The first large-scale application of asymmetric iminium ion catalysis has been reported by Xu et al. at Merck as a key step in an improved process for synthesis of telcagepant (68, Scheme 12), a calcitonin gene-related peptide (CGRP) receptor antagonist indicated for the treatment of acute migraine. 67 A first generation route to the API suitable for pilot plant manufacturing had previously been developed (Scheme 12).

Telcagepant (code name MK-0974) is a calcitonin gene-related peptide receptor antagonist which was an investigational drug for the acute treatment and prevention of migraine, developed by Merck & Co. In the acute treatment of migraine, it was found to have equal potency to rizatriptan [1] and zolmitriptan [2] in two Phase III clinical trials .

A highly efficient, asymmetric synthesis of telcagepant (1), a CGRP receptor antagonist for the treatment of migraine, is described. This synthesis features the first application of iminium 2008-07-01 · The latter route has been implemented to produce multigram quantities of telcagepant for extensive preclinical evaluation. Synthesis of the (3R,6S)-3-Amino-6-(2,3-difluorophenyl)azepan-2-one of Telcagepant (MK-0974), a Calcitonin Gene-Related Peptide Receptor Antagonist for the Treatment of Migraine Headache | Organic Letters. Second part of the synthesis of Telcagepant. Cyclisation involved the employment of a mixed anhydride, possible for the decreased nucleophilicity of the trifluoroethyl nitrogen, and was followed by a base promoted dynamic crystallisation process in aqueous NaOH/DMSO mixture, which allowed the isolation of the 2-acetamido caprolactam 60 in 73% overall yield from the enamide. Synthesis of the (3 R ,6 S )-3-Amino-6- (2,3-difluorophenyl)azepan-2-one of Telcagepant (MK-0974), a Calcitonin Gene-Related Peptide Receptor Antagonist for the Treatment of Migraine Headache. Share.

Telcagepant synthesis

Telcagepant has been investigated for the treatment of Migraine. It is an antagonist of the receptor for calcitonin gene-related peptide (CGRP), a primary neuropeptide involved in the pathophysiology of migraine. CGRP and its receptors are found in areas of the central and peripheral nervous system that are important for the Disclosed is an efficient synthesis for the manufacture of the caprolactam intermediate (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepan-2-one: Formula and salts thereof, and an efficient preparation of telcagepant using the caprolactam intermediate. A highly efficient, asymmetric synthesis of telcagepant (1), a CGRP receptor antagonist for the treatment of migraine, is described. This synthesis features the first application of iminium organocatalysis on an industrial scale. Asymmetric Synthesis of Telcagepant, a CGRP Receptor Antagonist for the Treatment of Migraine Feng Xu,* Michael Zacuto, Naoki Yoshikawa, Richard Desmond, Scott Hoerrner, Tetsuji Itoh, Michel Journet, Guy Humphrey, Cameron Cowden, Neil Strotman, Paul Devine Department of Process Research, Merck Research Laboratories, Rahway, NJ 07065, USA WO-2010144293-A1 chemical patent summary.

Telcagepant Accession Number DB12228 Description. Telcagepant has been investigated for the treatment of Migraine. It is an antagonist of the receptor for calcitonin gene-related peptide (CGRP), a primary neuropeptide involved in the pathophysiology of migraine.

Telcagepant Revisited January 25, 2017 Uncategorized Comments: 0. It's only fair to share Telcagepant, 2017-01-25 Disclosed is an efficient synthesis for the manufacture of the caprolactam intermediate (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl) azepan-2-one: Formula and salts thereof, and an efficient preparation of telcagepant using the caprolactam intermediate. A highly efficient, asymmetric synthesis of telcagepant (1), a CGRP receptor antagonist for the treatment of migraine, is described. This synthesis features the first application of iminium organocatalysis on an industrial scale.

Disclosed is an efficient synthesis for the manufacture of the caprolactam intermediate (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl) azepan-2-one: Formula and salts thereof, and an efficient preparation of telcagepant using the caprolactam intermediate.

CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. 2021-04-03 · Isolating only three intermediates, the overall yield of this cost-effective synthesis was up to 27%. This environmentally responsible synthesis contains all of the elements required for a manufacturing process and prepares telcagepant (1) with the high quality required for pharmaceutical use. TELCAGEPANT MK 0974 pubchem.compound:11319053 chemidplus:781649-09-0 drugbank:12228 chembl:CHEMBL236593 Drug Info: ChemblDrugs ChemblInteractions TTD DrugBank (0 Synthesis of telcagepant and intermediates thereof patents-wipo In early trials, the first oral nonpeptide CGRP antagonist, MK-0974 ( Telcagepant ), was shown effective in the treatment of migraine attacks, but elevated liver enzymes in two participants were found. Chemvon Biotechnology Co. Ltd. is supplier for Telcagepant.

Jan Stach, Jan Doubský . The 24th International Society of . Heterocyclic Chemistry Congress.
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The route described in the report is an example of a synthetic target driving the discovery of new chemistries. In 2010, the Xu group [61] reported an efficient total synthesis of a selective peptide receptor antagonist telcagepant (MK-0974) (Scheme 22), which is a migraine drug [62] This key sequence Telcagepant (1) is synthesized by a coupling reaction of two heterocyclic components 2 and 3 (Scheme 1).8 While an efficient and practical synthesis of the piperidine piece 3 was recently established in our laboratories,9 there remained a need for a better synthesis of the caprolactam component 2. F F N O N H F 3C N O N NH N O F F N O NH 2 F 3C Telcagepant (code name MK-0974) is a calcitonin gene-related peptide receptor antagonist which was an investigational drug for the acute treatment and prevention of migraine, developed by Merck & Co.. In the acute treatment of migraine, it was found to have equal potency to rizatriptan and zolmitriptan Disclosed is an efficient synthesis for the manufacture of the caprolactam intermediate (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl) azepan-2-one: Formula and salts thereof, and an efficient preparation of telcagepant using the caprolactam intermediate. Here Xu et al. of Merck Rahway disclose their efforts towards an improved multikilogram synthesis of telcagepant, a CGRP receptor antagonist for the treatment of migraines ( J. Org. Chem.

Synthesis of Telcagepant Significance: Telcagepant is a selective antago-nist of calcitonin gene related peptide (CGRP) that is in phase clinical trials for the treatment of mi-graine. The synthesis featured an enantioselective 1,4-addition of nitromethane, which is the first application of iminium organocatalysis (B Æ D) on The first large-scale application of asymmetric iminium ion catalysis has been reported by Xu et al. at Merck as a key step in an improved process for synthesis of telcagepant (68, Scheme 12), a calcitonin gene-related peptide (CGRP) receptor antagonist indicated for the treatment of acute migraine.
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Telcagepant (100) is a calcitonin gene-related peptide (CGRP) receptor antagonist which entered clinical trials for the treatment of acute migraine (Fig. 20, Table 22). 128 Development was terminated when elevated levels of the liver enzyme alanine transaminase were found in treated patients.

of Merck Rahway disclose their efforts towards an improved multikilogram synthesis of telcagepant, a CGRP receptor antagonist for the treatment of migraines ( J. Org. Chem. 2010, 75, 7829−7841). The route described in the report is an example of a synthetic target driving the discovery of new chemistries. In 2010, the Xu group [61] reported an efficient total synthesis of a selective peptide receptor antagonist telcagepant (MK-0974) (Scheme 22), which is a migraine drug [62] This key sequence Telcagepant (1) is synthesized by a coupling reaction of two heterocyclic components 2 and 3 (Scheme 1).8 While an efficient and practical synthesis of the piperidine piece 3 was recently established in our laboratories,9 there remained a need for a better synthesis of the caprolactam component 2. F F N O N H F 3C N O N NH N O F F N O NH 2 F 3C Disclosed is an efficient synthesis for the manufacture of the caprolactam intermediate (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl) azepan-2-one: Formula and salts thereof, and an efficient preparation of telcagepant using the caprolactam intermediate. Telcagepant, is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested.