AZ20

Base Information

• Chemical Name: AZ20
• CAS No.: 1233339-22-4
• Molecular Formula: C21H24N4O3S
• Molecular Weight: 412.51
• Mol file: 1233339-22-4.mol

Synonyms:AZ20;CS-1335;AZ-20; AZ 20;;AZ20 USP/EP/BP;(3R)-4-[2-(3H-indol-4-yl)-6-(1-methylsulfonylcyclopropyl)pyrimidin-4-yl]-3-methylmorpholine;(R)-4-(2-(1H-Indol-4-yl)-6-(1-(methylsulfonyl)cyclopropyl)pyrimidin-4-yl)-3-methylmorpholine;4-[4-(1-Methanesulfonylcyclopropyl)-6-[(3R)-3-methylmorpholin-4-yl]pyrimidin-2-yl]-1H-indole;4-[4-[(3R)-3-Methyl-4-morpholinyl]-6-[1-(methylsulfonyl)cyclopropyl]-2-pyrimidinyl]-1H-indole;1H-Indole, 4-[4-[(3R)-3-methyl-4-morpholinyl]-6-[1-(methylsulfonyl)cyclopropyl]-2-pyrimidinyl]-;4-[4-[(3R)-3-Methyl-4-morpholinyl]-6-[1-(methylsulfonyl)cyclopropyl]-2-pyrimidinyl]-1H-indole AZ20

Chemical Property of AZ20

Chemical Property:

• Boiling Point: 634.6±55.0 °C(Predicted)
• PKA: 15.65±0.30(Predicted)
• PSA: 93.13000
• Density: 1.42±0.1 g/cm3(Predicted)
• LogP: 3.24220
• Storage Temp.: -20°
• Solubility.: Soluble in DMSO (up to 20 mg/ml).

Purity/Quality:

98%,99%, ^*data from raw suppliers

AZ20 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: AZ20 (1233339-22-4) is a potent and highly selective inhibitor of Ataxia telangiectasia mutated and RAD3-related (ATR) kinase (IC50?= 5 nM in vitro; IC50?= 50 nM in HT29 colorectal adenocarcinoma cells).1?Combination therapy with AZ20 and gemcitabine resulted in synergistic inhibition of tumor cell growth and cell death initiation in pancreatic cancer cell lines.2
• Uses: AZ20 is a potent and selective inhibitor of ATR (ATM-Rad3-related) kinase with in vivo antitumor activity.

Technology Process of AZ20

There total 11 articles about AZ20 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: 64.0%

(3R)-4-[2-chloro-6-(1-methanesulfonylcyclopropyl)pyrimidin-4-yl]-3-methylmorpholine (1233339-68-8) + (1H-indo-4-yl)boronic acid → AZ20 (1233339-22-4)

Guidance literature:

With potassium phosphate; methanesulfonic acid(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II); In 1,2-dimethoxyethane; water; at 70 ℃; for 20h; Inert atmosphere;

DOI:10.1016/j.chempr.2018.02.002

Reference yield: 51.0%

(3R)-4-[2-chloro-6-(1-methanesulfonylcyclopropyl)pyrimidin-4-yl]-3-methylmorpholine (1233339-68-8) + indole-4-boronic acid (220465-43-0) → AZ20 (1233339-22-4)

Guidance literature:

With sodium carbonate; bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; water; at 90 ℃;

Reference yield:

(R)-4-(2-chloro-6-(methylsulfonylmethyl)pyrimidin-4-yl)-3-methylmorpholine (1233339-73-5) → AZ20 (1233339-22-4)

Guidance literature:

Multi-step reaction with 2 steps

1: sodium hydroxide; tetrabutylammomium bromide / water; toluene / 3 h / 60 °C / Inert atmosphere

2: bis-triphenylphosphine-palladium(II) chloride; sodium carbonate / 1,2-dimethoxyethane; water / 90 °C / Inert atmosphere

With bis-triphenylphosphine-palladium(II) chloride; tetrabutylammomium bromide; sodium carbonate; sodium hydroxide; In 1,2-dimethoxyethane; water; toluene; 2: |Suzuki Coupling;

DOI:10.1021/jm301859s

upstream raw materials:

(3R)-4-[2-chloro-6-(1-methanesulfonylcyclopropyl)pyrimidin-4-yl]-3-methylmorpholine

indole-4-boronic acid

[2-chloro-6-[(3R)-3-methylmorpholin-4-yl]pyrimidin-4-yl]methyl methanesulfonate

2,6-dichloropyrimidine-4-carboxylic acid methyl ester

Refernces

• 1、 Foote, Kevin M.,Blades, Kevin,Cronin, Anna,Fillery, Shaun,Guichard, Sylvie S.,Hassall, Lorraine,Hickson, Ian,Jacq, Xavier,Jewsbury, Philip J.,McGuire, Thomas M.,Nissink, J. Willem M.,Odedra, Rajesh,Page, Ken,Perkins, Paula,Suleman, Abid,Tam, Kin,Thommes, Pia,Broadhurst, Rebecca,Wood, Christine. "Discovery of 4-{4-[(3R)-3-methylmorpholin-4-yl]-6-[1-(methylsulfonyl) cyclopropyl]pyrimidin-2-yl}-1H-indole (AZ20): A potent and selective inhibitor of ATR protein kinase with monotherapy in vivo antitumor activity". . p. 2125 - 2138. Retrieved 2013/05/09.