36 results about "Nucleophilic aromatic substitution" patented technology

The present invention relates to a new method for the synthesis of purine LNA (Locked Nucleic Acid) analogues which provides a higher overall yield. The method comprising a regioselective 9-N purine glycosylation reaction followed by a one-pot nucleophilic aromatic substitution reaction of the 6-substituent in the purine ring and simultaneous nucleophile-induced intramolecular ring closure of the C-branched carbohydrate to form novel purine LNA analogues. The novel strategy is illustrated by the synthesis of the novel compound (1S,3R,4R,7S)-7-benzyloxy-1-methanesulfonylmethyl-3-(guanin-9-yl)-2,5-dioxabicyclo[2.2.1]heptane which is easily converted into (1S,3R,4R,7S)-7-hydroxy-1-hydroxymethyl-3-((2-N-isobutyrylguanin-9-yl)-2,5-dioxabicyclo[2.2.1]heptane after isobutyryl protection of the 2-amino purine group and subsequent substitution of 1-methanesulfonyl with benzoate, debenzoylation and debenzylation.

The present invention relates to the novel regioselective syntheses of 2,4-disubstituted pyrimidines through sequential nucleophilic aromatic substitutions.

The invention discloses a preparation method of high-performance carboxyl functionalized poly (arylene ether nitrile). The method comprises the following steps: synthesizing a carboxyl-containing monomer phenolphthalein by taking phenolphthalein and a zinc powder as raw materials, performing stepwise polymerization by virtue of nucleophilic aromatic substitution, and introducing the phenolphthalein structural units into a main chain of the poly (arylene ether nitrile), so as to obtain the high-performance carboxyl functionalized poly (arylene ether nitrile) copolymer. The polymer has a high glass-transition temperature, excellent heat stability and thermo-oxidative stability, high mechanical strength and good solubility in a polar solvent, has strong absorption in an ultraviolet region of280-330nm and also has blue-fluorescence functional characteristics under ultraviolet excitation, so that the poly (arylene ether nitrile) has functional diversity, and the application range of the product is widened. The theoretical direction and technical support are provided for simple and high-efficiency industrial production of the high-performance poly (arylene ether nitrile), the gap of functional development of the poly (arylene ether nitrile) is filled for preparing high-performance reactive functional composite materials, and the preparation method has excellent application prospects.

The disclosures herein provide a process for conducting a nucleophilic aromatic substitution reaction in an ionic liquid and forming a polymeric material.

The invention discloses sulphonated compound including a phosphine oxide structure, and the preparation method thereof, in particular to 3-sodium sulfonate-4-halogen phenyl-3a-sodium sulfonate phenyl-4a-halogen phenyl phosphine oxide and di (3-sodium sulfonate-4-halogen phenyl)-3a-sodium sulfonate phenyl phosphine oxide and the preparation method thereof. The compound is obtained by taking di (4-halogen phenyl) phenyl phosphine oxide as the raw material through the sulphonation reaction, and the structural formula is shown as follows: the compound can have the nucleophilic aromatic substitution reaction with a bifunctional monomer including two active hydrogens under the alkaline condition, thus sulphonated polymer including a phosphine oxide structural unit is obtained, the performance of the sulphonated polymer is excellent, and the sulphonated polymer yearns for being used for proton exchange membrane materials or other functional materials. X is F, Cl, Br, or I, and Y is H or -SO3Na.

The invention provides a preparation method of a 17hydroxy-pregnane-4-alkene-3, 20-diketone-21-acetic ester. The preparation method is characterized in that a compound as shown in a formula (II) described in the specification is subjected to cyanation, protection, nucleophilic substitution and esterification reaction, and the 17hydroxy-pregnane-4-alkene-3, 20-diketone-21-acetic ester as shown in the formula (I) is obtained. The preparation method provided by the invention has the advantages that the process is simple, the cost is low, the yield is high and stable, and the preparation method is suitable for industrial production.

The invention discloses an organic phosphine compound with a sulfonyl functional group, as well as a preparation method and application thereof. The organic phosphine compound with the sulfonyl functional group comprises a sulfonyl group, a phosphine-containing group and the functional group capable of leaving through nucleophilic substitution. During preparation, sulfonyl chloride and a reagent with a leaving group are reacted, and the functional group capable of leaving through nucleophilic substitution is introduced; then a carbon phosphine bond is built through nucleophilic substitution reaction or coupling reaction, and the phosphine-containing group is introduced. The organic phosphine compound with the sulfonyl functional group provided by the invention can be subjected to nucleophilic reaction with a nucleophilic reagent so as to quickly build a ligand library, provides a favorably technology for designing and synthesizing ligands, is good for accelerating the discovery and theoptimization of the reaction, and can be applied to nucleophilic substitution reaction with the nucleophilic reagent so as to build the phosphine-containing compound.

The invention relates to a cyclotriphosphazene derivative containing a sulfydryl group and a preparation method thereof, and belongs to the technical field of processing aids. The method comprises the following steps: adding thiophenol and a solvent to a reactor in an inert gas atmosphere; simultaneously, slowly adding a sodium compound to stir, and adding phosphonitrilic chloride trimer, so as to obtain reaction liquid, wherein the reaction temperature is 20-120 DEG C; leaching a reaction by-product, and removing the solvent by evaporating; and finally obtaining the cyclotriphosphazene derivative containing the sulfydryl group. By adopting the preparation method, the nucleophilic substitution is carried out by using sulfydryl and the phosphonitrilic chloride trimer; a hexasubstituted cyclotriphosphazene derivative (named) containing the sulfydryl group, which is accompanied with a little of incompletely-substituted penta-substitution product, is successfully synthetized; the molar ratio of the hexasubstituted cyclotriphosphazene derivative to the incompletely-substituted penta-substitution product is 2.61:1. The preparation method disclosed by the invention is mild in reaction condition, and has the characteristics of being easy to control, good in repeatability, high in yield and the like.

The invention provides methods and compositions for generating mutations in new nucleic acid molecules through incorporation of a transformable nucleoside into the nucleic acid and subsequent transformation of the nucleoside through oxidative-nucleophilic-aromatic-substitution chemistry, referred to as TimeLapse chemistry. The invention further provides methods for detecting the mutations, referred to as TimeLapse-seq.

The invention belongs to the technical field of chemical medicines, and specifically relates to a preparation method of an intermediate for leukemia treatment medicines. The method comprises the stepsof supporting N-[3-(triethoxysilyl)propyl]-4,5-dihydroimidazole onto silica, and then reacting with 1,4-butyl sultone and trifluoroacetic acid to generate a silica gel supported acidic ionic liquid;and catalyzing the reaction of 4-chloro-6-methoxy 7-fluoro-quinoline-3-carbonitrile and 2,4-dichloro-5-methoxyaniline by using the acidic ionic liquid as an acidic catalyst to generate an intermediate 4-(2,4-dichloro-5-methoxyphenylamine)-7-fluoro-6-methoxyquinoline-3-nitrile for leukemia treatment medicines. The yield is up to 90.2%, and the process is environment-friendly; and the silica gel supported acidic ionic liquid can be removed from the reaction system by simple filtration, and can catalyze the aromatic nucleophilic substitution reaction of various substrates.

Method for preparing carboxylic acid derivatives by aromatic nucleophilic substitution, in which a carboxylic acid derivative having a single carboxyl functional group, or one of the salts thereof, the carboxylic acid derivative having, in the ortho position of the carboxyl functional group, a leaving group, which is preferably an atom of fluorine or of chlorine or an alkoxy group, chiral or not, preferably a methoxy group, the carboxylic acid derivative not being substituted by an electro attractive group other than the leaving group if any; is reacted with a reactant MNu, where M is a metal and Nu is a nucleophile, chiral or not, the aromatic nucleophilic substitution reaction being carried out without a catalyst and without a step of protecting/deprotecting the acid functional group of the starting compound.

The invention discloses a preparation method of a pyridine derivative, and especially relates to a preparation method of 1-(2-(piperazine-1-group)ethyl)pyridine-2(1H)-ketone, the method takes 2-pyridone as an initial raw material, and 2-pyridone is subjected to nucleophilic substitution, chlorination, nucleophilic substitution and Boc removal to obtain the target product, and the compound is an important medicine intermediate.

The invention especially relates to a preparation method for a morpholine derivative, i.e., N-(4-bromobenzyl)-2-morpholineethylamine, belonging to the field of organic synthesis. According to the method, 4-bromobenzylamine is used as a starting raw material and subjected to acylation, nucleophilic substitution and reduction so as to prepare the morpholine derivative. The prepared morpholine derivative can enrich organic-synthesis molecule building blocks.

The invention belongs to the field of medicine, and discloses a (1R, 4R, 7R)-7-amino-2-azabicyclo [2, 2, 1] heptane derivative and a preparation method thereof. The preparation method comprises the following steps of: (S1) carrying out nucleophilic aromatic substitution reaction on compounds I-1 and I-2 to obtain a compound A-1; (S2) treating the compound A-1 with hydrochloric acid or trifluoroacetic acid for deprotection to obtain a compound A-2; and (S3) carrying out coupling reaction on the compound A-2 and organic acid or acyl chloride, or carrying out reaction on the compound A-2 and amine and triphosgene, or carrying out reaction on the compound A-2 and amine and carbonyl diimidazole to obtain the (1R, 4R, 7R)-7-amino-2-azabicyclo [2, 2, 1] heptane derivative. The (1R, 4R, 7R)-7-amino-2-azabicyclo [2, 2, 1] heptane derivative developed by the invention can avoid inhibition of JAK2 and selectively inhibit JAK1 or JAK1/Tyk2, and has important significance in treatment of autoimmune diseases.

In the method for producing an optically active 2,3-bisphosphinopyrazine derivative of the present invention, an optically active 2,3-bisphosphinopyrazine derivative represented by the following formula (3) is produced by the step of: preparing solution A containing 2,3-dihalogenopyrazine represented by the following formula (1)

and a carboxylic acid amide coordinating solvent, lithiating an optically active R- or S-isomer of a hydrogen-phosphine borane compound represented by the following formula (2)

to give a lithiated phosphine borane compound; adding solution B containing the lithiated phosphine borane compound to the solution A to perform an aromatic nucleophilic substitution reaction; and then performing a deboranation reaction.

(For symbols in the formulas, see the description.)