阅读说明：本技术 一种4-氯-7-甲基-1h-吲唑及其化学合成方法 (4-chloro-7-methyl-1H-indazole and chemical synthesis method thereof ) 是由 汤艳峰 王纯 丁欣宇 葛明 胡玉林 倪人捷 刘维群 张梦珂 沈璐婕 徐润生 于 2019-09-02 设计创作，主要内容包括：本发明涉及一种4-氯-7-甲基-1H-吲唑的化学合成方法。本发明以4-氯-2-氟甲苯为原料,经甲酰化反应、关环反应等两步反应制备了4-氯-7-甲基-1H-吲唑。为该化合物的合成提供了一种高效合成的方法。(The invention relates to a chemical synthesis method of 4-chloro-7-methyl-1H-indazole. The 4-chloro-7-methyl-1H-indazole is prepared by using 4-chloro-2-fluorotoluene as a raw material through two-step reactions such as formylation reaction, ring closing reaction and the like. Provides a high-efficiency synthesis method for the synthesis of the compound.)

1. A compound I, namely: the 4-chloro-7-methyl-1H-indazole is characterized in that the molecular structural formula is shown as a formula 1.

2. The chemical synthesis method of the compound I as claimed in claim 1, characterized in that the compound I is synthesized by two-step reaction by using 4-chloro-2-fluorotoluene as a raw material, and the synthetic route is shown as formula 2.

3. The chemical synthesis process of compound i according to claim 2, comprising the following synthesis steps:

(A) adding tetrahydrofuran into 4-chloro-2-fluorotoluene, controlling the reaction temperature, dropwise adding lithium diisopropylamide, reacting for 1h, dropwise adding N, N-dimethylformamide, and reacting for 0.5h to prepare 6-chloro-2-fluoro-3-methylbenzaldehyde;

(B) adding the 6-chloro-2-fluoro-3-methylbenzaldehyde obtained in the step (A) into dimethyl sulfoxide, then adding hydrazine hydrate, controlling the reaction temperature, and then separating out a low-boiling-point solvent and water to synthesize the 4-chloro-7-methyl-1H-indazole.

4. A process for the chemical synthesis of compound i according to claim 3, characterized in that: the reaction temperature in the step (A) is-80 to-60 ℃.

5. A process for the chemical synthesis of compound i according to claim 3, characterized in that: the reaction temperature of the step (B) is 120-140 ℃, and hydrazine hydrate is adopted in a volume ratio of 80%.

Technical Field

The invention relates to 4-chloro-7-methyl-1H-indazole and a chemical synthesis method thereof.

Background

Indazoles are important pharmaceutical intermediates, having a wide range of biological activities, such as antibacterial, anti-schizophrenic and anti-tumour. Indazole derivatives have been reported to exert anticancer effects by targeting various tyrosine kinases such as EGFR, FGFR, VEGF and the like. In addition, indazole is used as a fine chemical product intermediate and has wide application in the fields of catalysts, medicines, pesticides and the like. Therefore, the synthesis of indazole derivatives is of great importance.

4-chloro-7-methyl-1H-indazole is an important medical intermediate, so that the compound has important practical significance for the synthesis research of the compound.

Disclosure of Invention

The invention aims to provide a compound which can be used as a medical intermediate, namely 4-chloro-7-methyl-1H-indazole, and a high-efficiency chemical synthesis method thereof.

In order to achieve the purpose, the technical scheme of the invention is as follows:

a compound I, namely: the 4-chloro-7-methyl-1H-indazole is characterized in that the molecular structural formula is shown as a formula 1.

The chemical synthesis method of the compound I is characterized in that 4-chloro-2-fluorotoluene is used as a raw material, the compound I is synthesized through two-step reaction, and the synthetic route is shown as a formula 2.

The chemical synthesis method of the compound I is characterized by comprising the following synthesis steps:

(A) adding tetrahydrofuran into 4-chloro-2-fluorotoluene, controlling the reaction temperature, dropwise adding lithium diisopropylamide, reacting for 1h, dropwise adding N, N-dimethylformamide, and reacting for 0.5h to prepare 6-chloro-2-fluoro-3-methylbenzaldehyde;

(B) adding the 6-chloro-2-fluoro-3-methylbenzaldehyde obtained in the step (A) into dimethyl sulfoxide, then adding hydrazine hydrate, controlling the reaction temperature, and then separating out a low-boiling-point solvent and water to synthesize 4-chloro-7-methyl-1H-indazole;

further, the reaction temperature in the step (A) is-80 to-60 ℃.

Further, the reaction temperature in the step (B) is 120-140 ℃, and hydrazine hydrate is adopted in a volume ratio of 80%.

The invention has the beneficial effects that: the chemical synthesis method provided by the invention starts from 4-chloro-2-fluorotoluene as a raw material, and synthesizes 4-chloro-7-methyl-1H-indazole through two-step reaction.

Drawings

FIG. 1 is a 1H-NMR spectrum of compound I prepared in example 1.

Detailed description of the invention

The following detailed description will provide specific embodiments of the present invention. These embodiments are merely illustrative and not intended to limit the scope or the principles of the invention, which is defined by the claims and includes obvious modifications and variations based thereon.