42 results about "Diethyl aminomalonate" patented technology

The invention discloses a method for preparing 2-amino-2-[2-(4-alkyl phenyl) ethyl]-1,3-propanediol hydrochloride. The method comprises the following steps of: firstly, enabling a compound shown as a formula (II) and diethyl acetamidomalonate to be subjected to a condensation reaction under the action of a catalyst to obtain a compound shown as a formula (III); enabling the compound shown as the formula (III) as well as triethyl silane and titanium tetrachloride to be subjected to a reaction to prepare a compound (IV); then, continuously enabling the compound (IV) as well as lithium aluminum hydride and acetic anhydride to be subjected to a reaction to prepare a compound (V); and finally, enabling the compound (V) as well as lithium hydroxide and concentrated hydrochloric acid to be subjected to a reaction to obtain a compound shown as the formula (I). A midbody (III) prepared by using the method provided by the invention has enough purity and high yield up to over 95%, and purification through column chromatography is not needed in the reaction process, so that the next reaction can be directly carried out. The final target compound is synthesized by using easily purchased raw materials in a short way, and the method is short in production period, high in yield, mild in reaction condition, simple and feasible and suitable for industrial production.

The invention discloses a synthesis method of ticagrelor. The method comprises the steps of 1, adding thiourea and alkali to a solution where bi-aminomalonic acid diethyl ester is dissolved, wherein the mole ratio of bi-aminomalonic acid diethyl ester, thiourea and alkali is 1:(1.0-1.5):(2-2.3), and performing a reaction under the protection of nitrogen at 25-100 DEG C for 5-72 h to obtain a compound 2; 2, adding bromopropane to a solution where the compound 2 is dissolved at -2 DEG C-2 DEG C, and conducting stirring at 25-50 DEG C for 2-72 h to obtain a compound 3; 3, adding organic alkali and a chloride agent to the compound 3, raising the temperature to 20-75 DEG C, and performing a reaction for 3-8 h to obtain a compound 4; 4, synthesizing ticagrelor, wherein the compound ticagrelor is obtained by conducting substitution, loop closing, substitution and a hydrolysis reaction on the compound 4 (4,6-dichloro-2-propylthiopyrimidine-5-amine), the operation steps are greatly simplified, and the yield is drastically increased. The synthesis method of ticagrelor is simple in operation and high in reaction yield.

The invention provides a process for synthesizing rebamipide. The process comprises the following steps: taking aminomalonic acid diethyl ester and 4-chlorobenzoyl chloride as raw material substrates so as to prepare an intermediate 4-chlorobenzoyl diethyl aminomalonate; reacting with 4-bromomethylcarbostyril so as to obtain 2-(4-chlorobenzhylamino)-2-ethoxycarbonyl-3-[2(1H)-quinolinone-4-yl] ethyl propionate; and finally, heating and refluxing in a sodium alcoholate solution, concentrating, and re-crystallizing, thereby obtaining the final product. The rebamipide prepared by the process disclosed by the method is high in yield, and the purity can reach 99.2%.

The invention relates to a method for preparing 2-amino-4,6-dichloro-5-formamido pyrimidine. The method comprises the following steps of: performing nitrosation on malonic acid diethyl ester and acetic acid serving as raw materials and sodium nitrite at first; then, performing reduction and formylation with formic acid in the presence of zinc powder to form formyl amino malonic acid diethyl ester; finally, performing condensation and cyclization with guanidine hydrochloride to produce 2-amino-4,6-dichloro-5-formamido pyrimidine; performing chlorination by using quaternary ammonium salt as a catalyst; fractionally performing hydrolysis under an alkali action to obtain a product. The method has easily-available raw materials, and is short in reaction time, simple in aftertreatment and high in hydrolysis selectivity; the cost is obviously reduced; the total yield is up to 74 percent and the purity of the product is up to 99.0 percent.

The invention provides a method for preparing 2-p-octylphenethyl-2-aminopropanediol hydrochloride: the method comprises the following steps: styrene (II) and octanoyl chloride carry out Friedel-Crafts reaction to generate p-octanoyl Styrene (III); (III) carries out Michael addition reaction with acetamidodiethyl malonate under alkali action, generates 2-to-octanoylphenethyl-2-acetamidodiethyl malonate (IV ); (IV) reacts with triethylsilane to generate 2-to-octylphenethyl-2-acetamidodiethyl malonate (V); (V) generates 2-to-octylphenethyl through reduction and hydrolysis Base-2-aminopropanediol (VI), then acidified with hydrochloric acid to form a salt to obtain the product of the present invention. The invention has the advantages of short route, low cost, short cycle, less pollution and high yield. At the same time, the preparation method of the intermediate in the above preparation process is also provided.

The invention discloses a method for preparing an intermediate diethyl acetamidomalonate through organic synthesis. The preparation method is characterized by comprising the following steps of preparing oximinodiethyl malonate by using water as a solvent, using diethyl malonate, sodium nitrite and acetic acid as raw materials and adding a phase transfer catalyst; extracting oximinodiethyl malonate by using an organic solvent, and then distilling to remove the organic solvent; adding acetic acid into the system obtained in the third step, and adding zinc powder at 40-50 DEG C to perform reduction and acetic anhydride acylation; then removing the acetic acid solvent under reduced pressure, and crystallizing with water to obtain the diethyl acetamidomalonate product, wherein the reaction temperature of the reduction and acetic anhydride acylation is 40-50 DEG C, and the reaction time is 1-6.5 hours. The yield of diethyl acetamidomalonate obtained through the preparation method reaches over 80%, the purity of the product is high, the energy consumption is low, the environmental pollution is low, and the cost is low.

The invention discloses a pyrrolecarboxylic acid derivative synthesis method, which comprises: obtaining a group substituted formylacetone derivative by using a group substituted acetyl derivative andethyl acetate as raw materials; carrying out cyclization with diethyl aminomalonate hydrochloride to generate a pyrrolecarboxylic acid derivative ethyl ester; and carrying out a hydrolysis reaction to obtain the target product pyrrolecarboxylic acid derivative. According to the present invention, the method has characteristics of mild reaction conditions, simple purification, high yield and highproduct purity, and is suitable for process amplification and mass production.

The invention discloses a synthetic method for diethyl acetamidomalonate. The method comprises the following steps: firstly, performing a reaction in the presence of a metal salt and a ligand to prepare a mixed liquid containing the diethyl acetamidomalonate by taking diethyl malonate and acetamide as raw materials, air as an oxidant, and acetic acid as a solvent, performing distilling, and performing repeated extraction and recrystallization to obtain the diethyl acetamidomalonate in a white crystalline powder state. The method has the advantages that the metal salt and the ligand are cheap and easy to obtain, after the reaction is finished, the metal salt and the ligand can be further recycled through treatment, the air is taken as the oxidant, and therefore the production costs are greatly reduced; the yield of the product is more than 90%, the purity of the product is more than 99%, the conversion rates of the raw materials are high, and the reaction is complete; and the by-productis only water, no ''three waste'' (waste gas, waste water and solid waste) pollution problems exist, and the method meets environmental protection requirements.

The invention discloses a preparation method of diethyl acetamidomalonate. The preparation method comprises the following steps: adding diethyl malonate and sodium nitrite to organic solvent, dropwise adding acetic acid at the temperature of 0-5 DEG C, carrying out heat preservation on a reaction system for 10-15 h at the temperature of 35-45 DEG C after adding, filtering solid after the reaction, recycling the organic solvent after filter liquor is concentrated to obtain nitroso-diethyl malonate, adding the nitroso-diethyl malonate to acetic acid and acetic anhydride, slowly adding zinc powder to carry out reductive acylation reaction, carrying out heat preservation on feed liquid for 2 h at the temperature of 50-60 DEG C after the zinc powder is added, filtering zinc acetate generated by the reaction after the reductive acylation reaction, recycling the acetic acid after the filter liquor is concentrated, carrying out recrystallization on concentrate by using purified water, and drying to obtain the diethyl acetamidomalonate. The preparation method is low in production cost, sodium nitrite can react completely, and the sodium nitrite is not contained in byproduct sodium acetate generated by nitrosation reaction, so that subsequent treatment is facilitated.

Process for preparing AMD as medical intermediate from diethyl malonate is carried out by: preparing nitroso-diethyl malonate from diethyl malonate and sodium nitrite, using sodium acetate and sodiumsulfate and acetic acid as electrolyte, electrically reducing to prepare amino-diethyl malonate in frame bath with membranes, and acidating the reduced products to obtain AMD. It is simple and moderate, and has no pollution and high purity.

The invention discloses a synthesis method of ticagrelor. The method comprises the steps of 1, adding thiourea and alkali to a solution where bi-aminomalonic acid diethyl ester is dissolved, wherein the mole ratio of bi-aminomalonic acid diethyl ester, thiourea and alkali is 1:(1.0-1.5):(2-2.3), and performing a reaction under the protection of nitrogen at 25-100 DEG C for 5-72 h to obtain a compound 2; 2, adding bromopropane to a solution where the compound 2 is dissolved at -2 DEG C-2 DEG C, and conducting stirring at 25-50 DEG C for 2-72 h to obtain a compound 3; 3, adding organic alkali and a chloride agent to the compound 3, raising the temperature to 20-75 DEG C, and performing a reaction for 3-8 h to obtain a compound 4; 4, synthesizing ticagrelor, wherein the compound ticagrelor is obtained by conducting substitution, loop closing, substitution and a hydrolysis reaction on the compound 4 (4,6-dichloro-2-propylthiopyrimidine-5-amine), the operation steps are greatly simplified, and the yield is drastically increased. The synthesis method of ticagrelor is simple in operation and high in reaction yield.

The invention relates to the technical field of drug analysis, in particular to a method for detecting related substances in a sample of diethyl p-chlorobenzamidomalonate. The method comprises: dissolving a sample of diethyl p-chlorobenzamidomalonate in an organic solvent to obtain a sample solution; using reverse-phase high-performance liquid chromatography to detect the sample solution, and the chromatographic conditions are as follows: C18 chromatographic column; Phase A is 0.005-0.015 M potassium dihydrogen phosphate aqueous solution, pH value is 2-3; mobile phase B is acetonitrile; gradient elution. The present invention uses octadecylsilane-bonded silica gel as filler for reverse-phase chromatographic column analysis, and uses specific salt solution and organic solvent as mobile phase to carry out gradient elution to the sample solution of rebamipide raw material. The method is fast, simple, accurate and reproducible, and is suitable for the control of various related substances and the research of impurities.

The invention discloses a novel method for synthesizing 4,6-dichloro-2-(propylthio)-5-aminopyrimidine (I), namely an important intermediate of ticagrelor. The method comprises the following steps: carrying out a condensation reaction between substituted aminomalonic acid diethyl ester (III) and urea to generate 2,4,6-trihydroxy-5-substituted aminopyrimidine (IV); conducting chlorination on the obtained compound 2,4,6-trihydroxy-5-substituted aminopyrimidine (IV), to obtain 2,4,6-trichloro-5-aminopyrimidine (V); carrying out a reaction between the obtained compound 2,4,6-trichloro-5-aminopyrimidine (V), and propanethiol to generate 4,6-dichloro-2-(propylthio)-5-aminopyrimidine (I). The synthetic route adopted in the method is low in cost, simple to operate, and suitable for industrial production.

The invention provides a method for preparing L-serine-<15>N, which comprises the following steps: adopting Na<15>NO2 and diethyl malonate as raw materials to synthesize acetamino-diethyl malonate-<15>N; using the obtained acetamino-diethyl malonate-<15>N to synthesize N-acetyl-DL-serine-<15>N; detaching through enzyme method to obtain the L-serine-<15>N. The utilization rate of the <15>N raw material of the inventive preparation method is high, the optical purity of the purified product L-serine-<15>N is more than 98. 5% and the chemical purity is more than 98%, and the <15>N abundance in the product is more than 98%.

The invention discloses a preparation method of functional amino proline. The invention adopts the technical scheme that phthalic anhydride and urea are reacted to obtain phthalimide, the obtained phthalimide is dissolved into ethanol, the mixture is regulated to alkalinity by potassium hydroxide to generate phthalimide potassium, the phthalimide potassium is reacted with bromodiethyl malonate to obtain phthalyl diethyl malonate, the phthalyl diethyl malonate is reacted with 1,3-dibromopropane to generate phthalyl-2-bromopropyl diethyl malonate, the phthalyl-2-bromopropyl diethyl malonate is dissolved into the ethanol to be regulated to the alkalinity, and then the mixture is reacted with acid to generate a product of proline. Compared with the traditional preparation method of the proline, the invention can be repeatedly utilized by adopting phthalic anhydride as raw materials, lower the cost and also save expensive sodium borohydride reducing agent needed by the traditional prepared proline, therefore, the invention has the advantages of low cost, simple process, high yield and high purity and is more beneficial to mass production.