A kind of preparation method of multi-substituted 2-benzyl-1-isoquinolinone compound

Abstract

The invention discloses a preparation method of a polysubstituted 2-benzyl-1 (2H)-isoquinolone compound. In the presence of an iodine catalyst and tert-butyl hydroperoxide serving as an oxidizing agent, an isoquinoline compound experiences a benzyl free radical addition and amidation reaction to generate an isoquinolone compound, wherein the reaction temperature is 60-150 DEG C, and the reaction time is 0.5-72 hours. The reaction overcomes the shortcomings of metal catalyst use and complicated synthesis technology, the reaction raw materials and catalyst are cheap and easily available, the reaction conditions are mild, the reaction is insensitive to light, air and moisture, the yield is very high, and the product is easy to separate and purify and has a perfect application prospect.

Description

technical field [0001] The invention relates to a preparation method of multi-substituted 2-benzyl-1(2H)-isoquinolinone compounds. Background technique [0002] Multi-substituted 2-benzyl-1(2H)-isoquinolinones are biologically active drug molecules, and their skeletons exist in many natural products and biologically active compounds. For example, topoisomerase I is a class of enzymes present in the nucleus that can directly catalyze the transient single-strand breaks and ligation of DNA without energy cofactors (Wang, J. C. Nat. Rev. Mol. Cell Biol. 2002, 3 , 430), while camptothecin [1] It can selectively block topoisomerase I, thus developing into a good anticancer drug (Pommier, Y. Nat. Rev. Cancer 2006, 6 ,789). Some other 2-benzyl-1(2H)-isoquinolinone compounds also exhibit very important biological activities of promoting vasodilation and contraction, and are some specific drugs for treating hypertension. For example 8-methoxy-2-(4-methoxybenzyl)-1(2H)-isoquinol...

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Problems solved by technology

While the polysubstituted isoindole[2,1-b]-5(7H)-isoquinolinone [4] Because of its high biological activity similar to camptothecin, it has become a new anticancer drug that can replace camptothecin, but the synthesis steps are complicated, and there are only a few reports about its synthesis: using o-carboxyphenylacetic acid as the starting material through Five to seven-step synthesis (Adam Daïch et al. Synthesis 2015, 47 , 3583), and a three-step synthesis using o-tolualdehyde and o-cyanobenzyl alcohol as starting materials (W.-J. Cho. et al. Bioorg. Med. Chem. Lett. 2009, 19 , 2551), but the above methods all have the disadvantages of many steps, low yield, complicated operation, and the need for anhydrous and oxygen-free conditions.

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