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1-substituted isoquinoline ketone compound and preparation method thereof

A technology for isoquinolinones and compounds, applied in the field of 1-substituted isoquinolinone compounds and their preparation, can solve problems such as lack of universality, and achieve the effects of simple route, high yield and simple operation

Active Publication Date: 2019-10-11
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] For the asymmetric synthesis of 1-substituted tetrahydroisoquinoline skeleton, there are methods reported in the literature, although the asymmetric hydrogenation reaction of enamine or imine, tetrahydroisoquinoline or isoquinoline imine salt asymmetric Coupling reactions and multicomponent Mannich reactions are ideal for stereoselectivity, but they are not universally applicable in the asymmetric synthesis of natural products

Method used

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  • 1-substituted isoquinoline ketone compound and preparation method thereof
  • 1-substituted isoquinoline ketone compound and preparation method thereof
  • 1-substituted isoquinoline ketone compound and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Synthesis of compound 1a

[0026] Add phenylmagnesium bromide (5.3mL, 5.33mmol, 1M in THF) to 2,2'-bipyridine (833mg, 5.33mmol) in dichloromethane (15mL) under argon protection and ice-salt bath and stir for 15 Minutes, the dichloromethane solution (5mL) of compound 3 (500mg, 1.78mmol) was dripped into the reaction system, and after reacting for 1 hour, a saturated aqueous ammonium chloride solution was added, extracted three times with dichloromethane, and the organic phase was washed with saturated brine , dried, concentrated and purified by silica gel column to obtain white solid compound 1a (430 mg, 74%). 1 H NMR (400 MHz, CDCl 3 )δ7.53-7.49(m,1H),7.40-7.36(m,2H),7.34-7.28(m,2H),7.27-7.18(m,3H),7.12-7.08(m,1H),6.19( s,1H),3.90(d,J=18.8Hz,1H),3.68(d,J=18.8Hz,1H),1.15(s,9H)ppm.

[0027]Synthesis of compound 1b

[0028] 4-Methylphenylmagnesium bromide (5.3mL, 5.33mmol, 1M in THF) under argon protection and ice-salt bath

[0029] Add 2,2'-bipyridine (833mg, 5.33mmo...

Embodiment 2

[0067] The preparation of compounds 1b-n, 2b-2f was the same as in Example 1.

[0068] Synthesis of compound 1a

[0069]Add phenylmagnesium bromide (5.3mL, 5.33mmol, 1M in THF) to N-methylmorpholine (1.2mL, 10.66mmol) in dichloromethane (15mL) under argon protection and ice-salt bath and stir for 15 Minutes, the dichloromethane solution (5mL) of compound 3 (500mg, 1.78mmol) was dripped into the reaction system, and after reacting for 1 hour, a saturated aqueous ammonium chloride solution was added, extracted three times with dichloromethane, and the organic phase was washed with saturated brine , dried, concentrated and purified by silica gel column to obtain white solid compound 1a (314mg, 54%).

[0070] Synthesis of compound 2a

[0071] Add phenylmagnesium bromide (5.3mL, 5.33mmol, 1M in THF) to N-methylmorpholine (1.2mL, 10.66mmol) in dichloromethane (15mL) under argon protection and ice-salt bath and stir for 15 Minutes, the dichloromethane solution (5mL) of compound 4 ...

Embodiment 3

[0073] The preparation of compounds 1b-n, 2a-2f was the same as in Example 1.

[0074] Synthesis of compound 1a

[0075] Add phenylmagnesium bromide (5.3mL, 5.33mmol, 1M in THF) into triethylamine (1.5mL, 10.66mmol) in dichloromethane (15mL) under argon protection and ice-salt bath and stir for 15 minutes. Compound 3 (500 mg, 1.78 mmol) in dichloromethane solution (5 mL) was dropped into the reaction system. After reacting for 0.5 hours, saturated ammonium chloride aqueous solution was added, extracted three times with dichloromethane, the organic phase was washed with saturated brine, and dried. After concentration, it was purified by silica gel column to obtain white solid compound 1a (465 mg, 80%).

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Abstract

The invention belongs to the technical field of chemical synthesis and relates to a 1-substituted isoquinoline ketone compound and a preparation method thereof. A benzoazacyclo 1-substituted isoquinoline skeleton serving as an important heterocyclic skeleton exists in many natural products or medicines, shows various types of biological activity and mainly has antibacterial, anti-inflammation, anti-depression, anti-oxidation, anti-pathogenic microorganism, blood pressure and blood glucose reducing, immune regulating, pain alleviating and anti-irrhythmia functions and the like. Therefore, developing a novel synthesis method for implementing mass synthesis of the 1-substituted isoquinoline ketone compound is remarkably beneficial to research of a structure-activity relationship, a clinical novel process and the like so as to discover a series of excellent lead compounds with high activity and less toxic and side effects.

Description

technical field [0001] The invention belongs to the field of chemical synthesis, and relates to a 1-substituted isoquinolinone compound and a preparation method thereof. Background technique [0002] The prior art discloses that the benzazeterocyclic 1-substituted isoquinoline skeleton exists as an important heterocyclic skeleton in many natural products or drugs, and exhibits various biological activities, mainly including antibacterial, anti-inflammatory, anti-tumor, anti- Depression, anti-oxidation, anti-pathogenic microorganisms, lowering blood pressure, lowering blood sugar, regulating immunity, analgesia, anti-arrhythmia and other functions. For example, the benzisoquinoline Crispine A-E isolated from the medicinal plant Carduus crispus in my country has anti-tumor activity; A variety of benzisoquinoline alkaloids, including Corydaline and Canadine, have biological activities such as analgesia, local anesthesia, and anticancer; the benzisoquinoline alkaloid Noscapine, ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D217/24
CPCC07D217/24C07B2200/07
Inventor 司长梅周雯孙逊张艳雪周祝魏邦国
Owner FUDAN UNIV
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