78306-52-2

Usage

Uses

Used in Pharmaceutical Industry:
(2S-trans)-4-Methyl-2-piperidinecarboxylic Acid Ethyl Ester is used as a key intermediate in the preparation of Argatroban (A769000), a direct thrombin inhibitor. Argatroban is utilized for the treatment of thrombotic disorders, particularly in patients with heparin-induced thrombocytopenia (HIT), where the use of heparin is contraindicated. (2S-trans)-4-Methyl-2-piperidinecarboxylic Acid Ethyl Ester plays a crucial role in the synthesis of this life-saving medication, contributing to its therapeutic efficacy and safety profile.

Upstream product

• 134984-61-5 (6S)-1-<(R)-1-phenylethyl>-6-ethoxycarbonyl-4-methyl-3,4-didehydropiperidine 
• 79199-63-6 (2S,4S)-4-methyl pipecolic acid 
• 75-36-5 acetyl chloride 
• 134984-77-3 ethyl trans-(2S,4R)-1-<(R)-1-phenylethyl>-4-methylpipecolate 
• 78-79-5 isoprene 

Relevant academic research and scientific papers

Method for splitting argatroban isomer impurity

The invention provides a method for splitting an argatroban isomer impurity. The method comprises the following steps: performing salt formation by taking 4-methyl-2-piperidinecarboxylate racemate asa raw material and taking D-tartaric acid as a splitting agent to obtain (2S,4S)-4-methyl-2-piperidinecarboxylate-D-tartrate shown by a compound I; dissociating the compound I under an alkaline condition to obtain (2S,4S)-4-methyl-2-piperidinecarboxylate shown by a compound II. The splitting method provided by the invention is easy and convenient to operate, the total yield of splitting reaches 46.5 percent, and the chiral purity after splitting can reach 99.2 percent.

PROCESS INTERMEDIATES AND METHODS FOR THE PREPARATION OF PROCESS INTERMEDIATES FOR THE SYNTHESIS OF ARGATROBAN MONOHYDRATE

Methods are provided for the synthesis of key intermediates for the synthesis of Argatroban monohydrate, ethyl (2R,4R)-1-[(2S)-2-amino-5-[[imino(nitroamino)methyl]amino]-1-oxopentyl]-4-methylpiperidine-2-carboxylate compounded with HCl. Such intermediates are also provided.

HETEROCYCLIC THROMBIN INHIBITORS

Heterocyclic thrombin inhibitors are provided which have the structure STR1 wherein n, R, R 1, R 2, R 3, G, G x, R. sup.6', Ra, Xa, R 6, Rb, R 3, p, Q, A and R 4 are as defined herein.

Enantio- and Diastereo-selective Synthesis of Pipecolic Acid Derivatives using the Aza-Diels-Alder Reaction of Imines with Dienes

Optically active pipecolic acid derivatives can be prepared by the aza-Diels-Alder reaction of simple dienes with the imine derived from ethyl glyoxylate and chiral 1-phenylethylamine; the cycloadditions are regiospecific, highly diastereoselective within the heterocyclic ring (>92percent exo with cyclic dienes, and 100percent endo with acyclic dienes), and lead to high asymmetric induction in most cases (average d.e. = 72percent).

Asymmetric Synthesis of Pipecolic Acid Derivatives Using the Aza-Diels-Alder Reaction

Imines of the type R-N=CHCO2Et can be coerced into undergoing a (4+2) cycloaddition with substituted dienes if the reaction is carried out in DMF in the presence of both water and acid; these reactions show extremely high regio- and diastereoselectivity.U