74892-82-3Relevant articles and documents
Synthesis method of argatroban intermediate (2R,4R)-4-methyl piperidine-2-ethyl formate
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Paragraph 0029; 0030; 0031; 0032-0034; 0039-0044; 0046; 0048, (2017/09/01)
The invention relates to a synthesis method of an argatroban intermediate (2R,4R)-4-methyl piperidine-2-ethyl formate compound. The synthesis method comprises the following steps: (1) under the action of a rhodium catalyst and ferric oxalate, carrying out catalytic hydrogenation on (2R)-4-methyl-1-((S)-1-phenethyl)-1,2,3,6-tetrahydropyridine-2-ethyl formate, so that (2R,4R)-4-methyl-1-((S)-1-phenethyl)-2-pyridine ethyl formate is obtained; and (2) under the action of a palladium catalyst and ferric oxalate, removing benzyl, so that the (2R,4R)-4-methyl piperidine-2-ethyl formate is obtained. The synthesis method provided by the invention has the advantages that the ferric oxalate is introduced into a reaction system, two-step reaction yield is increased, especially the efficiency is the highest when the ferric oxalate and a rhodium-silicon dioxide catalyst are used together, and the cost is effectively reduced, so that the synthesis method is applicable to industrial production.
PROCESS INTERMEDIATES AND METHODS FOR THE PREPARATION OF PROCESS INTERMEDIATES FOR THE SYNTHESIS OF ARGATROBAN MONOHYDRATE
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, (2014/04/03)
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.
METHOD FOR THE PREPARATION OF PROCESS INTERMEDIATES FOR THE SYNTHESIS OF ARGATROBAN MONOHYDRATE
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Page/Page column 59, (2012/10/18)
Object of the present invention is a method for the synthesis of a key intermediate 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.
Diastereoselective synthesis of an argatroban intermediate, ethyl (2R,4R)-4-methylpipecolate, by means of a Mandyphos/rhodium complex-catalyzed hydrogenation
Ferraboschi, Patrizia,Mieri, Maria De,Grisenti, Paride,Lotz, Matthias,Nettekoven, Ulrike
experimental part, p. 1626 - 1631 (2012/01/03)
The synthetic antithrombotic argatroban is a dipeptide between the nonproteogenic (2R,4R)-4-methyl-2-piperidine carboxylic acid and l-arginine, in turn bonded to a methyltetrahydroquinoline sulfonyl group. An extensive screening of transition metal-based complexes with different ligands was performed in order to identify the best catalyst for the diastereoselective hydrogenation of a suitable 4,5-dehydropiperidine precursor aimed toward a synthesis of the (2R,4R)-4-methyl piperidine moiety. Copyright
ANTITHROMBOTIC AMIDINOTETRAHYDROPYRIDYLALANINE DERIVATIVES
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, (2008/06/13)
This invention is directed to compounds of formula (I), STR1 pharmaceutically acceptable salts thereof, and pharmaceutically acceptable solvates of either entity, wherein Y is optionally monounsaturated C 3-C 5 alkylene optionally substituted with C. sub.1-C 4 alkyl or methylene; R 1 is H; C 1-C 4 alkyl optionally substituted with C 1-C 4 alkoxy, OH, NR 5 R 6, CONR 5 R 6, C 3-C 6 cycloalkyl or aryl; or C 3-C 6 alkenyl; R 2 is H; C 1-C 4 alkyl optionally substituted with C 1-C 4 alkoxy, OH, NR 5 R 6, CONR 5 R 6, C 3-C 6 cycloalkyl or aryl; or CONR 5 R 6 ; R. sup.3 and R 4 are each independently selected from H; C 1-C. sub. 4 alkyl optionally substituted with NR 5 R 6 ; C 1-C. sub.4 alkoxy; halo; CONR 5 R 6 and aryl; aryl is phenyl optionally substituted with one, two or three substituents independently selected from C 1-C 4 alkyl, C 1-C 4 alkoxy, OH, halo and CF 3 ; R 5 and R 6 are each independently selected from H and C 1-C 4 alkyl; and m and n are each independently 1, 2 or 3; which are potent and selective thrombin inhibitors useful in the treatment of inter alia, deep vein thrombosis; reocclusion following thrombolytic therapy; chronic arterial obstruction; peripheral vascular disease; acute myocardial infarction; unstable angina; atrial fibrillation; thrombotic stroke; transient ischaemic attacks; restenosis and occlusion following angioplasty; or neurodegenerative disorders.
Enantio- and Diastereo-selective Synthesis of Pipecolic Acid Derivatives using the Aza-Diels-Alder Reaction of Imines with Dienes
Bailey, Patrick D.,Wilson, Robert D.,Brown, George R.
, p. 1337 - 1340 (2007/10/02)
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).
