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Method for preparing sulfonyl fluoride compound by activating carbon-hydrogen bond

A compound, sulfonyl fluoride technology, applied in the field of medicinal chemistry, can solve problems such as poor tolerance of functional groups, limited application, unstable raw materials, etc., and achieve the effect of good functional group tolerance

Inactive Publication Date: 2018-09-04
WUHAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The second is to use coupling reagents such as aryl iodide, aryl diazonium salt, aryl boric acid (ester) and its salt and vinylsulfonyl fluoride to realize 2-aryl-vinylsulfonyl fluoride through Heck coupling reaction However, these two methods or raw materials are difficult to prepare, or require the use of equivalent silver trifluoroacetate as an additive, or because the raw materials are unstable, explosive, or poorly tolerated by functional groups, which greatly limits its application
In view of the huge application value of 2-aryl-vinylsulfonyl fluoride and the rhodium-catalyzed alkenylation reaction involving vinylsulfonyl fluoride has not been reported, this patent intends to realize N- Oxidative coupling reaction of methoxybenzamide with vinylsulfonyl fluoride to provide a 2-aryl-vinylsulfonyl fluoride, sulfonyl fluoride-substituted lactone compound and sulfonyl fluoride-substituted γ-lactam Compound preparation method

Method used

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  • Method for preparing sulfonyl fluoride compound by activating carbon-hydrogen bond
  • Method for preparing sulfonyl fluoride compound by activating carbon-hydrogen bond
  • Method for preparing sulfonyl fluoride compound by activating carbon-hydrogen bond

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032]

[0033] To a 25 mL reaction tube was added N-methyl N-methylbenzamide (0.5 mmol), vinylsulfonyl fluoride (0.75 mmol), [Cp*RhCl 2 ] 2 (2.5mol%), AgSbF 6 (10mol%), Cu(OAc) 2 (20mol%), 1,4-dioxane (6mL), stirred and reacted in an oil bath at 100°C for 15h, the reaction solution was distilled under reduced pressure to recover 1,4-dioxane and vinylsulfonyl fluoride, and the residue was used Silica gel column chromatography purification (eluent is petroleum ether: ethyl acetate = 5:1 (v / v)), that is, yellow liquid (E)-2-(2-(methoxy(methyl)aminomethyl) Acyl)phenyl)vinylsulfonyl fluoride (123 mg, 90% yield). 1 HNMR (500MHz, CDCl 3 )δ7.88(d, J=15.5Hz, 1H), 7.62(d, J=7.6Hz, 1H), 7.56-7.47(m, 3H), 6.87(d, J=15.5Hz, 1H), 3.42( s,3H),3.36(s,3H). 19 FNMR (471MHz, CDCl 3 )δ61.8(s,1F). 13 CNMR (126MHz, CDCl 3)δ168.5(s), 146.0(d, J=2.0Hz), 136.6(s), 131.8(s), 130.1(s), 128.6(s), 128.0(s), 127.4(s), 120.2( d,J=27.7Hz),61.3(s),32.7(s).HRMSESI(m / z):[M+Na] + calcdforC 11 h ...

Embodiment 2

[0035]

[0036] To a 25 mL reaction tube was added N-methyl-N-methoxy-2-furancarboxamide (0.5 mmol), vinylsulfonyl fluoride (0.75 mmol), [Cp*RhCl 2 ] 2 (2.5mol%), AgSbF 6 (10mol%), Cu(OAc) 2 (20mol%), 1,4-dioxane (6mL), stirred and reacted in an oil bath at 100°C for 15h, the reaction solution was distilled under reduced pressure to recover 1,4-dioxane and vinylsulfonyl fluoride, and the residue was used Silica gel column chromatography purification (eluent is petroleum ether: ethyl acetate = 3:1 (v / v)), to obtain white solid (E)-2-(2-(methoxy(methyl)aminomethyl) Acyl)furyl)vinylsulfonyl fluoride (110.5 mg, 84% yield). 1 HNMR (500MHz, CDCl 3 )δ8.35(d, J=15.6Hz, 1H), 7.53(d, J=1.7Hz, 1H), 6.75(d, J=15.6Hz, 1H), 6.70(d, J=1.7Hz, 1H) ,3.82(s,3H),3.34(s,3H). 19 FNMR (471MHz, CDCl 3 )δ62.2(s,1F). 13 CNMR (126MHz, CDCl 3 )δ159.3(s), 146.9(s), 144.6(s), 139.5(s), 124.3(s), 120.4(d, J=28.7Hz), 109.2(s), 62.2(s), 33.7( s).Mp95-97℃.HRMSESI(m / z):[M+Na] + calcdforC 9 h 10 ...

Embodiment 3

[0038]

[0039] Add N,4-dimethoxy-N-methylbenzamide (0.5 mmol), vinylsulfonyl fluoride (0.75 mmol), [Cp*RhCl 2 ] 2 (2.5mol%), AgSbF 6 (0.5mmol), Cu(OAc) 2 (20mol%), 1,4-dioxane (6mL), stirred and reacted in an oil bath at 100°C for 15h, the reaction solution was distilled under reduced pressure to recover 1,4-dioxane and vinylsulfonyl fluoride, and the residue was used Purified by silica gel column chromatography (eluent is petroleum ether: ethyl acetate = 3:1 (v / v)) to obtain a white solid (6-methoxy-3-oxa-1,3-dihydroiso Benzofuran)methanesulfonyl fluoride (98.9 mg, 76% yield). 1 HNMR (500MHz, DMSO-d6) δ7.79(d, J=8.5Hz, 1H), 7.44(s, 1H), 7.18(d, J=8.5Hz, 1H), 6.03(d, J=8.5Hz, 1H), 5.02(dd, J=15.1, 9.6Hz, 1H), 4.61(dd, J=15.2, 9.4Hz, 1H), 3.89(s, 3H). 19 FNMR (471MHz, DMSO) δ61.0 (d, J=9.8Hz, 1F). 13 CNMR (126MHz, DMSO-d6) δ169.0(s), 165.0(s), 149.8(s), 127.2(s), 118.0(s), 117.7(s), 107.9(s), 74.3(s), 56.5(s), 53.9(d, J=13.8Hz).Mp175-177℃.HRMSESI(m / z):[M+Na] + calcd...

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Abstract

The invention discloses a method for preparing a sulfonyl fluoride compound by activating a carbon-hydrogen bond. The method comprises the following steps: mixing a raw material Weinreb amide with ethylenesulfonyl fluoride (ESF), a ruthenium catalyst, an additive, an oxidant and a solvent, performing a reaction at 20-120 DEG C for 15 h or more, and separating and purifying the obtained reaction product to obtain the sulfonyl fluoride compound. Compared with existing methods, the method has the characteristics of simplicity, high efficiency and good functional group tolerance. The method for preparing 2-aryl-ethylenesulfonyl fluoride, a sulfonyl fluoride-substituted lactone compound and a sulfonyl fluoride-substituted gamma-lactam compound through realizing an oxidative coupling reaction ofan N-methoxy-N-methyl amide compound and ethylenesulfonyl fluoride by ruthenium-catalyzed direct carbon-hydrogen bond functional group activation.

Description

technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to a method for preparing sulfonyl fluoride compounds through carbon-hydrogen bond activation. Background technique [0002] Sulfur(VI) FluorideExchange (SuFEx) is a new generation of Click Chemistry proposed by Nobel Prize winner Sharpless in 2014. This method is based on sulfonyl fluoride or fluorosulfonate Sulfonic acids are highly reactive with nucleophiles. Among all the fluorine-containing hexavalent sulfur building blocks that have been developed, sulfonyl fluoride compounds are considered to be unique covalent protein inhibitors and bioprobe scaffolds, and sulfonyl fluoride compounds have also been widely used through sulfur-fluorine exchange chemistry. Fluorinated reagents, isotope labeling reagents, surface modification, polymer synthesis and other fields. As a unique sulfonyl fluoride compound, 2-aryl-vinylsulfonyl fluoride has two nucleophilic reaction site...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C309/81C07C309/82C07C309/83C07C309/84C07C303/22C07D307/68C07D307/88C07D209/46C07D317/68C07D333/38C07D209/64C07D495/04
CPCC07C303/22C07D209/46C07D209/64C07D307/68C07D307/88C07D317/68C07D333/38C07D495/04C07C309/81C07C309/82C07C309/83C07C309/84
Inventor 秦华利李晨汪诗梦
Owner WUHAN UNIV OF TECH
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