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A kind of preparation method of 5-sulfonyloxy-8-amidoquinoline derivative

A technology of sulfonyloxy, quinoline, applied in the preparation of 5-sulfonyloxy-8-amidoquinoline derivatives, in the field of preparing 5-sulfonyloxy-8-acetamidoquinoline, capable of Solve the problems of expensive price, many reaction steps, and low yield, and achieve the effect of wide substrate adaptability, low-cost raw materials, and easy-to-obtain raw materials

Active Publication Date: 2019-08-13
CHINA PHARM UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But the price of starting material 5-hydroxyquinoline derivatives is expensive and not easy to obtain
The literature (Bioorg.andMed.Chem.Lett.2016, 26, 3307-3312) uses 5-aminoquinoline as a raw material to obtain 5-hydroxyquinoline through diazotization-hydrolysis, and the price of the raw material 5-aminoquinoline for this reaction is More expensive, the reaction is difficult to control, and the yield is low (56%); Document (Angew.Chem.2017,129,4549-4553) is raw material with 5-bromoquinoline, in C 44 h 62 NO 4 It is obtained by reaction under the catalysis of PPdS, wherein the raw material price of 5-bromoquinoline is relatively expensive, and the catalyst is not commercially available; literature (Heterocycles, 2001, 54, 105-108) 3-aminophenol is a raw material, which is protected by sulfonyl group, Michael addition and Cyclization and deprotection to obtain 5-hydroxyquinoline, although 3-aminophenol is cheap and easy to obtain, but there are many reaction steps, the total yield is less than 10%, and there are many "three wastes", which is not conducive to environmental protection

Method used

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  • A kind of preparation method of 5-sulfonyloxy-8-amidoquinoline derivative
  • A kind of preparation method of 5-sulfonyloxy-8-amidoquinoline derivative
  • A kind of preparation method of 5-sulfonyloxy-8-amidoquinoline derivative

Examples

Experimental program
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Effect test

Embodiment 1

[0015] Preparation of 5-(4-methylbenzenesulfonyloxy)-8-acetamidoquinoline (I-1)

[0016]

[0017] Add tetrahydrofuran (100mL), 8-acetamidoquinoline (II-1) (1.86g, 0.01mol), N,N'-bis(4-methylbenzenesulfonyl)hydrazine (III- 1) (3.70g, 0.011mol) and iodobenzene trifluoroacetate (14.2g, 0.033mol), stirred at room temperature for 1 hour, filtered, washed the filter cake with dichloromethane, removed the solvent under reduced pressure to obtain crude product, column chromatography ( Petroleum ether / ethyl acetate as eluent, gradient elution) to obtain 2.78 g of white solid, yield 78%, m.p.163-167°C. 1 H NMR (300MHz, CDCl 3 )δ (ppm): 9.78 (s, 1H), 8.85 (d, J = 2.8Hz, 1H), 8.65 (d, J = 8.6Hz, 1H), 8.44 (d, J = 8.4Hz, 1H), 7.79 (d,J=8.1Hz,2H),7.53(dd,J=8.4,4.2Hz,1H),7.36(d,J=7.9Hz,2H),7.01(d,J=8.6Hz,1H),2.49 (s,3H),2.38(s,3H); 13 C NMR (75MHz, CDCl 3 )δ (ppm): 168.27, 148.29, 145.29, 138.95, 133.31, 131.67, 130.84, 129.44, 128.14, 126.77, 122.41, 121.60, 119.31, 114.62, 24.52, 2...

Embodiment 2

[0019] Preparation of 5-(4-tert-butylbenzenesulfonyloxy)-8-acetamidoquinoline (I-2)

[0020]

[0021] Add tetrahydrofuran (100mL), II-1 (1.86, 0.01mol), N,N'-di(4-tert-butylbenzenesulfonyl)hydrazine (III-2) (4.66g, 0.011mmol) into a 250mL four-neck flask and iodobenzene trifluoroacetate (14.2g, 0.033mmol), stirred and reacted at room temperature for 1 hour, filtered, washed the filter cake with dichloromethane, and removed the solvent under reduced pressure to obtain a crude product. Column chromatography (petroleum ether / ethyl acetate was eluting reagent, gradient elution) to obtain white solid 2.71g, yield 68%, m.p.142-145 ℃. 1 H NMR (300MHz, CDCl 3 )δ (ppm): 9.74 (s, 1H), 8.81 (s, 1H), 8.66 (d, J = 8.4Hz, 1H), 8.33 (d, J = 8.5Hz, 1H), 7.81 (d, J = 7.1Hz, 2H), 7.55(d, J=7.1Hz, 2H), 7.47(s, 1H), 7.08(d, J=7.5Hz, 1H), 2.37(s, 3H), 1.36(s, 9H) ; 13 C NMR (75MHz, CDCl 3 )δ (ppm): 168.26, 158.30, 148.20, 138.91, 137.83, 133.30, 131.59, 130.74, 127.95, 125.82, 122.38, 121....

Embodiment 3

[0023] Preparation of 5-Benzenesulfonyloxy-8-acetamidoquinoline (I-3)

[0024]

[0025] Use II-1 (1.86g, 0.01mol), N,N'-diphenylsulfonylhydrazine (III-3) (3.43g, 0.011mmol) and iodobenzene trifluoroacetate (14.2g, 0.033mmol) as raw materials. The operation was the same as in Example 1 to obtain 2.46 g of a white solid with a yield of 72%, m.p.165-168°C. 1 H NMR (300MHz, CDCl 3 )δ (ppm): 9.77 (s, 1H), 8.85 (d, J = 4.3Hz, 1H), 8.67 (d, J = 8.6Hz, 1H), 8.39 (d, J = 8.4Hz, 1H), 7.92 (d, J=7.3Hz, 2H), 7.72(t, J=7.4Hz, 1H), 7.60–7.48(m, 3H), 7.04(d, J=8.6Hz, 1H), 2.38(s, 3H) ; 13 C NMR (75MHz, CDCl 3 )δ (ppm): 168.33, 148.33, 138.34, 137.61, 134.49, 134.07, 130.67, 128.86, 128.10, 122.29, 121.67, 119.40, 119.30, 114.59, 24.58.

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Abstract

The invention relates to the field of organic synthesis, and concretely relates to a preparation method of a 5-sulfonyl oxy-8-carboxamidoquinoline derivative, in particular to the method for preparing the 5-sulfonyl oxy-8-carboxamidoquinoline derivative by adopting 8-acetamido quinoline as a raw material. The method is characterized by comprising the steps of adopting trifluoroacetic acid iodobenzene as an oxidizing agent, carrying out C-H functionalization reaction on 8-carboxamidoquinoline and various different N,N'-disulphohydrazide compounds under metal-free catalysis, and obtaining a C5-site sulfonyl oxy substituted product. Compared with the document, the preparation method provided by the invention has the characteristics that the raw materials are easily obtained, the substrate adaption range is wide, the yield is high and the like.

Description

technical field [0001] The present invention relates to the field of organic synthesis. It specifically relates to a preparation method of 5-sulfonyloxy-8-amidoquinoline derivatives, in particular to a method for preparing 5-sulfonyloxy-8-acetylaminoquinoline from 8-acetylaminoquinoline . Background technique [0002] Quinoline ring is the core structure of many natural products, and its derivatives have various biological activities. Literature (J.Med.Chem.2010,53,8228–8240 and Bioorg.Med.Chem.Lett.2010,20,7092–7096) reported that it was used as an important intermediate for the preparation of 5-HT 1 Receptor antagonist active molecules, literature (J.Med.Chem.2011, 54, 2127-2142) also reported that it is a key intermediate for the synthesis of c-Met inhibitors. [0003] The synthesis of 5-sulfonyloxyquinoline derivatives reported in the literature all use 5-hydroxyquinoline derivatives as starting materials. Such as literature (Bioorg.Med.Chem.2008,16,6707-6723) and (J...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D215/40C07D409/12
CPCC07D215/40C07D409/12
Inventor 朱启华吴欢欢徐云根贺新王致斌崔芷莹纪德重其他发明人请求不公开姓名
Owner CHINA PHARM UNIV
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