Nintedanib Ethanesulfonate Salt

Base Information

• Chemical Name: Nintedanib Ethanesulfonate Salt
• CAS No.: 656247-18-6
• Molecular Formula: C31H33N5O4.C2H6O3S
• Molecular Weight: 649.768
• Mol file: 656247-18-6.mol

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 Esylate

Chemical Property of Nintedanib Ethanesulfonate Salt

Chemical Property:

• PSA: 160.46000
• LogP: 4.62470
• Storage Temp.: -20°C Freezer
• Solubility.: DMSO (Slightly), Methanol (Slightly)

Purity/Quality:

>95% ^*data from raw suppliers

NintedanibEsylate ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• 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.
• Uses: Nintedanib Esylate is the salt form of Nintedanib, which is angiokinase inhibitor and is used in the treatment of idiopathic pulmonary fibrosis. Also inhibits the process blood vessel formation which may be used to assist in cancer therapy.

Technology Process of Nintedanib Ethanesulfonate Salt

There total 19 articles about Nintedanib Ethanesulfonate Salt 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: 100.0%

nintedanib (656247-17-5,928326-83-4) + ethanesulfonic acid (594-45-6) → methyl (3Z)-3-[({4-[N-methyl-2-(4-methylpiperazin-1-yl)acetamido]phenyl}amino)(phenyl)methylidene]-2-oxo-2,3-dihydro-1H-indole-6-carboxylate ethanesulfonate salt (656247-18-6)

Guidance literature:

In methanol; for 4h; Reflux;

Reference yield:

2-oxo-2,3-dihydro-1H-indole-6-carboxylic acid methyl ester (14192-26-8) → methyl (3Z)-3-[({4-[N-methyl-2-(4-methylpiperazin-1-yl)acetamido]phenyl}amino)(phenyl)methylidene]-2-oxo-2,3-dihydro-1H-indole-6-carboxylate ethanesulfonate salt (656247-18-6)

Guidance literature:

Multi-step reaction with 5 steps

1: toluene; cyclohexane / 6 h / 80 - 90 °C / Inert atmosphere

2: acetic anhydride / toluene / 4 h / Reflux

3: methanol; potassium hydroxide / 3 h / Reflux

4: methanol / N,N-dimethyl-formamide / 5 h / Reflux

5: methanol / 4 h / Reflux

With methanol; acetic anhydride; potassium hydroxide; In methanol; cyclohexane; N,N-dimethyl-formamide; toluene;

Reference yield:

2-chloro-N-methyl-N-(4-nitrophenyl)acetamide (2653-16-9) → methyl (3Z)-3-[({4-[N-methyl-2-(4-methylpiperazin-1-yl)acetamido]phenyl}amino)(phenyl)methylidene]-2-oxo-2,3-dihydro-1H-indole-6-carboxylate ethanesulfonate salt (656247-18-6)

Guidance literature:

Multi-step reaction with 4 steps

1: acetic acid; iron / water / 1.5 h / 20 - 45 °C

2: methanol; N,N-dimethyl-formamide / 12 h / 60 - 65 °C

3: N,N-dimethyl-formamide / 45 - 50 °C

4: isopropyl alcohol; methanol; water / 1 h / 0 - 65 °C

With iron; acetic acid; In methanol; water; N,N-dimethyl-formamide; isopropyl alcohol;

DOI:10.1080/00397911.2017.1297459

upstream raw materials:

nintedanib

ethanesulfonic acid

2-oxo-2,3-dihydro-1H-indole-6-carboxylic acid methyl ester

methyl 1-(2-chloroacetyl)-2-oxoindoline-6-carboxylate

Downstream raw materials:

nintedanib

Refernces

• 1、 -. "Preparation of novel crystal form I of nintedanib ethanesulfonate salt". Paragraph 0028-0029. . Retrieved 2021/06/26.
• 2、 -. "Preparation method of high-purity nintedanib ethanesulfonate". Paragraph 0013; 0057-0199; 0210; 0212-0218; 0225. . Retrieved 2020/11/12.