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Deuterated synthesis method of indole compound

A synthesis method and compound technology, applied in the field of deuterated synthesis of indole compounds, can solve the problems of poor deuterated position selectivity, severe reaction conditions, expensive deuterium sources, etc., and achieve good substrate applicability, low cost, The effect of high deuteration rate

Active Publication Date: 2020-08-14
ZHEJIANG UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] In view of the above defects or improvement needs of the prior art, the object of the present invention is to provide a deuteration synthesis method of indole compounds, wherein through the reaction process of its hydrogen-deuterium exchange reaction, the type and composition of each raw material used Compared with the prior art, it can effectively solve the problems of poor deuterated position selectivity and low deuterated rate of deuterated indole compounds, as well as harsh reaction conditions in the preparation process. The problem of expensive deuterium source used

Method used

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  • Deuterated synthesis method of indole compound
  • Deuterated synthesis method of indole compound
  • Deuterated synthesis method of indole compound

Examples

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Embodiment 1

[0042] Example 1 : This embodiment relates to the general synthetic method of the 2-selective deuterated indole compound 3-1a to 3-1p of formula (3-1) by the indole compound shown in formula (3), and its preparation method is According to the following reaction equation.

[0043]

[0044] The substituted indole (0.5mmol) of the N-methoxyamide shown in formula (3), D 2 O(1mL), Cp*Co(Co)I 2 (0.025mmol, 12.0mg), NaOAc (0.5mmol, 41mg) and CH 3 CN (3mL) was added to a 10mL reaction tube containing a stirrer, and the reaction was stirred at 90°C for 12 hours. After cooling to room temperature, the solvent was removed by rotary evaporation, and purified by column chromatography (petroleum ether: ethyl acetate 4:1) to obtain Selective 2-position deuterated indole compounds shown in formula (3-1).

[0045] This example specifically relates to the synthesis method of compound 3-1a.

[0046]

[0047] Using N-methoxyamide indole as raw material, 3-1a was obtained according to the...

Embodiment 2

[0048] Example 2 : The synthetic method of compound 3-1b

[0049]

[0050] According to the same method described in Example 1, using the 3-methyl-substituted N-methoxyamide indole as a raw material, its 2-position deuterated compound 3-1b was obtained. The product detection data is as follows: white solid, yield 80 %; 1 H NMR (500MHz, CDCl 3 ):δ8.31(1H,s),8.13(1H,m),7.51(1H,dt,J=7.5,1.0Hz),7.34(1H,m),7.26(1H,m),3.87(3H, s),2.25(3H,s);HRMS(ESI)m / z calcd for C 11 h 12 DN 2 o 2 [M+H] + 206.1034, found 206.1033.

Embodiment 3

[0051] Example 3 : The synthetic method of compound 3-1c

[0052]

[0053] According to the same method described in Example 1, the 2-position deuterated compound 3-1c was obtained using the 4-position methyl-substituted N-methoxyamide indole as a raw material, and the product detection data were as follows: white solid, yield 77 %; 1 H NMR (500MHz, CDCl 3 ): δ8.59(1H, s), 7.93(1H, d, J=8.0Hz), 7.22(1H, m), 7.04(1H, dd, J=7.5, 0.5Hz), 6.62(1H, d, J=0.5Hz), 3.87(3H,s), 2.51(3H,s); HRMS(ESI) m / z calcd for C 11 h 12 DN 2 o 2 [M+H] + 206.1034, found 206.1030.

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Abstract

The invention provides a deuterated synthesis method of an indole compound, which comprises the following steps: carrying out hydrogen-deuterium exchange on the indole compound through a carbon-hydrogen bond activation reaction guided by a guide group DG at a proper reaction temperature for proper time under the mixed reaction of heavy water, a catalyst, alkali and a solvent to generate a deuterated indole product. The method provided by the invention is mild in reaction condition, simple in process, low in cost, good in deuteration position selectivity and high in yield and deuteration rate,moreover, relatively cheap heavy water is used as a deuterium source, so that the use of an expensive deuterium source in the preparation process of the deuterated compound is effectively avoided, andthe preparation cost of the deuterated compound can be further reduced.

Description

technical field [0001] The invention belongs to the field of organic compound synthesis, and in particular relates to a method for deuterated synthesis of indole compounds. Background technique [0002] deuterium( 2 H or D) are stable and non-radioactive, and are widely used in many research fields, including labeling in microanalysis, improvement of pharmacokinetic properties of chemical substances in drug discovery, and kinetic isotope effect studies. Response research. Indole is arguably the most ubiquitous heterocyclic ring in nature and is essential to our life. They are found in nucleic acids, vitamins, antibiotics, hormones, alkaloids and pigments. Indole derivatives are widely used in the production of a large number of industrial products ranging from pharmaceuticals, insecticides to herbicides. The multifunctionality of deuterium and indole means that deuterated indole may have good development potential, and the preparation of deuterated indole compounds is pa...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/42C07D209/08C07D209/14C07B59/00
CPCC07B59/002C07B2200/05C07D209/08C07D209/14C07D209/42
Inventor 邹宏斌张金泉张帅众
Owner ZHEJIANG UNIV
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