Brigatinib

Base Information

• Chemical Name: Brigatinib
• CAS No.: 1197953-54-0
• Molecular Formula: C29H39ClN7O2P
• Molecular Weight: 584.09
• Mol file: 1197953-54-0.mol

Synonyms:Brigatinib;AP26113 (Brigatinib);Brigatinib, AP26113;5-Chloro-N4-[2-(dimethylphosphinyl)phenyl]-N2-[2-methoxy-4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]-2,4-pyrimidinediamine

Chemical Property of Brigatinib

Chemical Property:

• Boiling Point: 781.8±70.0 °C(Predicted)
• PKA: 8.14±0.42(Predicted)
• PSA: 95.67000
• Density: 1.31±0.1 g/cm3(Predicted)
• LogP: 5.17680
• Storage Temp.: -20°C
• Solubility.: Soluble in DMSO (1 mg/ml with warming)

Purity/Quality:

Brigatinib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Indications: Brigatinib is prescribed for patients with specific forms of NSCLC that have spread to various sections of the body in people who have been on previous treatment with other cancer medications such as crizotinib, and their condition has become worse or they indicate minimal signs of improvement.
• Description: Brigatinib is a small molecule inhibitor of both ALK and EGFR [195]. In preclinical models, “triple-mutant EGFR”-positive cells (activating EGFR mutation/ T790M/C797S) responded to the combination of brigatinib with an anti-EGFR monoclonal antibody, cetuximab or panitumumab [196]. Single-agent activity of brigatinib in a phase I/II trial was only 5% [197], possibly compounded by low plasma concentrations [196], but the addition of an anti-EGFR monoclonal antibody remains to be clinically tested. The preclinical data with brigatinib and EAI045?in laboratory models with a C797S mutation demonstrate that combination therapies with an anti-EGFR monoclonal antibody may lead to overcoming resistance to osimertinib.
• Uses: Brigatinib is a tyrosine kinase receptor Mer (MERTK) inhibitor and can be used in combination with epidermal growth factor receptor (EGFR) inhibitors for the treatment of cancer.

Technology Process of Brigatinib

There total 10 articles about Brigatinib 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: 86.1%

1-methyl-piperazine (109-01-3) + C24H27ClN5O3P → 5-chloro-N4-[2-(dimethylphosphonyl)phenyl]-N2-{2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}pyrimidine-2,4-diamine (1197953-54-0)

Guidance literature:

1-methyl-piperazine; C₂₄H₂₇ClN₅O₃P; In 1,4-dioxane; for 0.333333h;

With sodium tris(acetoxy)borohydride; In 1,4-dioxane; at 20 ℃;

Reference yield: 80.3%

2-methoxy-4-[4-(4-methylpiperazin-1-yl)-piperidin-1-yl]-phenylamine + (2-((2,5-dichloropyrimidin-4-yl)amino)phenyl)dimethyl phosphine oxide (1197953-49-3) → 5-chloro-N4-[2-(dimethylphosphonyl)phenyl]-N2-{2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}pyrimidine-2,4-diamine (1197953-54-0)

Guidance literature:

With triethylamine; In 1,2-dimethoxyethane; ethanol; at 120 ℃; for 5h; Sealed tube;

Reference yield:

4-fluoro-2-methoxy-1-nitrobenzene (448-19-1) → 5-chloro-N4-[2-(dimethylphosphonyl)phenyl]-N2-{2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}pyrimidine-2,4-diamine (1197953-54-0)

Guidance literature:

Multi-step reaction with 3 steps

1: potassium carbonate / N,N-dimethyl-formamide / 18 h / 120 °C

2: hydrogen; palladium on activated charcoal / ethanol / 3 h / 2585.81 Torr

3: hydrogenchloride / ethanol; 2-methoxy-ethanol / 5.5 h / 120 °C / Sealed tube

With hydrogenchloride; palladium on activated charcoal; hydrogen; potassium carbonate; In ethanol; 2-methoxy-ethanol; N,N-dimethyl-formamide;

upstream raw materials:

(2-((2,5-dichloropyrimidin-4-yl)amino)phenyl)dimethyl phosphine oxide

2-iodophenylamine

(2-aminophenyl)dimethyl phosphorus oxide

4-fluoro-2-methoxy-1-nitrobenzene

Refernces

• 1、 -. "Preparation method of ALK inhibitor Brigatinib". Paragraph 0059-0063. . Retrieved 2020/06/02.
• 2、 -. "CRYSTALLINE FORMS OF 5-CHLORO-N4-[-2-(DIMETHYLPHOSPHORYL) PHENYL]-N2-{2-METHOXY-4-[4-(4-METHYLPIPERAZIN-1-YL) PIPERIDIN-1-YL] PYRIMIDINE-2,4-DIAMINE". Paragraph 00373; 00374; 00375. . Retrieved 2016/05/24.