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Preparation method of isoquinolone and derivatives thereof

A technology for isoquinolinone and derivatives, which is applied in the field of pharmaceutical chemical intermediates and related chemistry, can solve the problems of low multi-step reaction yield, unsuitable for industrial production, harsh reaction conditions, etc., and achieves good therapeutic effect and mild conditions. , the effect of short synthetic route

Active Publication Date: 2015-05-20
DALIAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The reaction condition of this method is very harsh, needs low-temperature operation, multi-step reaction yield is low, is also not suitable for industrialized production [referring to: (a) Davis, S.E.; Cameron Church, A.; Mazat Griffith, C.L.; Beam, C.F.Synth. Commun.1997,27,2961.(b)Fisher,L.E.;Muchowski,J.M.;Clark,R.D.J.Org.Chem.1992,57,2700.(c)Poindexter,G.S.J.Org.Chem.1982,47,3787.]

Method used

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  • Preparation method of isoquinolone and derivatives thereof
  • Preparation method of isoquinolone and derivatives thereof
  • Preparation method of isoquinolone and derivatives thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Embodiment 1: the synthesis of 3-phenylisoquinolinone (3a)

[0032]

[0033] 2-Bromobenzonitrile (90.48mg, 0.5mmol), copper acetate (1.0mg, 0.01mmol), potassium tert-butoxide (56.0mg, 0.5mmol), methyl phenyl ketone (60.0mg, 0.5mmol) were sequentially Add it into the Schlenk reaction flask, vacuum and nitrogen replacement 3 times, in nitrogen atmosphere, add toluene 0.2mL, 30 ℃ react for 4 hours, after the reaction is over, remove the solvent under reduced pressure, column chromatography separation (eluent is petroleum Ether: ethyl acetate = 20:1, V:V) to obtain 0.091 g of a light yellow solid product with a yield of 82%. Mp 204–205°C. 1 H NMR (400MHz, CDCl 3 )δ6.79(s,1H),7.45–7.55(m,4H),7.60(d,J=7.6Hz,1H),7.65–7.69(m,1H),7.75–7.78(m,2H),8.41 (d,J=8.0Hz,1H),10.44(s,1H).

Embodiment 2

[0034] Embodiment 2: the synthesis of 3-p-tolylisoquinolinone (3b)

[0035]

[0036] 2-Bromobenzonitrile (90.48mg, 0.5mmol), copper acetate (9.1mg, 0.1mmol), potassium tert-butoxide (56.0mg, 0.5mmol), and the corresponding phenyl ketone (134.0mg, 1.0mmol) were sequentially Add it into a Schlenk reaction flask, replace it with vacuum and nitrogen for 3 times, add 1.0 mL of methanol in a nitrogen atmosphere, and react at 50°C for 5 hours. After the reaction, remove the solvent under reduced pressure, and separate by column chromatography (the eluent is petroleum Ether:ethyl acetate=20:1, V:V) to obtain 0.099g of white solid product with a yield of 85%. Mp 224–226°C. 1 H NMR (400MHz, CDCl 3 )δ2.43(s,3H),6.76(s,1H),7.32(d,J=8.0Hz,2H),7.46–7.50(m,1H),7.59(d,J=7.7Hz,1H), 7.64–7.67(m,3H),8.41(d,J=8.0Hz,1H),10.23(s,1H).

Embodiment 3

[0037] Embodiment 3: the synthesis of 3-(4-methoxyphenyl) isoquinolinone (3c)

[0038]

[0039] 2-Bromobenzonitrile (90.48mg, 0.5mmol), copper acetate (18.2mg, 0.2mmol), potassium tert-butoxide (84.0mg, 1.0mmol), and the corresponding phenyl ketone (90.0mg, 0.75mmol) were sequentially Add it into the Schlenk reaction flask, vacuum, nitrogen replacement 3 times, in nitrogen atmosphere, add ethylene glycol dimethyl ether 0.5mL, 60 ℃ of reaction 6 hours, after reaction finishes, remove solvent under reduced pressure, column chromatography separates ( The eluent is petroleum ether: ethyl acetate=20:1, V:V), and 0.111 g of a white solid product is obtained, with a yield of 88%; Mp 237-239°C. 1 H NMR (400MHz, DMSO-d 6 )δ4.07(s,3H),7.10(s,1H),7.30(d,J=8.6Hz,2H),7.68–7.72(m,1H),7.92–8.02(m,4H),8.44(d ,J=8.0Hz,1H),11.71(s,1H).

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Abstract

The invention belongs to the technical field of pharmaceutical and chemical intermediates and related chemicals and relates to a preparation method of isoquinolone and derivatives thereof. The isoquinolone and derivatives thereof are important biologically active molecules, skeletal structures frequently appear in natural molecules and drug molecules, and have better therapeutic effect on hypertension, cancer and anxiety disorders and important applications in the fields of organic synthesis and pharmaceutical chemistry. The method is short in synthesis route, mild in conditions and simple in operation and is expected to achieve industrial production and has the advantages of short synthetic route, mild conditions, simple operation and high yield and the like. The isoquinolone and derivatives thereof have greater application value and social and economic benefits.

Description

technical field [0001] The invention belongs to the field of pharmaceutical and chemical intermediates and related chemical technologies, and relates to a preparation method of isoquinolinone and derivatives thereof. Background technique [0002] Isoquinolinones and their derivatives are a class of important bioactive molecules. Their skeleton structures frequently appear in natural molecules and drug molecules. They have good therapeutic effects on hypertension, lung cancer and anxiety. It has important applications in the fields of medicinal chemistry and so on. [0003] About the synthesis of isoquinolinone compound, generally adopt following two kinds of methods: [0004] (1) Transition metal-catalyzed cyclization of arylamides with alkynes [0005] [0006] The reaction condition of this method is very harsh, needs high-temperature reaction condition usually; Use noble metal catalysts such as rhodium, palladium, be not suitable for industrialized production [referr...

Claims

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Application Information

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IPC IPC(8): C07D217/24
CPCC07D217/24
Inventor 包明于晓强冯秀娟默罕默德谢里夫马佑王娇
Owner DALIAN UNIV OF TECH