Basic information Safety Supplier Related
ChemicalBook >  Product Catalog >  Organic Chemistry >  Amides >  Sulfonic acids amino compound >  Nintedanib Ethanesulfonate Salt

Nintedanib Ethanesulfonate Salt

Basic information Safety Supplier Related

Nintedanib Ethanesulfonate Salt Basic information

Product Name:
Nintedanib Ethanesulfonate Salt
Synonyms:
  • (3Z)-2,3-Dihydro-3-[[[4-[methyl[2-(4-methyl-1-piperazinyl)acetyl]amino]phenyl]amino]phenylmethylene]-2-oxo-1H-indole-6-carboxylic acid methyl ester ethanesulfonate
  • Nintedanib ethanesulfonate
  • BIBF 1120 esylate
  • BIBF-1120 esylate
  • Nintedanib esylate
  • BIBF1120/nintedanib ethanesulfonate salt
  • Trinidad Neeb esylate
  • Intedanib ethanesulfonate
CAS:
656247-18-6
MF:
C31H33N5O4.C2H6O3S
MW:
649.75706
Product Categories:
  • API
Mol File:
656247-18-6.mol
More
Less

Nintedanib Ethanesulfonate Salt Chemical Properties

form 
Yellow solid.
More
Less

Nintedanib Ethanesulfonate Salt Usage And Synthesis

Description

Nintedanib esylate is a potent, oral triple angiokinase inhibitor developed by Boehringer Ingelheim that targets proangiogenic and pro-fibrotic pathways mediated by the vascular endothelial growth factor receptor, fibroblast growth factor receptor and plateletderived growth factor receptor families, as well as Src and Flt-3 kinases. It was approved for the treatment of idiopathic pulmonary fibrosis (IPF), a condition in which the lungs become progressively scarred over time, by the US FDA in October 2014 and by the EMA in January 2015. The FDA granted nintedanib esylate fast-track, priority review, orphan product, and breakthrough designations. The drug was also approved by the EMA in November 2014 for treatment of non-small cell lung cancer in combination with docetaxel after first-line chemotherapy.

Definition

ChEBI: An organosulfonate salt obtained by combining nintedanib with one molar equivalent of ethanesulfonic acid. A kinase inhibitor used for the treatment of idiopathic pulmonary fibrosis and cancer.

Chemical Synthesis

The synthesis of indolinone 197 commenced with commercial 4-chloro-3-nitro-benzoic acid (194)—esterification of which preceded displacement of the chloride by dimethyl malonate (195) in the presence of base to generate nitrobenzene 196. Hydrogenation of 196 under acidic conditions furnished 6-methyoxycarbonyl- substituted oxindole 197 by decarboxylative cyclization in 87% yield. Acylation of indolinone 197 with chloroacetic anhydride in refluxing toluene and subsequent condensation with trimethyl orthobenzoate resulted in indolone 198, which was isolated in 86% yield over the two-step sequence. While these two steps could reportedly be combined into a one-pot protocol using acetic anhydride as the solvent, the stepwise procedure was found to be more amenable for large-scale synthesis due to fewer complications with undesired side products. Subjection of 198 to methanolic potassium hydroxide followed by condensation with aniline fragment 199 in refluxing methanol and then exposure to aqueous ethanesulfonic acid in methanol provided nintedanib esylate (XXIII) in 82% over the three-step sequence.
Aniline fragment 199 was prepared in three steps and 82% overall yield via initial acylation of N-methyl-4-nitroaniline 200 with chloro acetylchloride followed by displacement of the a-amidochloride with N-methylpiperazine and hydrogenative reduction of the nitro group gave the desired aniline.183,184

Nintedanib Ethanesulfonate SaltSupplier

Shanghai Jinyin Biological Technology Co., Ltd Gold
Tel
Email
814527417@qq.com
Jinan XuanDe Chemical Co., Ltd. Gold
Tel
0531-88803958-
Email
xuandechem@126.com
Chembest Research Laboratories Limited Gold
Tel
021-20908456-
Email
sales@BioChemBest.com
Wuhu Sumu Pharmaceutical Technology Co., Ltd. Gold
Email
3145613242@qq.com
WuHu Linze pharmaceutical Co.,Ltd. Gold
Tel
Email
2030235803@qq.com