A kind of synthetic method of pyrazoline nucleoside analog with quaternary carbon center

A technology of pyrazoline nucleosides and synthetic methods, applied in the field of organic synthesis in organic chemistry

Inactive Publication Date: 2020-09-08
HENAN NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, compared with this, the reports of 1.3-dipolar cycloaddition of allenes with cumulative double bonds and diazo compounds are relatively rare.
At the same time, the synthesis of pyrazolines containing quaternary carbon centers is rarely reported in the literature.

Method used

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  • A kind of synthetic method of pyrazoline nucleoside analog with quaternary carbon center
  • A kind of synthetic method of pyrazoline nucleoside analog with quaternary carbon center
  • A kind of synthetic method of pyrazoline nucleoside analog with quaternary carbon center

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Experimental program
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Effect test

Embodiment 1

[0026]

[0027]

[0028] a Unless otherwise noted, reaction conditions were: cat.(20mol%),1a(0.05mmol),2a(0.3mmol)in solvent(1.0mL)under N 2 for 48h. b Total yield of 3aa and 4aa. c Isolated yield. d Determined by 1 H NMR spectroscopy of the crude reaction mixture. e 2a and Pd 2 (dba) 3 were added for two times in mesitylene.

[0029] In the screening process of reaction conditions, the influence of the catalyst on the reaction was first investigated (entries 1-6, 9-14), and DPPB was determined to be the best catalyst for obtaining various pyrazolines, Pd 2 (dba) 3 The best catalyst for obtaining a single 1-pyrazoline.

[0030] In the case of other conditions being fixed, only the influence of the solvent on the reaction was investigated (entries 15-17), and it was determined that toluene was the best solvent for obtaining various pyrazolines, and mesitylene was the best solvent for synthesizing 1-pyrazoline .

[0031] With other conditions fixed, only the inf...

Embodiment 2

[0033] Taking compounds 1a and 2a as an example, the reaction in Pd 2 (dba) 3 The reaction steps under catalysis are as follows:

[0034]

[0035] Weigh 9.4mg (0.05mmol, 1equiv) of compound 1a and put it in a clean 15mL reaction tube, then add 2.3mg of Pd 2 (dba) 3 (0.005 mmol, 5%) catalyst. The reaction tube was sealed, and the air in the reaction bottle was evacuated through a three-way tube, and then nitrogen gas was introduced, and 19.2 mg of compound 2a (0.15 mmol, 3 equiv) was weighed and dissolved in 1 mL of mesitylene solution, and added to the reaction with a syringe , and the reaction was completely carried out under nitrogen conditions at 100°C. After 24 hours of reaction, inject 2.3 mg of Pd again 2 (dba) 3 (0.005mmol, 5%) catalyst, 19.2mg of compound 2a (0.15mmol, 3equiv) in mesitylene solvent, continue to react for 24 hours. Detect with TCL and find that raw material disappears substantially. The reaction solution was taken out, and the solvent in the ...

Embodiment 3

[0041] Taking 1a and 2a compounds as an example, the reaction steps of this reaction under the catalysis of bis(diphenylphosphine)butane DPPB are as follows:

[0042]

[0043] Weigh 18.8 mg (0.1 mmol, 1 equiv) of compound 1a into a clean 20 mL reaction tube, then add 8.5 mg of DPPB (0.02 mmol, 20%) catalyst. The reaction tube was sealed, and the air in the reaction flask was evacuated through a three-way tube, and then nitrogen gas was introduced, and 38.4 mg of compound 2a (0.3 mmol, 3 equiv) was weighed and dissolved in 1.5 mL of toluene solution, and added to the reaction with a syringe. And make the reaction completely under nitrogen condition, 100 degrees centigrade, carry out. After 48 hours of reaction, it was detected by TCL that the raw materials basically disappeared. The reaction solution was taken out, and the solvent in the solution was spin-dried with a vacuum rotary evaporator, and column chromatography was used to separate the solvent in a 3:1 development s...

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Abstract

The invention discloses a method for synthesizing pyrazoline nucleoside analogs with a quaternary carbon center, belonging to the technical field of organic chemistry. Starting from 9-alkenyl purine 1 and α-alkyl / aryl diazoacetate 2, DPPB or Pd 2 (dba) 3 As a catalyst, after the reaction, a pyrazoline-like purine nucleoside analog 3 with a quaternary carbon center is obtained, and the reaction yield is moderate to excellent. In the present invention, the diversity and singleness of pyrazoline products can be effectively controlled by changing the catalytic system, and the pyrazoline-like purine nucleoside analog 5 can be obtained after the product is further hydrogenated.

Description

technical field [0001] The invention relates to the synthesis of purine nucleoside analogs, in particular to a method for synthesizing pyrazoline nucleoside analogs with a quaternary carbon center, and belongs to the field of organic synthesis in organic chemistry. Background technique [0002] Pyrazolines containing quaternary carbon centers are ubiquitous in many bioactive molecules. Representative examples of such pyrazoline compounds include the commercially available herbicide safener mefenpyr-ethyl, the insecticide RH 3421, and the chloroquinine pyrazoline with good antimalarial activity. Therefore, the construction of pyrazolines with quaternary carbon centers is very promising. [0003] The synthesis of pyrazolines by 1,3-dipolar cycloaddition of diazo esters is a very classic synthetic method. The cycloaddition reactions of alkenes or alkynes with alkyl diazo or diazoacetates have been extensively reported. However, compared with this, the reports of 1.3-dipolar ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D473/30C07D473/40C07D473/34
CPCC07D473/30C07D473/34C07D473/40
Inventor 郭海明谢明胜郭真王东超王海霞渠桂荣
Owner HENAN NORMAL UNIV
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