66 results about "4-Piperidinone" patented technology

The invention discloses a 2,2,6,6,-tetramethyl-4-piperidone continuous synthesis method. The 2,2,6,6,-tetramethyl-4-piperidone continuous synthesis method comprises the following steps of 1, filling an acidic resin into a fixed bed reactor, and carrying out heating so that a temperature of the fixed bed reactor is in a range of 40 to 70 DEG C, and 2, feeding acetone and ammonia gas into the fixed bed reactor according to a mole ratio of 3-9: 1 under the conditions of acetone hourly space velocity of 0.15 to 1.17h<-1> and ammonia gas hourly space velocity of 5.25 to 124.20h<-1>, and cooling the product to obtain a 2,2,6,6,-tetramethyl-4-piperidone crude product. The 2,2,6,6,-tetramethyl-4-piperidone continuous synthesis method has simple processes and a low cost, is suitable for industrial continuous production, does not adopt an organic solvent or water as a solvent, avoids the pollution produced by the organic solvent on the environment, has mild reaction conditions, can be carried out at a temperature of 40 to 70 DEG C, has low energy consumption, and avoids the influence caused by impurities produced at a high temperature on the product.

The invention relates to the field of organic synthesis and medicine, and discloses a preparation method for N-substituted methyl-3,5-disubstituted benzylidene base-4-piperidone and biological activity for efficiently inhibiting cell line proliferation such as leukemia, ovarian cancer, breast cancer, liver cancer and esophagus cancer. The method includes: starting from various substituted methylamine and methyl acrylate, sequentially going through Michael addition, Dieckmann condensation, acidolysis and decarboxylation to obtain N-substituted methyl-4-piperidone, and subjecting the N-substituted methyl-4-piperidone to aldol reaction with substituted benzaldehyde to obtain a target compound N-substituted methyl-3,5-disubstituted benzylidene base-4-piperidone. The target compound can selectively and efficiently inhibit cell line proliferation such as leukemia, ovarian cancer, breast cancer, liver cancer and esophagus cancer, and activity of inhibiting carcinoma cell line proliferation is obviously higher than conventional chemotherapeutic 5-fluorouracil.

The invention provides a novel 3,5-bis(aryl-methyne)-1-substituted-4-piperidone compound as well as a synthetic method and application thereof in the preparation of anti-cancer medicines. The structural formula of the novel 3,5-bis(aryl-methyne)-1-substituted-4-piperidone compound is as shown in a formula (I), wherein R1 is selected from hydrogen, propyl, benzyl, 2-phenethyl, acetyl and ethyoxyl carbonyl, R2, R3 and R4 are respectively and independently selected from fluorine, chlorine, bromine, C1-C12 alkenyl, C1-C12 alkyl, C1-C12 alkoxy, C1-C12 carboxylic acids, C1-C12 carboxylic esters and amide to which the C1-C12 carboxylic acids are corresponding, and n is 0 or 1. The compound has good anticancer activity and no toxic or side effects, is simple in synthetic method and suitable for preparation of the anti-cancer medicines.

The invention discloses a method for non-membrane electrochemical synthesis of 2,2,6,6-tetramethyl-piperidinol. A non-membrane electrolytic cell is adopted, a Pb plate is taken as an anode, a Zn plate is taken as a cathode, sodium sulfate is taken as supporting electrolyte, a certain amount of sodium hydroxide and raw material of piperidone are added, two different organic latent solvents of methanol and ethanol are respectively added, and distilled water is added for preparing electrolyte. The electrochemical synthesis of piperidinol is carried out under a certain current density and electric quantity. The results show that the 2,2,6,6-tetramethyl-piperidinol can be directly obtained by taking 2,2,6,6-tetramethyl-4-piperidone as the raw material and carrying out the electrochemical synthesis under the condition of not using a membrane. The method can solve the technical defects of short service life of the membrane, high cost, difficult industrialization and the like caused by using the membrane. On the whole, the method is characterized by simple operation, easy obtainment of equipment, simple process flow, low investment cost and the like, and can carry out industrial production.

The invention discloses a preparation method of a homopiperazine derivative. The preparation method comprises the following steps of: (1) reacting 4-piperidone hydrochloride hydrate with an amino protective agent to prepare amino-protected 4-piperidone; (2) performing oximation reaction on the amino-protected 4-piperidone to prepare amino-protected 4-oxime piperidone; (3) performing molecular rearrangement on the amino-protected 4-oxime piperidone to prepare amino-protected 5-carbonyl homopiperazine; and (4) performing reduction reaction on the amino-protected 5-carbonyl homopiperazine to prepare amino-protected homopiperazine. The 4-piperidone hydrochloride hydrate is taken as a raw material, and is subjected to amino protection, oximation, rearrangement, reduction and deprotection to prepare the homopiperazine, and the amino-protected homopiperazine is reduced by sodium borohydride in the presence of an adjuvant to prepare the homopiperazine, so that lithium aluminum hydride which has high safety risk and cost in a preparation process of the conventional method is avoided. The whole process is easy to control, reaction conditions of each step are mild, the method is suitable forindustrial production, the yield is 75 percent, the raw material with low cost is used, and production cost is effectively reduced.

The invention discloses a method for preparing 4-(N-phenylpropionamide)-4-methoxymethyl-piperidine hydrochloride, which belongs to the technical field of preparation of medicinal intermediates. The 4-(N-phenylpropionamide)-4-methoxymethyl-piperidine hydrochloride is synthesized by using 1-phenyl-4-piperidone and aniline as initiative raw materials and by seven reactions. In raw materials used in the invention, trimethyl cyanato silane is used in place of potassium cyanide or sodium cyanide which is a highly toxic raw material to make the operation and management more convenient; potassium tert-butoxide and other alkalis are used in place of sodium hydride which is a dangerous and flammable reagent to improve the safety of scale-up production; propionic anhydride is used in place of highly irritant propionyl chloride to improve the safety, purity and yield of experiments; dimethyl sulfate is used in place of expensive methyl iodide to further control the production cost; and the high-pressure liquid chromatography (HPLC) purity of the obtained 4-(N-phenylpropionamide)-4-methoxymethyl-piperidine hydrochloride product can reach 99.7 percent, the single impurity content is less than 0.1 percent, the total yield can reach 23 percent, and the product is a hydrochloride which is favorable for storage and transport.

The invention provides a tetrahydropyridopyridone derivative as shown in a general formula (I), and a preparation method thereof. The method comprises the following steps of: preparing N,N-bi(methoxycarbonyl group) substituted benzylamine (b) by carrying out Michael addition on substituted benzylamine (a) and methyl acrylate, carrying out Dieckmann condensation on (b) under the action of sodium alcoholate, subsequently carrying out hydrolysis and decarboxylation under the action of acid so as to obtain N-substituted benzyl-4-piperidone (d), carrying out an aldol condensation reaction on (d) and bimolecular aromatic aldehyde so as to obtain N-substituted-3,5-bi(substituted benzylidene piperidine-4-ketone (e), and refluxing and heating (e) malononitrile and ammonium acetate in ethanol so as to obtain a final product as shown in the general formula (I). The tetrahydropyridopyridone derivative is simple in process and convenient to produce in scale, and the compound (I) has a good inhibition effect on multiplication of leukemia K562 cells, ovarian cancer HO-8910 cells and liver cancer SMMC-7721 cells. Therefore, the invention further provides an application of the compound as shown in the general formula (I) in preparing medicaments for preventing multiplication of the leukemia K562 cells, the ovarian cancer HO-8910 cells and the liver cancer SMMC-7721 cells.

The invention provides 2, 3, 5, 7-tetrasubstituted dihydro-pyrazolo piperidine derivative and a preparation method and application thereof. The derivative is 2, 3-bis(substituted phenyl)-5-subsituted arylmethyl-7-substituted benzylidene dihydro-pyrazolo piperidine derivative, having the following formula (I). The preparation method includes using substituted arylmethyl amine and methyl acrylate as raw materials; subjecting the materials to Michael addition, Dieckmann condensation and hydrolysis-decarboxylation sequentially; allowing for Aldol reaction with substituted benzaldehyde to obtain intermediate N-substituted arylmethyl-3, 5-bis(substituted benzylidene)-4-piperidone; allowing for condensation with substituted phenylhydrazine to obtain a compound according to the formula (I). The derivative is efficient in inhibiting multiplication of various carcinoma cell lines such as leukemia, esophagus cancer, ovarian cancer and breast cancer in human, is well stably metabolic in liver microsomes of human and rat, is free of direct and competitive inhibition on five enzymes of liver microsomes, such as CYP3A4, CYP2D6, CYP2C9, CYP1A2 and CYP2C19, is highly bioavailable, is low in toxicity to normal cells, and is available for the preparation of drugs for the cancers.

A preparing method of 2,2,6,6-tetramethyl-4-piperidylamine by a catalytic amination method is disclosed. The preparing method includes following steps of: (1) adding 2,2,6,6-tetramethyl-4-piperidone, sodium hydroxide, ammonia water and a skeleton nickel catalyst into a high-pressure kettle having a condenser, a pressure gage, a stirrer and a thermocouple, feeding nitrogen to replace air in the kettle, feeding hydrogen until the pressure is 2.5 MPa, stirring, heating to 110 DEG C, and reacting for 30 min; and (2) after the reaction is completed, cooling to room temperature, stopping stirring, venting, taking reaction materials out, filtering, subjecting filtrate to distillation under atmospheric pressure to distill ammonia gas and water, subjecting the residue in the kettle to vacuum distillation, and collecting a fraction that is the 2,2,6,6-tetramethyl-4-piperidylamine. The preparing method adopts the skeleton nickel as the catalyst, synthesizes the 2,2,6,6-tetramethyl-4-piperidylamine by hydrogenation and amination, and is high in yield and purity of products.

The invention discloses a preparation method of N,N-bis(2,2,6,6-tetramethyl-4-piperidinyl)-1,6-hexamethylenediamine (called hexamethylenediamine piperidine for short). The preparation method comprises the following steps: 1) carrying out a dehydration reaction on 2,2,6,6-tetramethyl-4-piperidone (called tetramethyl piperidone for short) and 1,6-hexanediamine to prepare a Schiff base intermediate; 2) carrying out a hydrogenation reaction on the Schiff base intermediate in the presence of a catalyst to obtain hexamethylenediamine piperidine. The preparation method disclosed by the application is low in reaction pressure, and the requirements of the bearing pressure of equipment are reduced, so that the production safety is greatly improved and the cost is reduced; a non-polar solvent is used, so that side effects are reduced, and a post-treatment method is simple and convenient, so that the production efficiency is increased, industrialized mass production can be adapted better, and the obtained target compound is high in purity and slight in colour.

The invention relates to a preparation method of 3-amino-4-alkoxyimino piperidine. More particularly, the preparation method provided by the invention comprises the following steps: performing nucleophilic addition reaction on ethyl 3-aminopropionate hydrochloride and acrylonitrile in the presence of alkali; treating with di-tert-butyl dicarbonate to obtain ethyl N-tert-butoxycarbonyl-3-(2-cyanoethyl)aminopropionate; performing cyclization in the presence of strong alkali to obtain 1-N-tert-butoxycarbonyl-3-cyano-4-piperidone, and performing oximation to obtain 1-N-tert-butoxycarbonyl-3-cyano-4-alkoxyimino piperidine; sequentially performing cyano hydrolysis and Hofmann degradation reaction on the latter to obtain 1-N-tert-butoxycarbonyl-3-amino-4-alkoxyimino piperidine; and finally, performing deprotection to obtain the 3-amino-4-alkoxyimino piperidine and salt thereof.

The invention relates to seven 4-acetylamino benzene sulfonyl substituted 3,5-bis(arylidene)-4-piperidinone compounds having anti-tumor and anti-inflammatory activities, and belongs to the technical field of anti-tumor and anti-inflammatory medicines. A preparation method of the 4-acetylamino benzene sulfonyl substituted 3,5-bis(arylidene)-4-piperidinone compounds comprises the following steps: firstly, respectively performing claisen-schmidt condensation reaction on 4-piperidinone hydrochloride and two aromatic aldehyde and performing column chromatography to obtain a 3,5-bis(arylidene)-N-H-4-piperidinone hydrochloride intermediate product (BAP-H) having different substituents; then performing benzene sulfonylation on the 3,5-bis(arylidene)-N-H-4-piperidinone hydrochloride intermediate product and 4-acetylsulphanilyl chloride to obtain the 4-acetylamino benzene sulfonyl substituted 3,5-bis(arylidene)-4-piperidinone compounds (BAP). The compounds have good anti-tumor and anti-inflammatory activities, can avoid the genetic toxicity of currently-used anti-tumor medicines, has little toxicity to normal cells, and also has good anti-inflammatory activity. The preparation method is simple and convenient to operate, is mild in reaction conditions, is high in synthetic yield, and is beneficial for being widely popularized in anti-tumor and anti-inflammatory fields.

The invention relates to a method for preparing intermediate 2,2,6,6-tetramethyl-4-piperidylamine. The method is characterized by comprising the following steps: step 1), in the presence of a catalyst1, reacting acetone with ammonia gas to produce 2,2,6,6-tetramethyl-4-piperidinone and water; and step 2), in the presence of a catalyst 2, reacting the 2,2,6,6-tetramethyl-4-piperidinone with ammonia gas to produce 2,2,6,6-tetramethyl-4-piperidylimine and water, and reacting the 2,2,6,6-tetramethyl-4-piperidylimine with hydrogen gas to produce the 2,2,6,6-tetramethyl-4-piperidylamine, wherein the catalyst 1 is ammonium nitrate, and the catalyst 2 is a sodium hydroxyphenyl phosphate modified framework nickel catalyst. The method provided by the invention has the advantages of short synthetictime, a high conversion rate of the acetone and a high repeating utilization rate of the raw materials.

The invention relates to a preparation method for a rifamycin S derivative. According to the preparation method, 3-amino-4-imine rifamycin S as shown in a formula II which is described in the specification and a 4-piperidone derivative as shown in a formula III which is described in the specification are added according to a certain feeding mode and subjected to a condensation reaction in the presence of an organic solvent, ammonium acetate and zinc dust so as to produce the rifamycin S derivative as shown in a formula I which is described in the specification. The feeding mode is that the 3-amino-4-imine rifamycin S is added into a reaction system in a final step, so 3-amino-4-imine rifamycin S is prevented from reduction and hydrolysis. The preparation method increases the utilization rate of materials and is shortened in reaction time, so high-efficiency high-yield preparation of the rifamycin S derivative is realized, and the yield and content of the rifamycin S derivative reach 80% or above and 95% or above, respectively; and the preparation method overcomes the problems of long reaction time, low yield, many impurities and high cost, and is simple to operate, highly efficient, environment friendly and beneficial for large-scale production.

The invention relates to six tert-butyl substituted asymmetrical piperidone compounds with anti-tumor activities and a preparation method thereof, and belongs to the technical field of anti-tumor medicaments and a preparation method thereof. According to the preparation method, a Claisen-Schmidt condensation reaction is performed on N-methyl-4-piperidone, 4-tert-butylbenzaldehyde and another aromatic aldehyde to obtain products A-F. The compounds have high anti-tumor activities, genotoxicity of the conventional anti-tumor medicaments can be avoided, and the toxicity to normal cells is low. The preparation method is easy and convenient to operate, is mild in the reaction condition, is high in synthesis yield, and can be widely popularized in the anti-tumor field.

A process for synthesizing N-benzyl-4-piperidyl formaldehyde as the intermediate for preparing donepezil to treat senile dementia includes reacting between N-benzyl-4-piperidinone and Liuyelide to generate 6-benzyl-1-oxo-6-azaspiro[2,5] octane, and catalytic reforming with magnesium bromide-ether. Its advantage is high output rate.

The invention discloses a method for producing hydrochloride of a dopamine D4 receptor agonist A-412997. The method comprises the following steps of: obtaining lithium pyridine by using a cheap reagent of butyl lithium as an exchange reagent; reacting with N-Boc-4-piperidone to obtain a compound of 1-N-Boc-4-(2-pyridyl)-4-hydroxypiperidine; removing water molecules, adding Boc, hydrogenating, removing the Boc and performing other steps to obtain a compound of 4-(2-pyridyl)piperidine dihydrochloride; and performing substitution on the 4-(2-pyridyl)piperidine dihydrochloride and a compound of chloracetyl m-toluidine to obtain the target product, namely the hydrochloride of the dopamine D4 receptor agonist A-412997. The process flow is simple, the method is suitable for industrial production, the reagent has low price, the yield is high, the total yield is 44.5 percent, and the method is an effective method for producing the hydrochloride of A-412997.

The invention relates to two 3,5-bis(3-aminophenyl)methylene-4-piperidone compounds with antitumor activity and a preparation method thereof, and belongs to the technical field of antitumor drugs and preparation methods thereof.The preparation method of the compounds includes the steps that 4-piperidone and m-nitrobenzaldehyde are subjected to a Clayson-Schmidt condensation reaction to obtain an intermediate, and then the intermediate is subjected to reduction with a reducing agent to obtain the products A and B.The compounds are good in antitumor activity, can avoid the genotoxicity of antitumor drugs used at present and have little toxicity on normal cells.The preparation method is easy and convenient to implement, reaction conditions are mild, the synthesis yield is high, and thus the preparation method can be widely popularized in the antitumor field easily.

Dibenzylidene and heterobenzylideneacetone derivatives, related 4-piperidones, related 4-thiopyranones and the corresponding sulfinyl- and sulfonyl-analogues for their use for prophylaxis or treatment of trypanosomiasis and leishmaniasis.