Osimertinib mesylate CAS 1421373-66-1
Introduction：Basic information about Osimertinib mesylate CAS 1421373-66-1, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Osimertinib mesylate Basic information
| Product Name: | Osimertinib mesylate |
| Synonyms: | AZD-9291 (Mesylate);N-[2-[[2-(Dimethylamino)ethyl]methylamino]-4-methoxy-5-[[4-(1-methyl-1H-indol-3-yl)-2-pyrimidinyl]amino]phenyl]-2-propenamide methanesulfonate (1:1);AZD-9291 mesylateN-[2-[[2-(Dimethylamino)ethyl]methylamino]-4-methoxy-5-[[4-(1-methyl-1H-indol-3-yl)-2-pyrimidinyl]amino]phenyl]-2-propenamide methanesulfonate (1:1);Osimertinib;N-[2-(2-dimethylaminoethylmethylamino)-4-methoxy-5-[[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino]phenyl]prop-2-enamide mesylate salt;Osimertinib Mesylate(AZD9291);Osimertinib mesylate;Mereletinib mesylate |
| CAS: | 1421373-66-1 |
| MF: | C29H37N7O5S |
| MW: | 595.72 |
| EINECS: | 200-064-1 |
| Product Categories: | AZD09;API;1421373-66-1 |
| Mol File: | 1421373-66-1.mol |
Osimertinib mesylate Chemical Properties
| Melting point | >232°C (dec.) |
| storage temp. | -20°C Freezer, Under inert atmosphere |
| solubility | DMSO (Slightly), Methanol (Slightly) |
| form | Solid |
| color | Off-White to Yellow |
| InChI | InChI=1S/C28H33N7O2.CH4O3S/c1-7-27(36)30-22-16-23(26(37-6)17-25(22)34(4)15-14-33(2)3)32-28-29-13-12-21(31-28)20-18-35(5)24-11-9-8-10-19(20)24;1-5(2,3)4/h7-13,16-18H,1,14-15H2,2-6H3,(H,30,36)(H,29,31,32);1H3,(H,2,3,4) |
| InChIKey | FUKSNUHSJBTCFJ-UHFFFAOYSA-N |
| SMILES | S(O)(=O)(=O)C.CN1C2=CC=CC=C2C(C2C=CN=C(NC3C=C(NC(=O)C=C)C(N(C)CCN(C)C)=CC=3OC)N=2)=C1 |
Safety Information
| HS Code | 29339900 |
| 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 | Osimertinib mesylate (AZD9291) is the mesylate form of osimertinib, which is an oral, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) drug. |
| 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. |
| Application | Osimertinib mesylate is approved to treat:Non-small cell lung cancer that has certain EGFR gene mutations. It is used in adults:As adjuvant therapy after surgery to remove the cancer; As the first therapy for cancer that has spread to other parts of the body, orin patients whose cancer has spread to other parts of the body and got worse during or after treatment with another EGFR tyrosine kinase inhibitor. |
| Brand name | TagrissoTM |
| General Description | Class: receptor tyrosine kinase Treatment: NSCLC Oral bioavailability = 70% Elimination half-life = 48 h Protein binding = 94.7% |
| Side effects | Osimertinib mesylate 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 withnitroaniline 205 (available from a one-step nitration from thecommercially available des-nitroaniline) provided aminopyrazine206. Next, SNAr reaction of 206 with N,N,N??-trimethylated ethylenediamine delivered 207 in near quantitativeyield, and this was followed by nitro reduction with ironunder acidic conditions to give rise to the triaminated arene208 in 85% yield. Because acrylates are notoriously difficult toinstall directly due to their highly reactive nature andpropensity to polymerize, a clever two-step acylation/elimination sequence was employed using 3-chloropropanoylchloride, and this was immediately followed by mesylate saltformation, which furnished the osimertinib mesylate (XXVI) inexcellent yield. This seven-step process which derives fromreadily available feedstock delivered the final product in nearly57% overall yield from starting materials 202 and 203. |
| References | [1] Patent: WO2013/14448, 2013, A1. Location in patent: Page/Page column 67 [2] Journal of Medicinal Chemistry, 2014, vol. 57, # 20, p. 8249 - 8267 [3] Patent: CN106699736, 2017, A. Location in patent: Paragraph 0050; 0051; 0052; 0053 [4] Patent: CN106674202, 2017, A. Location in patent: Paragraph 0076 [5] Patent: CN106543060, 2017, A. Location in patent: Paragraph 0088; 0089 |
Osimertinib mesylate Preparation Products And Raw materials
| Raw materials | Mutated EGFR-IN-1-->AZD-9291-->N,N-Diisopropylethylamine-->Ethyl acetate-->Ethanol-->Acryloyl chloride-->Methanesulfonic acid |
