42 results about "Diethyl aminomalonate" patented technology

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.

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.