1421373-66-1 Usage
Description
Osimertinib is active against exon 19 deletions, exon 21 mutations, and also the
exon 20 T790M mutations. It is preferentially selective for mutated EGFR, and
therefore toxicity at therapeutic doses is lower than for first- and second-generation
agents. Notably, osimertinib is able to cross the blood-brain barrier, making it active
against disease in the CNS.
Uses
AZD-9291 Mesylate is a potent and selective epidermal growth factor receptor (EGFR) inhibitor.
Definition
ChEBI: A methanesulfonate (mesylate) salt prepared from equimolar amounts of osimertinib and methanesulfonic acid. Used for treatment of EGFR T790M mutation positive non-small cell lung cancer.
Indications
The collection of ibrutinib (Imbruvica(R), Pharmacyclics Inc.), afatinib, and osimertinib represents the small, yet expanding, group of covalent SMKIs. Ibrutinib is a non-receptor Bruton’s tyrosine kinase inhibitor approved for the treatment of relapsed chronic lymphocytic leukemia. Afatinib, approved for NSCLC in 2013 and squamous NSCLC in 2016, is a second-generation irreversible EGFR inhibitor that targets wild-type EGFR, the mutant T790M EGFR, and HER2. Osimertinib (AZD9291), which was approved by FDA in November 2015, is a third-generation irreversible EGFR inhibitor that selectively targets the mutant T790M EGFR. Rociletinib, which shares a high degree of structural similarity with that of osimertinib, is a promising covalent EGFR inhibitor developed by Clovis Oncology aimed for the treatment of patients with EGFR T790M-mutated NSCLC, until the company terminated its development in May 2016 following a negative vote fromthe FDA’sOncologic Drugs Advisory Committee.
Side effects
Osimertinib toxicity is dose-dependent and is associated with fewer gastrointestinal
and dermatologic adverse events than with other approved EGFR TKIs.
Synthesis
Friedel-Crafts arylation of commercial N-methylindole
(203) with commercial dichloropyrimidine 202 gave the 3-
pyrazinyl indole 204 in good yield. Subsequent SNAr with
nitroaniline 205 (available from a one-step nitration from the
commercially available des-nitroaniline) provided aminopyrazine
206. Next, SN
Ar reaction of 206 with N,N,N′-
trimethylated ethylenediamine delivered 207 in near quantitative
yield, and this was followed by nitro reduction with iron
under acidic conditions to give rise to the triaminated arene
208 in 85% yield. Because acrylates are notoriously difficult to
install directly due to their highly reactive nature and
propensity to polymerize, a clever two-step acylation/
elimination sequence was employed using 3-chloropropanoyl
chloride, and this was immediately followed by mesylate salt
formation, which furnished the osimertinib mesylate (XXVI) in
excellent yield. This seven-step process which derives from
readily available feedstock delivered the final product in nearly
57% overall yield from starting materials 202 and 203.
Check Digit Verification of cas no
The CAS Registry Mumber 1421373-66-1 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,4,2,1,3,7 and 3 respectively; the second part has 2 digits, 6 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 1421373-66:
(9*1)+(8*4)+(7*2)+(6*1)+(5*3)+(4*7)+(3*3)+(2*6)+(1*6)=131
131 % 10 = 1
So 1421373-66-1 is a valid CAS Registry Number.
1421373-66-1Relevant articles and documents
Preparation method of osimertinib mesylate
-
, (2021/11/19)
The invention discloses a preparation method of osimertinib mesylate. 4-fluoro-2-methoxy-5-nitroaniline and 3-(2-chloro-4-pyrimidinyl)-1-methyl-1H-indole are subjected to a condensation reaction and then subjected to a nucleophilic substitution reaction with N, N-dimethylethylenediamine, a high-purity compound shown in the formula (6) is obtained through Eschweiler-Clarke amine reductive alkylation, water serves as a solvent, acetic acid and the like serve as a cosolvent, catalytic hydrogenation is performed, amidation reaction with acryloyl chloride is carried out to obtain high-purity osimertinib and salifying with methanesulfonic acid is carried out to obtain osimertinib mesylate, and compared with the patent CN103702990B, the method is simple and convenient to operate, less in environmental pollution, high in yield, low in cost, good in product quality and more suitable for industrial production.
Synthetic method of osimertinib AZD9291
-
, (2019/01/23)
The invention provides a synthetic method of osimertinib AZD9291; an intermediate (III) is synthesized by adopting CoCl2/SoCl2 to catalyze; an intermediate (VIII) is synthesized by adopting CoSO4.7H2Oto carry out catalytic reduction; in the preparation of an intermediate (X), sodium carbonate is used as an acid binding agent; and the intermediate (X) and methane sulfonic acid are adopted for salification in a mixed solvent of ethyl alcohol and isopropyl alcohol to prepare the AZD9291. The synthetic method provided by the invention is high in yield, mild in reaction condition, simple in after-treatment and suitable for industrial production.
Preparation method for osimertinib mesylate
-
, (2018/04/28)
The invention discloses a preparation method for osimertinib mesylate. The chemical name of osimertinib mesylate is N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidine-2-yl)amino)phenyl)acrylamide mesylate (AZD9291), and the chemical formula is C28H33N7O2.CH4O3S. The process of the preparation technique of the preparation method is simple, materials areeasy to obtain, and the preparation method is cost-efficient and environment-friendly, can help realize industrialization, can promote the economic and technological development of osimertinib activeingredients, reduces production cost, and is suitable for mass production.