Neratinib

Base Information

• Chemical Name: Neratinib
• CAS No.: 698387-09-6
• Deprecated CAS: 736156-77-7
• Molecular Formula: C30H29ClN6O3
• Molecular Weight: 557.052
• Hs Code.: 29334900
• European Community (EC) Number: 811-237-1
• UNII: JJH94R3PWB
• DSSTox Substance ID: DTXSID70220132
• Nikkaji Number: J2.688.659G
• Wikipedia: Neratinib
• Wikidata: Q6995920
• NCI Thesaurus Code: C49094
• RXCUI: 1940643
• Pharos Ligand ID: V4KPNPBCJPMY
• Metabolomics Workbench ID: 152922
• ChEMBL ID: CHEMBL180022
• Mol file: 698387-09-6.mol

Synonyms:HKI 272;HKI-272;HKI272;N-(4-(3-chloro-4-(2-pyridinylmethoxy)anilino)-3-cyano-7-ethoxy-6-quinolyl)-4-(dimethylamino)-2-butenamide;neratinib;neratinib maleate;Nerlynx

Chemical Property of Neratinib

Chemical Property:

• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.667
• Boiling Point: 756.97 °C at 760 mmHg
• PKA: 12.37±0.43(Predicted)
• Flash Point: 411.601 °C
• PSA: 112.40000
• Density: 1.337 g/cm³
• LogP: 6.07848
• Storage Temp.: Refrigerator
• Solubility.: Chloroform (Slightly), DMSO (Slightly, Heated, Sonicated), Methanol (Slightly, Heated)
• XLogP3: 4.9
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 11
• Exact Mass: 556.1989665
• Heavy Atom Count: 40
• Complexity: 881

Purity/Quality:

99.0% MIN ^*data from raw suppliers

Neratinib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: CCOC1=C(C=C2C(=C1)N=CC(=C2NC3=CC(=C(C=C3)OCC4=CC=CC=N4)Cl)C#N)NC(=O)C=CCN(C)C
• Isomeric SMILES: CCOC1=C(C=C2C(=C1)N=CC(=C2NC3=CC(=C(C=C3)OCC4=CC=CC=N4)Cl)C#N)NC(=O)/C=C/CN(C)C
• Recent ClinicalTrials: INdividualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT)
• Recent EU Clinical Trials: Phase II Study of Neratinib and Trastuzumab +/- Vinorelbine p.o.
• Description: The receptor tyrosine kinase HER2 (ErbB2) is a key component of epidermal growth factor receptor complexes that are known to have central roles in cell proliferation and cancer. Neratinib is an orally active, irreversible inhibitor of the HER2 kinase (IC50 = 59 nM). It also potently inhibits several mutants of HER2 and shows 10-fold or greater selectivity over a wide variety of other kinases. As an irreversible inhibitor, neratinib may circumvent acquired resistance developed against reversible inhibitors, including gefitinib . Neratinib has been evaluated in clinical trials against cancers characterized by HER2 overexpression or HER2 activating mutations.
• Uses: An oral, irreversible dual EGFR/HER2 inhibitor for breast and non-small cell lung cancer. Antitumor agent. Neratinib (HKI-272) is a highly selective HER2 and EGFR inhibitor with IC50 of 59 nM and 92 nM, respectively. An oral, irreversible dual EGFR/HER2 inhibitor for breast and non-small cell lung cancer. Antitumor agent

Technology Process of Neratinib

There total 28 articles about Neratinib which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 98.0%

6-amino-4-[[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]amino]-7-ethoxyquinoline-3-carbonitrile (848139-78-6) + 4-N,N-dimethylaminocrotonoylchloride Hydrochloride (501332-27-0) → neratinib (698387-09-6)

Guidance literature:

With sodium hydroxide; In 1-methyl-pyrrolidin-2-one; water; at 10 - 40 ℃; for 15h; Solvent;

Reference yield: 95.9%

2-(N,N-dimethylamino)ethoxide (52334-92-6) + diethyl ({[4-({3-chloro-4-[(pyridin-2-yl)methoxy]phenyl}amino)-3-cyano-7-ethoxyquinolin-6-yl]carbamoyl}methyl)phosphonate (1269662-79-4) → neratinib (698387-09-6)

Guidance literature:

diethyl ({[4-({3-chloro-4-[(pyridin-2-yl)methoxy]phenyl}amino)-3-cyano-7-ethoxyquinolin-6-yl]carbamoyl}methyl)phosphonate; With sodium ethanolate; lithium chloride; In ethanol; at -5 ℃; for 0.5h;

2-(N,N-dimethylamino)ethoxide; In ethanol; for 0.666667h; Temperature; Solvent; Reagent/catalyst;

Reference yield: 95.2%

dimethylaminoacetaldehyde diethyl acetal (3616-56-6) + diethyl ({[4-({3-chloro-4-[(pyridin-2-yl)methoxy]phenyl}amino)-3-cyano-7-ethoxyquinolin-6-yl]carbamoyl}methyl)phosphonate (1269662-79-4) → neratinib (698387-09-6)

Guidance literature:

dimethylaminoacetaldehyde diethyl acetal; With hydrogenchloride; water; at 0 - 40 ℃; Inert atmosphere;

diethyl ({[4-({3-chloro-4-[(pyridin-2-yl)methoxy]phenyl}amino)-3-cyano-7-ethoxyquinolin-6-yl]carbamoyl}methyl)phosphonate; With sodium ethanolate; lithium chloride; In ethanol; water; at -20 ℃; for 3h;

DOI:10.1007/s11164-012-0822-4

upstream raw materials:

3-chloro-4-(2-pyridylmethoxy)aniline

4-chloro-6-(5-(dimethylamino)-2-oxopent-3-enyl)-7-ethoxyquinoline-3-carbonitrile

(2E)-(N,N-dimethylamino)-2-butenoyl chloride

4-Chloro-7-ethoxy-6-nitro-quinoline-3-carbonitrile

Downstream raw materials:

(E)-4-((4-((3-chloro-4-(pyridin-2-ylmethoxy)phenyl)amino)-3-cyano-7-ethoxyquinolin-6-yl)amino)-N,N-dimethyl-4-oxobut-2-en-1-amine oxide

neratinib maleate monohydrate

Refernces

• 1、 -. "Preparation method of neratinib". Page/Page column 10-11. . Retrieved 2019/11/04.
• 2、 -. "SOLID STATE FORMS OF NERATINIB AND SALTS THEREOF". Paragraph 0076. . Retrieved 2018/02/28.