CN112939973B - Beta-carboline heterozygous triazole compound as well as preparation method and application thereof - Google Patents

Beta-carboline heterozygous triazole compound as well as preparation method and application thereof Download PDF

Info

Publication number
CN112939973B
CN112939973B CN202110143623.4A CN202110143623A CN112939973B CN 112939973 B CN112939973 B CN 112939973B CN 202110143623 A CN202110143623 A CN 202110143623A CN 112939973 B CN112939973 B CN 112939973B
Authority
CN
China
Prior art keywords
indole
triazole
tetrafluoroborate
pyridinyl
carboline
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202110143623.4A
Other languages
Chinese (zh)
Other versions
CN112939973A (en
Inventor
郭亮
张洁
朱思玉
代斌
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shihezi University
Original Assignee
Shihezi University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shihezi University filed Critical Shihezi University
Priority to CN202110143623.4A priority Critical patent/CN112939973B/en
Publication of CN112939973A publication Critical patent/CN112939973A/en
Application granted granted Critical
Publication of CN112939973B publication Critical patent/CN112939973B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
    • C07D471/14—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

The invention relates to a beta-carboline heterozygous triazole compound, and a preparation method and application thereof. The invention discloses a novel compound beta-carboline heterozygous triazole compound and application of the beta-carboline heterozygous triazole compound in preparing antitumor drugs. The beta-carboline heterozygous triazole compound is a novel compound, has better anti-tumor activity, and can be applied to anti-tumor drugs.

Description

Beta-carboline heterozygous triazole compound as well as preparation method and application thereof
Technical Field
The invention belongs to the field of medicinal chemistry, and particularly relates to a beta-carboline heterozygous triazole compound as well as a preparation method and application thereof.
Background
The beta-carboline derivative is an alkaloid with wide biological and pharmacological activities, and has wide application in the aspects of anti-tumor, anti-malaria, antibacterial and the like. In addition, the beta-carboline derivative is widely existing in nature and in food and beverage, that is to say, the beta-carboline derivative can be separated from natural products, and the method for synthesizing the beta-carboline derivative is also various.
The [1,2,3] triazolo [1,5-a ] pyridine compound has a unique triazole framework and is also an important pharmacophore, and has good pharmaceutical activity in the aspects of sterilization, anticancer and antiviral. There are a number of drugs containing this fragment that are currently in the pharmaceutical market, such as antibacterial drugs: azolidinone, quinolone, vancomycin, fluconazole; anticancer drug: cobustatin and artemsinin; antiviral drugs: amprevir, zanavir, et al, as shown below.
Figure BDA0002930174730000011
In view of the above, the invention provides a new compound-beta-carboline heterozygous triazole compound, which has important significance for discovering drugs with potential application prospects.
Disclosure of Invention
The invention aims to provide a beta-carboline heterozygous triazole compound which is a new structural type compound.
In order to achieve the above purpose, the technical scheme adopted is as follows:
a beta-carboline heterozygous triazole compound has a chemical structural general formula:
Figure BDA0002930174730000021
/>
further, in the chemical structural general formula of the beta-carboline heterozygous triazole compound, R 1 Is one of alkyl, aryl and substituted aryl;
R 9 is one of hydrogen, C1-C4 straight-chain or branched alkyl, aralkyl, substituted aralkyl and aryl;
R 2 aryl, substituted aryl, and the like; x is one of trifluoromethanesulfonic acid and tetrafluoroboric acid.
Further, the beta-carboline heterozygous triazole compound is any one of the following compounds:
11-methyl-2-phenyl-11H- [1,2,3] triazole [1',5':1, 2-pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 11-butyl-2-phenyl-11H- [1,2,3] triazole [1',5':1,2] indole-2-tetrafluoroborate, 11-benzyl-2-phenyl-11H- [1,2,3] triazole [1',5':1,2] pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 11- (4-fluorobenzyl) -2-phenyl-11H- [1,2,3] triazole [1',5':1,2] pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 11- (3-chlorobenzyl) -2-phenyl-11H- [1,2,3] triazole [1',5':1,2] triazole [3,4-b ] indole-2-tetrafluoroborate, 2-phenyl-11- (3-phenylpropyl) -11H- [1,2, 3-b ] indole-2-tetrafluoroborate, 11- (3-phenyl-propyl) -11H- [1,2, 3-b ] indole-2-triazole [1',5':1, 4-b ] indole-2-4-tetrafluoroborate, 11- (3-chlorobenzyl) -2-phenyl-11H- [1,2, 3-b ] triazole [1',5':1, 2-b ] indole-2-4-tetrafluoroborate, 11, 5':1,2] pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 11-benzyl-2- (4-chlorophenyl) -11H- [1,2,3] triazol [1',5':1,2] pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 11- (4-fluorobenzyl) -2- (4-chlorophenyl) -11H- [1,2,3] triazol [1',5':1,2] pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 9-ethyl-10-methyl-2-phenyl-9H- [1,2,3] triazol [1',5':1,6] pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 9-butyl-10-methyl-2-phenyl-9H- [1,2,3] triazol [1',5':1,6] pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 9-ethyl-10-methyl-2-phenyl-9H- [1',5':1,6] pyridinyl [1, 4-b ] indole-2-tetrafluoroborate, 9-ethyl-10-methyl-2-b ] indole-2-triazole [1',5':1, 4-b ] indole-2-4-tetrafluoroborate, 9- [1, 6] pyridinyl [1, 6] indole-2-yl ] tetrafluoroborate, 9-methyl-2-4-yl ] 2-yl-4-yl-2-yl-4-yl-carbonyl-amine 2-phenyl-9- (3-phenylpropyl) -9H- [1,2,3] triazole [1',5':1,6] pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 9-benzyl-10-methyl-2-phenyl-9H- [1,2,3] triazole [1',5':1, 6-pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 9- (3-chlorobenzyl) -10-methyl-2-phenyl-9H- [1,2,3] triazol [1',5':1,6] pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 2- (4-fluorophenyl) -10-methyl-9H- [1,2,3] triazol [1',5':1,6] pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 9-ethyl-2- (4-fluorophenyl) -10-methyl-9H- [1,2,3] triazol [1',5':1,6] pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 2- (4-fluorophenyl) -9- (4-fluorobenzyl) -9H- [1,2,3] triazol [1',5':1,6] pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 9-ethyl-2- (4-fluorophenyl) -10-methyl-9H- [1,2,3] triazol 2-tetrafluoroborate, 2- (4-fluorophenyl) -9H- [1,2,3] triazol [1',5':1,6] indole-2-tetrafluoroborate 2- (4-chlorophenyl) -9- (4-fluorobenzyl) -10-methyl-9H- [1,2,3] triazole [1',5':1,6] pyridinyl [3,4-b ] indole-2-tetrafluoroborate.
The invention also aims to provide the application of the beta-carboline heterozygous triazole compound in preparing antitumor drugs.
The invention also aims to provide a preparation method of the beta-carboline heterozygous triazole compound, which designs the beta-carboline and the [1,2,3] triazolo [1,5-a ] pyridine in one molecule to obtain the beta-carboline heterozygous triazole compound. The preparation method has better yield.
In order to achieve the above purpose, the technical scheme adopted is as follows:
the preparation method of the beta-carboline heterozygous triazole compound comprises the following steps:
Figure BDA0002930174730000031
further, S10 synthesizes an intermediate:
toluene is added into the corresponding 9-substituted-1-aldehyde-beta-carboline, p-toluenesulfonyl hydrazide and cesium carbonate, after stirring and dissolving, a catalyst CuI is added, and the mixture is heated to react at 80 ℃; monitoring the reaction by TLC, concentrating under vacuum after the reaction is finished, purifying the obtained crude product by silica gel column chromatography to obtain an intermediate of yellow solid powder, namely [1,2,3] triazole heterozygous beta-carboline;
s20, synthesizing a target compound:
the [1,2,3] is then added to the mixture]Triazole heterozygote beta-carboline, diaryl iodized salt and catalyst Cu (CN) 4 PF 6 After mixing, DCE solvent was added for dissolution, stirred at 80 ℃, and the progress of the reaction was monitored by TLC; after the reaction is finished, purifying the obtained crude product through silica gel column chromatography to obtain a target compound which is solid powder, namely the beta-carboline heterozygous triazole compound.
Still further, the molar ratio of the corresponding 9-substituted-1-aldehyde-beta-carboline, p-toluenesulfonyl hydrazide, cesium carbonate to CuI is 0.3:0.38:0.45:0.03;
the dosage ratio of the [1,2,3] triazole heterozygous beta-carboline, diaryl iodized salt and the DCE solvent is 0.2mmol:0.3mmol:2mL.
The preparation method of the beta-carboline heterozygous triazole compound is characterized by comprising the following steps of:
Figure BDA0002930174730000041
further, S10 synthesizes an intermediate:
adding ethanol solvent into corresponding 1, 9-disubstituted-3-aldehyde-beta-carboline for dissolution, then adding hydrazine hydrate, stirring the solution at room temperature, and monitoring the reaction by TLC;
after the reaction is completed, filtering to obtain hydrazone productDissolving the mixture in dichloromethane solvent, and adding active MnO in portions 2 Stirring the solution at room temperature for reaction, and monitoring the reaction by TLC;
after the reaction is finished, filtering to remove solid residues, concentrating under reduced pressure in vacuum to remove a solvent, and purifying the obtained crude product by silica gel column chromatography to obtain an intermediate of yellow solid powder, namely [1,2,3] triazole heterozygous beta-carboline;
s20, synthesizing a target compound:
the [1,2,3] is then added to the mixture]Triazole heterozygote beta-carboline, diaryl iodized salt and catalyst Cu (CN) 4 PF 6 After mixing, DCE solvent was added for dissolution, stirred at 80 ℃, and the progress of the reaction was monitored by TLC; after the reaction is finished, purifying the obtained crude product through silica gel column chromatography to obtain a target compound which is solid powder, namely the beta-carboline heterozygous triazole compound.
Still further, the corresponding 1, 9-disubstituted-3-aldehyde-beta-carboline, hydrazine hydrate and active MnO 2 The ratio of the ethanol solvent to the dichloromethane solvent is 1mmol:2mmol:2.5mmol:2mL:3mL;
the dosage ratio of the [1,2,3] triazole heterozygous beta-carboline, diaryl iodized salt and the DCE solvent is 0.2mmol:0.3mmol:2mL.
Compared with the prior art, the invention has the beneficial effects that:
1. the invention designs beta-carboline and [1,2,3] triazolo [1,5-a ] pyridine in one molecule to obtain the beta-carboline heterozygous triazole compound.
2. The beta-carboline heterozygous triazole compound is a novel compound, has better anti-tumor activity on the cellular level, and can be applied to anti-tumor drugs.
Detailed Description
In order to further illustrate the beta-carboline heterozygous triazole compound, the preparation method and the application thereof, which achieve the expected aim, the following is a detailed description of the specific implementation mode, the structure, the characteristics and the efficacy of the beta-carboline heterozygous triazole compound, the preparation method and the application thereof, which are provided by the invention, in combination with the preferred embodiment. In the following description, different "an embodiment" or "an embodiment" do not necessarily refer to the same embodiment. Furthermore, the particular features, structures, or characteristics of one or more embodiments may be combined in any suitable manner.
The following describes the preparation method and application of the beta-carboline heterozygous triazole compound in further detail by combining specific examples:
example 1.
The intermediate was synthesized using the following equation:
Scheme 1
Figure BDA0002930174730000051
intermediate compound 2: 9-substituted-1-aldehyde-beta-carboline (0.3 mmol) is weighed, p-toluenesulfonyl hydrazine (0.38 mmol) and cesium carbonate (0.45 mmol) are added into a reaction tube, then toluene is added, stirring and dissolving are carried out, cuI (0.03 mmol) is used as a catalyst, the catalyst is added into the dissolved mixed solution, the mixed solution is heated, and the reaction is carried out at 80 ℃ for 10min. After the reaction is monitored by TLC, the toluene solvent is concentrated under reduced pressure in vacuo, and the obtained crude product is purified by silica gel column chromatography (EtOAc/PE) to obtain the product compound 2- [1,2,3] triazolo [1',5':1,2] pyrido [3,4-b ] indole as a yellow solid powder.
Example 2.
The procedure of example 2 is the same as in example 1, wherein R 9 Methyl, the resulting product is 11-methyl-11H- [1,2,3]]Triazolo [1',5':1,2]Pyrido [3,4-b]Indoles.
11-methyl-11H- [1,2,3]]Triazolo [1',5':1,2]Pyrido [3,4-b]Indole (2 a): pale yellow solid, yield: 84%. 1 H NMR(400MHz,DMSO-d 6 )δ8.84(dd,J＝7.2,0.8Hz,1H),8.78(d,J＝0.8Hz,1H),8.22(dt,J＝8.0,0.8Hz,1H),7.93(d,J＝7.2Hz,1H),7.80(dt,J＝8.4,0.8Hz,1H),7.54–7.49(m,1H),7.36–7.31(m,1H),4.23(s,3H). 13 C NMR(100MHz,DMSO-d 6 )δ139.99,128.50,125.75,125.33,123.50,122.16,120.98,120.75,117.88,114.20,110.98,110.25,31.89.
Example 3.
The procedure of example 3 is the same as in example 1, wherein R 9 Butyl, the product obtained is 11-butyl-11H- [1,2,3]]Triazolo [1',5':1,2]Pyrido [3,4-b]Indoles.
11-butyl-11H- [1,2,3]]Triazolo [1',5':1,2]Pyrido [3,4-b]Indole (2 b): tan solid, yield: 73%. 1 H NMR(400MHz,DMSO-d 6 )δ8.88(dd,J＝7.2,0.8Hz,1H),8.70(d,J＝0.8Hz,1H),8.23(dt,J＝8.0,0.8Hz,1H),7.95(d,J＝7.2Hz,1H),7.81(d,J＝8.4Hz,1H),7.54–7.49(m,1H),7.37–7.32(m,1H),4.70(t,J＝7.2Hz,2H),1.85–1.76(m,2H),1.40–1.30(m,2H),0.86(t,J＝7.2Hz,3H). 13 C NMR(100MHz,DMSO-d 6 )δ139.51,127.67,125.80,125.07,123.41,122.26,120.99,120.84,117.99,114.51,111.10,110.23,44.66,32.32,19.94,14.19.
Example 4.
The procedure of example 4 is the same as in example 1, wherein R 9 Is isobutyl, and the obtained product is 11-isobutyl-11H- [1,2,3]]Triazolo [1',5':1,2]Pyrido [3,4-b]Indoles.
11-isobutyl-11H- [1,2,3]]Triazolo [1',5':1,2]Pyrido [3,4-b]Indole (2 c): yellow solid, yield: 77%. 1 H NMR(400MHz,DMSO-d 6 )δ8.87(d,J＝7.2Hz,1H),8.68(s,1H),8.23(d,J＝7.6Hz,1H),7.96(d,J＝7.2Hz,1H),7.81(d,J＝8.4Hz,1H),7.53–7.46(m,1H),7.33(t,J＝7.6Hz,1H),4.51(d,J＝7.6Hz,2H),2.29–2.18(m,1H),0.92(d,J＝6.8Hz,6H). 13 C NMR(100MHz,DMSO-d 6 )δ139.89,127.92,125.78,125.21,123.56,122.19,121.01,120.84,118.07,114.51,111.56,110.25,51.70,29.76,20.11.
Example 5.
The procedure of example 5 is the same as in example 1, wherein R 9 3-phenylpropyl, the product obtained is 11- (3-phenylpropyl) -11H- [1,2,3]Triazolo [1',5':1,2]Pyrido [3,4-b]Indoles.
11- (3-phenylpropyl) -11H- [1,2,3]Triazolo [1',5':1,2]Pyrido [3,4-b]Indole (2 d): pale yellow solid, yield: 83%. 1 H NMR(400MHz,DMSO-d 6 )δ8.86(dd,J＝7.2,0.8Hz,1H),8.39(d,J＝0.8Hz,1H),8.23(d,J＝7.9Hz,1H),7.93(d,J＝7.2Hz,1H),7.76(d,J＝8.0Hz,1H),7.54–7.49(m,1H),7.34(t,J＝7.6Hz,1H),7.32–7.26(m,2H),7.23–7.17(m,3H),4.70(t,J＝7.6Hz,2H),2.75(t,J＝7.6Hz,2H),2.15–2.07(m,2H). 13 C NMR(100MHz,DMSO-d 6 )δ141.53,139.40,128.83,128.73,127.60,126.45,125.84,124.99,123.13,122.31,121.06,120.88,118.03,114.55,110.96,110.23,44.42,32.58,31.86.
Example 6.
The procedure of example 6 is the same as in example 1, wherein R 9 Is benzyl, and the obtained product is 11-benzyl-11H- [1,2,3]]Triazolo [1',5':1,2]Pyrido [3,4-b]Indoles.
11-benzyl-11H- [1,2,3]Triazolo [1',5':1,2]Pyrido [3,4-b]Indole (2 e): yellow solid, yield: 70%. 1 H NMR(400MHz,DMSO-d 6 )δ8.91(dd,J＝7.2,0.8Hz,1H),8.60(d,J＝0.8Hz,1H),8.28(d,J＝8.0Hz,1H),8.01(d,J＝7.2Hz,1H),7.85(d,J＝8.4Hz,1H),7.53–7.48(m,1H),7.39–7.34(m,1H),7.29–7.21(m,3H),7.16–7.12(m,2H),6.02(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ139.92,137.73,129.23,127.95,127.91,126.84,126.12,125.09,123.53,122.47,121.38,120.98,118.43,115.01,111.38,110.30,47.92.
Example 7.
The procedure of example 7 is the same as in example 1, wherein R 9 4-fluorobenzyl, the resulting product is 11- (4-fluorobenzyl) -11H- [1,2,3]Triazolo [1',5':1,2]Pyrido [3,4-b]Indoles.
11- (4-fluorobenzyl) -11H- [1,2,3]Triazolo [1',5':1,2]Pyrido [3,4-b]Indole (2 f): pale yellow solid, yield: 75%. 1 H NMR(400MHz,DMSO-d 6 )δ8.91(d,J＝7.2Hz,1H),8.63(s,1H),8.28(d,J＝8.0Hz,1H),8.01(d,J＝7.2Hz,1H),7.85(d,J＝8.4Hz,1H),7.54–7.49(m,1H),7.37(t,J＝7.6Hz,1H),7.20–7.16(m,2H),7.13–7.07(m,2H),6.01(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ163.08(d,J＝242.0Hz),139.80,133.91(d,J＝3.0Hz),128.92(d,J＝8.3Hz),127.84,126.18,125.06,123.49,122.53,121.45,121.03,118.52,116.17(d,J＝21.4Hz),115.10,111.38,110.31,47.22.
Example 8.
The procedure of example 8 is the same as in example 1, wherein R 9 Is 3-chlorobenzyl, and the obtained product is 11- (3-chlorobenzyl) -11H- [1,2,3]Triazolo [1',5':1,2]Pyrido [3,4-b]Indoles.
11- (3-chlorobenzyl) -11H- [1,2,3]Triazolo [1',5':1,2]Pyrido [3,4-b]Indole (2 g): cream yellow solid, yield: 80%. 1 H NMR(400MHz,DMSO-d 6 )δ8.92(dd,J＝7.2,0.8Hz,1H),8.63(d,J＝0.8Hz,1H),8.30(d,J＝7.6Hz,1H),8.02(d,J＝7.2Hz,1H),7.85(d,J＝8.4Hz,1H),7.55–7.50(m,1H),7.40–7.36(m,1H),7.31–7.24(m,3H),6.95(dt,J＝6.8,1.6Hz,1H),6.05(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ140.32,139.83,133.81,131.23,127.96,127.86,126.83,126.27,125.32,125.01,123.42,122.51,121.56,121.09,118.62,115.15,111.31,110.33,47.29.
Example 9.
The procedure of example 9 is the same as in example 1, wherein R 9 2,3,4,5, 6-pentafluorobenzyl, the product obtained is 11- (2, 3,4,5, 6-pentafluorobenzyl) -11H- [1,2,3]Triazolo [1',5':1,2]Pyrido [3,4-b]Indoles.
11- (2, 3,4,5, 6-pentafluorobenzyl) -11H- [1,2,3]Triazolo [1',5':1,2]Pyrido [3,4-b]Indole (2 h): yellow solid, yield: 72%. 1 H NMR(400MHz,DMSO-d 6 )δ8.94(d,J＝7.2Hz,1H),8.91(s,1H),8.26(d,J＝8.0Hz,1H),7.99(d,J＝7.2Hz,1H),7.60–7.47(m,2H),7.36(t,J＝7.2Hz,1H),6.15(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ146.89(m),144.03(m),139.10,138.84(m),136.33(m),128.58,126.40,125.26,123.75,122.81,121.75,121.14,118.81,114.98,110.89(m),110.50,110.12,38.13.
Example 10.
The intermediate was synthesized using the following equation:
Scheme 2
Figure BDA0002930174730000091
intermediate compound 4: 1, 9-disubstituted-3-aldehyde- β -carboline (1 mmol) was weighed into a reaction tube, then 2mL of ethanol solvent was added for dissolution, hydrazine hydrate (12 mmol) was added, the solution was stirred at room temperature, and the reaction was monitored by TLC. After the reaction was completed, the solvent was removed by filtration, the resulting hydrazone product was dissolved in 3mL of methylene chloride solvent, and the active MnO was added in portions 2 (2.5 mmol) and the reaction was monitored by TLC, after the reaction was completed, the solid residue was removed by filtration, and after the solvent was removed by concentration under reduced pressure, the crude product was purified by silica gel column chromatography (EtOAc/PE) to give the product compound 4, [1,2,3]]Triazolo [1',5':1,6]Pyrido [3,4-b]Indole is a yellow solid powder.
Example 11.
The procedure of example 11 is the same as in example 10, wherein R 1 Is hydrogen, R 9 Methyl, the resulting product is 9-methyl-9H- [1,2,3]]Triazolo [1',5':1,6]Pyrido [3,4-b]Indoles.
9-methyl-9H- [1,2,3]]Triazolo [1',5':1,6]Pyrido [3,4-b]Indole (4 a): yellow solid, yield: 83%. 1 H NMR(400MHz,DMSO-d 6 )δ9.41(s,1H),8.63(s,1H),8.28(s,1H),8.23(d,J＝7.6Hz,1H),7.59(t,J＝7.6Hz,1H),7.50(d,J＝8.0Hz,1H),7.22(t,J＝7.2Hz,1H),3.79(s,3H). 13 C NMR(100MHz,DMSO-d 6 )δ145.95,135.86,130.77,129.96,127.57,124.69,122.50,120.94,119.87,109.46,106.89,104.66,29.98.
Example 12.
The procedure of example 12 is the same as in example 10, wherein R 1 Is hydrogen, R 9 Butyl, the resulting product is 9-butyl-9H- [1,2,3]]Triazolo [1',5':1,6]Pyrido [3,4-b]Indoles.
9-butyl-9H- [1,2,3]]Triazolo [1',5':1,6]Pyrido [3,4-b]Indole (4 b): yellow solid, yield: 72%. 1 H NMR(400MHz,DMSO-d 6 )δ9.50(t,J＝1.2Hz,1H),8.68(d,J＝1.2Hz,1H),8.29(d,J＝1.2Hz,1H),8.26(dt,J＝7.6,0.8Hz,1H),7.62–7.57(m,1H),7.54(d,J＝8.0Hz,1H),7.25–7.20(m,1H),4.34(t,J＝7.2Hz,2H),1.81–1.73(m,2H),1.41–1.31(m,2H),0.90(t,J＝7.2Hz,3H). 13 C NMR(100MHz,DMSO-d 6 )δ145.39,135.13,130.76,129.98,127.66,124.67,122.65,121.03,119.86,109.73,106.99,104.80,43.04,30.17,20.20,14.25.
Example 13.
The procedure of example 13 is the same as in example 10, wherein R 1 Is hydrogen, R 9 Is 3-phenylpropyl, and the obtained product is 9- (3-phenylpropyl) -9H- [1,2,3]Triazolo [1',5':1,6]Pyrido [3,4-b]Indoles.
9- (3-phenylpropyl) -9H- [1,2,3]Triazolo [1',5':1,6]Pyrido [3,4-b]Indole (4 c): yellow solid, yield: 76%. 1 H NMR(400MHz,DMSO-d 6 )δ9.47(s,1H),8.68(s,1H),8.29(s,1H),8.27(d,J＝7.6Hz,1H),7.61–7.56(m,1H),7.50(d,J＝8.0Hz,1H),7.28–7.15(m,6H),4.38(t,J＝7.2Hz,2H),2.72(t,J＝7.2Hz,2H),2.15–2.06(m,2H). 13 C NMR(100MHz,DMSO-d 6 )δ145.34,141.80,135.11,130.80,130.00,128.77,128.61,127.70,126.31,124.70,122.69,121.10,119.94,109.64,107.04,104.81,43.09,32.88,29.73.
Example 14.
The procedure of example 14 is the same as in example 10, wherein R 1 Is hydrogen, R 9 Methyl, the resulting product is 9-benzyl-9H- [1,2,3]]Triazolo [1',5':1,6]Pyrido [3,4-b]Indoles.
9-benzyl-9H- [1,2,3]]Triazolo [1',5':1,6]Pyrido [3,4-b]Indole (4 d): yellow solid, yield: 66%. 1 H NMR(400MHz,DMSO-d 6 )δ9.50(s,1H),8.72(s,1H),8.29(d,J＝8.0Hz,2H),7.59–7.55(m,2H),7.30(d,J＝4.4Hz,4H),7.27–7.23(m,2H),5.62(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ145.42,137.31,135.33,130.92,130.09,129.13,127.93,127.73,127.50,124.83,122.73,121.24,120.28,110.06,107.26,105.05,46.46.
Example 15.
The procedure of example 15 is the same as in example 10, wherein R 1 Is hydrogen, R 9 4-methoxybenzyl, the resulting product is 6-methyl-2-phenyl-2, 6-dihydroimidazo [1',5':1,6]Pyrido [3,4-b]Indole compounds-4-chloro salt.
9- (4-methoxybenzyl) -9H- [1,2,3]Triazolo [1',5':1,6]Pyrido [3,4-b]Indole (4 e): yellow solid, yield: 63%. 1 H NMR(400MHz,DMSO-d 6 )δ9.50(s,1H),8.70(s,1H),8.28(d,J＝8.0Hz,2H),7.62–7.55(m,2H),7.30–7.22(m,3H),6.85(d,J＝8.8Hz,2H),5.53(s,2H),3.67(s,3H). 13 C NMR(100MHz,DMSO-d 6 )δ159.10,145.39,135.20,130.88,130.06,129.16,129.03,127.77,124.80,122.71,121.25,120.20,114.51,110.14,107.21,105.08,55.48,45.94.
Example 16.
The procedure of example 16 is the same as in example 10, wherein R 1 Is hydrogen, R 9 4-fluorobenzyl, the resulting product is 9- (4-fluorobenzyl) -9H- [1,2,3]Triazolo [1',5':1,6]Pyrido [3,4-b]Indoles.
9- (4-fluorobenzyl) -9H- [1,2,3]Triazolo [1',5':1,6]Pyrido [3,4-b]Indole (4 f): yellow solid, yield: 71%. 1 H NMR(400MHz,DMSO-d 6 )δ9.54(t,J＝1.2Hz,1H),8.72(d,J＝1.2Hz,1H),8.31–8.28(m,2H),7.60–7.55(m,2H),7.40–7.34(m,2H),7.28–7.23(m,1H),7.17–7.10(m,2H),5.61(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ160.74(d,J＝241.9Hz),145.28,135.22,133.53(d,J＝3.1Hz),130.94,130.12,129.69(d,J＝8.4Hz),127.74,124.85,122.76,121.29,120.35,116.04(d,J＝21.3Hz),110.04,107.30,105.07,45.73.
Example 17.
The procedure of example 17 is the same as in example 10, wherein R 1 Is hydrogen, R 9 Is 3-chlorobenzyl, and the obtained product is 9- (3-chlorobenzyl) -9H- [1,2,3]Triazolo [1',5':1,6]Pyrido [3,4-b]Indoles.
9- (3-chlorobenzyl) -9H- [1,2,3]Triazolo [1',5':1,6]Pyrido [3,4-b]Indole (4 g): yellow solid, yield: 73%. 1 H NMR(400MHz,DMSO-d 6 )δ9.55(t,J＝1.2Hz,1H),8.73(d,J＝1.2Hz,1H),8.32-8.29(m,2H),7.61-7.55(m,2H),7.42(s,1H),7.34-7.31(m,2H),7.29-7.24(m,1H),7.22-7.17(m,1H),5.64(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ145.27,139.93,135.27,133.71,131.11,130.99,130.19,127.97,127.70,127.45,126.07,124.90,122.81,121.30,120.47,109.99,107.40,105.09,45.89.
Example 18.
The procedure of example 18 is the same as in example 10, wherein R 1 Is hydrogen, R 9 Is hydrogen, and the obtained product is 9H 1,2,3]Triazole [1',5':1,6]Pyrido [3,4-b]Indoles.
9H-[1,2,3]Triazole [1',5':1,6]Pyrido [3,4-b]Indole (4 h): yellow solid, yield: 82%. 1 H NMR(400MHz,DMSO-d 6 )δ11.04(s,1H),9.19(s,1H),8.66(s,1H),8.27(s,1H),8.24(d,J＝7.6Hz,1H),7.55-7.50(m,1H),7.44(d,J＝8.0Hz,1H),7.22-7.16(m,1H). 13 C NMR(100MHz,DMSO-d 6 )δ145.31,134.27,130.87,129.92,128.51,124.52,122.56,121.08,119.75,111.55,106.75,105.52.
Example 19.
The procedure of example 19 is the same as in example 10, wherein R 1 Is methyl, R 9 Is hydrogen, and the obtained product is 10-methyl-9H- [1,2,3]]Triazole [1',5':1,6]Pyridine [3,4-b]Indoles.
10-methyl-9H- [1,2,3]]Triazole [1',5':1,6]Pyridine [3,4-b]Indole (4 i): orange solid, yield: 76%. 1 H NMR(400MHz,DMSO-d 6 )δ11.16(s,1H),8.54(s,1H),8.31(s,1H),8.23(d,J＝7.6Hz,1H),7.56-7.51(m,1H),7.46(d,J＝8.0Hz,1H),7.21-7.17(m,1H),3.06(s,3H). 13 C NMR(100MHz,DMSO-d 6 )δ145.09,131.84,131.11,129.68,127.56,124.96,122.55,121.52,119.59,115.63,111.38,103.96,13.20.
Example 20.
The procedure of example 20 is the same as in example 10, wherein R 1 Is phenyl, R 9 Is hydrogen, and the obtained product is 10-phenyl-9H- [1,2,3]]Triazole [1',5':1,6]Pyrido [3,4-b]Indoles.
10-phenyl-9H- [1,2,3]]Triazole [1',5':1,6]Pyrido [3,4-b]Indole (4 j): yellow solid, yield: 62%. 1 H NMR(400MHz,DMSO-d 6 )δ10.89(s,1H),8.69(s,1H),8.35(s,1H),8.26(d,J＝7.6Hz,1H),7.98(d,J＝6.8Hz,2H),7.70(t,J＝7.6Hz,2H),7.63(t,J＝7.2Hz,1H),7.51(t,J＝7.6Hz,1H),7.43(d,J＝8.0Hz,1H),7.21(t,J＝7.2Hz,1H). 13 C NMR(100MHz,DMSO-d 6 )δ145.54,131.83,131.52,130.58,130.36,129.89,129.77,129.36,128.64,125.07,122.43,121.33,119.90,117.59,111.91,106.11.
Example 21.
The procedure of example 21 is the same as in example 10, wherein R 1 Is 4-chlorophenyl, R 9 Is hydrogen, the product obtained is 10- (4-chlorophenyl) -9H- [1,2,3]]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indoles.
10- (4-chlorophenyl) -9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole (4 k): yellow solid, yield: 68%. 1 H NMR(400MHz,DMSO-d 6 )δ10.95(s,1H),8.69(s,1H),8.36(s,1H),8.25(d,J＝7.6Hz,1H),8.04-7.99(m,2H),7.78-7.73(m,2H),7.54-7.50(m,1H),7.42(d,J＝8.0Hz,1H),7.21(td,J＝7.6,0.8Hz,1H). 13 C NMR(100MHz,DMSO-d 6 )δ145.48,134.39,132.57,132.06,131.48,129.84,129.43,129.17,128.66,125.24,122.46,121.32,119.99,116.27,111.83,106.49.
Example 22.
The procedure of example 22 is the same as in example 10, wherein R 1 Is 4-methoxyphenyl, R 9 Is hydrogen, and the obtained product is 10- (4-methoxyphenyl) -9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indoles.
10- (4-methoxyphenyl) -9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole (4 l): yellow solid, yield 83%. 1 H NMR(400MHz,DMSO-d 6 )δ10.94(s,1H),8.69(d,J＝3.6Hz,1H),8.36(s,1H),8.25(d,J＝8.0Hz,1H),8.04-7.99(m,2H),7.77-7.73(m,2H),7.54-7.49(m,1H),7.41(d,J＝8.0Hz,1H),7.21(t,J＝7.6Hz,1H). 13 C NMR(100MHz,DMSO-d 6 )δ145.48,134.39,132.59,132.07,131.48,129.85,129.44,129.32,129.18,128.66,125.25,122.48,121.33,120.01,116.28,111.84,106.51,40.68,39.46.
Example 23.
The procedure of example 23 is the same as in example 10, wherein R 1 Is 3,4, 5-trimethoxyphenyl, R 9 Is hydrogen, and the obtained product is 10- (3, 4, 5-trimethoxyphenyl)-9H-[1,2,3]Triazole [1',5':1,6]Pyridine [3,4-b]Indoles.
10- (3, 4, 5-trimethoxyphenyl) -9H- [1,2,3]Triazole [1',5':1,6]Pyridine [3,4-b]Indole (4 m): yellow solid, yield: 78%. 1 H NMR(400MHz,DMSO-d 6 )δ10.91(s,1H),8.66(s,1H),8.35(s,1H),8.25(d,J＝7.6Hz,1H),7.54-7.50(m,1H),7.44(d,J＝8.4Hz,1H),7.26(s,2H),7.21-7.18(m,1H),3.87(s,6H),3.84(s,3H). 13 C NMR(100MHz,DMSO-d 6 )δ153.66,145.44,138.70,131.81,131.54,129.74,128.48,125.47,124.94,122.43,121.29,119.84,117.69,111.85,108.13,105.87,60.54,56.51.
Example 24.
The procedure of example 24 is the same as in example 10, wherein R 1 Is methyl, R 9 Ethyl, the resulting product is 9-ethyl-10-methyl-9H- [1,2,3]]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indoles.
9-ethyl-10-methyl-9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole (4 n): yellow solid, yield: 70%. 1 H NMR(400MHz,DMSO-d 6 )δ8.52(s,1H),8.29(s,1H),8.20(d,J＝7.6Hz,1H),7.59-7.52(m,2H),7.26-7.16(m,1H),4.45(q,J＝7.2Hz,2H),3.22(s,3H),1.34(t,J＝7.2Hz,3H). 13 C NMR(100MHz,DMSO-d 6 )δ145.53,131.07,130.72,129.78,128.11,125.02,122.11,121.11,119.97,115.94,109.56,104.07,14.86,13.70.
Example 25.
The procedure of example 25 is the same as in example 10, wherein R 1 Is methyl, R 9 Butyl, the resulting product is 9-butyl-10-methyl-9H- [1,2,3]]Triazole [1',5':1,6]Pyrido [3,4-b]Indoles.
9-butyl-10-methyl-9H- [1,2,3]Triazole [1',5':1,6]Pyrido [3,4-b]Indole (4 o): yellow solid, yield: 72%. 1 H NMR(400MHz,DMSO-d 6 )δ9.00(s,1H),8.64(s,1H),8.23(dt,J＝7.8,1.0Hz,1H),7.62(ddd,J＝8.4,7.2,1.2Hz,1H),7.50(dt,J＝8.4,0.8Hz,1H),7.34(m,1H),4.63-4.56(m,2H),3.13(s,3H),2.02-1.76(m,2H),1.60-1.39(m,2H),1.01(t,J＝7.6M Hz,4H). 13 C NMR(100MHz,DMSO-d 6 )δ146.06,131.26,130.73,129.76,128.11,125.04,122.09,120.96,119.94,116.02,109.84,104.11,44.45,31.82,19.97,14.18,13.85.
Example 26.
The procedure of example 26 is the same as in example 10, wherein R 1 Is methyl, R 9 Is benzyl, and the obtained product is 9-benzyl-10-methyl-9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indoles.
9-benzyl-10-methyl-9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole (4 p): yellow solid, yield: 71%. 1 H NMR(400MHz,DMSO-d 6 )δ8.63(s,1H),8.33(s,1H),8.29(d,J＝8.0Hz,1H),7.58-7.49(m,2H),7.34-7.31(m,2H),7.29-7.23(m,2H),7.12(d,J＝7.2Hz,2H),5.76(s,2H),3.02(s,3H). 13 C NMR(100MHz,DMSO-d 6 )δ146.40,138.67,131.80,130.94,130.00,129.38,128.09,127.73,126.01,125.21,122.27,121.11,120.43,116.26,109.85,104.41,48.05,13.56.
Example 27.
The procedure of example 27 is the same as in example 10, wherein R 1 Is methyl, R 9 4-fluorobenzyl, the resulting product is 9- (4-fluorobenzyl) -10-methyl-9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indoles.
9- (4-fluorobenzyl) -10-methyl-9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole (4 q): yellow solid, yield: 76%. 1 H NMR(400MHz,DMSO-d 6 )δ8.64(s,1H),8.33(s,1H),8.30(d,J＝8.0Hz,1H),7.58-7.50(m,2H),7.27(t,J＝7.2Hz,1H),7.17-7.14(m,4H),5.75(s,2H),3.03(s,3H). 13 C NMR(100MHz,DMSO-d 6 )δ160.60(d,J＝241.6Hz),146.25,134.73(d,J＝2.7Hz),131.67,130.95,130.00,128.03(d,J＝7.9Hz),125.21,122.25,121.15,120.49,116.07(d,J＝21.2Hz),109.82,104.41,47.42,13.56.
Example 28.
The procedure of example 28 is the same as in example 10, wherein R 1 Is methyl, R 9 Is 3-chlorobenzyl, and the obtained product is 9- (3-chlorobenzyl) -10-methyl-9H- [1,2,3]Triazole [1',5':1,6]Pyridine [3,4-b]Indoles.
9- (3-chlorobenzyl) -10-methyl-9H- [1,2,3]Triazole [1',5 ]':1,6]Pyridine [3,4-b]Indole (4 r): yellow solid, yield: 77%. 1 H NMR(400MHz,DMSO-d 6 )δ8.69(s,1H),8.34(s,1H),8.32(d,J＝8.0Hz,1H),7.60–7.51(m,2H),7.35-7.33(m,2H),7.3026(m,2H),7.02-7.00(m,1H),5.81(s,2H),3.03(s,3H). 13 C NMR(100MHz,DMSO-d 6 )δ146.29,141.41,134.02,131.77,131.38,131.04,130.13,128.14,127.81,126.07,125.31,124.66,122.39,121.21,120.66,116.37,109.88,104.60,47.64,13.61.
Example 29.
The intermediates of examples 1-28 were used to prepare beta-carboline hybrid triazoles using the following reaction scheme:
Scheme 3
Figure BDA0002930174730000151
compound 5: weighing [1,2,3]]Triazolo [1',5':1,2]Pyrido [3,4-b]Indole (0.2 mmol), diaryliodonium salt (0.3 mmol), catalyst Cu (CN) 4 PF 6 In the reaction tube, DCE (2 mL) solvent was then added for dissolution, and the mixture was stirred at 80℃and the progress of the reaction was monitored by TLC. After the reaction is completed, the obtained crude product is purified by silica gel column chromatography (MeOH/DMF) to obtain the product, namely the beta-carboline heterozygous triazole compound, which is solid powder.
Compound 6 was synthesized by the same method as compound 5.
Example 30.
The procedure of example 30 is the same as in example 29, wherein R 2 Is phenyl, R 9 Is methyl, X is tetrafluoroborate, and the obtained product is 11-methyl-2-phenyl-11H- [1,2,3]]Triazole [1',5':1,2]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborates.
11-methyl-2-phenyl-11H- [1,2,3]Triazole [1',5':1,2]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborate (5 a): yellow solid, yield: 75.7%. 1 H NMR(400MHz,DMSO-d 6 )δ10.69(s,1H),9.32(d,J＝7.2Hz,1H),8.76(d,J＝7.2Hz,1H),8.45(d,J＝8.0Hz,1H),8.30(d,J＝7.6Hz,2H),7.98(d,J＝8.4Hz,1H),7.89–7.69(m,3H),7.72(t,J＝7.6Hz,1H),7.50(t,J＝7.6Hz,1H),4.41(s,3H). 13 C NMR(100MHz,DMSO-d 6 )δ140.99,135.73,132.56,131.03,128.00,127.62,127.49,122.67,122.30,121.74,121.45,120.41,117.96,117.69,117.46,111.68,32.53.
Example 31.
The procedure of example 31 is the same as in example 29, wherein R 2 Is phenyl, R 9 Is butyl, X is tetrafluoroborate, and the obtained product is 11-butyl-2-phenyl-11H- [1,2,3]]Triazole [1',5':1,2]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborates.
11-butyl-2-phenyl-11H- [1,2,3]Triazole [1',5':1,2]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborate (5 b): yellow green solid, yield: 83.1%. 1 H NMR(400MHz,DMSO-d 6 )δ10.54(s,1H),9.33(d,J＝7.2Hz,1H),8.77(d,J＝7.2Hz,1H),8.46(d,J＝8.0Hz,1H),8.28(d,J＝7.6Hz,2H),8.00(d,J＝8.4Hz,1H),7.90–7.81(m,3H),7.70(t,J＝7.6Hz,1H),7.49(t,J＝7.6Hz,1H),4.91(t,J＝6.8Hz,2H),1.92–1.84(m,2H),1.38–1.28(m,2H),0.85(t,J＝7.2Hz,3H). 13 C NMR(100MHz,DMSO-d 6 )δ140.63,135.77,132.55,130.94,128.03,127.42,126.77,123.03,122.33,121.83,121.60,120.31,118.13,117.80,117.64,111.92,45.07,32.09,19.89,14.26.
Example 32.
The procedure of example 32 is the same as that of example 29, wherein R 2 Is phenyl, R 9 Is benzyl, X is tetrafluoroborate, and the obtained product is 11-benzyl-2-phenyl-11H- [1,2,3]]Triazole [1',5':1,2]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborates.
11-benzyl-2-phenyl-11H- [1,2,3]Triazole [1',5':1,2]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborate (5 c): yellow green solid, yield: 82.1%. 1 H NMR(400MHz,DMSO-d 6 )δ10.66(s,1H),9.41(d,J＝7.2Hz,1H),8.82(d,J＝7.2Hz,1H),8.50(d,J＝8.0Hz,1H),8.23(d,J＝6.8Hz,2H),7.88–7.79(m,5H),7.66(t,J＝7.6Hz,1H),7.51(t,J＝7.6Hz,1H),7.42(s,1H),7.36–7.28(m,2H),7.15(d,J＝7.2Hz,1H),6.19(s,2H). 13 C NMR(101MHz,DMSO-d 6 )δ140.32,139.23,135.68,133.93,132.60,131.24,131.03,128.35,127.64,127.33,126.01,122.77,122.67,122.02,119.91,118.72,118.18,117.71,112.13,48.00.
Example 33.
The procedure of example 33 is the same as in example 29, wherein R 2 Is phenyl, R 9 Is 4-fluorobenzyl, X is tetrafluoroborate, and the resulting product is 11- (4-fluorobenzyl) -2-phenyl-11H- [1,2,3]Triazole [1',5':1,2]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborates.
11- (4-fluorobenzyl) -2-phenyl-11H- [1,2,3]Triazole [1',5':1,2]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborate (5 d): yellow green solid, yield: 75.5%. 1 H NMR(400MHz,DMSO-d 6 )δ10.68(s,1H),9.40(d,J＝7.2Hz,1H),8.81(d,J＝7.2Hz,1H),8.49(d,J＝8.0Hz,1H),8.24(d,J＝8.0Hz,2H),7.90–7.79(m,4H),7.68–7.63(m,1H),7.50(t,J＝7.6Hz,1H),7.38–7.34(m,2H),7.15–7.09(m,2H),6.16(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ160.92(d,J＝242.5Hz),140.36,135.70,132.95(d,J＝3.1Hz),132.59,131.02,129.69(d,J＝8.2Hz),128.26,127.66,127.17,122.70,122.68,122.05,121.98,119.93,118.64,118.18,117.71,116.00(d,J＝21.4Hz),112.24,47.87.
Example 34.
The procedure of example 34 is the same as in example 29, wherein R 2 Is phenyl, R 9 Is 3-chlorobenzyl, X is tetrafluoroborate, and the product obtained is 11- (3-chlorobenzyl) -2-phenyl-11H- [1,2,3]Triazole [1',5':1,2]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborates.
11- (3-chlorobenzyl) -2-phenyl-11H- [1,2,3]Triazole [1',5':1,2]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborate (5 e): yellow solid, yield: 63%. 1 H NMR(400MHz,DMSO-d 6 )δ10.68(s,1H),9.40(d,J＝7.2Hz,1H),8.81(dd,J＝7.2,1.2Hz,1H),8.48(d,J＝8.0Hz,1H),8.26–8.20(m,2H),7.87–7.80(m,4H),7.64(t,J＝7.6Hz,1H),7.49(t,J＝7.6Hz,1H),7.31–7.27(m,4H),6.18(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ140.45,136.76,135.71,132.57,131.00,129.29,128.33,128.20,127.66,127.56,127.26,122.68,122.65,122.02,121.94,119.90,118.59,118.10,117.71,112.30,48.61.
Example 35.
The procedure of example 35 is the same as in example 29, wherein R 2 Is phenyl, R 9 Is 3-phenylpropyl, X is tetrafluoroborate, and the product obtained is 2-phenyl-11- (3-phenylpropyl) -11H- [1,2,3]Triazole [1',5':1,2]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborates.
2-phenyl-11- (3-phenylpropyl) -11H- [1,2,3]Triazole [1',5':1,2]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborate (5 f) as a yellow-green solid, yield: 74.4%. 1 H NMR(400MHz,DMSO-d 6 )δ10.47(s,1H),9.35(d,J＝7.2Hz,1H),8.77(d,J＝7.2Hz,1H),8.47(d,J＝8.0Hz,1H),8.28–8.23(m,2H),7.95(d,J＝8.4Hz,1H),7.90–7.83(m,3H),7.71(t,J＝7.6Hz,1H),7.51(t,J＝7.6Hz,1H),7.20–7.15(m,2H),7.12–7.06(m,3H),4.98(t,J＝7.2Hz,2H),2.68(t,J＝7.2Hz,2H),2.27–2.19(m,2H). 13 C NMR(100MHz,DMSO-d 6 )δ141.33,140.53,135.74,132.58,130.97,128.69,128.56,128.09,127.42,126.88,126.35,123.02,122.41,121.90,121.70,120.29,118.15,117.88,117.68,111.84,44.92,32.43,31.27.
Example 36.
The procedure of example 36 is the same as in example 29, wherein R 2 Is 4-fluorophenyl, R 9 Is benzyl, X is tetrafluoroborate, and the obtained product is 11-benzyl-2- (4-fluorophenyl) -11H- [1,2,3]Triazole [1',5':1,2]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborates.
11-benzyl-2- (4-fluorophenyl) -11H- [1,2,3]Triazole [1',5':1,2]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborate (5 g): yellow solid, yield: 77.8%. 1 H NMR(400MHz,DMSO-d 6 )δ10.26(s,1H),10.13(s,1H),9.37(s,1H),8.58(d,J＝8.0Hz,1H),8.31–8.23(m,2H),7.80–7.74(m,2H),7.72–7.66(m,2H),7.46–7.42(m,1H),7.37–7.27(m,5H),5.81(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ162.57(d,J＝248.1Hz),145.46,138.56,136.57,132.47(d,J＝3.0Hz),131.97,131.74,130.49,129.25,128.26,127.61,125.24(d,J＝9.4Hz),124.07,122.14,121.91,120.40,117.83(d,J＝23.6Hz),111.19,110.27,106.68,46.93.
Example 37.
Operation of example 37The procedure is as in example 29, wherein R 2 Is 4-fluorophenyl, R 9 Is 4-fluorobenzyl, X is tetrafluoroborate, and the resulting product is 11- (4-fluorobenzyl) -2- (4-fluorophenyl) -11H- [1,2,3]Triazole [1',5':1,2]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborates.
11- (4-fluorobenzyl) -2- (4-fluorophenyl) -11H- [1,2,3]Triazole [1',5':1,2]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborate (5 h): yellow solid, yield: 79.2%. 1 H NMR(400MHz,DMSO-d 6 )δ10.66(s,1H),9.39(d,J＝7.2Hz,1H),8.82(d,J＝7.2Hz,1H),8.48(d,J＝8.0Hz,1H),8.29(dd,J＝8.8,4.4Hz,2H),7.87(d,J＝8.4Hz,1H),7.74(t,J＝8.4Hz,2H),7.66(t,J＝7.6Hz,1H),7.50(t,J＝7.6Hz,1H),7.36(t,J＝7.6Hz,2H),7.12(t,J＝8.8Hz,2H),6.15(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ162.86(d,J＝248.9Hz),160.92(d,J＝242.6Hz),140.35,132.92(d,J＝3.1Hz),132.17(d,J＝2.9Hz),129.77(d,J＝8.3Hz),128.28,127.57,127.11,125.50(d,J＝9.5Hz),122.71,122.03,121.99,120.22,118.58,118.22,117.98,117.76,116.22(d,J＝21.4Hz),112.24,47.87.
Example 38.
The procedure of example 38 is the same as in example 29, wherein R 2 Is 4-chlorophenyl, R 9 Is benzyl, X is tetrafluoroborate, and the obtained product is 11-benzyl-2- (4-chlorophenyl) -11H- [1,2,3]Triazole [1',5':1,2]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborates.
11-benzyl-2- (4-chlorophenyl) -11H- [1,2,3]Triazole [1',5':1,2]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborate (5 i): yellow solid, yield: 73.1%. 1 H NMR(400MHz,DMSO-d 6 )δ10.25(s,1H),10.11(s,1H),9.36(s,1H),8.57(d,J＝7.6Hz,1H),8.23(d,J＝8.8Hz,2H),7.91(d,J＝8.4Hz,2H),7.76(d,J＝4.0Hz,2H),7.47–7.42(m,1H),7.38–7.25(m,6H),5.80(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ145.46,138.63,136.64,136.53,134.80,132.01,131.77,130.93,130.54,129.25,128.28,127.61,124.34,124.06,122.03,121.95,120.39,111.20,110.31,106.67,46.94.
Example 39.
The procedure of example 39 was the same as in example 29, wherein,R 2 is 4-chlorophenyl, R 9 Is 4-fluorobenzyl, X is tetrafluoroborate, and the resulting product is 11- (4-fluorobenzyl) -2- (4-chlorophenyl) -11H- [1,2,3]Triazole [1',5':1,2]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborates.
11- (4-fluorobenzyl) -2- (4-chlorophenyl) -11H- [1,2,3]Triazole [1',5':1,2]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborate (5 j): yellow solid, yield: 82.7%. 1 H NMR(400MHz,DMSO-d 6 )δ10.70(s,1H),9.40(d,J＝7.2Hz,1H),8.82(d,J＝7.2Hz,1H),8.48(d,J＝8.0Hz,1H),8.28(d,J＝8.4Hz,2H),7.96(d,J＝8.4Hz,2H),7.87(d,J＝8.4Hz,1H),7.66(t,J＝7.6Hz,1H),7.50(t,J＝7.6Hz,1H),7.36(t,J＝7.6Hz,2H),7.12(t,J＝8.8Hz,2H),6.15(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ160.92(d,J＝242.5Hz),140.35,137.17,134.49,132.91(d,J＝3.0Hz),131.06,129.79(d,J＝8.3Hz),128.30,127.62,127.13,124.44,122.73,122.03,121.99,120.12,118.60,118.23,117.89,116.22(d,J＝21.3Hz),112.25,47.88.
Example 40.
The procedure of example 40 is the same as in example 29, wherein R 1 Is methyl, R 2 Is phenyl, R 9 Is ethyl, X is tetrafluoroborate, and the obtained product is 9-ethyl-10-methyl-2-phenyl-9H- [1,2,3]]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborates.
9-ethyl-10-methyl-2-phenyl-9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborate (6 a): yellow solid, yield: 71.6%. 1 H NMR(400MHz,DMSO-d 6 )δ10.23(s,1H),9.24(s,1H),8.55(d,J＝8.0Hz,1H),8.29(d,J＝7.6Hz,2H),7.87–7.75(m,5H),7.43(t,J＝7.2Hz,1H),4.71(q,J＝6.4Hz,2H),3.37(s,3H),1.46(t,J＝7.2Hz,3H). 13 C NMR(100MHz,DMSO-d 6 )δ145.58,136.14,134.60,132.08,131.74,131.48,131.04,130.90,123.50,122.49,121.70,121.58,120.10,118.11,110.70,107.48,46.23,15.19,14.12.
Example 41.
The procedure of example 30 is the same as in example 29, wherein R 1 Is methyl, R 2 Is phenyl, R 9 Is butyl, X is tetrafluoroboric acidRoot, the obtained product is 9-butyl-10-methyl-2-phenyl-9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborates.
9-butyl-10-methyl-2-phenyl-9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborate (6 b): yellow solid, yield: 76.6%. 1 H NMR(400MHz,DMSO-d 6 )δ10.24(s,1H),9.26(s,1H),8.56(d,J＝8.0Hz,1H),8.29(d,J＝7.6Hz,2H),7.90–7.72(m,5H),7.43(t,J＝7.2Hz,1H),4.67(t,J＝7.6Hz,2H),3.36(s,3H),1.89–1.80(m,2H),1.49–1.37(m,2H),0.95(t,J＝7.2Hz,3H). 13 C NMR(100MHz,DMSO-d 6 )δ146.13,136.16,134.76,132.10,131.71,131.53,131.07,130.91,123.47,122.53,121.68,121.63,119.97,118.21,111.01,107.50,44.76,32.09,19.94,14.27,14.23.
Example 42.
The procedure of example 42 is the same as in example 29, wherein R 1 Is methyl, R 2 Is phenyl, R 9 Is benzyl, X is tetrafluoroborate, and the obtained product is 9-benzyl-2-phenyl-9H- [1,2,3]]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborates.
9-benzyl-2-phenyl-9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborate (6 c): yellow solid, yield: 79.8%. 1 H NMR(400MHz,DMSO-d 6 )δ10.23(s,1H),10.12(s,1H),9.35(s,1H),8.58(d,J＝8.0Hz,1H),8.20(d,J＝7.6Hz,2H),7.87–7.71(m,5H),7.46–7.42(m,1H),7.38–7.26(m,5H),5.80(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ145.46,138.57,136.56,136.01,132.09,131.96,131.81,130.93,130.49,129.25,128.27,127.61,124.05,122.52,121.90,121.75,120.40,111.17,110.23,106.69,46.93.
Example 43.
The procedure of example 43 is the same as in example 29, wherein R 1 Is hydrogen, R 2 Is phenyl, R 9 4-methoxybenzyl, X is tetrafluoroborate, and the resulting product is 9- (4-methoxybenzyl) -2-phenyl-9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborates.
9- (4-methoxybenzyl) -2-phenyl-9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborate (6 d): yellow green solid, yield: 74%. 1 H NMR(400MHz,DMSO-d 6 )δ10.21(s,1H),10.12(s,1H),9.31(s,1H),8.55(d,J＝7.6Hz,1H),8.20(d,J＝7.6Hz,2H),7.84–7.73(m,5H),7.43(t,J＝7.2Hz,1H),7.35(d,J＝8.4Hz,2H),6.88(d,J＝8.8Hz,2H),5.70(s,2H),3.69(s,3H). 13 C NMR(100MHz,DMSO-d 6 )δ159.35,145.38,138.37,136.01,132.08,131.90,131.72,130.93,130.48,129.23,128.41,123.99,122.50,121.81,121.70,120.38,114.60,111.22,110.14,106.64,55.55,46.43.
Example 44.
The procedure of example 44 is the same as in example 29, wherein R 1 Is hydrogen, R 2 Is phenyl, R 9 Is 4-fluorobenzyl, X is tetrafluoroborate, and the resulting product is 9- (4-fluorobenzyl) -9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborates.
9- (4-fluorobenzyl) -9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborate (6 e): yellow solid, yield: 85%. 1 H NMR(400MHz,DMSO-d 6 )δ10.23(s,1H),10.14(s,1H),9.35(s,1H),8.58(d,J＝8.0Hz,1H),8.24–8.16(m,2H),7.86–7.73(m,5H),7.49–7.39(m,3H),7.20–7.13(m,2H),5.78(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ160.93(d,J＝242.1Hz),145.33,138.45,136.01,132.80(d,J＝3.0Hz),132.11,132.00,131.83,130.94,130.52,129.80(d,J＝8.2Hz),124.09,122.51,121.96,121.77,120.45,115.97(d,J＝21.4Hz),111.14,110.26,106.71,46.22.
Example 45.
The procedure of example 45 is the same as in example 29, wherein R 1 Is hydrogen, R 2 Is phenyl, R 9 Is 3-phenylpropyl, X is tetrafluoroborate, and the product obtained is 2-phenyl-9- (3-phenylpropyl) -9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborates.
2-phenyl-9- (3-phenylpropyl) -9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborate (6 f) as a yellow-green solid, yield: 82.8%. 1 H NMR(400MHz,DMSO-d 6 )δ10.47(s,1H),9.35(d,J＝7.2Hz,1H),8.77(d,J＝7.2Hz,1H),8.47(d,J＝8.0Hz,1H),8.27(d,J＝7.2Hz,2H),7.95(d,J＝8.4Hz,1H),7.91–7.82(m,3H),7.71(t,J＝8.0Hz,1H),7.51(t,J＝7.6Hz,1H),7.22–7.15(m,2H),7.12–7.07(m,3H),4.98(t,J＝7.2Hz,2H),2.75–2.63(t,J＝7.2Hz,2H),2.29–2.18(m,2H). 13 C NMR(100MHz,DMSO-d 6 )δ141.33,140.52,135.74,132.58,130.97,128.69,128.56,128.08,127.41,126.87,126.35,123.02,122.40,121.89,121.70,120.28,118.14,117.88,117.67,111.83,44.91,32.43,31.27.
Example 46.
The procedure of example 46 is the same as in example 29, wherein R 1 Is methyl, R 2 Is phenyl, R 9 Is benzyl, X is tetrafluoroborate, and the obtained product is 9-benzyl-10-methyl-2-phenyl-9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborates.
9-benzyl-10-methyl-2-phenyl-9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborate (6 g): yellow solid, yield: 79.4%. 1 H NMR(400MHz,DMSO-d 6 )δ10.24(s,1H),9.32(s,1H),8.61(d,J＝8.0Hz,1H),8.25(d,J＝6.8Hz,2H),7.85–7.74(m,5H),7.49–7.44(m,1H),7.38–7.28(m,3H),7.15(d,J＝6.8Hz,2H),6.00(s,2H),3.15(s,3H). 13 C NMR(100MHz,DMSO-d 6 )δ146.41,137.95,136.13,135.32,132.11,131.92,131.84,131.05,130.87,129.53,128.05,126.05,123.62,122.60,122.06,121.81,120.14,118.34,110.95,107.76,48.17,13.93.
Example 47.
The procedure of example 47 is the same as in example 29, wherein R 1 Is methyl, R 2 Is phenyl, R 9 Is 3-chlorobenzyl, X is tetrafluoroborate, and the product obtained is 9- (3-chlorobenzyl) -10-methyl-2-phenyl-9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborates.
9- (3-chlorobenzyl) -10-methyl-2-phenyl-9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborate (6 h) yellow solid, yield: 56.9%. 1 H NMR(400MHz,DMSO-d 6 )δ10.25(s,1H),9.33(s,1H),8.62(d,J＝7.6Hz,1H),8.26(d,J＝7.2Hz,2H),7.88–7.70(m,5H),7.50–7.45(m,1H),7.39–7.36(m,2H),7.29(s,1H),7.08–7.05(m,1H),6.01(s,2H),3.15(s,3H). 13 C NMR(100MHz,DMSO-d 6 )δ146.22,140.60,136.12,135.28,134.17,132.13,131.98,131.92,131.48,131.08,130.88,128.12,126.10,124.73,123.67,122.59,122.20,121.82,120.21,118.42,110.87,107.82,47.71,13.94.
Example 48.
The procedure of example 48 is the same as that of example 29, wherein R 1 Is methyl, R 2 Is 4-fluorophenyl, R 9 Is hydrogen, X is tetrafluoroborate, and the obtained product is 2- (4-fluorophenyl) -10-methyl-9H- [1,2,3]]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborates.
2- (4-fluorophenyl) -10-methyl-9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborate (6 i) as yellow solid, yield: 62%. 1 H NMR(400MHz,DMSO-d 6 )δ12.50(s,1H),10.25(s,1H),9.21(s,1H),8.51(d,J＝7.6Hz,1H),8.45–8.26(m,2H),7.84–7.54(m,4H),7.38(t,J＝7.2Hz,1H),3.18(s,3H). 13 C NMR(100MHz,DMSO-d 6 )δ162.55(d,J＝248.0Hz),145.11,135.60,132.65(d,J＝2.9Hz),131.60,131.58,130.39,125.17(d,J＝9.3Hz),123.84,121.91,121.23,120.54,117.88,117.80(d,J＝23.7Hz),112.33,107.60,13.38.
Example 49.
The procedure of example 49 is the same as in example 29, wherein R 1 Is methyl, R 2 Is 4-fluorophenyl, R 9 Is ethyl, X is tetrafluoroborate, and the obtained product is 9-ethyl-2- (4-fluorophenyl) -10-methyl-9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborates.
9-ethyl-2- (4-fluorophenyl) -10-methyl-9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborate (6 j) as yellow solid, yield: 79%. 1 H NMR(400MHz,DMSO-d 6 )δ10.25(s,1H),9.27(s,1H),8.55(d,J＝7.6Hz,1H),8.34(d,J＝8.8Hz,2H),7.93(d,J＝8.8Hz,2H),7.84–7.76(m,2H),7.43(t,J＝7.2Hz,1H),4.72(q,J＝7.2Hz,2H),3.37(s,3H),1.46(t,J＝7.2Hz,3H). 13 C NMR(100MHz,DMSO-d 6 )δ145.61,136.63,134.94,134.70,131.81,131.47,131.12,130.90,124.26,123.54,121.84,121.77,120.10,118.13,110.77,107.61,15.19,14.14.
Example 50.
The procedure of example 50 is the same as in example 29, wherein R 1 Is hydrogen, R 2 Is 4-fluorophenyl, R 9 Is 4-fluorobenzyl, X is tetrafluoroborate, and the resulting product is 2- (4-fluorophenyl) -9- (4-fluorobenzyl) -9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborates.
2- (4-fluorophenyl) -9- (4-fluorobenzyl) -9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborate (6 k) as yellow solid, yield: 72.2%. 1 H NMR(400MHz,DMSO-d 6 )δ10.20(s,1H),10.13(s,1H),9.36(s,1H),8.57(d,J＝7.6Hz,1H),8.30–8.22(m,2H),7.80–7.74(m,2H),7.70(t,J＝8.4Hz,2H),7.47–7.40(m,3H),7.21–7.13(m,2H),5.78(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ162.59(d,J＝248.3Hz),160.93(d,J＝242.3Hz),145.33,138.45,132.75(d,J＝3.2Hz),132.47(d,J＝3.0Hz),132.02,131.76,130.53,129.78(d,J＝8.3Hz),125.24(d,J＝9.3Hz),124.07,122.09,121.98,120.43,117.85(d,J＝23.6Hz),115.97(d,J＝21.3Hz),111.15,110.25,106.67,46.22.
Example 51.
The procedure of example 51 is the same as in example 29, wherein R 1 Is methyl, R 2 Is 4-chlorophenyl, R 9 Is ethyl, X is tetrafluoroborate, and the product obtained is 2- (4-chlorophenyl) -9-ethyl-10-methyl-9H- [1,2,3]]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborates.
2- (4-chlorophenyl) -9-ethyl-10-methyl-9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborate (6 l): yellow solid, yield: 80.9%. 1 H NMR(400MHz,DMSO-d 6 )δ10.25(s,1H),9.27(s,1H),8.55(d,J＝7.6Hz,1H),8.34(d,J＝8.8Hz,2H),7.93(d,J＝8.8Hz,2H),7.84–7.76(m,2H),7.43(t,J＝7.2Hz,1H),4.72(q,J＝7.2Hz,2H),3.37(s,3H),1.46(t,J＝7.2Hz,3H). 13 C NMR(100MHz,DMSO-d 6 )δ145.61,136.63,134.94,134.70,131.81,131.47,131.12,130.90,124.26,123.54,121.84,121.77,120.10,118.13,110.77,107.61,15.19,14.14.
Example 52.
The procedure of example 52 is the same as in example 29, wherein R 1 Is methyl, R 2 Is 4-chlorophenyl, R 9 4-fluorobenzyl group and X is tetrafluoroborate, the resulting product is 2- (4-chlorophenyl) -9- (4-fluorobenzyl) -10-methyl-9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborates.
2- (4-chlorophenyl) -9- (4-fluorobenzyl) -10-methyl-9H- [1,2,3]Triazole [1',5':1,6]Pyridinyl [3,4-b ]]Indole-2-tetrafluoroborate (6 m) as yellow solid, yield: 78.7%. 1 H NMR(400MHz,DMSO-d 6 )δ10.24(s,1H),10.13(s,1H),9.36(s,1H),8.57(d,J＝7.6Hz,1H),8.28–8.18(m,2H),7.97–7.88(m,2H),7.82–7.73(m,2H),7.50–7.38(m,3H),7.17(t,J＝8.8Hz,2H),5.78(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ160.93(d,J＝242.3Hz),145.34,138.52,136.66,134.80,132.74(d,J＝3.0Hz),132.05,131.80,130.95,130.57,129.79(d,J＝8.3Hz),124.34,124.09,122.04,122.01,120.43,115.97(d,J＝21.3Hz),111.18,110.33,106.69,46.23.
The chemical structural formulas of the products prepared in examples 2-52 are shown in Table 1.
TABLE 1
Figure BDA0002930174730000251
/>
Figure BDA0002930174730000261
/>
Figure BDA0002930174730000271
Example 53.
In vitro anti-tumor Activity Studies
With A549 (lung cancer cell), BGC-823 (gastric cancer cell), CT-26 (colon cancer cell), bel-7402 (liver cancer cell)) And MCF-7 (breast cancer cells) as targets, and the inhibition activity of target compounds on tumor cell lines was tested by adopting an MTT method. The cell lines in good growth state and logarithmic phase are respectively grown at 1×10 4 Individual mL -1 Is inoculated in 96-well plates and placed in CO at 37 DEG C 2 Culturing in incubator for 24 hr, discarding old solution, replacing fresh culture solution, adding sterilized compound to be tested, culturing for 48 hr, discarding culture solution, and adding 20 μl of culture solution containing 5 mg/mL -1 RPMI1640 culture medium of MTT was further cultured for 4 hours, 100. Mu.L of DMSO was added to each well after carefully removing the supernatant, the pellet was dissolved by shaking for about 10 minutes, then the OD value was measured by an ELISA reader, the wavelength was 490nm, and the IC of each sample was obtained by a mapping method 50 Values. The specific results are shown in Table 2
TABLE 2 in vitro antitumor Activity of target Compounds
Figure BDA0002930174730000272
/>
Figure BDA0002930174730000281
/>
Figure BDA0002930174730000291
a IC 50 The values represent the drug concentration required to inhibit tumor cell growth by 50%.
b The tumor cell lines represented are: a549 (lung cancer cells), BGC-823 (stomach cancer cells), CT-26 (colon cancer cells), bel-7402 (liver cancer cells) and MCF-7 (breast cancer cells).
c The values in the table are the average of the results of three parallel experiments.
As shown in Table 2, the 2, 6-dihydroimidazo [1',5':1,6] pyrido [3,4-b ] indole compounds have better anti-tumor activity, and can be applied to anti-tumor drugs.
The foregoing description is only a preferred embodiment of the present invention, and is not intended to limit the embodiment of the present invention in any way, but any simple modification, equivalent variation and modification of the above embodiment according to the technical substance of the embodiment of the present invention still fall within the scope of the technical solution of the embodiment of the present invention.

Claims (8)

1. The beta-carboline heterozygous triazole compound is characterized by having a chemical structural general formula:
Figure FDA0004135748230000011
the beta-carboline heterozygous triazole compound is any one of the following compounds:
11-methyl-2-phenyl-11H- [1,2,3] triazole [1',5':1, 2-pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 11-butyl-2-phenyl-11H- [1,2,3] triazole [1',5':1,2] indole-2-tetrafluoroborate, 11-benzyl-2-phenyl-11H- [1,2,3] triazole [1',5':1,2] pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 11- (4-fluorobenzyl) -2-phenyl-11H- [1,2,3] triazole [1',5':1,2] pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 11- (3-chlorobenzyl) -2-phenyl-11H- [1,2,3] triazole [1',5':1,2] triazole [3,4-b ] indole-2-tetrafluoroborate, 2-phenyl-11- (3-phenylpropyl) -11H- [1,2, 3-b ] indole-2-tetrafluoroborate, 11- (3-phenyl-propyl) -11H- [1,2, 3-b ] indole-2-triazole [1',5':1, 4-b ] indole-2-4-tetrafluoroborate, 11- (3-chlorobenzyl) -2-phenyl-11H- [1,2, 3-b ] triazole [1',5':1, 2-b ] indole-2-4-tetrafluoroborate, 11, 5':1,2] pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 11-benzyl-2- (4-chlorophenyl) -11H- [1,2,3] triazol [1',5':1,2] pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 11- (4-fluorobenzyl) -2- (4-chlorophenyl) -11H- [1,2,3] triazol [1',5':1,2] pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 9-ethyl-10-methyl-2-phenyl-9H- [1,2,3] triazol [1',5':1,6] pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 9-butyl-10-methyl-2-phenyl-9H- [1,2,3] triazol [1',5':1,6] pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 9-ethyl-10-methyl-2-phenyl-9H- [1',5':1,6] pyridinyl [1, 4-b ] indole-2-tetrafluoroborate, 9-ethyl-10-methyl-2-b ] indole-2-triazole [1',5':1, 4-b ] indole-2-4-tetrafluoroborate, 9- [1, 6] pyridinyl [1, 6] indole-2-yl ] tetrafluoroborate, 9-methyl-2-4-yl ] 2-yl-4-yl-2-yl-4-yl-carbonyl-amine 2-phenyl-9- (3-phenylpropyl) -9H- [1,2,3] triazole [1',5':1,6] pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 9-benzyl-10-methyl-2-phenyl-9H- [1,2,3] triazole [1',5':1, 6-pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 9- (3-chlorobenzyl) -10-methyl-2-phenyl-9H- [1,2,3] triazol [1',5':1,6] pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 2- (4-fluorophenyl) -10-methyl-9H- [1,2,3] triazol [1',5':1,6] pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 9-ethyl-2- (4-fluorophenyl) -10-methyl-9H- [1,2,3] triazol [1',5':1,6] pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 2- (4-fluorophenyl) -9- (4-fluorobenzyl) -9H- [1,2,3] triazol [1',5':1,6] pyridinyl [3,4-b ] indole-2-tetrafluoroborate, 9-ethyl-2- (4-fluorophenyl) -10-methyl-9H- [1,2,3] triazol 2-tetrafluoroborate, 2- (4-fluorophenyl) -9H- [1,2,3] triazol [1',5':1,6] indole-2-tetrafluoroborate 2- (4-chlorophenyl) -9- (4-fluorobenzyl) -10-methyl-9H- [1,2,3] triazole [1',5':1,6] pyridinyl [3,4-b ] indole-2-tetrafluoroborate.
2. The use of the beta-carboline heterozygous triazole compound of claim 1 in preparing antitumor drugs.
3. The method for preparing the beta-carboline heterozygous triazole compound of claim 1, which is characterized in that the chemical reaction formula of the preparation method is as follows:
Figure FDA0004135748230000021
4. a method of manufacture as claimed in claim 3, comprising the specific steps of:
s10, synthesizing an intermediate:
toluene is added into the corresponding 9-substituted-1-aldehyde-beta-carboline, p-toluenesulfonyl hydrazide and cesium carbonate, after stirring and dissolving, a catalyst CuI is added, and the mixture is heated to react at 80 ℃; monitoring the reaction by TLC, concentrating under vacuum after the reaction is finished, purifying the obtained crude product by silica gel column chromatography to obtain an intermediate of yellow solid powder, namely [1,2,3] triazole heterozygous beta-carboline;
s20, synthesizing a target compound:
the [1,2,3] is then added to the mixture]Triazole heterozygote beta-carboline, diaryl iodized salt and catalyst Cu (CN) 4 PF 6 After mixing, DCE solvent was added for dissolution, stirred at 80 ℃, and the progress of the reaction was monitored by TLC; after the reaction is finished, purifying the obtained crude product through silica gel column chromatography to obtain a target compound which is solid powder, namely the beta-carboline heterozygous triazole compound.
5. The process according to claim 4, wherein,
the molar ratio of the corresponding 9-substituted-1-aldehyde-beta-carboline, p-toluenesulfonyl hydrazide, cesium carbonate and CuI is 0.3:0.38:0.45:0.03;
the dosage ratio of the [1,2,3] triazole heterozygous beta-carboline, diaryl iodized salt and the DCE solvent is 0.2mmol:0.3mmol:2mL.
6. The method for preparing the beta-carboline heterozygous triazole compound of claim 1, which is characterized in that the chemical reaction formula of the preparation method is as follows:
Figure FDA0004135748230000031
7. the preparation method as claimed in claim 6, which comprises the following steps:
s10, synthesizing an intermediate:
adding ethanol solvent into corresponding 1, 9-disubstituted-3-aldehyde-beta-carboline for dissolution, then adding hydrazine hydrate, stirring the solution at room temperature, and monitoring the reaction by TLC;
after the reaction is completed, filtering, dissolving the obtained hydrazone product in dichloroIn methane solvent, and adding active MnO in batches 2 Stirring the solution at room temperature for reaction, and monitoring the reaction by TLC;
after the reaction is finished, filtering to remove solid residues, concentrating under reduced pressure in vacuum to remove a solvent, and purifying the obtained crude product by silica gel column chromatography to obtain an intermediate of yellow solid powder, namely [1,2,3] triazole heterozygous beta-carboline;
s20, synthesizing a target compound:
the [1,2,3] is then added to the mixture]Triazole heterozygote beta-carboline, diaryl iodized salt and catalyst Cu (CN) 4 PF 6 After mixing, DCE solvent was added for dissolution, stirred at 80 ℃, and the progress of the reaction was monitored by TLC; after the reaction is finished, purifying the obtained crude product through silica gel column chromatography to obtain a target compound which is solid powder, namely the beta-carboline heterozygous triazole compound.
8. The process according to claim 7, wherein,
the corresponding 1, 9-disubstituted-3-aldehyde-beta-carboline, hydrazine hydrate and active MnO 2 The ratio of the ethanol solvent to the dichloromethane solvent is 1mmol:2mmol:2.5mmol:2mL:3mL;
the dosage ratio of the [1,2,3] triazole heterozygous beta-carboline, diaryl iodized salt and the DCE solvent is 0.2mmol:0.3mmol:2mL.
CN202110143623.4A 2021-02-02 2021-02-02 Beta-carboline heterozygous triazole compound as well as preparation method and application thereof Active CN112939973B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202110143623.4A CN112939973B (en) 2021-02-02 2021-02-02 Beta-carboline heterozygous triazole compound as well as preparation method and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202110143623.4A CN112939973B (en) 2021-02-02 2021-02-02 Beta-carboline heterozygous triazole compound as well as preparation method and application thereof

Publications (2)

Publication Number Publication Date
CN112939973A CN112939973A (en) 2021-06-11
CN112939973B true CN112939973B (en) 2023-05-12

Family

ID=76241589

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202110143623.4A Active CN112939973B (en) 2021-02-02 2021-02-02 Beta-carboline heterozygous triazole compound as well as preparation method and application thereof

Country Status (1)

Country Link
CN (1) CN112939973B (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114621225A (en) * 2022-04-06 2022-06-14 石河子大学 Imidazopyridoindole compound and preparation method and application thereof
CN116199687B (en) * 2023-03-10 2024-04-19 石河子大学 Beta-carboline-3-position connected 1,2, 3-triazole compound as well as preparation method and application thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104557916A (en) * 2014-12-03 2015-04-29 西北农林科技大学 2-substituted-beta-carboline compounds and application thereof in preparing drugs for preventing or treating tumors
CN111349096A (en) * 2020-04-14 2020-06-30 石河子大学 Indole compound and preparation method and application thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104557916A (en) * 2014-12-03 2015-04-29 西北农林科技大学 2-substituted-beta-carboline compounds and application thereof in preparing drugs for preventing or treating tumors
CN111349096A (en) * 2020-04-14 2020-06-30 石河子大学 Indole compound and preparation method and application thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
朱思玉.β-咔啉并三唑衍生物的设计、合成及生物活性研究.《石河子大学硕士学位论文》.2022,第二-四章. *

Also Published As

Publication number Publication date
CN112939973A (en) 2021-06-11

Similar Documents

Publication Publication Date Title
CN112939973B (en) Beta-carboline heterozygous triazole compound as well as preparation method and application thereof
EP1634881B1 (en) Harmine derivatives, intermediates used in their preparation, preparation processes and use thereof
ES2733460T3 (en) Ibrutinib co-crystals
EP1115725B1 (en) Tetrahydropyridoethers
CN111349096B (en) Indole compound and preparation method and application thereof
KR20030070049A (en) Thioether Substituted Imidazoquinolines
CN112125911B (en) CDK9 inhibitor and preparation method and application thereof
EP1317434A1 (en) Preparation of risperidone
NL1024676C2 (en) HIV integrase inhibitors, pharmaceutical preparations and methods for their use.
TW201704234A (en) Crystals of azabicyclic compound
CN112174957A (en) Method for synthesizing 5-selenoindolo [2,1-a ] isoquinoline-6 (5H) -ketone compound
CN110041310A (en) A kind of preparation method and application of Imatinib derivative
JP7420403B2 (en) Compounds used as kinase inhibitors and their applications
JP2010536807A (en) Indropyridine as an inhibitor of kinesin spindle protein (EG5)
JP2022547915A (en) Compound having Axl and c-Met kinase inhibitory activity and production and use thereof
CN112898302B (en) Beta-carboline heterozygous imidazole compound and preparation method and application thereof
EP3322709B1 (en) Crystalline forms of (3r)-3-cyclopentyl-3-[4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propanenitrile salts and preparation thereof
CN107652218B (en) Dihydropyrrolidone derivative and application thereof in preparation of antitumor drugs
CN114437114B (en) Application and preparation of diketopiperazine natural product and derivative and obtained derivative
CN113816959A (en) Isochrysine analogue prepared from enrofloxacin as raw material and preparation method and application thereof
CN110357892B (en) Tetrahydropyrimidino [1,2-a ] indole derivative and synthesis method and application thereof
CN112430206B (en) Preparation method of chiral/racemic 6-substituted indole compound
Bouattour et al. Microwave Assisted a Practical Synthesis of 4-Imino-3-phenyl-3, 4-dihydro-1H-chromeno [2, 3-d] pyrimidine-2 (5H)-thione Derivatives and Exploration of Their Biological Activities
CN112876456A (en) Cinnoline compound PI3K kinase inhibitor, preparation method thereof and application thereof in pharmacy
CN116199687B (en) Beta-carboline-3-position connected 1,2, 3-triazole compound as well as preparation method and application thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant