M+H] + calcd forC 25 H 17 Br 2 N 2 : 502.9753; found: 502.9758.

实施例22Example 22

在25mL密封管中加入化合物1h(1.0mmol,246mg)、化合物2a(0.5mmol,72.6mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于110℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1,v/v)得到白色固体产物3h(167mg,69％)。该化合物的表征数据如下：1H NMR(400MHz,DMSO-d6):δ(ppm)11.81(s,1H),8.43(s,2H),8.30(d,J＝4.4Hz,1H),8.24–8.15(m,4H),8.08(d,J＝7.2Hz,1H),7.74–7.67(m,2H),7.52(d,J＝7.6Hz,1H),7.28–7.17(m,2H)；13C NMR(100MHz,DMSO-d6)δ(ppm)153.6,146.1,139.3,137.2,131.7,131.6,130.7,128.4,127.2,126.8,124.6,121.9,120.5,119.5,116.3,112.8,112.3；HRMS(ESI):m/z[M+H]+calcd for C25H15Cl4N2:482.9984；found:482.9988。Add compound 1h (1.0mmol, 246mg), compound 2a (0.5mmol, 72.6mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube ring (2 mL), and then placed in an oil bath at 110° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=10/1, v/v) to obtain the white solid product 3h (167 mg, 69%). The characterization data of this compound are as follows: 1 H NMR (400MHz, DMSO-d 6 ): δ (ppm) 11.81 (s, 1H), 8.43 (s, 2H), 8.30 (d, J=4.4Hz, 1H), 8.24 –8.15(m,4H),8.08(d,J=7.2Hz,1H),7.74–7.67(m,2H),7.52(d,J=7.6Hz,1H),7.28–7.17(m,2H); 13 C NMR (100MHz, DMSO-d 6 ) δ (ppm) 153.6, 146.1, 139.3, 137.2, 131.7, 131.6, 130.7, 128.4, 127.2, 126.8, 124.6, 121.9, 120.5, 119.5, 116.3, 112.8, 112.3 HRMS; (ESI): m/z[M+H] + calcd for C 25 H 15 Cl 4 N 2 : 482.9984; found: 482.9988.

实施例23Example 23

在25mL密封管中加入化合物1i(1.0mmol,227mg)、化合物2a(0.5mmol,72.6mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于110℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1,v/v)得到白色固体产物3i(131.5mg,59％)。该化合物的表征数据如下：1H NMR(400MHz,DMSO-d6):δ(ppm)11.86(s,1H),8.93(s,2H),8.57(d,J＝8.4Hz,2H),8.43(s,2H),8.40(d,J＝2.4Hz,1H),8.26–8.21(m,1H),8.17(d,J＝7.2Hz,2H),8.12(d,J＝8.8Hz,2H),8.01(d,J＝6.8Hz,2H),7.63–7.55(m,5H),7.32–7.25(m,2H)；13C NMR(100MHz,DMSO-d6)δ(ppm)156.3,145.7,137.3,136.7,133.3,133.2,128.7,128.2,127.6,126.7,126.6,126.4,126.1,124.8,122.0,120.6,119.5,116.2,113.4,112.4；HRMS(ESI):m/z[M+H]+calcd for C33H23N2:447.1856；found:447.1859。Add compound 1i (1.0mmol, 227mg), compound 2a (0.5mmol, 72.6mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube ring (2 mL), and then placed in an oil bath at 110° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=10/1, v/v) to obtain the white solid product 3i (131.5 mg, 59%). The characterization data of this compound are as follows: 1 H NMR (400MHz, DMSO-d 6 ): δ (ppm) 11.86 (s, 1H), 8.93 (s, 2H), 8.57 (d, J=8.4Hz, 2H), 8.43 (s,2H),8.40(d,J=2.4Hz,1H),8.26–8.21(m,1H),8.17(d,J=7.2Hz,2H),8.12(d,J=8.8Hz,2H) ,8.01(d,J=6.8Hz,2H),7.63–7.55(m,5H),7.32–7.25(m,2H); 13 C NMR(100MHz,DMSO-d 6 )δ(ppm)156.3,145.7, 137.3,136.7,133.3,133.2,128.7,128.2,127.6,126.7,126.6,126.4,126.1,124.8,122.0,120.6,119.5,116.2,113.4,112.4; HRMS(ESI):m/z[M+H] + calcd for C 33 H 23 N 2 : 447.1856; found: 447.1859.

实施例24Example 24

在25mL密封管中加入化合物1j(1.0mmol,183mg)、化合物2a(0.5mmol,72.6mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于110℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1,v/v)得到白色固体产物3j(116.3mg,65％)。该化合物的表征数据如下：1H NMR(400MHz,DMSO-d6):δ(ppm)11.82(s,1H),8.28(s,1H),8.19–8.05(m,3H),7.98(s,2H),7.66(d,J＝4.4Hz,2H),7.55(d,J＝5.2Hz,1H),7.29–7.10(m,4H)；13C NMR(100MHz,DMSO-d6)δ(ppm)151.8,145.4,144.6,137.2,128.4,128.3,126.8,125.4,124.7,122.0,120.6,119.5,113.5,112.7,112.4；HRMS(ESI):m/z[M+Na]+calcd for C21H14N2NaS2:381.0491；found:381.0492。Add compound 1j (1.0mmol, 183mg), compound 2a (0.5mmol, 72.6mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube ring (2 mL), and then placed in an oil bath at 110° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=10/1, v/v) to obtain the white solid product 3j (116.3 mg, 65%). The characterization data of the compound are as follows: 1 H NMR (400MHz, DMSO-d 6 ): δ(ppm)11.82(s,1H),8.28(s,1H),8.19–8.05(m,3H),7.98(s, 2H), 7.66(d, J=4.4Hz, 2H), 7.55(d, J=5.2Hz, 1H), 7.29–7.10(m, 4H); 13 C NMR(100MHz, DMSO-d 6 )δ(ppm )151.8, 145.4, 144.6, 137.2, 128.4, 128.3, 126.8, 125.4, 124.7, 122.0 , 120.6, 119.5 , 113.5, 112.7, 112.4; 14 N 2 NaS 2 : 381.0491; found: 381.0492.

实施例25Example 25

在25mL密封管中加入化合物1k(1.0mmol,183mg)、化合物2a(0.5mmol,72.6mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于110℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1,v/v)得到白色固体产物3k(128.9mg,72％)。该化合物的表征数据如下：1H NMR(400MHz,DMSO-d6):δ(ppm)11.78(s,1H),8.38(d,J＝2.0Hz,2H),8.25(d,J＝2.8Hz,1H),8.16–8.12(m,1H),8.08(s,2H),7.97(d,J＝5.2Hz,2H),7.70–7.66(m,2H),7.57–7.52(m,1H),7.29–7.19(m,2H)；13C NMR(100MHz,DMSO-d6)δ(ppm)152.8,145.3,142.4,137.2,126.8,126.7,126.5,124.8,124.2,121.9,120.5,119.6,115.1,113.1,112.3；HRMS(ESI):m/z[M-H]-calcd for C21H13N2S2:357.0526；found:357.0521。Add compound 1k (1.0mmol, 183mg), compound 2a (0.5mmol, 72.6mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube ring (2 mL), and then placed in an oil bath at 110° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=10/1, v/v) to obtain the white solid product 3k (128.9 mg, 72%). The characterization data of this compound are as follows: 1 H NMR (400MHz, DMSO-d 6 ): δ(ppm) 11.78(s, 1H), 8.38(d, J=2.0Hz, 2H), 8.25(d, J=2.8Hz ,1H),8.16–8.12(m,1H),8.08(s,2H),7.97(d,J＝5.2Hz,2H),7.70–7.66(m,2H),7.57–7.52(m,1H), 7.29–7.19(m,2H); 13 C NMR(100MHz,DMSO-d 6 )δ(ppm)152.8,145.3,142.4,137.2,126.8,126.7,126.5,124.8,124.2,121.9,120.5,119.6,115.1, 113.1, 112.3; HRMS(ESI): m/z[MH] - calcd for C 21 H 13 N 2 S 2 : 357.0526; found: 357.0521.

实施例26Example 26

在25mL密封管中加入化合物1l(1.0mmol,203mg)、化合物2a(0.5mmol,72.6mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于110℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1,v/v)得到白色固体产物3l(147.3mg,74％)。该化合物的表征数据如下：1H NMR(400MHz,DMSO-d6):δ(ppm)11.52(s,1H),8.47(d,J＝7.2Hz,2H),7.53(d,J＝8.0Hz,1H),7.47(d,J＝2.4Hz,1H),7.40(t,J＝7.2Hz,2H),7.34–7.28(m,2H),7.23(d,J＝7.2Hz,2H),7.20–7.13(m,2H),7.00(t,J＝7.2Hz,1H),2.86–2.73(m,4H),2.73–2.66(m,4H)；13C NMR(100MHz,DMSO-d6)δ(ppm)149.1,141.3,137.8,136.1,134.9,130.5,128.6,127.6,126.8,126.5,125.0,124.7,121.4,119.4,118.9,111.9,110.1,27.5,25.6；HRMS(ESI):m/z[M+H]+calcd for C29H23N2:399.1856；found:399.1855。Add compound 1l (1.0mmol, 203mg), compound 2a (0.5mmol, 72.6mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube ring (2 mL), and then placed in an oil bath at 110° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated through a silica gel column (petroleum ether/ethyl acetate=10/1, v/v) to obtain a white solid product 3l (147.3 mg, 74%). The characterization data of this compound are as follows: 1 H NMR (400MHz, DMSO-d 6 ): δ(ppm) 11.52(s, 1H), 8.47(d, J=7.2Hz, 2H), 7.53(d, J=8.0Hz ,1H),7.47(d,J=2.4Hz,1H),7.40(t,J=7.2Hz,2H),7.34–7.28(m,2H),7.23(d,J=7.2Hz,2H),7.20 –7.13(m,2H),7.00(t,J＝7.2Hz,1H),2.86–2.73(m,4H),2.73–2.66(m,4H); 13 C NMR(100MHz,DMSO-d 6 )δ [ M+H] + calcd for C 29 H 23 N 2 : 399.1856; found: 399.1855.

实施例27Example 27

在25mL密封管中加入化合物1b(1.0mmol,177mg)、化合物2b(0.5mmol,79.6mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于110℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1,v/v)得到白色固体产物3m(138.6mg,77％)。该化合物的表征数据如下：1H NMR(400MHz,DMSO-d6):δ(ppm)11.66(s,1H),8.30(d,J＝7.6Hz,4H),8.22(d,J＝2.8Hz,1H),8.17(s,2H),7.85(s,1H),7.57(t,J＝7.6Hz,4H),7.49(t,J＝7.2Hz,2H),7.41(d,J＝8.4Hz,1H),7.06(d,J＝8.0Hz,1H),2.48(s,3H)；13C NMR(100MHz,DMSO-d6)δ(ppm)156.2,145.8,139.3,135.5,129.2,129.0,128.8,126.8,126.6,125.0,123.6,118.8,115.7,112.8,112.1,21.6；HRMS(ESI):m/z[M+Na]+calcd for C26H20N2Na:383.1519；found:383.1518。Add compound 1b (1.0mmol, 177mg), compound 2b (0.5mmol, 79.6mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube ring (2 mL), and then placed in an oil bath at 110° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=10/1, v/v) to obtain the white solid product 3m (138.6 mg, 77%). The characterization data of this compound are as follows: 1 H NMR (400MHz, DMSO-d 6 ): δ(ppm) 11.66(s, 1H), 8.30(d, J=7.6Hz, 4H), 8.22(d, J=2.8Hz ,1H),8.17(s,2H),7.85(s,1H),7.57(t,J=7.6Hz,4H),7.49(t,J=7.2Hz,2H),7.41(d,J=8.4Hz ,1H),7.06(d,J＝8.0Hz,1H),2.48(s,3H); 13 C NMR(100MHz,DMSO-d 6 )δ(ppm)156.2,145.8,139.3,135.5,129.2,129.0, 128.8, 126.8, 126.6, 125.0, 123.6, 118.8, 115.7, 112.8, 112.1, 21.6; HRMS (ESI): m/z[M+Na] + calcd for C 26 H 20 N 2 Na: 383.1519; found: 383.1518.

实施例28Example 28

在25mL密封管中加入化合物1b(1.0mmol,177mg)、化合物2c(0.5mmol,79.6mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于110℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1,v/v)得到白色固体产物3n(113.4mg,63％)。该化合物的表征数据如下：1H NMR(400MHz,DMSO-d6):δ(ppm)11.64(s,1H),8.31(d,J＝7.2Hz,4H),8.23(d,J＝2.4Hz,1H),8.19(s,2H),7.99(d,J＝8.4Hz,1H),7.57(t,J＝7.6Hz,4H),7.48(t,J＝7.2Hz,2H),7.32(s,1H),7.06(d,J＝8.4Hz,1H),2.45(s,3H)；13C NMR(100MHz,DMSO-d6)δ(ppm)156.2,145.7,139.3,137.7,131.1,129.0,128.7,126.8,126.0,122.7,122.3,119.1,115.5,113.1,112.1,21.3；HRMS(ESI):m/z[M+Na]+calcd for C26H20N2Na:383.1519；found:383.1520。Add compound 1b (1.0mmol, 177mg), compound 2c (0.5mmol, 79.6mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube ring (2 mL), and then placed in an oil bath at 110° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=10/1, v/v) to obtain the white solid product 3n (113.4 mg, 63%). The characterization data of this compound are as follows: 1 H NMR (400MHz, DMSO-d 6 ): δ(ppm) 11.64(s, 1H), 8.31(d, J=7.2Hz, 4H), 8.23(d, J=2.4Hz ,1H),8.19(s,2H),7.99(d,J=8.4Hz,1H),7.57(t,J=7.6Hz,4H),7.48(t,J=7.2Hz,2H),7.32(s ,1H),7.06(d,J＝8.4Hz,1H),2.45(s,3H); 13 C NMR(100MHz,DMSO-d 6 )δ(ppm)156.2,145.7,139.3,137.7,131.1,129.0, 128.7, 126.8, 126.0, 122.7, 122.3, 119.1, 115.5, 113.1, 112.1, 21.3; HRMS (ESI): m/z[M+Na] + calcd for C 26 H 20 N 2 Na: 383.1519; found: 383.1520.

实施例29Example 29

在25mL密封管中加入化合物1b(1.0mmol,177mg)、化合物2d(0.5mmol,79.6mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于110℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1,v/v)得到白色固体产物3o(118.8mg,66％)。该化合物的表征数据如下：1H NMR(400MHz,DMSO-d6):δ(ppm)11.75(s,1H),8.34–8.29(m,5H),8.21(s,2H),7.95(d,J＝8.0Hz,1H),7.57(t,J＝7.4Hz,4H),7.49(t,J＝7.2Hz,2H),7.14(t,J＝7.6Hz,1H),7.04(d,J＝6.8Hz,1H),2.55(s,3H)；13C NMR(100MHz,DMSO-d6)δ(ppm)156.2,145.7,139.2,136.7,129.0,128.7,126.8,126.4,124.5,122.5,121.6,120.8,116.9,115.6,113.7,16.9；HRMS(ESI):m/z[M+H]+calcd for C26H21N2:361.1699；found:361.1696。Add compound 1b (1.0mmol, 177mg), compound 2d (0.5mmol, 79.6mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube ring (2 mL), and then placed in an oil bath at 110° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=10/1, v/v) to obtain the white solid product 3o (118.8 mg, 66%). The characterization data of this compound are as follows: 1 H NMR (400MHz, DMSO-d 6 ): δ (ppm) 11.75 (s, 1H), 8.34–8.29 (m, 5H), 8.21 (s, 2H), 7.95 (d, J=8.0Hz, 1H), 7.57(t, J=7.4Hz, 4H), 7.49(t, J=7.2Hz, 2H), 7.14(t, J=7.6Hz, 1H), 7.04(d, J= 6.8Hz,1H),2.55(s,3H); 13 C NMR(100MHz,DMSO-d 6 )δ(ppm)156.2,145.7,139.2,136.7,129.0,128.7,126.8,126.4,124.5,122.5,121.6, 120.8, 116.9, 115.6, 113.7, 16.9; HRMS(ESI): m/z[M+H] + calcd for C 26 H 21 N 2 : 361.1699; found: 361.1696.

实施例30Example 30

在25mL密封管中加入化合物1b(1.0mmol,177mg)、化合物2e(0.5mmol,87.6mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于110℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1,v/v)得到白色固体产物3p(101.5mg,54％)。该化合物的表征数据如下：1H NMR(400MHz,DMSO-d6):δ(ppm)11.65(s,1H),8.33–8.28(m,4H),8.22(d,J＝2.4Hz,1H),8.16(s,2H),7.56(t,J＝7.4Hz,4H),7.51–7.46(m,3H),7.43(d,J＝8.8Hz,1H),6.94–6.87(m,1H),3.85(s,3H)；13C NMR(100MHz,DMSO-d6)δ(ppm)156.2,154.4,145.7,139.2,132.3,129.0,128.8,127.1,126.8,125.2,115.5,113.1,113.0,111.6,101.4,55.4；HRMS(ESI):m/z[M+Na]+calcd for C26H20N2NaO:399.1468；found:399.1468。Add compound 1b (1.0mmol, 177mg), compound 2e (0.5mmol, 87.6mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube ring (2 mL), and then placed in an oil bath at 110° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=10/1, v/v) to obtain the white solid product 3p (101.5 mg, 54%). The characterization data of this compound are as follows: 1 H NMR (400MHz, DMSO-d 6 ): δ (ppm) 11.65 (s, 1H), 8.33–8.28 (m, 4H), 8.22 (d, J=2.4Hz, 1H) ,8.16(s,2H),7.56(t,J=7.4Hz,4H),7.51–7.46(m,3H),7.43(d,J=8.8Hz,1H),6.94–6.87(m,1H), 3.85(s,3H); 13 C NMR(100MHz,DMSO-d 6 )δ(ppm)156.2,154.4,145.7,139.2,132.3,129.0,128.8,127.1,126.8,125.2,115.5,113.1,113.0,111.6, 101.4, 55.4; HRMS (ESI): m/z [ M +Na] + calcd for C26H20N2NaO : 399.1468; found: 399.1468.

实施例31Example 31

在25mL密封管中加入化合物1b(1.0mmol,177mg)、化合物2f(0.5mmol,125.6mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于110℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1,v/v)得到白色固体产物3q(126.5mg,56％)。该化合物的表征数据如下：1H NMR(400MHz,DMSO-d6):δ(ppm)11.69(s,1H),8.29(d,J＝7.2Hz,4H),8.24(d,J＝2.8Hz,1H),8.12(s,2H),7.61–7.55(m,5H),7.52–7.44(m,5H),7.37–7.28(m,3H),7.04–6.97(m,1H),5.26(s,2H)；13C NMR(100MHz,DMSO-d6)δ(ppm)156.3,153.4,145.7,139.3,137.9,132.4,129.0,128.7,128.4,127.6,127.3,127.2,126.8,125.1,115.5,113.1(3),113.0(9),112.7,102.9,69.8；HRMS(ESI):m/z[M+H]+calcd for C32H25N2O:453.1961；found:453.1962。Add compound 1b (1.0mmol, 177mg), compound 2f (0.5mmol, 125.6mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube ring (2 mL), and then placed in an oil bath at 110° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=10/1, v/v) to obtain the white solid product 3q (126.5 mg, 56%). The characterization data of this compound are as follows: 1 H NMR (400MHz, DMSO-d 6 ): δ(ppm) 11.69(s, 1H), 8.29(d, J=7.2Hz, 4H), 8.24(d, J=2.8Hz ,1H),8.12(s,2H),7.61–7.55(m,5H),7.52–7.44(m,5H),7.37–7.28(m,3H),7.04–6.97(m,1H),5.26(s ,2H); 13 C NMR (100MHz, DMSO-d 6 ) δ (ppm) 156.3, 153.4, 145.7, 139.3, 137.9, 132.4, 129.0, 128.7, 128.4, 127.6, 127.3, 127.2, 126.8, 125.1, 115.5, 113.1 (3), 113.0(9), 112.7, 102.9, 69.8; HRMS (ESI): m/z[M+H] + calcd for C 32 H 25 N 2 O: 453.1961; found: 453.1962.

实施例32Example 32

在25mL密封管中加入化合物1b(1.0mmol,177mg)、化合物2g(0.5mmol,81.6mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于110℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1,v/v)得到白色固体产物3r(125.6mg,69％)。该化合物的表征数据如下：1H NMR(400MHz,DMSO-d6):δ(ppm)11.91(s,1H),8.37(s,1H),8.33(d,J＝6.8Hz,4H),8.16(s,2H),7.83(d,J＝10.0Hz,1H),7.56(d,J＝6.4Hz,5H),7.49(d,J＝6.4Hz,2H),7.10(t,J＝8.8Hz,1H)；13C NMR(100MHz,DMSO-d6)δ(ppm)159.0,156.7,156.3,145.1,139.2,133.9,129.0,128.7,128.5,126.9,125.0,124.9,115.6,113.7,113.6,113.4,113.3,110.3,110.0,104.5,104.2；HRMS(ESI):m/z[M+Na]+calcd for C25H17FN2Na:387.1268；found:387.1271。Add compound 1b (1.0mmol, 177mg), compound 2g (0.5mmol, 81.6mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube ring (2 mL), and then placed in an oil bath at 110° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=10/1, v/v) to obtain the white solid product 3r (125.6 mg, 69%). The characterization data of this compound are as follows: 1 H NMR (400MHz, DMSO-d 6 ): δ (ppm) 11.91 (s, 1H), 8.37 (s, 1H), 8.33 (d, J=6.8Hz, 4H), 8.16 (s,2H),7.83(d,J=10.0Hz,1H),7.56(d,J=6.4Hz,5H),7.49(d,J=6.4Hz,2H),7.10(t,J=8.8Hz ,1H); 13 C NMR (100MHz, DMSO-d 6 ) δ (ppm) 159.0, 156.7, 156.3, 145.1, 139.2, 133.9, 129.0, 128.7, 128.5, 126.9, 125.0, 124.9, 115.6, 113.7, 113.6, 113.4 , 113.3, 110.3, 110.0, 104.5, 104.2; HRMS (ESI): m/z[M+Na] + calcd for C 25 H 17 FN 2 Na: 387.1268; found: 387.1271.

实施例33Example 33

在25mL密封管中加入化合物1b(1.0mmol,177mg)、化合物2h(0.5mmol,81.6mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于110℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1,v/v)得到白色固体产物3s(123.7mg,68％)。该化合物的表征数据如下：1H NMR(400MHz,DMSO-d6):δ(ppm)11.87(s,1H),8.37–8.28(m,5H),8.20(s,2H),8.16–8.09(m,1H),7.57(t,J＝7.6Hz,4H),7.49(t,J＝7.2Hz,2H),7.38–7.32(m,1H),7.14–7.06(m,1H)；13C NMR(100MHz,DMSO-d6)δ(ppm)160.2,157.8,156.3,145.1,139.2,137.3,137.2,129.0,128.7,126.9,121.7,120.7,120.6,115.7,113.6,109.0,108.8,98.4,98.2；HRMS(ESI):m/z[M+Na]+calcd for C25H17FN2Na:387.1268；found:387.1270。Add compound 1b (1.0mmol, 177mg), compound 2h (0.5mmol, 81.6mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube ring (2 mL), and then placed in an oil bath at 110° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=10/1, v/v) to obtain the white solid product 3s (123.7 mg, 68%). The characterization data of this compound are as follows: 1 H NMR (400MHz, DMSO-d 6 ): δ (ppm) 11.87 (s, 1H), 8.37–8.28 (m, 5H), 8.20 (s, 2H), 8.16–8.09 ( 13 C NMR (100MHz,DMSO-d 6 )δ(ppm)160.2,157.8,156.3,145.1,139.2,137.3,137.2,129.0,128.7,126.9,121.7,120.7,120.6,115.7,113.6,109.0,108.8,92.4,9 HRMS (ESI): m/z [M+Na] + calcd for C 25 H 17 FN 2 Na: 387.1268; found: 387.1270.

实施例34Example 34

在25mL密封管中加入化合物1b(1.0mmol,177mg)、化合物2i(0.5mmol,89.8mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于110℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1,v/v)得到白色固体产物3t(123.8mg,65％)。该化合物的表征数据如下：1H NMR(400MHz,DMSO-d6):δ(ppm)11.98(s,1H),8.34(d,J＝2.4Hz,1H),8.31(d,J＝8.0Hz,4H),8.14(s,2H),8.04(s,1H),7.56(t,J＝7.6Hz,5H),7.48(t,J＝7.2Hz,2H),7.28–7.20(m,1H)；13C NMR(100MHz,DMSO-d6)δ(ppm)156.4,144.9,139.2,135.7,129.1,128.7,128.2,126.9,125.8,125.1,122.0,118.4,115.9,113.9,113.3；HRMS(ESI):m/z[M+Na]+calcd for C25H17ClN2Na:403.0972；found:403.0976。Add compound 1b (1.0mmol, 177mg), compound 2i (0.5mmol, 89.8mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube ring (2 mL), and then placed in an oil bath at 110° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=10/1, v/v) to obtain the white solid product 3t (123.8 mg, 65%). The characterization data of this compound are as follows: 1 H NMR (400MHz, DMSO-d 6 ): δ(ppm) 11.98(s, 1H), 8.34(d, J=2.4Hz, 1H), 8.31(d, J=8.0Hz ,4H),8.14(s,2H),8.04(s,1H),7.56(t,J=7.6Hz,5H),7.48(t,J=7.2Hz,2H),7.28–7.20(m,1H) 13 C NMR (100MHz, DMSO-d 6 ) δ (ppm) 156.4, 144.9, 139.2, 135.7, 129.1, 128.7, 128.2, 126.9, 125.8, 125.1, 122.0, 118.4, 115.9, 113.9, 113.3; HRMS (ESI) : m/z[M+Na] + calcd for C 25 H 17 ClN 2 Na: 403.0972; found: 403.0976.

实施例35Example 35

在25mL密封管中加入化合物1b(1.0mmol,177mg)、化合物2j(0.5mmol,89.8mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于110℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1,v/v)得到白色固体产物3u(112.4mg,59％)。该化合物的表征数据如下：1H NMR(400MHz,DMSO-d6):δ(ppm)11.98(s,1H),8.34(d,J＝2.4Hz,1H),8.31(d,J＝8.0Hz,4H),8.14(s,2H),8.04(s,1H),7.56(t,J＝7.6Hz,5H),7.48(t,J＝7.2Hz,2H),7.28–7.20(m,1H)；13C NMR(100MHz,DMSO-d6)δ(ppm)156.4,144.9,139.2,135.7,129.1,128.7,128.2,126.9,125.8,125.1,122.0,118.4,115.9,113.9,113.3；HRMS(ESI):m/z[M+Na]+calcd for C25H17ClN2Na:403.0972；found:403.0976。Add compound 1b (1.0mmol, 177mg), compound 2j (0.5mmol, 89.8mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube ring (2 mL), and then placed in an oil bath at 110° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated through a silica gel column (petroleum ether/ethyl acetate=10/1, v/v) to obtain the product 3u (112.4 mg, 59%) as a white solid. The characterization data of this compound are as follows: 1 H NMR (400MHz, DMSO-d 6 ): δ(ppm) 11.98(s, 1H), 8.34(d, J=2.4Hz, 1H), 8.31(d, J=8.0Hz ,4H),8.14(s,2H),8.04(s,1H),7.56(t,J=7.6Hz,5H),7.48(t,J=7.2Hz,2H),7.28–7.20(m,1H) 13 C NMR (100MHz, DMSO-d 6 ) δ (ppm) 156.4, 144.9, 139.2, 135.7, 129.1, 128.7, 128.2, 126.9, 125.8, 125.1, 122.0, 118.4, 115.9, 113.9, 113.3; HRMS (ESI) : m/z[M+Na] + calcd for C 25 H 17 ClN 2 Na: 403.0972; found: 403.0976.

实施例36Example 36

在25mL密封管中加入化合物1b(1.0mmol,177mg)、化合物2k(0.5mmol,101.6mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于110℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1,v/v)得到白色固体产物3v(82.8mg,41％)。该化合物的表征数据如下：1H NMR(400MHz,DMSO-d6):δ(ppm)12.19(s,1H),8.53(d,J＝2.4Hz,1H),8.32(d,J＝7.6Hz,4H),8.23–8.17(m,4H),7.85–7.81(m,1H),7.57(t,J＝7.4Hz,4H),7.49(t,J＝7.2Hz,2H),3.89(s,3H)；13C NMR(100MHz,DMSO-d6)δ(ppm)167.0,156.4,144.8,139.1,136.5,130.2,129.1,128.8,128.2,126.9,122.9,121.1,119.4,115.9,114.1,113.9,52.0；HRMS(ESI):m/z[M+H]+calcd for C27H21N2O2:405.1598；found:405.1596。Add compound 1b (1.0mmol, 177mg), compound 2k (0.5mmol, 101.6mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube ring (2 mL), and then placed in an oil bath at 110° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. It was filtered, spin-dried, and separated by silica gel column (petroleum ether/ethyl acetate=10/1, v/v) to obtain the white solid product 3v (82.8 mg, 41%). The characterization data of this compound are as follows: 1 H NMR (400MHz, DMSO-d 6 ): δ(ppm) 12.19(s, 1H), 8.53(d, J=2.4Hz, 1H), 8.32(d, J=7.6Hz ,4H),8.23–8.17(m,4H),7.85–7.81(m,1H),7.57(t,J＝7.4Hz,4H),7.49(t,J＝7.2Hz,2H),3.89(s, 3H); 13 C NMR (100MHz, DMSO-d 6 ) δ (ppm) 167.0, 156.4, 144.8, 139.1, 136.5, 130.2, 129.1, 128.8, 128.2, 126.9, 122.9, 121.1, 119.4, 115.9, 114.1, 113.9, 52.0; HRMS (ESI): m/z [M+H] + calcd for C 27 H 21 N 2 O 2 : 405.1598; found: 405.1596.

实施例37Example 37

在25mL密封管中加入化合物1b(1.0mmol,177mg)、化合物2l(0.5mmol,95mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于110℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1,v/v)得到白色固体产物3w(138.8mg,71％)。该化合物的表征数据如下：1H NMR(400MHz,DMSO-d6):δ(ppm)12.47(s,1H),8.58(d,J＝8.0Hz,1H),8.40(d,J＝2.8Hz,1H),8.36–8.30(m,4H),8.25–8.18(m,3H),7.56(t,J＝7.4Hz,4H),7.48(t,J＝7.2Hz,2H),7.42(t,J＝8.0Hz,1H)；13C NMR(100MHz,DMSO-d6)δ(ppm)156.4,143.9,139.0,133.0,129.4,129.3,129.1,129.0,128.7,128.1,127.0,120.2,119.3,116.6,115.3；HRMS(ESI):m/z[M+H]+calcd for C25H18N3O2:392.1394；found:392.1394。Add compound 1b (1.0mmol, 177mg), compound 2l (0.5mmol, 95mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube (2mL), and then placed in an oil bath at 110°C and stirred for 12h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. Filtered, spin-dried, separated by silica gel column (petroleum ether/ethyl acetate=10/1, v/v) to obtain the white solid product 3w (138.8 mg, 71%). The characterization data of this compound are as follows: 1 H NMR (400MHz, DMSO-d 6 ): δ(ppm) 12.47(s, 1H), 8.58(d, J=8.0Hz, 1H), 8.40(d, J=2.8Hz ,1H),8.36–8.30(m,4H),8.25–8.18(m,3H),7.56(t,J＝7.4Hz,4H),7.48(t,J＝7.2Hz,2H),7.42(t, J＝8.0Hz, 1H); 13 C NMR (100MHz, DMSO-d 6 ) δ (ppm) 156.4, 143.9, 139.0, 133.0, 129.4, 129.3, 129.1, 129.0, 128.7, 128.1, 127.0, 120.2, 119.3, 116.6 , 115.3; HRMS (ESI): m/z[M+H] + calcd for C 25 H 18 N 3 O 2 : 392.1394; found: 392.1394.

实施例38Example 38

在25mL密封管中加入化合物1b(1.0mmol,177mg)、化合物2m(0.5mmol,79.6mg)、碘单质(0.5mmol,127mg)、吡啶(0.5mmol,39.6mg)和1,4-二氧六环(2mL)，然后置于110℃油浴中搅拌反应12h。加入50mL水淬灭反应，用乙酸乙酯萃取(50mL×3)，之后有机相用质量浓度为10％的Na2S2O3溶液和饱和食盐水依次洗涤，无水硫酸钠干燥。过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1,v/v)得到白色固体产物3x(124.2mg,69％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3):δ(ppm)8.32(d,J＝7.6Hz,4H),8.15(d,J＝7.6Hz,1H),8.02(s,2H),7.63(t,J＝7.4Hz,4H),7.58–7.52(m,2H),7.47–7.34(m,4H),3.79(s,3H)；13C NMR(100MHz,CDCl3)δ(ppm)157.1,144.7,139.8,137.6,128.7,128.6,128.0,127.0,125.6,122.3,120.6,119.7,116.5,114.1,109.9,32.8；HRMS(ESI):m/z[M+H]+calcd for C26H21N2:361.1699；found:361.1701。Add compound 1b (1.0mmol, 177mg), compound 2m (0.5mmol, 79.6mg), iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and 1,4-dioxane into a 25mL sealed tube ring (2 mL), and then placed in an oil bath at 110° C. and stirred for 12 h. The reaction was quenched by adding 50 mL of water, extracted with ethyl acetate (50 mL×3), and then the organic phase was washed successively with 10% Na 2 S 2 O 3 solution and saturated brine, and dried over anhydrous sodium sulfate. Filtered, spin-dried, separated by silica gel column (petroleum ether/ethyl acetate=10/1, v/v) to obtain the white solid product 3x (124.2 mg, 69%). The characterization data of this compound are as follows: 1 H NMR (400MHz, CDCl 3 ): δ(ppm) 8.32(d, J=7.6Hz, 4H), 8.15(d, J=7.6Hz, 1H), 8.02(s, 2H ),7.63(t,J＝7.4Hz,4H),7.58–7.52(m,2H),7.47–7.34(m,4H),3.79(s,3H); 13 C NMR(100MHz,CDCl 3 )δ( ppm) 157.1, 144.7, 139.8, 137.6, 128.7, 128.6, 128.0, 127.0, 125.6, 122.3, 120.6, 119.7, 116.5, 114.1, 109.9, 32.8; HRMS(ESI): m/z[M+H] + calcd for C 26 H 21 N 2 : 361.1699; found: 361.1701.

以上实施例描述了本发明的基本原理、主要特征及优点，本行业的技术人员应该了解，本发明不受上述实施例的限制，上述实施例和说明书中描述的只是说明本发明的原理，在不脱离本发明原理的范围下，本发明还会有各种变化和改进，这些变化和改进均落入本发明保护的范围内。The above embodiments have described the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited by the above embodiments. What are described in the above embodiments and description are only to illustrate the principles of the present invention. Without departing from the scope of the principle of the present invention, there will be various changes and improvements in the present invention, and these changes and improvements all fall within the protection scope of the present invention.

Claims (5)

1. a kind of synthetic method of 3- (4- pyridine) Benzazole compounds, it is characterised in that specific steps are as follows: by acetic acid oxime esters Compound 1 and 3- formyl indole class compound 2 are dissolved in solvent, catalyst and nitrogenous organic base are then added, in seal pipe In reacted in 100-130 DEG C target product 3- (4- pyridine) Benzazole compounds 3 be made, the reaction equation in the synthetic method Are as follows:
Wherein R1For phenyl, substituted-phenyl, 2- naphthalene or thienyl, which is 3,4- methylenedioxyphenyl, 3,4- bis- Chloro phenyl or mono-substituted benzenes base, the substituent group on mono-substituted benzenes base phenyl ring are methyl, methoxyl group, nitro, chlorine or bromine, R2 For hydrogen, methyl, methoxyl group, methoxybenzyl, fluorine, chlorine, carbomethoxy or nitro, R3For hydrogen or methyl, solvent is toluene, chlorobenzene, second Nitrile, Isosorbide-5-Nitrae-dioxane, tetrahydrofuran or n,N-Dimethylformamide, catalyst be elemental iodine, N- N-iodosuccinimide or Ammonium iodide, nitrogenous organic base are triethylamine, diethylamine, pyridine, Isosorbide-5-Nitrae-diazabicylo [2.2.2] octane, 1,8- diaza two 11 carbon -7- alkene of ring or quinoline.
2. the synthetic method of 3- (4- pyridine) Benzazole compounds according to claim 1, it is characterised in that: the acetic acid The molar ratio of oxime ester compound 1,3- formyl indole or derivatives thereof 2, catalyst and nitrogenous organic base is 2:1:1: 1, the charge ratio of acetic acid oxime ester compound 1 and solvent is 1mmol:2mL.
3. a kind of synthetic method of 3- (4- pyridine) Benzazole compounds, it is characterised in that specific steps are as follows: by acetic acid oxime esters Compound 1l and 3- formyl indole 2a is dissolved in solvent Isosorbide-5-Nitrae-dioxane, and catalyst iodine simple substance and nitrogenous organic is then added Alkali pyridine reacts in 110 DEG C in seal pipe and target product quinoline -4- Carbox amide 3l is made, in the synthetic method Reaction equation are as follows:
4. the synthetic method of 3- (4- pyridine) Benzazole compounds according to claim 3, it is characterised in that: the acetic acid The molar ratio of oxime ester compound 1l, 3- formyl indole 2a, catalyst iodine simple substance and nitrogenous organic base pyridine are 2:1: 1:1, acetic acid oxime ester compound 1l and solvent Isosorbide-5-Nitrae-dioxane charge ratio are 1mmol:2mL.
5. the synthetic method of 3- (4- pyridine) Benzazole compounds according to claim 1 or 3, it is characterised in that the 3- (4- pyridine) Benzazole compounds 3 are one of following compounds:
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CN113527536A (en) * 2020-04-21 2021-10-22 杭州德柯医疗科技有限公司 Fluorine-containing polysaccharide high molecular compound and preparation method thereof

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113527536A (en) * 2020-04-21 2021-10-22 杭州德柯医疗科技有限公司 Fluorine-containing polysaccharide high molecular compound and preparation method thereof
CN113527536B (en) * 2020-04-21 2024-03-22 杭州德柯医疗科技有限公司 Fluorine-containing polysaccharide high molecular compound and preparation method thereof

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