571188-82-4Relevant articles and documents
Low-cost preparation method of palbociclib
-
Paragraph 0066-0071, (2021/11/26)
The invention discloses a low-cost preparation method of palbociclib. The method comprises the steps: taking 4-(6-aminopyridin-3-yl)piperazine-1-carboxylic acid tert-butyl ester as an initial raw material, taking large-steric-hindrance alkali as an acid-binding agent, carrying out nucleophilic substitution reaction with a compound represented by a formula 3, carrying out post-treatment, quenching and dealkalizing to obtain a large-particle compound represented by a formula 4; then taking n-butyl alcohol and water as solvents, taking diisopropylethylamine as an acid-binding agent and a protective agent, and under the action of a composite catalyst palladium chloride and cuprous iodide, carrying out a Herk alkylation reaction with n-butyl vinyl ether; and under the protection of an organic alkali, refining with an ester solvent to obtain a high-purity compound represented by a formula 5 with high yield, and hydrolyzing the compound represented by the formula 5 through a mixed solvent of n-butyl alcohol, anisole and water under an acidic condition to obtain a finished product of palbociclib. The method greatly reduces the usage amount of a palladium catalyst, and is simple and convenient to operate, less in environmental pollution, high in yield, high in product quality and more suitable for industrial production.
A new route for the synthesis of Palbociclib
Li, Shu-ting,Chen, Jun-qing,Feng, Cheng-liang,Yang, Wan-feng,Ji, Min
, p. 3043 - 3051 (2019/10/19)
Abstract: In this paper, a novel synthetic method for Palbociclib was reported. It was synthesized in eight steps from 2-(methylthio) pyrimidin-4-(3H)-one with approximately 10% overall yield. This protocol started material 2-(methylthio) pyrimidin-4-(3H)-one, involved nucleophilic substitution by thionyl chloride, bromination, nucleophilic substitution by cyclopentylamine, a one pot-two step method (Heck reaction, ring close sequence), oxidation and bromination, cross-coupling reaction, Heck reaction, aqueous workup to afford Palbociclib. This synthetic route used inexpensive raw material and reagents, involved readily controllable reaction conditions and reduced environmental hazards. Graphic abstract: Synthesis of Palbociclib, a small molecule CDK inhibitor, starting from 2-(methylthio) pyrimidin-4-(3H)-one by 8 steps reaction. This method afforded the Palbociclib in 10% yield. [Figure not available: see fulltext.].
Preparation method and product of palbociclib
-
Paragraph 0038; 0039; 0040; 0043; 0044; 0045, (2019/02/27)
The invention discloses a preparation method of palbociclib. The preparation method comprises the following steps: 1) dissolving 4-(6-aminopyridine-3-yl)-piperazine-1-tertiary butyl carboxylate into asolvent A, adding an alkali reagent, activating at 0-20 DEG C, adding 6-bromine-2-chlorine-8-cyclopentyl-5-methyl-pyridino-[2,3-D]-pyrimidine-7(8H)-ketone, adjusting the solution to acid after a reaction is completed, cooling and filtering, taking filter cakes, and drying the filter cakes to obtain an intermediate I; 2) in the presence of an inert atmosphere, dissolving the intermediate I and butyl vinyl ether into a solvent B, catalyzing with a catalyst at 95-105 DEG C, cooling and separating a crystal after the reaction is completed, filtering, and taking the filter cakes, and drying the filter cakes to obtain an intermediate II; 3) dissolving the intermediate II into a solvent C, adding an acid, adjusting the solution to acid after the reaction is completed, filtering, and taking and centrifuging filtrate to obtain a target product, namely palbociclib. By adjusting reaction parameters and optimizing preparation process procedures, the preparation method is high in product yield, good in purity, simple and mild in process conditions and applicable to industrial large-scale production.