Synthetic method of 2-aminoindane or derivatives thereof

Abstract

The present invention relates to a synthesis method of 2-aminoindane or its derivatives, comprising the following steps: performing cyclization reaction on the compound of formula (I) with acrylamide to obtain the compound of formula (II); preparing the compound of formula (II) Carrying out the Hoffman degradation reaction to obtain the compound of formula (Ⅲ); carrying out the reduction reaction of the compound of formula (Ⅲ) to obtain 2-aminoindan or its derivatives of formula (Ⅳ); wherein, R 1 , R 2 , R 3 and R 4 Each independently selected from: H, C1-C30 alkanyl, C3-C30 cycloalkyl, C1-C30 alkoxy, C6-C30 aromatic hydrocarbon, C6-C30 aromatic alkyl alkoxy or C3 ~C30 heterocyclic aromatic hydrocarbon group. The synthetic method has easy-to-obtain raw materials, simple process and high yield.

Description

technical field [0001] The invention relates to the technical field of organic synthesis, in particular to a synthesis method of 2-aminoindane or derivatives thereof. Background technique [0002] 2-Aminoindane is an important class of pharmaceutical intermediates, widely used, such as indacaterol for the treatment of obstructive airway diseases, dipipril for antihypertensive drugs, ambrolidine for antiarrhythmic drugs, and potential antipsychotics. The selective dopamine D3 receptor antagonist for disease application, the microsomal triglyceride transfer protein (MTP) antagonist LAB687, etc. all use derivatives such as 2-aminoindan. [0003] At present, the synthesis methods of 2-aminoindane mainly include the following methods: 1) Direct addition of tert-butyl chlorocarbamate to indene, followed by reduction to obtain 2-aminoindane, but the yield is low and the process is stable Poor, does not have industrial practical value. 2) Indanone is used as a raw material, reacte...

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Problems solved by technology

[0003] At present, the synthesis methods of 2-aminoindane mainly include the following methods: 1) Direct addition of tert-butyl chlorocarbamate to indene, followed by reduction to obtain 2-aminoindane, but the yield is low and the process is stable Poor, no industrial practical value

2) Indanone is used as a raw material, reacted with isoamyl nitrite, and then reduced by palladium carbon under high pressure to obtain the target product (EP1018514A1), the conditions are harsh and the cost is high

3) Zhu Ning et al. reported that 1-indanone was obtained by bromination, Gabriel synthesis, deprotection, carbonyl condensation into hydrazone and Woff-Kishner-Huang reaction to obtain the final product, which involved flammable and explosive dangerous reagents, and the reaction temperature was harsh. Complicated, poor atom economy and other defects

4) Swiss company Novatis reported the preparation of 2-aminoindane derivatives through six steps of protection of 2-aminoindane, acetylation, palladium-carbon pressure reduction, acetylation, and palladium-carbon pressure reduction again. Synthetic methods also have problems such as long steps, high cost, and serious environmental pollution.

6) Wang Kunpeng et al. reported that through 2-indanone in Bn-NH 2 And the one-pot synthesis of 2-aminoindan under the hydrogenation condition of Pd / C catalyst also has the problems of difficult acquisition of raw materials and the need for operations such as high-pressure hydrogenation reduction

[0004] To sum up, there are many types of synthetic routes in public reports, but they all have many shortcomings, such as cumbersome steps, low yields in key steps, and difficult access to raw materials, which are not conducive to large-scale industrial production.

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