The present disclosure discloses a novel biochip substrate, a preparation method and an application thereof. The surface of the novel biochip substrate contains active vinyl sulfone groups. The preparation method involves a one-step reaction of a compound containing vinyl sulfone groups on both ends with a silicon-hydroxyl group on the surface of a silicon-based biochip substrate material under catalytic conditions, to prepare the biochip substrate. The application immobilizes biomacromolecules by conducting Michael addition of amino or sulfydryl group in biomacromolecules and the vinyl sulfone group on the surface of the biochip substrate, realizing biological functionalization thereof. The biochip substrate has high-density active vinyl sulfone groups, which can be used for immobilization of various biomolecules with mild fixation conditions and simple operation. The preparation method does not require complex pretreatment processes, and has high operability and reproducibility, low cost, mild reaction conditions, simple operation, and environmentally friendly, which is a broad-spectrum biochip substrate with great potential.

The present disclosure discloses a novel biochip substrate, a preparation method and an application thereof. The surface of the novel biochip substrate contains active vinyl sulfone groups. The preparation method involves a one-step reaction of a compound containing vinyl sulfone groups on both ends with a silicon-hydroxyl group on the surface of a silicon-based biochip substrate material under catalytic conditions, to prepare the biochip substrate. The application immobilizes biomacromolecules by conducting Michael addition of amino or sulfydryl group in biomacromolecules and the vinyl sulfone group on the surface of the biochip substrate, realizing biological functionalization thereof. The biochip substrate has high-density active vinyl sulfone groups, which can be used for immobilization of various biomolecules with mild fixation conditions and simple operation. The preparation method does not require complex pretreatment processes, and has high operability and reproducibility, low cost, mild reaction conditions, simple operation, and environmentally friendly, which is a broad-spectrum biochip substrate with great potential.

The present invention relates to novel uses of stable inorganic peroxoacids as catalysts in the preparation of alkanesulfonic acids from alkanes and sulfur trioxide, methods for the production of alkanesulfonic acids employing said catalysts as well as reaction mixtures comprising said catalysts. The invention particularly relates to the production of methanesulfonic acid from methane and sulfur trioxide employing stable inorganic peroxoacids as catalysts.

The present invention relates to novel uses of stable inorganic peroxoacids as catalysts in the preparation of alkanesulfonic acids from alkanes and sulfur trioxide, methods for the production of alkanesulfonic acids employing said catalysts as well as reaction mixtures comprising said catalysts. The invention particularly relates to the production of methanesulfonic acid from methane and sulfur trioxide employing stable inorganic peroxoacids as catalysts.

The subject of the present invention is a process for producing a sulfonic acid which is sparingly corrosive, or even non-corrosive, with respect to stainless steels, said process comprising at least the steps of adding at least one nitrite to a sulfonic acid, curing, with stirring, with sparging of the mixture and recovering the low-corrosion sulfonic acid obtained.

The invention also relates to the low-corrosion sulfonic acid obtained according to the process of the invention, and also to the use thereof as low-corrosion sulfonic acid.

The disclosure provides a novel process and synthetic intermediates for making belzutifan, a HIF-2a inhibitor, useful for the treatment of certain VHL-related indications and cancer.

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The disclosure provides a novel process and synthetic intermediates for making belzutifan, a HIF-2a inhibitor, useful for the treatment of certain VHL-related indications and cancer.

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Provided is a method for preparing apremilast of formula I. Method one: (S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethylamine N-acetyl-L-leucine salt of formula II is reacted with 3-acetylaminophthalic anhydride of formula III in an aprotic solvent to produce the compound of formula I; method two: (S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethylamine N-acetyl-L-leucine salt of formula II is reacted with 3-acetylaminophthalic anhydride of formula III in an organic solvent in the presence of an organic alkali or an alkali metal hydride to produce the compound of formula I. The method for preparing apremilast requires inexpensive raw materials and reagents, is suitable for industrial production, and has great economic effects.

Provided is a method for preparing apremilast of formula I. Method one: (S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethylamine N-acetyl-L-leucine salt of formula II is reacted with 3-acetylaminophthalic anhydride of formula III in an aprotic solvent to produce the compound of formula I; method two: (S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethylamine N-acetyl-L-leucine salt of formula II is reacted with 3-acetylaminophthalic anhydride of formula III in an organic solvent in the presence of an organic alkali or an alkali metal hydride to produce the compound of formula I. The method for preparing apremilast requires inexpensive raw materials and reagents, is suitable for industrial production, and has great economic effects.

The present invention relates to an improved process for the preparation of Apremilast of formula (I). ##STR00001##