Synthesis method of alpha-cyano quaternary carbon substituted tetrahydroisoquinoline compound

A technology of tetrahydroisoquinoline and cyano quaternary carbon, which is applied in the synthesis of α-cyano quaternary carbon substituted tetrahydroisoquinoline compounds and the field of synthesis of isoquinoline compounds, which can solve the problem of narrow substrate application range, The reaction process is complicated, the reaction conditions are harsh, etc., and the reaction operation is convenient and practical, the activity is high, and the reaction conditions are mild.

Active Publication Date: 2021-03-16
XI'AN PETROLEUM UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Although some research progress has been made in the synthesis of α-cyanoquaternary carbon-substituted tetrahydroisoquinolines, there are still some problems, such as harsh reaction conditions, narrow scope of substrate application, introduction and removal of protective agents. In addition to complicating the reaction process and increasing by-products, it is of great research value and practical significance to study an efficient synthetic method to synthesize α-cyanoquaternary carbon-substituted tetrahydroisoquinoline compounds.

Method used

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  • Synthesis method of alpha-cyano quaternary carbon substituted tetrahydroisoquinoline compound
  • Synthesis method of alpha-cyano quaternary carbon substituted tetrahydroisoquinoline compound
  • Synthesis method of alpha-cyano quaternary carbon substituted tetrahydroisoquinoline compound

Examples

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Effect test

Embodiment 1

[0033] Example 1 A synthetic method of 1-phenyl-1-cyano-2-methyl-1,2,3,4-tetrahydroisoquinoline

[0034] This example provides a synthetic method of 1-phenyl-1-cyano-2-methyl-1,2,3,4-tetrahydroisoquinoline, which is to weigh 103.7 mg of 1-phenyl- Add 3,4-dihydroisoquinoline and 212.9mg iodomethane into 3mL 1,2-dichloroethane, continue to stir and dissolve, heat to 40°C, maintain 40°C for 30min, continue to stir and cool down to room temperature, then Add 99.2 mg of trimethylsilyl cyanide, 58.1 mg of potassium fluoride and 26.5 mg of sodium carbonate, and continue to stir at room temperature for addition reaction for 24 hours. After the completion of the reaction, the reaction solution is extracted with dichloromethane and purified by column chromatography. , that is, 113.7mg of 1-phenyl-1-cyano-2-methyl-1,2,3,4-tetrahydroisoquinoline was obtained, the nuclear magnetic pattern is shown in figure 1 and figure 2 , the yield is 92%, and the chemical reaction formula is

[0035...

Embodiment 2～11

[0037] Embodiment 2~11 The synthetic method of 1-phenyl-1-cyano-2-methyl-1,2,3,4-tetrahydroisoquinoline

[0038] Examples 2 to 11 provide a synthetic method of 1-phenyl-1-cyano-2-methyl-1,2,3,4-tetrahydroisoquinoline respectively, and the synthetic methods are all the same as in the examples 1 are basically the same, the only difference is that the raw materials and some process parameters are different, and the specific data are shown in Table 1.

[0039] Table 1: Table of process parameters for the synthesis method of 1-phenyl-1-cyano-2-methyl-1,2,3,4-tetrahydroisoquinoline provided in Examples 2-11

[0040]

[0041] Other steps are all the same as in Example 1, and the obtained products are all 1-phenyl-1-cyano-2-methyl-1,2,3,4-tetrahydroisoquinoline, and the structural formula is

Embodiment 12

[0042] Example 12 A synthetic method of 1-cyano-2-methyl-1-(3-methylphenyl)-1,2,3,4-tetrahydroisoquinoline

[0043] This embodiment provides a synthetic method of 1-cyano-2-methyl-1-(3-tolyl)-1,2,3,4-tetrahydroisoquinoline, which is to weigh 110.6mg 1 -(3-Tolyl)-3,4-dihydroisoquinoline, 212.9mg methyl iodide, added to 3mL 1,2-dichloroethane, stirring continuously to dissolve, heating to 40°C, maintaining 40°C for 30min , continue to stir and lower to room temperature, then add 99.2mg trimethylsilyl cyanide, 58.1mg potassium fluoride and 26.5mg sodium carbonate, continue to stir at room temperature for addition reaction for 48h, use TLC to detect the completion of the reaction, use dichloromethane The reaction solution was extracted and purified by column chromatography to obtain 130.3 mg of 1-cyano-2-methyl-1-(3-methylphenyl)-1,2,3,4-tetrahydroisoquinoline, yield 99%, the chemical reaction formula is

[0044]

[0045] 2-Methyl-1-(m-tolyl)-1,2,3,4-tetrahydroisoquinoline-1-...

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Abstract

The invention belongs to the field of organic synthesis, and discloses a synthesis method of an alpha-cyano quaternary carbon substituted tetrahydroisoquinoline compound, which comprises the followingsteps: converting an isoquinoline compound into a high-activity imine salt intermediate, and carrying out addition reaction on the high-activity imine salt intermediate and a cyano source to obtain the alpha-cyano quaternary carbon substituted tetrahydroisoquinoline compound. The invention is simple and practical to operate, mild in reaction condition and high in yield and purity of the obtainedproduct. The invention is suitable for synthesis of isoquinoline compounds, and is especially suitable for synthesis of alpha-cyano quaternary carbon substituted tetrahydroisoquinoline compounds.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and relates to a method for synthesizing isoquinoline compounds, in particular to a method for synthesizing α-cyanoquaternary carbon-substituted tetrahydroisoquinoline compounds. Background technique [0002] In the prior art, tetrahydroisoquinoline compounds, as a class of important organic amine compounds, widely exist in natural products and bioactive molecules. Chiral tetrahydroisoquinoline alkaloids usually have very good biological activity, and are also an important class of drug intermediates, which are closely related to the life activities of the human body. Among them, tetrahydroisoquinoline compounds substituted with C-1 quaternary carbon have abundant biological activities. Such as C-1 quaternary carbon substituted tetrahydroisoquinoline compound MK-801, also known as dizocyclopine / dizocilpine (dizocilpine), belongs to an effective and highly selective NMDA (N-methyl-D- Aspartic ac...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D217/26
CPCC07D217/26
Inventor 姬悦张学韩薇薇王嗣昌吴亚刘雪梅
Owner XI'AN PETROLEUM UNIVERSITY
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