BIBF-1120

Base Information

• Chemical Name: BIBF-1120
• CAS No.: 928326-83-4
• Molecular Formula: C₃₁H₃₃N₅O₄
• Molecular Weight: 539.634
• Mol file: 928326-83-4.mol

Synonyms:Nintedanib;Nintedanib (BIBF 1120);

Chemical Property of BIBF-1120

Chemical Property:

• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.658
• Boiling Point: 742.199 °C at 760 mmHg
• Flash Point: 402.667 °C
• PSA: 94.22000
• Density: 1.284 g/cm³
• LogP: 3.70270

Purity/Quality:

99% ^*data from raw suppliers

BIBF-1120 95.00% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: BIBF 1120 is a triple kinase inhibitor blocking vascular endothelial growth factor receptor, PDGF receptor, and FGF receptor, which has a potential to inhibit tumor growth and pulmonary fibrosis.

Technology Process of BIBF-1120

There total 84 articles about BIBF-1120 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: 98.7%

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) → nintedanib (656247-17-5,928326-83-4)

Guidance literature:

With sodium hydrogencarbonate; In water; ethyl acetate; at 40 ℃; for 1h;

Reference yield: 96.0%

N-[(4-methyl-piperazin-1-yl)methylcarbonyl]-N-methyl-p-phenylendiamine (262368-30-9) + methyl (E)-3-(chloro(phenyl)methylene)-2-oxoindoline-6-carboxylate → nintedanib (656247-17-5,928326-83-4)

Guidance literature:

In N,N-dimethyl-formamide; at 80 ℃; Inert atmosphere;

DOI:10.1002/anie.202103323

Reference yield: 94.6%

N-[(4-methyl-piperazin-1-yl)methylcarbonyl]-N-methyl-p-phenylendiamine (262368-30-9) + (E)-1-acetyl-3-(methoxy-phenyl-methylene)-2-oxo-2,3-dihydro-1H-indole-6-carboxylic acid methyl ester (1168152-07-5) → nintedanib (656247-17-5,928326-83-4)

Guidance literature:

N-[(4-methyl-piperazin-1-yl)methylcarbonyl]-N-methyl-p-phenylendiamine; (E)-1-acetyl-3-(methoxy-phenyl-methylene)-2-oxo-2,3-dihydro-1H-indole-6-carboxylic acid methyl ester; With methanol; In N,N-dimethyl-formamide; at 75 ℃; for 4h; Large scale;

With methanol; potassium hydroxide; In N,N-dimethyl-formamide; Temperature; Large scale;

upstream raw materials:

N-[(4-methyl-piperazin-1-yl)methylcarbonyl]-N-methyl-p-phenylendiamine

methyl 1-acetyl-3-[ethoxy(phenyl)methylidene]-2-oxo-2,3-dihydro-7H-indole-6-carboxylate

(Z)-1-acetyl-3-(ethoxy-phenyl-methylene)-2-oxo-2,3-dihydro-1H-indole-6-carboxylic acid methyl ester

3-[methoxy(phenyl)methylene]-2-oxoindoline-6-carboxylic acid methyl ester

Refernces

• 1、 -. "Refining method of amino intermediate". Paragraph 0059; 0060. . Retrieved 2021/03/03.
• 2、 Bajohr, Jonathan,Lautens, Mark,Mirabi, Bijan,Rodríguez, José F.,Whyte, Andrew,Zhang, Anji. "Cycloisomerization of Carbamoyl Chlorides in Hexafluoroisopropanol: Stereoselective Synthesis of Chlorinated Methylene Oxindoles and Quinolinones". . p. 18478 - 18483. Retrieved 2021/07/19.