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Method for synthesizing 3-methyl-6-nitro-1H-indazole by microchannel diazo reaction

A technology of diazo reaction and synthesis method, which is applied in the direction of organic chemistry to achieve the effects of avoiding serious corrosion of equipment, improving reaction efficiency, and improving selectivity

Inactive Publication Date: 2019-02-26
SHENZHEN HUAXIAN PHARMA TECH CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] In order to solve and avoid the diazotization reaction safety problem in the production process of 3-methyl-6-nitro-1H-indazole, and improve the reaction selectivity and conversion rate, the present invention provides a microchannel reactor Method of diazotizing 2-ethyl-5-nitroaniline concentrated acid solution to synthesize 3-methyl-6-nitro-1H-indazole in a continuous flow mode

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  • Method for synthesizing 3-methyl-6-nitro-1H-indazole by microchannel diazo reaction
  • Method for synthesizing 3-methyl-6-nitro-1H-indazole by microchannel diazo reaction

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Embodiment 1

[0027] Embodiment 1: The device used in this embodiment is a high-throughput microchannel reactor, the number of mixed reaction modules is determined according to the flow rate and reaction residence time, and the heat exchange medium is heat transfer oil. The method that present embodiment adopts microchannel reactor to synthesize 3-methyl-6-nitro-1H-indazole is to carry out according to the following steps:

[0028] Step 1, dissolving 2-ethyl-5-nitroaniline in acetic acid to form a solution with a mass concentration of 22% and a sodium nitrite aqueous solution with a mass concentration of 30% as the reaction material, and using a metering pump to feed the reaction material into the microchannel Carry out preheating in each straight channel module in the reactor, control the mol ratio=1:1.3 of flow control 2-ethyl-5-nitroaniline and sodium nitrite, control the acetic acid of 2-ethyl-5-nitroaniline Solution flow rate: 20mL / min, control the flow rate of sodium nitrite aqueous s...

Embodiment 2

[0031] Embodiment 2: The device used in this embodiment is a high-throughput microchannel reactor, the number of mixed reaction modules is determined according to the flow rate and reaction residence time, and the heat exchange medium is heat transfer oil. The method that present embodiment adopts microchannel reactor to synthesize 3-methyl-6-nitro-1H-indazole is to carry out according to the following steps:

[0032] Step 1, dissolving 2-ethyl-5-nitroaniline in acetic acid to form a solution with a mass concentration of 22% and a sodium nitrite aqueous solution with a mass concentration of 30% as the reaction material, and using a metering pump to feed the reaction material into the microchannel Carry out preheating in each straight passage module in the reactor, control the mol ratio=1:1.2 of flow control 2-ethyl-5-nitroaniline and sodium nitrite, control the acetic acid of 2-ethyl-5-nitroaniline Solution flow rate: 22mL / min, control the flow rate of sodium nitrite aqueous s...

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Abstract

The invention discloses a method for synthesizing 3-methyl-6-nitro-1H-indazole by a microchannel diazo reaction, and belongs to the technical field of synthesis of pharmaceutical intermediates. According to the method, 2-ethyl-5-nitroaniline, acetic acid and an aqueous nitrous acid solution are taken as starting raw materials, and 3-methyl-6-nitro-1H-indazole is synthesized by diazo cyclization ina short time of tens of seconds to a few minutes in a microchannel reactor. The materials are introduced into the microchannel reactor by a metering pump and then are subjected to preheating, mixingand a nitration reaction, and a 3-methyl-6-nitro-1H-indazole product is obtained. The method is simple and safe to operate, efficient continuous production of the 3-methyl-6-nitro-1H-indazole productis realized, and besides, the environmental pollution caused by the method is obviously reduced.

Description

technical field [0001] The invention belongs to the technical field of synthesis of pharmaceutical intermediates, in particular to a high-throughput continuous flow microchannel reactor, which utilizes sodium nitrite to diazotize the cyclization of 2-ethyl-5-nitroaniline to synthesize 3- Process for methyl-6-nitro-1H-indazole. Background technique [0002] 3-Methyl-6-nitro-1H-indazole is an important intermediate of the patented drug Pazopanib, a drug developed by GlaxoSmithKline that interferes with the survival and growth of recalcitrant tumors A novel oral angiogenesis inhibitor of neovascularization targeting the vascular endothelial growth factor receptor (VEGFR), which acts by inhibiting neovascularization of tumor blood supply. It is indicated for the treatment of advanced renal cell carcinoma (a type of kidney cancer in which cancer cells are found in the kidney tubules), soft tissue sarcoma (STS), epithelial ovarian cancer, and non-small cell lung cancer (NSCLC). ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D231/56
CPCC07D231/56
Inventor 周章涛叶伟平费安杰顾晓丹钟林
Owner SHENZHEN HUAXIAN PHARMA TECH CO LTD