A kind of chiral sulfonamide derivative and its preparation method and application

A technology for sulfonamides and derivatives, applied in the field of chiral sulfonamide derivatives and their preparation, can solve the problems of unfavorable sulfonamide derivatives using industrial synthesis, non-recyclable chemical waste, low atom economy and the like , to achieve the effect of low cost, less waste and fewer reaction steps

Active Publication Date: 2022-05-24
SUN YAT SEN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the above-mentioned methods have disadvantages such as harsh reaction conditions, cumbersome operation steps, use of air-sensitive reagents or transition metal catalysts, most of them involve multi-step reactions, and thus non-recyclable chemical wastes will be produced in the intermediate process, and it takes a long time. , high cost, low atom economy and other defects, so the above methods are not conducive to the application of chiral sulfonamide derivatives in organic synthesis and their industrial synthesis

Method used

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  • A kind of chiral sulfonamide derivative and its preparation method and application
  • A kind of chiral sulfonamide derivative and its preparation method and application
  • A kind of chiral sulfonamide derivative and its preparation method and application

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[0088] The preparation method for synthesizing chiral sulfonamide derivatives of the present invention comprises sulfonamide, imine, rhodium acetate, The molecular sieve is dissolved in an organic solvent to prepare a mixed solution; the aryl diazoacetate is dissolved in an organic solvent to prepare a diazo compound solution; at -10°C, the diazo compound solution is added to the aforementioned mixed solution with a syringe pump; at the same time Vigorous stirring; after the dropwise addition of the diazo compound solution, continue stirring at -10°C for 60 minutes until the diazo compound is completely consumed; the crude product is subjected to column chromatography (with ethyl acetate: petroleum ether = 1:20~1:20) 10 is the eluent) to give pure product.

[0089] The synthetic reaction process is as follows:

[0090]

[0091] In the reaction formula (II),

[0092] R is aryl or alkyl, selected from phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 4-methoxyphenyl,...

Embodiment 1

[0097]

[0098] p-Toluenesulfonamide (0.36 mmol), p-chlorobenzylidene aniline (0.30 mmol), rhodium acetate (0.006 mmol), (R)-3,3'-bis(triphenylsilyl)binaphthol phosphate (0.03mmol), Molecular sieve (150 mg) was dissolved in 3.0 mL of anhydrous toluene to prepare mixed solution A; methyl phenyldiazoacetate was dissolved in 1.0 mL of anhydrous toluene to prepare diazo compound solution B; at -10°C, solution B was dissolved At -10°C, the mixed solution A was added with a syringe pump within 1 hour. After the injection of liquid B, the reaction system continued to stir at -10°C for 60 minutes. After the reaction is completed, filter to obtain the filtrate by rotary evaporation to remove the solvent, and then purify the crude product by column chromatography to obtain the pure product, which is a white solid. Its structure is shown in formula (a). The product was isolated in 83% yield, with a dr value greater than 20:1 and an ee value of 99%. of the product 1 The schematic ...

Embodiment 2

[0101]

[0102] p-4-tert-Butylbenzenesulfonamide (0.36 mmol), p-chlorobenzylidene aniline (0.30 mmol), rhodium acetate (0.006 mmol), (R)-3,3'-bis(triphenylsilyl) Binaphthol phosphate (0.03mmol), Molecular sieve (150 mg) was dissolved in 3.0 mL of anhydrous toluene to prepare mixed solution A; methyl phenyldiazoacetate was dissolved in 1.0 mL of anhydrous toluene to prepare diazo compound solution B; at -10°C, solution B was dissolved At -10°C, the mixed solution A was added with a syringe pump within 1 hour. After the injection of liquid B, the reaction system continued to stir at -10°C for 60 minutes. After the reaction is completed, filter to obtain the filtrate by rotary evaporation to remove the solvent, and then purify the crude product by column chromatography to obtain the pure product, which is a white solid. Its structure is shown in formula (b). The product was isolated in 78% yield, with a dr value greater than 20:1 and an ee value of 90%. of the product 1 ...

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Abstract

The invention discloses a chiral sulfonamide derivative, the structural formula is as follows, wherein, R is an aryl group, an alkyl group, a cycloalkyl group, a heterocyclic group, a substituted aryl group, a substituted alkyl group, or a substituted heterocyclic group; Ar 1 Aryl, substituted aryl; Ar 2 Aryl, substituted aryl, heterocyclic aryl; Ar 3 Aryl, substituted aryl, heterocyclic aryl; the present invention uses sulfonamide, aryl diazoacetate, imine as raw material, 4Å molecular sieve as water absorbing agent, rhodium acetate, chiral phosphoric acid to form a catalytic system, In an organic solvent, the chiral sulfonamide derivatives are obtained through one-step reaction. The synthesis method of the invention has the advantages of high atom economy, high selectivity and high yield, and has mild reaction conditions and simple and safe operation. The chiral sulfonamide derivatives with two quaternary carbon centers of the present invention are potential drug active molecules, are widely used in the field of medicine, and have great application prospects.

Description

technical field [0001] The invention relates to the field of synthetic medicine and chemical industry, and mainly relates to an efficient, fast, concise and green chiral sulfonamide derivative and a preparation method and application thereof. Background technique [0002] The sulfonamide structure is the core structural unit of a variety of drugs. It was recognized as an antibacterial drug by artificial synthesis from the very beginning, and now it has been widely used in antifungal, antiviral, antituberculous, antiparasitic, antitumor, and antiinflammatory. class of extremely important synthetic drugs. Based on their unique pharmacological activities, chiral sulfonamide derivatives also occupy an extremely important position in the development of new drugs. In the past few decades, a series of chiral induction, chiral resolution, etc. The method obtained chiral sulfonamide derivatives. However, the above-mentioned methods have problems such as harsh reaction conditions, c...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D285/10C07C311/19C07C311/14C07C311/06C07D333/34C07C303/36C07B45/04A61P35/00
CPCA61P35/00C07B45/04C07C311/06C07C311/14C07C311/19C07D285/10C07D333/34C07C2601/02Y02P20/584
Inventor 胡文浩余思凡邱晃刘耿鑫
Owner SUN YAT SEN UNIV
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