1374248-77-7

Basic information

• Product Name: Ubrogepant
• Synonyms: Ubrogepant;MK-1602
• CAS NO: 1374248-77-7
• Molecular Formula: C29H26F3N5O3
• Molecular Weight: 549.54
• Product Categories: API
• Mol File: 1374248-77-7.mol

Chemical Properties

• Boiling Point: 729.4±60.0 °C(Predicted)
• Appearance: /
• Density: 1.45±0.1 g/cm3(Predicted)
• PKA: 11.08±0.20(Predicted)
• CAS DataBase Reference: Ubrogepant(CAS DataBase Reference)
• NIST Chemistry Reference: Ubrogepant(1374248-77-7)
• EPA Substance Registry System: Ubrogepant(1374248-77-7)

Safety Data

• Hazardous Substances Data: 1374248-77-7(Hazardous Substances Data)

Usage

Uses

Ubrogepant, is a new drug possible used for the treatment of migraine.

Upstream product

• 1456804-09-3 C₂₃H₂₈ClN₃O₃ 
• 6186-22-7 4-bromophenyl acetone 
• 1375541-21-1 (S)-2′-oxo-1′,2′,5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridine]-3-carboxylic acid 
• 1059186-43-4 (6S)-3-amino-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one 
• 1189570-15-7 (6S)-3-iodo-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one 
• 1375541-24-4 methyl (6S)-2'-oxo-1',2’,5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridine]-3-carboxylate 
• 1375542-65-6 methyl (6S)-2'-oxo-1'-{[2-(trimethylsilyl)ethoxy]methyl}-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridine]-3-carboxylate 
• 1455358-06-1 1-(tert-butyl)-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one 
• 1455358-36-7 C₁₃H₁₆N₂O₃ 
• 1455358-11-8 1-(tert-butyl)-3-((5-chloro-3-(hydroxymethyl)pyridin-2-yl)methyl)-1H-pyrrolo[2,3-b]pyridin-2(3H)-one 
• 1455358-12-9 1-(tert-butyl)-3-((5-chloro-3-(chloromethyl)pyridin-2-yl)methyl)-1H-pyrrolo[2,3-b]pyridin-2(3H)-one 
• 1455358-14-1 (S)-1'-(tert-butyl)-3-chloro-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one 
• 1375477-14-7 tert-butyl [(3S,5S,6R)-5-(3-chlorophenyl)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)piperidin-3-yl]carbamate 
• 103-79-7 1-phenyl-acetone 

Relevant articles and documents

Calcitonin gene-related peptide (CGRP) receptor antagonist treatment of migraine

Migraine is ranked as the sixth cause of years lost due to disability, with around 1.04 billion migraine sufferers globally. Triptans are considered the standard for acute migraine treatment, but an important number of migraineurs do not respond to them and these drugs are contraindicated in patients with cardiovascular disease. Migraine therapy is currently undergoing tremendous development, i.e., 5-HT1F receptor agonists (ditans), anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies, and small-molecule CGRP receptor antagonists (gepants). Ubrogepant (MK-1620) is a small-molecule, potent and selective CGRP receptor antagonist. In two phase III clinical trials (ACHIEVE I and II), ubrogepant showed, at 2 hours, significant percentages of pain freedom, and absence of the most bothersome symptoms in migraine patients. In a phase III study to assess the long-term (52-week) safety and tolerability, ubrogepant displayed good tolerability, and no signs of hepatic toxicity. In March 2019, the U.S. Food and Drug Administration accepted the new drug application (NDA) for ubrogepant for the acute treatment of migraine.

Practical Asymmetric Synthesis of a Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonist Ubrogepant

The development of a scalable asymmetric route to a new calcitonin gene-related peptide (CGRP) receptor antagonist is described. The synthesis of the two key fragments was redefined, and the intermediates were accessed through novel chemistry. Chiral lactam 2 was prepared by an enzyme mediated dynamic kinetic transamination which simultaneously set two stereocenters. Enzyme evolution resulted in an optimized transaminase providing the desired configuration in >60:1 syn/anti. The final chiral center was set via a crystallization induced diastereomeric transformation. The asymmetric spirocyclization to form the second fragment, chiral spiro acid intermediate 3, was catalyzed by a novel doubly quaternized phase transfer catalyst and provided optically pure material on isolation. With the two fragments in hand, development of their final union by amide bond formation and subsequent direct isolation is described. The described chemistry has been used to deliver over 100 kg of our desired target, ubrogepant.

PIPERIDINONE CARBOXAMIDE AZAINDANE CGRP RECEPTOR ANTAGONISTS

The present invention is directed to piperidinone carboxamide azaindane derivatives which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.