57 results about "Curtius rearrangement" patented technology

The invention provides a preparation method of trans-(1R, 2S)-2-(3, 4-difluoro phenyl) cyclopropylamine. The preparation method comprises the following steps: enabling racemic chloro phenethyl alcohol (I) and N-protection proline to undergo a reaction under the effects of a condensing agent A1 and a catalyst C1, and obtaining chiral chlorohydrin (II); enabling the chiral chlorohydrin (II) to generate an epoxy compound (III) under the conditions of alkalinity; enabling the epoxy compound (III) and TEPA to react and generate cyclopropyl ethyl formate (IV) under the conditions of alkalinity; removing ester from cyclopropyl ethyl formate (IV) under the conditions of alkalinity, and generating cyclopropanecarboxylic acid (V); and enabling cyclopropanecarboxylic acid (V) and azide to generate a target compound (3) by Curtius rearrangement. The preparation method has the advantages that the steps of a used synthetic process route are few, the operation is simple, and industrial production is achieved easily; a kinetic resolution method is utilized to synthesize chiral chlorohydrin (II) and is simple in reaction conditions and easy to operate; and a TEPA method is utilized synthesize the cyclopropyl ethyl formate, the product yield is high, cis-trans selectivity is good, and the purity is over 99%.

The invention provides a preparation method for 3-(4-methyl-1H-imidazole-1-yl)-5-(trifluoromethyl)aniline. The method includes: S1. subjecting a compound A and 4-methyl-1H-imidazole to coupling reaction to generate a coupling product; S2. carrying out hydrazinolysis reaction on the coupling product to generate a hydrazinolysis product; and S3. subjecting the hydrazinolysis product to diazotization and Curtius rearrangement reaction in order to generate 3-(4-methyl-1H-imidazole-1-yl)-5-(trifluoromethyl)aniline. Specifically, the compound A is 3-halogen-5-trifluoromethylbenzoic acid, a salt derivative of 3-halogen-5-trifluoromethylbenzoic acid or an ester derivative of 3-halogen-5-trifluoromethylbenzoic acid. The method for preparation of 3-(4-methyl-1H-imidazole-1-yl)-5-(trifluoromethyl)aniline provided by the invention has the characteristics of short synthesis route, low cost of raw materials, mild reaction conditions and high yield, thus being applicable to large-scale industrial production.

The invention belongs to the technical field of medicine and discloses a 2',3'-dihydrospiro[cyclopropane-1,1'-indene]-2-amine derivative of a formula (I) as well as a preparation method thereof. The preparation method comprises the following steps: performing Witting reaction on II to obtain III, catalyzing cyclopropanation reaction of ethyl diazoacetate and the III by rhodium acetate to obtain IVand V, performing hydrolysis, performing Curtius rearrangement to obtain VI and VII; (1) removing Boc from the VI or VII and performing reduction and ammoniation to obtain a compound VIII or IX; or (2) performing substitution on the VI or VII and 2-chlorine-1-morpholine ethane-1-ketone to obtain X or XI; or (3) performing reduction and ammoniation on the VI or VII and (4-oxycyclohexyl)tert-butylcarbamate, and removing Boc to obtain a compound XII or XIII; or (4) performing Suzuki coupling on the VI or VII and substituted arylboronic acid, removing Boc to obtain XIV or XV, and performing reduction and ammoniation to obtain VIII or IX. The derivative of the formula (I) has high inhibition activity, has high selectivity on homologous enzyme such as monoamine oxidase and LSD2, and is expected to be developed into a medicine for treating diseases such as acute myelogenous leukemia.

The invention discloses a method for preparing ethyl trans-4-amino-cyclohexanecarboxylate hydrochloride, and belongs to the field of organic chemistry. Trans-1,4--cyclohexanedicarboxylic acid is usedas an initial material and reacts with anhydrous ethanol to produce intermediate diester A under the condition of a sulfuric acid catalyst, monoester is hydrolyzed by intermediate diester A to obtainintermediate monoacid B, the intermediate monoacid B and DPPA are subjected to Curtius rearrangement to obtain intermediate C, the intermediate C is deprotected by hydrogen chloride ethyl acetate solution to obtain final product ethyl trans-4-amino-cyclohexanecarboxylate hydrochloride I. The process adopted by the invention has the advantages of short reaction steps, cheap raw materials, mild reaction conditions and high yield, and is suitable for industrialized large-scale production.

The invention relates to a preparation method of a carbamyl amino pyrazol derived compound, belongs to the technical field of drug intermediates and aims to solve the problem that an existing synthetic route is complicated and is uneasy to operate. The preparation method of the carbamyl amino pyrazol derived compound comprises the steps that in the presence of an acid-binding agent, a compound shown in a formula II and triphenyl halomethane perform condensation reaction in an organic solvent to obtain an intermediate product compound shown in a formula III; then, in the presence of inorganic base, the compound shown in the formula III is subjected to ester hydrolysis reaction, and a compound shown in a formula IV is obtained; the compound and trinitride perform Curtius rearrangement reaction to obtain a compound shown in a formula V; the compound shown in the formula V and BoxEDA perform condensation reaction to obtain the carbamyl amino pyrazol derived compound. The preparation methodhas the advantages that raw materials are easy to obtain, a reaction route operation is simple, and the product yield and purity are high.

The invention discloses an intermediate compound used for synthesizing valnemulin hydrochloride. The chemical structure of the intermediate compound used for synthesizing valnemulin hydrochloride is represented by a formula in the invention. A preparation method of the intermediate compound comprises following steps: beta-hydroxyisovaleric acid is subjected to Curtius rearrangement reaction so as to obtain 2-methyl-2-hydroxy propylamine; 2-methyl-2-hydroxy propylamine and D-valine Dane salt are subjected to mixed anhydride method reaction so as to obtain an amide product; the amide product is subjected to hydroxy activation under alkaline conditions with methylsulfonyl chloride, and then is reacted with potassium thioacetate. The preparation method of valnemulin hydrochloride comprises following steps: pleuromutilin is reacted with paratoluensulfonyl chloride so as to obtain pleuromutilin p-tosylate; pleuromutilin p-tosylate is reacted with the intermediate compound, and hydrochloric acid deprotection is carried out so as to obtain valnemulin hydrochloride. In the preparation method of valnemulin hydrochloride, no dimethyl cysteamine hydrochloride is needed, production conditions are mild, no environment pollution is caused, and the preparation method is suitable for industrialized production.

A preparation method of 2, 3, 4, 9-tetrahydro-beta-carboline-1-one comprises: chloridizing indole-3-propionic acid (III) with a chloridizing agent in an aprotic solvent to prepare indole-3- propionyl chloride (IV), or carrying out condensation reaction between indole-3-propionic acid (III) and chloro-formate in an aprotic solvent under catalysis of an acid binding agent to prepare an active mixed acid anhydride (V); then carrying out an azidation reaction with an azidation reagent to prepare indolepropionyl azide (VI); carrying out a Curtius rearrangement reaction to prepare indoleethyl isocyanate(VII); and finally preparing 2, 3, 4, 9-tetrahydro-beta-carbolin-1-one through a cyclization reaction under catalysis of an acid catalyst. The method is mild in reaction conditions, simple to operate, less in pollution, cheap and accessible in raw materials, simple in technology, high in yield, and ingenious in technology design; and the azidation reaction, Curtius rearrangement and the cyclization are carried out by one-pot synthesis; and in the reaction process, there are not complex operations such as column chromatography, repeated recrystallization and the like, and the technology scaling-up is easy to operate.

The invention relates to a preparation method of chiral baclofen, belonging to the field of synthesis of chiral compounds. The synthetic route of the method comprises the following steps: condensing the initial raw material 3-(4-chlorphenyl)glutaric acid to obtain 3-(4-chlorphenyl)glutaric anhydride; preparing the 3-(4-chlorphenyl)glutaric anhydride into a key intermediate (S)-3-(4-chlorphenyl)monoglutarate under the action of a chiral catalyst; and carrying out Curtius rearrangement (or Hofmann rearrangement) reaction to obtain the chiral baclofen. The method has the advantages of short reaction steps and is simple to operate; and the product has the advantages of high ee value, low cost and high yield.

The invention provides a method for synthesizing 2-(1-imidazol)ethylamine, which uses imidazole and ethyl acrylate as raw material, and includes steps of preparing intermediate (1) ethyl 2-(1-imidazol)propionate from the raw material through Michel addition reaction; preparing intermediate (2) 2-(1-imidazol)propionohydrazide from the intermediate (1) through hydrazinolysis reaction; and obtainingthe object product 2-(1-imidazol)ethylamine from the intermediate (2) through Curtius rearrangement reaction. The invention has total yield of 72% by imidazole, stable reaction, mild condition, and convenient operation and control.

The invention belongs to the technical field of macromolecular synthetic chemistry, and particularly relates to polyethylene glycol omega-amino acid and a preparation method thereof. The method comprises the following steps of: oxidizing hydroxys at two ends of polyethylene glycol into carboxyls, loading the polyethylene glycol of which the end groups are the carboxyls to resin by nucleophilic substitution reaction, and protecting the free carboxyls through methyl ester; and cracking the double-carboxyl polyethylene glycol of which one end is protected by the methyl ester from the resin, and then modifying the free carboxyls by azidation reaction and Curtius rearrangement reaction to obtain tert-butyloxycarbonyl protected amino. The method overcomes the defect that the conventional method for synthesizing the polyethylene glycol omega-amino acid has complex separation and purification. Because of the adoption of solid-phase reaction, azidation reaction and Curtius rearrangement reaction, the method has the advantages of mild condition, short synthetic route and simple separation and purification, and the yield reaches over 70 percent. The polyethylene glycol omega-amino acid can be widely applied to the fields of targeted medicament synthesis, biological sensing, immunoassay, polypeptide synthesis and the like.

The invention discloses a method for synthesizing 3-amino-1-adamantanol. The structural formula of the 3-amino-1-adamantanol is as follows. Using adamantanecarboxylic acid as starting material, the method synthesizes the 3-amino-1-adamantanol according to the following reaction steps: bromate 3-amino-1-adamantanol is synthesized by way of bromination, modified curtius rearrangement and hydrolyzation, and finally, bromate is removed by a alkaline liquor treatment method, so that the 3-amino-1-adamantanol is obtained. The invention has the advantages of simple and easy operation, available materials, less reaction steps and high product yield.

A preparation method of 2, 3, 4, 9-tetrahydro-beta-carboline-1-one comprises: chloridizing indole-3-propionic acid (III) with a chloridizing agent in an aprotic solvent to prepare indole-3- propionyl chloride (IV), or carrying out condensation reaction between indole-3-propionic acid (III) and chloro-formate in an aprotic solvent under catalysis of an acid binding agent to prepare an active mixed acid anhydride (V); then carrying out an azidation reaction with an azidation reagent to prepare indolepropionyl azide (VI); carrying out a Curtius rearrangement reaction to prepare indoleethyl isocyanate(VII); and finally preparing 2, 3, 4, 9-tetrahydro-beta-carbolin-1-one through a cyclization reaction under catalysis of an acid catalyst. The method is mild in reaction conditions, simple to operate, less in pollution, cheap and accessible in raw materials, simple in technology, high in yield, and ingenious in technology design; and the azidation reaction, Curtius rearrangement and the cyclization are carried out by one-pot synthesis; and in the reaction process, there are not complex operations such as column chromatography, repeated recrystallization and the like, and the technology scaling-up is easy to operate.

The invention prepares amine compounds based on novel catalytic Curtius rearrangement reaction. Transition metal catalyzed sp 2 C‑N bond formation is an efficient method for the synthesis of arylamines, catalyzing sp 3 The coupling reaction of C-N bond is also reported from time to time, but at the same time, sp 2 and sp 3 Methods for C‑N bond generation are relatively underdeveloped. The present invention uses resource-rich organic carboxylic acids as carbon sources and easily prepared alkane / aryloxyacyl azides as nitrogen sources, at as low as 0.1 mol% of DMAP and Cu(OAc) 2 Under catalysis, with gas N 2 and CO 2 One-pot generation of protected alkyl, alkenyl, and aryl amines as the only by-product. The reaction can be applied to the late functionalization of natural products and drug molecules, the synthesis of chiral alkylamines, and the rapid construction of different ureas and primary amines. Mechanistic studies reveal that the reaction proceeds through a cascade of carboxylic acid activation, azidation, Curtius rearrangement, and nucleophilic addition.

The invention relates to a systhesis method of lenvatinib. The method comprises the following steps: by taking 2-chloro-4-methyl hydroxybenzoate and 4-chloro-7-methoxyquinoline-6-amide as starting raw materials, carrying out substitution reaction to obtain 4-[3-chloro-4-methoxycarbonyl phenoxy]-7-methoxy-6-quinolinecarboxamide, carrying out an alkaline hydrolysis reaction to obtain 4-(3-chloro-4-carboxyphenoxy)-7-methoxy-6-quinolinecarboxamide, carrying out a Curtius rearrangement reaction on the 4-(3-chloro-4-carboxyphenoxy)-7-methoxy-6-quinolinecarboxamide and diphenyl azide phosphate (DPPA), and carrying out a reaction on the obtained product and cyclopropylamine to obtain lenvatinib through a one-pot method. The invention provides a novel method for synthesizing lenvatinib. The method has the advantages of simple reaction steps, simple and easily available raw materials, simple operation and low production cost.