Process for the manufacture of (E)-4-N,N-dialkylamino crotonic acid in HX salt form and use thereof for synthesis of EGFR tyrosine kinase inhibitors

US9242965B2 · kind B2 · utility

Assignee

• Boehringer Ingelheim International GmbH · DE

Inventors

• Juncheng Zheng · Shanghai, CN
• Da Deng · Detroit, US
• Guanghua Lv · Shanghai, CN
• Jun Yan · Newark, US
• Joerg Brandenburg · Ingelheim am Rhein, DE
• Jutta Kroeber · Bingen, DE
• Ulrich Scholz · Bad Hersfeld, DE

Key dates

• Filing date: Dec 19, 2014
• Grant date: Jan 26, 2016
• Expiry date: Dec 19, 2034

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07C227/18
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

The present invention is directed to an efficient process for the manufacture of (E)-4-N,N-dialkylamino crotonic acid in HX salt form of formula Iwherein R1 and R2 independently denote C1-3-alkyl groups and X− denotes an acid anion, such as the chloride, bromide, tosylate, mesylate or trifluoroacetate anion, with high quality, and a process for synthesis of EGFR tyrosine kinase inhibitors with heterocyclic quinazoline, quinoline or pyrimidopyrimidine core structure, using the acid addition salt I and activated derivatives thereof as intermediates.