37 results about "2-chloropyrimidine" patented technology

The invention relates to a synthetic method of an anti-tumor medicine, namely N-[2-[[2-(dimethylamino) ethyl] methyl amino]-4-methoxy-5-[[4-(1-methyl-1H-indole-3-yl)-2-pyrimidyl] amino] phenyl]-2-acrylamide (AZD9291) and a key intermediate of the anti-tumor medicine. The synthetic method comprises the following steps: performing Boc acid anhydride protection on 4-fluoro-2-methoxy-5-nitroaniline to obtain 4-fluoro-2-methoxy-5-nitroanilino tert-butyl formate, then reacting with N,N,N'-trimethylethylenediamine to obtain 4-(N,N,N'-trimethylethylenediamino)-2-methoxy-5-nitroanilino tert-butyl formate, then reducing to obtain 2-(N,N,N'-trimethylethylenediamino)-4-methoxy-5-tert-butyl carbamate phenylamine, then completely reacting with acryloyl chloride and directly removing a Boc protecting group to obtain 2-methoxy-4-N,N,N'-trimethylethylenediamino-5-acrylamido phenylamine, and finally reacting with 3-(2-chloropyrimidine-4-yl)-1-methylindole to obtain AZD9291. A process disclosed by the invention is simple in step, relatively high in yield, mild in reaction condition and easy for realization of industrial production.

The invention provides a preparation method of rosuvastatin calcium. The method comprises the following steps: carrying out condensation reaction on 4-(4-fluorophenyl)-6-isopropyl-2 chloropyrimidine-5-formaldehyde and (3R)-tertiary butyl dimethylsiloxo-5-oxo-6-triphenyl phosphaalkene hexanoate; and then removing a silylether protecting group of hydroxyl, carrying out stereoselectivity reduction, reacting with 2,2-dimethoxy propane, condensing with N-methyl methane sulfonamide, removing propylidene protection, hydrolyzing an ester group, salifying and carrying out other steps, so as to obtain the rosuvastatin calcium. According to the preparation method, the yield is stable, and the price of reagents is cheap; and the method is easy to operate and is beneficial to industrial production.

The invention discloses a synthesis method of 6-ethyl-4-hydroxyl-5-fluorine-2-cloro pyridine ammonium salt with a structure showed as a formula (I), comprising the following steps: taking 2-fluorine-3-oxo valerate as a starting material, and condensing with O-methylisourea in alcoholic solution of sodium alcoholate to prepare an intermediate (II); carrying out acid-catalyzed hydrolysis on the intermediate (II) to prepare an intermediate (III); carrying out chlorinated reaction on the intermediate (III) by adopting chlorinated reagent to prepare a compound (IV); and preparing an intermediate (V) by the compound (IV) in alkaline water solution through hydroxyl substitution, and ammoniating the intermediat (V) by ammonia water to form salt, namely, obtaining the 6-ethyl-4-hydroxyl-5-fluorine-2-cloro pyridine ammonium salt. The synthesis method adopts cheap and easily-obtained starting raw material, avoids the use of format reagent and iodine, simplifies operations, reduces environmentalpollution, is beneficial to industrial production and has lower production cost and good product quality.

The invention discloses a method for synthesizing 2,2'-dindolylmethane compounds. Firstly, 1-(pyrimidinyl-2-yl)-1H-indole compounds are generated in the mode that indole or substituded indole reacts with 2-chloropyrimidine under the sodium hydride alkaline condition with indole compounds as raw materials, indole guiding groups are introduced into the indole compounds, then the 1-(pyrimidinyl-2-base)-1H-indole compounds are subjected to a dimerization reaction under the action of acetic acid copper, silver nitrate and a toluene solvent, and finally the 2,2'-dindolylmethane compounds are synthesized. A direct carbon activation reaction method is applied, reaction steps are reduced, economical efficiency of reaction is improved, the target product 2,2'-dindolylmethane compounds are efficiently synthesized under the mild condition, indole groups can be removed after the 2,2'-dindolylmethane compounds are de-protected, 2,2'-dindolylmethane is generated, and the structural unit has wide biological activity and application prospects.

The invention relates to a low-cost preparation method for palbociclib. The low-cost preparation method comprises the following steps: by taking 2,4-dichloro-5-cyanopyrimidine as an initial raw material, performing cyano Grignard and hydrolysis so as to obtain 5-acetyl-2,4-dichloropyrimidine, protecting carbonyl, performing amination, removing carbonyl, performing acylation reaction by using diketene and amino so as to obtain 5-acetyl-4-acetoacetamide-2-chloropyrimidine, performing intramolecular dehydration on the product so as to obtain 6-acetyl-8-cyclopentyl-5-methyl-2-chlorine-8H-pyridino-[2,3-d] pyrimidine-7-ketone, protecting 6 acetyl groups by using carbonyl, further realizing reaction with an aminopyridine derivative so as to obtain 4-{6-[(6-1,1 dialkoxyl) ethyl-8-cyclopentyl-5-methyl-7-keton-7,8 dihydropyridino-[2,3-d]pyrimidine-2-amino]-pyridine-3-yl}-piperazine-1-carboxylic acid tert-butyl ester, and finally performing acid hydrolysis and neutralization to obtain palbociclib free alkali. By adopting the low-cost preparation method, the raw materials are easy to obtain, the cost is low, and the environment can be protected.