4-Amino-5-fluoro-3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]quinolin-2(1H)-one

Base Information

• Chemical Name: 4-Amino-5-fluoro-3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]quinolin-2(1H)-one
• CAS No.: 405169-16-6
• Molecular Formula: C21H21 F N6 O
• Molecular Weight: 392.42900
• Mol file: 405169-16-6.mol

Synonyms:2(1H)-Quinolinone,4-amino-5-fluoro-3-[5-(4-methyl-1-piperazinyl)-1H-benzimidazol-2-yl]- (9CI);4-Amino-5-fluoro-3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]quinolin-2(1H)-one;Dovitinib

Chemical Property of 4-Amino-5-fluoro-3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]quinolin-2(1H)-one

Chemical Property:

• PKA: 9.44±0.70(Predicted)
• PSA: 94.04000
• Density: 1.386
• LogP: 3.12860
• Storage Temp.: -20°
• Solubility.: Soluble in DMSO (up to 30 mg/ml).

Purity/Quality:

99% ^*data from raw suppliers

4-AMINO-5-FLUORO-3-[5-(4-METHYLPIPERAZIN-1-YL)-1H-BENZIMIDAZOL-2-YL]QUINOLIN-2(1H)-ONE 95 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: Dovitinib (405169-16-6) is a potent kinase inhibitor. Inhibits FLT3 (IC50 = 1 nM), c-KIT (IC50 = 2 nM), FGFR (IC50 = 8 nM), VEGFR1/2/3 (IC50 = 10 nM), PDGFRβ (IC50 = 27 nM), and CSF-1R (IC50 = 36 nM).1 Active in cell culture and in whole animals. Dovitinib selectively blocks the growth B9 cells transformed by wild type, or activated mutant FGFR3. Induces apoptosis, or sensitizes cells to induction of apoptosis by other means in a variety of cancer cell lines.
• Uses: Compound used in treating melanoma Dovitinib (TKI258, CHIR-258) is a multitargeted tyrosine kinase inhibitor of FLT3 and c-KIT with IC50 of 1 nM and 2 nM, respectively. Dovitinib (TKI258, CHIR258) is a novel multi-target inhibitor for Flt3, c-Kit, FGFR1/3, VEGFR1/2/3, PDGFRα/β with IC50 of 1 nM, 2 nM, 8 nM/9 nM and 10 nM/13 nM/8 nM, 210 nM/27 nM respectively. Dovitinib is a receptor tyrosine kinase inhibitor that targets vascular endothelial growth factor-2, basic fibroblast growth factor-1, and platelet-derived growth factor β receptors (IC50s = 65, 11, and 5 nM, respectively). At 0.04 μM, dovitinib can inhibit endothelial cell proliferation and motility. These antiangiogenic effects have been proposed to be the mechanism by which dovitinib inhibits hepatocellular carcinoma growth and metastasis. Dovitinib has been evaluated in clinical trials for the treatment of advanced solid tumors.

Technology Process of 4-Amino-5-fluoro-3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]quinolin-2(1H)-one

There total 15 articles about 4-Amino-5-fluoro-3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]quinolin-2(1H)-one 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: 88.4%

[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]acetic acid ethyl ester (402948-37-2) + 2-amino-6-fluorobenzonitrile (77326-36-4) → 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one (405169-16-6,804551-71-1)

Guidance literature:

[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]acetic acid ethyl ester; 2-amino-6-fluorobenzonitrile; In toluene; at 20 - 65 ℃; for 2h; Inert atmosphere;

With potassium tert-butylate; In toluene; at 50 ℃; for 2h; Temperature;

Reference yield: 60.0%

ethyl 2-[5-(4-methylpiperazinyl)benzimidazol-2-yl]acetate + 2-amino-6-fluorobenzonitrile (77326-36-4) → 4-amino-5-fluoro-3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]quinolin-2(1H)-one (405169-16-6)

Guidance literature:

With lithium hexamethyldisilazane; In tetrahydrofuran; at 20 ℃; for 5h;

DOI:10.1021/jm800790t

Reference yield: 60.0%

ethyl 2-[5-(4-methylpiperazinyl)benzimidazol-2-yl]acetate + 2-amino-6-fluorobenzonitrile (77326-36-4) → 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one (405169-16-6,804551-71-1)

Guidance literature:

With lithium hexamethyldisilazane; In tetrahydrofuran;

DOI:10.1016/j.tetlet.2005.11.113

upstream raw materials:

2-amino-6-fluorobenzonitrile

[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]acetic acid ethyl ester

1-methyl-piperazine

5-chloro-2-nitroaniline

Downstream raw materials:

4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one DL-lactic acid salt

Refernces

• 1、 -. "Method for preparing dovitinib intermediate with microchannel reaction device". Paragraph 0032; 0045-0048-0051-0052; 0055-0056; 0059. . Retrieved 2018/10/19.
• 2、 Renhowe, Paul A.,Pecchi, Sabina,Shafer, Cynthia M.,Machajewski, Timothy D.,Jazan, Elisa M.,Taylor, Clarke,Antonios-McCrea, William,McBride, Christopher M.,Frazier, Kelly,Wiesmann, Marion,Lapointe, Gena R.,Feucht, Paul H.,Warne, Robert L.,Heise, Carla C.,Menezes, Daniel,Aardalen, Kimberly,Ye, Helen,He, Molly,Le, Vincent,Vora, Jayesh,Jansen, Johanna M.,Wernette-Hammond, Mary Ellen,Harris, Alex L.. "Design, structure-activity relationships and in vivo characterization of 4-Amino-3-benzimidazol-2-ylhydroquinolin-2-ones: Novel class of receptor tyrosine kinase inhibitors". experimental part. p. 278 - 292. Retrieved 2009/10/17.