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Preparation method of polysubstituted 2-benzyl-1-isoquinolone compound

A technology for isoquinolinones and compounds, which is applied in the field of preparation of multi-substituted 2-benzyl-1-isoquinolinone compounds, can solve the problems of complex synthesis steps, complex operations, and many steps, and achieve easy separation and purification , mild reaction conditions and high yield

Inactive Publication Date: 2016-04-20
XIANGTAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

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 (AdamDa?chetal.Synthesis2015,47,3583), and a three-step synthesis using o-tolualdehyde and o-cyanobenzyl alcohol as starting materials (W.-J.Cho.etal.Bioorg. Med.Chem.Lett.2009, 19, 2551), but the above methods have many steps, low yield, complicated operation, and need anhydrous and oxygen-free conditions, etc.

Method used

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  • Preparation method of polysubstituted 2-benzyl-1-isoquinolone compound
  • Preparation method of polysubstituted 2-benzyl-1-isoquinolone compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017] Embodiment 1, preparation 2-benzyl-1 (2H)-isoquinolinone compound

[0018] The reaction formula is as follows:

[0019] Formula (Ia)

[0020] The specific preparation method is: without special protection, add magneton, isoquinoline (51.6mg, 0.4mmol), and then add iodine (1mg, 1mol%), 5.0M-6.0M to a clean single-necked flask under air Concentration of tert-butyl hydroperoxide (360mg, 2mmol) in the organic phase was added, and toluene (728.8mg, 8mmol) was added. Toluene was used as a reactant and as a solvent. After 12 hours of reaction at 120°C, TLC analysis showed that the raw materials were different. Quinoline is completely consumed. The reaction was quenched by stopping the heating. No extraction, direct wet loading, 200-300 mesh silica gel column chromatography, eluting with a mixed solvent of ethyl acetate and petroleum ether (1:8). 79.0 mg of the compound represented by the structural formula of formula Ia was isolated, with a yield of 84%;

[0021] The pr...

Embodiment 2

[0026] Embodiment 2, the 2-benzyl-1 (2H)-isoquinolinone compound shown in preparation formula Ia

[0027] The reaction formula is as follows:

[0028] Formula (Ia)

[0029] The specific preparation method is: without special protection, add magnetons, isoquinoline (51.6mg, 0.4mmol), and then add potassium iodide (99.6mg, 150mol%), 70% mass fraction of tert-butyl hydroperoxide (205mg, 1.6mmol) in the water phase was added toluene (364.4mg, 4mmol), and toluene was used as both a reactant and a solvent. After reacting at 150°C for 0.5 hours, TLC analysis showed that the raw material isoquinone The phylloline is completely consumed. The reaction was quenched by stopping the heating. No extraction, direct wet loading, 200-300 mesh silica gel column chromatography, eluting with a mixed solvent of ethyl acetate and petroleum ether (1:8). 48.0 mg of the compound represented by the structural formula of formula Ia was isolated, with a yield of 51%;

[0030] Compound structure an...

Embodiment 3

[0031] Embodiment 3, the 2-benzyl-1 (2H)-isoquinolinone compound shown in preparation formula Ia

[0032] The reaction formula is as follows:

[0033] Formula (Ia)

[0034]The specific preparation method is: without special protection, add magneton, isoquinoline (51.6mg, 0.4mmol), and then add cuprous iodide (7.6mg, 10mol%), 70% The mass fraction of tert-butyl hydroperoxide (152mg, 1.2mmol) in the water phase was added toluene (364.4mg, 4mmol). Toluene was used as both a reactant and a solvent. After 36 hours of reaction at 90°C, TLC analysis showed that The raw material isoquinoline is completely consumed. The reaction was quenched by stopping the heating. No extraction, direct wet loading, 200-300 mesh silica gel column chromatography, eluting with a mixed solvent of ethyl acetate and petroleum ether (1:8). 73.3mg of the compound represented by the structural formula of formula Ia was isolated, with a yield of 78%;

[0035] Compound structure analysis and identificati...

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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 type of enzyme present in the nucleus that can directly catalyze the transient single-strand break and join of DNA without energy cofactors (Wang, J.C.Nat.Rev.Mol.CellBiol.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)-isoquinolinone [2] With 8-m...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D217/24C07D237/32C07D239/91
CPCC07D217/24C07D237/32C07D239/91
Inventor 杨罗罗文坤
Owner XIANGTAN UNIV
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