Disclosed in the present invention is a method for synthesizing a 4-chloropyrrolopyrimidine compound or a derivative thereof, comprising the following steps: reacting an alkylene oxide compound with a cyanoacetate compound by taking an alkaline substance as a catalyst to generate intermediate 1, and further carrying out ring closure to obtain intermediate 2; by taking an alkaline substance as a catalyst, reacting a formamidine acetate compound with intermediates 1 and 2 by using a one-pot method to obtain a 6-amino-5-(2-hydroxyethyl)pyrimidin-4-ol compound; further by using the one-pot method, using an oxidizing agent to oxidize the 6-amino-5-(2-hydroxyethyl)pyrimidin-4-ol compound into an aldehyde compound, and then further carrying out ring closure to obtain a 4-hydroxypyrrolopyrimidine compound; and adding an organic alkali for a chlorination reaction between the 4-hydroxypyrrolopyrimidine compound and phosphorus oxychloride to obtain the 4-chloropyrrolopyrimidine compound. In the present invention, the 4-chloropyrrolopyrimidine compound is synthesized by using a novel synthesis strategy, and the synthesis has a simple operation, cost effective raw materials, and a relatively high yield and is suitable for large-scale production in factories.
Disclosed in the present invention are a 4-methoxypyrrole derivative and a synthesis method therefor. The synthesis method comprises the following synthesis steps: step 1), using m-difluorobenzene (compound (I)) as a starting raw material, reacting same with an oxalyl chloride monoester in a solvent under the catalysis of aluminum trichloride, and subjecting same to a post-treatment to prepare a compound (II); step 2), subjecting the compound (II) to a dehydration reaction with methyl 3-aminopropionate or a salt thereof in a solvent, and subjecting same to a post-treatment to prepare a compound (III); step 3), subjecting the compound (III) to an intramolecular ring-forming reaction in a solvent under the action of an alkali, and subjecting same to a post-treatment to prepare a compound (IV); and step 4), reacting the compound (IV) with dimethyl sulfate in a solvent under the action of an alkali, and subjecting same to a post-treatment to prepare a product compound (V). The 4-methoxypyrrole derivative and the synthesis method therefor of the present invention have the advantages whereby the raw materials are easy to obtain, the yield is relatively high, the quality is good, and the operation is simple and convenient.
The present disclosure discloses a method for the preparation of sulfinpyrazone, which is produced in two steps with a total yield of 48%, wherein thiophenol as the starting material is electrocatalytically coupled with dichloroethane to obtain 2-chloroethyl phenyl sulfoxide, which then undergoes a substitution reaction with 1,2-diphenyl-3,5-pyrazolidinedione to produce sulfinpyrazone. Compared with the prior art, the present method is characterized by high yield, short steps, less three wastes, good chemical selectivity, no need to use strong bases and oxidants, safe and simple operation, and easy to realize industrial production.
The present disclosure relates to the field of drug synthesis, and discloses a method for the preparation of trans-N-benzyloxycarbonyl-(3-hydroxy-2-piperidinyl)-2-propanone as an intermediate of halofuginone. In the preparation method according to the present disclosure, for the first time, trans-N-benzyloxycarbonyl-(3-hydroxy-2-piperidinyl)-2-propanone as shown in Formula I is obtained from amino-substituted pentanal and a thiazolyl sulfoxide compound as raw materials by Mislow-Evans rearrangement reaction and subsequent Lewis acid catalysis. The method for the preparation of trans-N-benzyloxycarbonyl-(3-hydroxy-2-piperidinyl)-2-propanone as an intermediate of halofuginone according to the present disclosure has high yields and stable qualities, provides a new reference route for the synthesis of trans-N-benzyloxycarbonyl-(3-hydroxy-2-piperidinyl)-2-propanone, avoids the reduction of pyridine, and overcomes the disadvantage of requiring the use of an expensive metal catalyst Rh/Al2O3.
The present invention relates to the field of drug synthesis. Disclosed is a preparation method for halofuginone intermediate trans-N-benzyloxycarbonyl-(3-hydroxy-2-piperidinyl)-2-acetone. The preparation method of the present invention comprises: first using animo-substituted valeraldehyde and a thiazole sulfoxide compound as raw materials, carrying out an Mislow-Evans rearrangement reaction, and then preparing trans-N-benzyloxycarbonyl-(3-hydroxy-2-piperidinyl)-2-acetone shown in formula I under the catalysis of Lewis acid. The preparation method for halofuginone intermediate trans-N-benzyloxycarbonyl-(3-hydroxy-2-piperidinyl)-2-acetone of the present invention is high in yield and stable in quality, provides a new route reference for the synthesis of trans-N-benzyloxycarbonyl-(3-hydroxy-2-piperidinyl)-2-acetone, avoids the reduction of pyridine, and overcomes the defect that an expensive Rh/Al2O3 metal catalyst needs to be used.
C07D 211/42 - Oxygen atoms attached in position 3 or 5
C07C 269/06 - Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
C07C 271/18 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by doubly-bound oxygen atoms
Disclosed in the present invention is a preparation method for sulfinpyrazone. The sulfinpyrazone is prepared by means of the steps of: using thiophenol as an initiator, electrocatalytically coupling same with dichloroethane to obtain 2-chloroethyl phenyl sulfide, then subjecting same to a substitution reaction with 1,2-diphenyl-3,5-pyrazolidinedione to obtain sulfinpyrazone. The method is a two-step reaction, and has a total yield of 48%. Compared with the prior art, the method has the characteristics of a high yield, short steps, few three wastes, good chemical selectivity, no need for a strong base and oxidant, safe and convenient operation and easy realization of industrial production.
The invention discloses a method for synthesizing 1,7-naphthyridine derivatives, which relates to the technical field of synthesizing pharmaceutical intermediates and organic chemical intermediates, wherein the method includes: (1) 2-chloro-3-amino-pyridine being used as Compound I as a starting material, and protecting an amino group to prepare Compound II; (2) the Compound II reacting with an aldehydation reagent under alkaline conditions to obtain Compound III; (3) cyclizing the Compound III with acrylate compounds under the action of Lewis acid to prepare compound IV.
The present invention relates to the field of synthesis and preparation of medical intermediates. Disclosed is a synthesis method for a medical intermediate cyclopropyl-containing chiral amine hydrochloride. According to the present invention, a compound (I) cycloprogyl dehyde is used as an initial raw material, and a target product chiral amine hydrochloride is obtained by means of condensation, alkylation, debenzylation, chiral resolution and salification reactions. The synthesis method for the medical intermediate cyclopropyl-containing chiral amine hydrochloride in the present invention has the characteristics of low cost and simple operation.
C07C 209/62 - Preparation of compounds containing amino groups bound to a carbon skeleton by cleaving carbon-to-nitrogen, sulfur-to-nitrogen, or phosphorus-to-nitrogen bonds, e.g. hydrolysis of amides, N-dealkylation of amines or quaternary ammonium compounds
C07C 209/74 - Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton by halogenation, hydrohalogenation, dehalogenation, or dehydrohalogenation
C07C 209/68 - Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
C07C 211/17 - Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of a saturated carbon skeleton containing rings other than six-membered aromatic rings containing only non-condensed rings
C07C 211/25 - Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings other than six-membered aromatic rings
C07C 211/27 - Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring having amino groups linked to the six-membered aromatic ring by saturated carbon chains
C07C 249/02 - Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of compounds containing imino groups
C07C 251/18 - Compounds containing nitrogen atoms doubly- bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to carbon atoms of rings other than six-membered aromatic rings
11.
PREPARATION METHOD FOR S-CONFIGURATION PHENYLETHYLAMINE HYDROCHLORIDE COMPOUND
The present invention relates to the technical field of the synthetic preparation for medicines, and relates to a preparation method for an S-configuration phenylethylamine hydrochloride compound. The preparation method comprises the following steps: step (1), performing a Friedel-Crafts reaction on m-dimethoxybenzene and acetyl chloride under a Lewis acid condition to generate an intermediate A; (2) reacting the intermediate A with hydroxylamine hydrochloride, without isolating the intermediate A, to generate an intermediate B; step (3), reducing the intermediate B under a reducing agent condition to obtain a compound C; step (4) resolving the compound C by means of an organic acid to obtain an organic salt of an S-configuration compound D; and step (5) dissociating the organic salt and then performing saltification to obtain a target product compound E. The preparation method of the present invention has the characteristics of simple purification, low cost, high efficiency, high yield and suitability for industrial mass production.
C07C 213/08 - Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
C07C 213/10 - SeparationPurificationStabilisationUse of additives
C07C 217/58 - Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
12.
METHOD FOR SYNTHESIZING 1,7-NAPHTHYRIDINE DERIVATIVE
Disclosed is a method for synthesizing a 1,7-naphthyridine derivative, relating to the technical field of the synthesis of pharmaceutical intermediates and organic chemical intermediates. The method comprises the following steps of synthesis: (1) using 2-chloro-3-amino-pyridine as a compound I, using the compound I as a starting material, and protecting an amino group thereof to prepare a compound II; (2) reacting the compound II with a hydroformylation reagent under alkaline conditions to obtain a compound III; and (3) the compound III undergoing a cyclization reaction with an acrylate compound under the action of a Lewis acid so as to prepare a compound IV. The described synthesis method is suitable for industrial production, and the cost are low and operation is simple.
