BAY 80-6946 (Copanlisib)

Base Information

• Chemical Name: BAY 80-6946 (Copanlisib)
• CAS No.: 1032568-63-0
• Molecular Formula: C23H28N8O4
• Molecular Weight: 480.52
• Mol file: 1032568-63-0.mol

Synonyms:BAY 80-6946

Chemical Property of BAY 80-6946 (Copanlisib)

Chemical Property:

• PKA: 8.42±0.20(Predicted)
• PSA: 146.23000
• Density: 1.51
• LogP: 0.37240
• Solubility.: insoluble in DMSO; insoluble in H2O; insoluble in EtOH

Purity/Quality:

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

BAY80-6946 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Uses: BAY 80-6946 is a highly selective intravenous PI3K inhibitor with potent p110α and p110δ activities in tumor cell lines and xenograft models.

Technology Process of BAY 80-6946 (Copanlisib)

There total 19 articles about BAY 80-6946 (Copanlisib) 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: 96.0%

2-amino-pyrimidine-5-carboxylic acid (3167-50-8) + 7-methoxy-8-[3-(morpholin-4-yl)propoxy]-2,3-dihydroimidazo[1,2-c]quinazolin-5-amine (1032570-74-3) → copanlisib (1032568-63-0)

Guidance literature:

With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20 ℃; for 17h; Large scale;

Reference yield: 64.6%

N-[7-(3-morpholin-4-ylpropoxy)-8-methoxyquinazoline-4(3H)-one-2-yl]-2-amino-5-pyrimidinecarboxamide + 2-chloroethanamine hydrochloride (870-24-6) → copanlisib (1032568-63-0)

Guidance literature:

N-[7-(3-morpholin-4-ylpropoxy)-8-methoxyquinazoline-4(3H)-one-2-yl]-2-amino-5-pyrimidinecarboxamide; With trichlorophosphate; at 80 ℃; Inert atmosphere;

2-chloroethanamine hydrochloride; at 80 - 90 ℃; Inert atmosphere;

Reference yield:

vanillin acetate (881-68-5) → copanlisib (1032568-63-0)

Guidance literature:

Multi-step reaction with 8 steps

1.1: nitric acid; sulfuric acid / dichloromethane; water / 12 h / 3 - 5 °C / Flow reactor; Large scale

1.2: 3 h / 30 °C / Large scale

2.1: potassium carbonate / N,N-dimethyl-formamide / 0.25 h / 25 - 30 °C

2.2: 2 h / 30 °C

3.1: dichloromethane / 1 h / 20 °C / Large scale

3.2: 1.5 h / 22 - 25 °C / Large scale

4.1: ; hydrogen / tetrahydrofuran / 0.5 h / 45 °C / 2250.23 Torr

5.1: triethylamine / dichloromethane / 0.25 h / 5 °C / Large scale

5.2: 2 h / 5 - 22 °C / Large scale

6.1: hydrogen; 5%-palladium/activated carbon / water; N,N-dimethyl-formamide / 18 h / 60 °C / 2250.23 Torr / Large scale

7.1: water; N,N-dimethyl-formamide / 5 h / 90 °C / Large scale

8.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 17 h / 20 °C / Large scale

With sulfuric acid; 5%-palladium/activated carbon; hydrogen; nitric acid; potassium carbonate; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In tetrahydrofuran; dichloromethane; water; N,N-dimethyl-formamide;

upstream raw materials:

2-amino-pyrimidine-5-carboxylic acid

7-methoxy-8-[3-(morpholin-4-yl)propoxy]-2,3-dihydroimidazo[1,2-c]quinazolin-5-amine

4-(benzyloxy)-3-methoxy-2-nitrobenzaldehyde

3-(benzyloxy)-6-(4,5-dihydro-1H-imidazol-2-yl)-2-methoxyaniline

Refernces

• 1、 -. "SYNTHESIS OF COPANLISIB AND ITS DIHYDROCHLORIDE SALT". Page/Page column 55. . Retrieved 2016/06/01.
• 2、 Scott, William J.,Hentemann, Martin F.,Rowley, R. Bruce,Bull, Cathy O.,Jenkins, Susan,Bullion, Ann M.,Johnson, Jeffrey,Redman, Anikó,Robbins, Arthur H.,Esler, William,Fracasso, R. Paul,Garrison, Timothy,Hamilton, Mark,Michels, Martin,Wood, Jill E.,Wilkie, Dean P.,Xiao, Hong,Levy, Joan,Stasik, Enrico,Liu, Ningshu,Schaefer, Martina,Brands, Michael,Lefranc, Julien. "Discovery and SAR of Novel 2,3-Dihydroimidazo[1,2-c]quinazoline PI3K Inhibitors: Identification of Copanlisib (BAY 80-6946)". . p. 1517 - 1530. Retrieved 2016/08/27.