WZ4002

Base Information

• Chemical Name: WZ4002
• CAS No.: 1213269-23-8
• Molecular Formula: C25H27ClN6O3
• Molecular Weight: 494.981
• Mol file: 1213269-23-8.mol

Synonyms:WZ-4002;

Chemical Property of WZ4002

Chemical Property:

• PKA: 12.78±0.70(Predicted)
• PSA: 95.34000
• Density: 1.314
• LogP: 5.27620
• Solubility.: ≥24.7 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH

Purity/Quality:

WZ4002 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Uses: A novel mutant-selective EGFR kinase inhibitor of EGFRL858R and EGFRL858R/T790M with IC50s of 2 nM and 8 nM, respectively. WZ 4002 is an EGFR phosphorylation inhibitor.

Technology Process of WZ4002

There total 9 articles about WZ4002 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: 36.0%

4-(3-aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl) pyrimidin-2-amine (1213269-26-1) + acryloyl chloride (814-68-6,25189-84-8) → N-(3-(5-chloro-2-(2-methoxy-4-(4-methylpiperazin-1-yl)phenylamino)pyrimidin-4-yloxy)phenyl)acrylamide (1213269-23-8)

Guidance literature:

With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 ℃; for 2h;

DOI:10.1016/j.bmcl.2017.09.048

Reference yield:

2-methoxy-4-(4-methylpiperazin-1-yl)aniline (122833-04-9) → N-(3-(5-chloro-2-(2-methoxy-4-(4-methylpiperazin-1-yl)phenylamino)pyrimidin-4-yloxy)phenyl)acrylamide (1213269-23-8)

Guidance literature:

Multi-step reaction with 3 steps

1: trifluoroacetic acid / iso-butanol / 100 °C

2: platinum(IV) oxide; hydrogen / methanol

3: N-ethyl-N,N-diisopropylamine / dichloromethane

With platinum(IV) oxide; hydrogen; N-ethyl-N,N-diisopropylamine; trifluoroacetic acid; In methanol; dichloromethane; iso-butanol;

DOI:10.1016/j.bmcl.2010.12.036

Reference yield:

2,5-dichloro-4-(3-nitrophenoxy)pyrimidine (76661-24-0) → N-(3-(5-chloro-2-(2-methoxy-4-(4-methylpiperazin-1-yl)phenylamino)pyrimidin-4-yloxy)phenyl)acrylamide (1213269-23-8)

Guidance literature:

Multi-step reaction with 3 steps

1: trifluoroacetic acid / iso-butanol / 100 °C

2: platinum(IV) oxide; hydrogen / methanol

3: N-ethyl-N,N-diisopropylamine / dichloromethane

With platinum(IV) oxide; hydrogen; N-ethyl-N,N-diisopropylamine; trifluoroacetic acid; In methanol; dichloromethane; iso-butanol;

DOI:10.1016/j.bmcl.2010.12.036

upstream raw materials:

4-(3-aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl) pyrimidin-2-amine

acryloyl chloride

2-methoxy-4-(4-methylpiperazin-1-yl)aniline

5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)-4-(3-nitrophenoxy)pyrimidin-2-amine

Downstream raw materials:

N-(3-((5-chloro-2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)oxy)phenyl)-3-(dimethylamino)propanamide

N-(3-((5-chloro-2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)oxy)phenyl)-3-(diethylamino)propanamide

N-(3-((5-chloro-2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)oxy)phenyl)-3-(pyrrolidin-1-yl)propanamide

N-(3-((5-chloro-2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)oxy)phenyl)-3-(piperidin-1-yl)propanamide

Refernces

• 1、 Han, Chun,Wan, Ledong,Ji, Hongbin,Ding, Ke,Huang, Zhangjian,Lai, Yisheng,Peng, Sixun,Zhang, Yihua. "Synthesis and evaluation of 2-anilinopyrimidines bearing 3-aminopropamides as potential epidermal growth factor receptor inhibitors". . p. 75 - 83. Retrieved 2014/04/03.
• 2、 -. "EGFR INHIBITORS AND METHODS OF TREATING DISORDERS". Page/Page column 124-125. . Retrieved 2010/11/18.