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Preparation method of 5-sulfonyl oxy-8-carboxamidoquinoline derivative

A technology of sulfonyloxy and quinoline, which is applied in the preparation of 5-sulfonyloxy-8-amidoquinoline derivatives, and in the field of preparing 5-sulfonyloxy-8-acetamidoquinoline, can Solve the problems of high price, low yield, and many reaction steps, and achieve the effect of wide substrate adaptation, easy availability of raw materials, and low cost of raw materials

Active Publication Date: 2017-09-08
CHINA PHARM UNIV
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  • Summary
  • 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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  • Preparation method of 5-sulfonyl oxy-8-carboxamidoquinoline derivative
  • Preparation method of 5-sulfonyl oxy-8-carboxamidoquinoline derivative
  • Preparation method of 5-sulfonyl oxy-8-carboxamidoquinoline derivative

Examples

Experimental program
Comparison scheme
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, and removed the solvent under reduced pressure to obtain the crude product. Column chromatography ( Petroleum ether / ethyl acetate as eluent, gradient elution) to obtain white solid 2.78g, yield 78%, mp163-167°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 = 8.1 Hz, 2H), 7.53 (dd, J = 8.4, 4.2 Hz, 1H), 7.36 (d, J = 7.9 Hz, 2H), 7.01 (d, J = 8.6 Hz, 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, 21...

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'-bis(4-tert-butylbenzenesulfonyl)hydrazine (III-2) (4.66g, 0.011mmol) into a 250mL four-necked flask And iodobenzene trifluoroacetate (14.2g, 0.033mmol), stirred at room temperature for 1 hour, filtered, washed the filter cake with dichloromethane, and removed the solvent under reduced pressure to obtain the crude product. Column chromatography (petroleum ether / ethyl acetate as elution Reagent, gradient elution) to obtain 2.71 g of white solid, yield 68%, mp142-145°C. 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, 121.49, 119.46, 114.70, 34.87, 30.48, 24.52....

Embodiment 3

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

[0024]

[0025] Using 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 is the same as that in Example 1, to obtain 2.46 g of 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 invention relates to the field of organic synthesis. Specifically, it relates to a method for preparing 5-sulfonyloxy-8-amidoquinoline derivatives, in particular to a method for preparing 5-sulfonyloxy-8-acetamidoquinoline using 8-acetamidoquinoline as a raw material . Background technique [0002] Quinoline ring is the core structure of many natural products, and its derivatives have a variety of 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. For example, the literature (Bioorg.Med.Chem.2008,16,6707-6...

Claims

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Application Information

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Patent Type & Authority Applications(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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