AP26113

Base Information

• Chemical Name: AP26113
• CAS No.: 1197958-12-5
• Molecular Formula: C26H34ClN6O2P
• Molecular Weight: 529.01
• Mol file: 1197958-12-5.mol

Synonyms:AP26113

Chemical Property of AP26113

Chemical Property:

• Boiling Point: 737.6±70.0 °C(Predicted)
• PKA: 9.27±0.20(Predicted)
• PSA: 95.66000
• Density: 1.29±0.1 g/cm3(Predicted)
• LogP: 4.96410
• Solubility.: ≥26.45 mg/mL in DMSO; insoluble in H2O; ≥55.9 mg/mL in EtOH

Purity/Quality:

>95% ^*data from raw suppliers

AP26113 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: AP26113 (also known as Brigatinib) is an investigated small molecule for targeted cancer therapy. It is a potent dual inhibitor of anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR). It is mainly under investigation for its treatmentefficacy on non-small cell lung cancer (NSCLC) where ALK is activated and EGFP mutations frequently occur.
• Uses: AP 26113 is a potent anaplastic lymphoma kinase (ALK) inhibitor. It is also an epidermal growth factor (EGFR) receptor tyrosine kinase inhibitor used for treatment of lung cancer.

Technology Process of AP26113

There total 9 articles about AP26113 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: 66.3%

N2-[4-[4-(dimethylamino)-1-piperidyl]-2-methoxyphenyl]-N4-[2-(dimethylphosphoryl)phenyl]-2,4-diaminopyrimidine → (2-((5-chloro-2-((4-(4-(dimethylamino)piperidin-1-yl)-2-methoxyphenyl )amino)pyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide (1197958-12-5)

Guidance literature:

With N-chloro-succinimide; In acetonitrile; at 20 ℃;

Reference yield:

1-(4-amino-3-methoxyphenyl)-N,N-dimethylpiperidine-4-amine (1089279-91-3) + (2-((2,5-dichloropyrimidin-4-yl)amino)phenyl)dimethyl phosphine oxide (1197953-49-3) → (2-((5-chloro-2-((4-(4-(dimethylamino)piperidin-1-yl)-2-methoxyphenyl )amino)pyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide (1197958-12-5)

Guidance literature:

With hydrogenchloride; In ethanol; 2-methoxy-ethanol; at 120 ℃; for 6h;

DOI:10.1021/acs.jmedchem.6b00306

Reference yield:

1-(4-amino-3-methoxyphenyl)-N,N-dimethylpiperidine-4-amine (1089279-91-3) → (2-((5-chloro-2-((4-(4-(dimethylamino)piperidin-1-yl)-2-methoxyphenyl )amino)pyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide (1197958-12-5)

Guidance literature:

Multi-step reaction with 4 steps

1.1: nitric acid / methanol / 0 °C / Reflux

2.1: N,N-dimethyl-formamide / 115 - 125 °C / Reflux

3.1: 1,8-diazabicyclo[5.4.0]undec-7-ene; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate / acetonitrile / 24 h / 20 - 60 °C / Inert atmosphere

3.2: 50 - 55 °C

4.1: N-chloro-succinimide / acetonitrile / 20 °C

With N-chloro-succinimide; nitric acid; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; 1,8-diazabicyclo[5.4.0]undec-7-ene; In methanol; N,N-dimethyl-formamide; acetonitrile;

upstream raw materials:

1-(4-amino-3-methoxyphenyl)-N,N-dimethylpiperidine-4-amine

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

1-(3-methoxy-4-nitrophenyl)-N,N-dimethylpiperidine-4-amine

4-fluoro-2-methoxy-1-nitrobenzene

Refernces

• 1、 Huang, Wei-Sheng,Liu, Shuangying,Zou, Dong,Thomas, Mathew,Wang, Yihan,Zhou, Tianjun,Romero, Jan,Kohlmann, Anna,Li, Feng,Qi, Jiwei,Cai, Lisi,Dwight, Timothy A.,Xu, Yongjin,Xu, Rongsong,Dodd, Rory,Toms, Angela,Parillon, Lois,Lu, Xiaohui,Anjum, Rana,Zhang, Sen,Wang, Frank,Keats, Jeffrey,Wardwell, Scott D.,Ning, Yaoyu,Xu, Qihong,Moran, Lauren E.,Mohemmad, Qurish K.,Jang, Hyun Gyung,Clackson, Tim,Narasimhan, Narayana I.,Rivera, Victor M.,Zhu, Xiaotian,Dalgarno, David,Shakespeare, William C.. "Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase". . p. 4948 - 4964. Retrieved 2016/06/13.