Binimetinib

Base Information

• Chemical Name: Binimetinib
• CAS No.: 606143-89-9
• Deprecated CAS: 1073666-70-2,1201685-05-3,1417448-81-7
• Molecular Formula: C17H15BrF2N4O3
• Molecular Weight: 441.232
• Hs Code.: 2933998090
• European Community (EC) Number: 639-995-7
• UNII: 181R97MR71
• DSSTox Substance ID: DTXSID70209422
• Nikkaji Number: J3.336.515B
• Wikipedia: Binimetinib
• Wikidata: Q19903515
• NCI Thesaurus Code: C84865
• RXCUI: 2049122
• Pharos Ligand ID: T5F4WDQXB4V3
• Metabolomics Workbench ID: 153039
• ChEMBL ID: CHEMBL3187723
• Mol file: 606143-89-9.mol

Synonyms:binimetinib;MEK162;Mektovi

Chemical Property of Binimetinib

Chemical Property:

• Melting Point: >203oC (dec.)
• PKA: 14.20±0.10(Predicted)
• PSA: 91.90000
• Density: 1.67
• LogP: 3.65910
• Storage Temp.: -20°C
• Solubility.: Soluble in DMSO (up to at least 25 mg/ml)
• XLogP3: 3.1
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 6
• Exact Mass: 440.02956
• Heavy Atom Count: 27
• Complexity: 521

Purity/Quality:

99.9% ^*data from raw suppliers

MEK162 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CN1C=NC2=C1C=C(C(=C2F)NC3=C(C=C(C=C3)Br)F)C(=O)NOCCO
• Recent ClinicalTrials: Testing the Use of Fulvestrant and Binimetinib Targeted Treatment for NF1 Mutation in Hormone Receptor-Positive Metastatic Breast Cancer, A ComboMATCH Treatment Trial
• Recent EU Clinical Trials: A PHASE 2, RANDOMIZED, OPEN-LABEL STUDY OF ENCORAFENIB AND BINIMETINIB PLUS PEMBROLIZUMAB VERSUS NIVOLUMAB AND IPILIMUMAB IN PARTICIPANTS WITH BRAF V600E/K MUTATION-POSITIVE MELANOMA WHO PROGRESSED DURING OR AFTER PRIOR TREATMENT WITH ANTI?PD-1 THERAPY
• Recent NIPH Clinical Trials: Addition of binimetinib after refractory to encorafenib and cetuximab in patients with BRAF V600E-mutatnt metastatic colorectal cancer
• Description: Binimetinib (606143-89-9) is a potent (IC50?= 12 nM) and selective allosteric inhibitor of MEK1/2.1,2?Recently approved by the FDA for treatment of melanoma in combination with Encorafenib. Binimetinib has had limited success as monotherapy but has shown promise in combination with other chemotherapeutic agents.3-5
• Uses: MEK 162 is a MEK1/2 inhibitor allowing it to be a effective anti-cancer medication.

Technology Process of Binimetinib

There total 21 articles about Binimetinib 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:

6-(4-bromo-2-fluoro-phenylamino)-7-fluoro-3-methyl-3 Hbenzoimidazole-5-carboxylic acid (2-vinyloxy-ethoxy)-amide → 6-(4-bromo-2-fluoro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide (606143-89-9)

Guidance literature:

With hydrogenchloride; In ethanol; for 24h;

Reference yield:

6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid-(2-tert-butoxyethoxy)amide (1604812-70-5) → 6-(4-bromo-2-fluoro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide (606143-89-9)

Guidance literature:

With phosphoric acid; water; In acetonitrile; at 20 - 53 ℃; for 6.25h;

Reference yield:

methyl 5-[(4-bromo-2-fluorophenyl)amino]-4-fluoro-1-methyl-1H-benzo[d]imidazole-6-carboxylate (1415559-93-1) → 6-(4-bromo-2-fluoro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide (606143-89-9)

Guidance literature:

Multi-step reaction with 3 steps

1: water; sodium hydroxide / tetrahydrofuran / 2 h

2: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 48 h / 20 °C

3: hydrogenchloride / ethanol / 24 h

With hydrogenchloride; water; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; sodium hydroxide; In tetrahydrofuran; ethanol; N,N-dimethyl-formamide;

upstream raw materials:

6-(4-bromo-2-fluoro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid methyl ester

methyl 5-[(4-bromo-2-fluorophenyl)amino]-4-fluoro-1-methyl-1H-benzo[d]imidazole-6-carboxylate

6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid

6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid-(2-tert-butoxyethoxy)amide

Refernces

• 1、 -. "PROCESS OF PREPARATION OF BENZIMIDAZOLE COMPOUNDS". . . Retrieved 2020/10/28.
• 2、 -. "COMBINATION THERAPY". . . Retrieved 2013/10/08.