791602-75-0

Usage

Uses

Used in Pharmaceutical Industry:
4-Chloro-5,7-difluoroquinazoline is used as a key intermediate in the synthesis of (anilino)quinazoline derivatives, which are known as EGFR tyrosine kinase inhibitors. These inhibitors play a crucial role in the treatment of various types of cancer by targeting and inhibiting the epidermal growth factor receptor (EGFR), a protein that is often overexpressed in cancer cells, leading to uncontrolled cell growth and tumor formation. By inhibiting EGFR, these derivatives can effectively slow down or stop the growth and progression of cancer cells, making them valuable in the development of targeted cancer therapies.

Upstream product

• 379228-58-7 5,7-difluoroquinazolin-4(3H)-one 

Downstream Products

• 791602-76-1 N-(3-chloro-4-fluorophenyl)-5,7-difluoro-quinazolin-4-amine 
• 379230-38-3 7-fluoro-N-(5-chloro-1,3-benzodioxol-4-yl)-5-(tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine 
• 893428-67-6 C₂₀H₂₈N₄O₄ 

Relevant academic research and scientific papers

POCl3 Chlorination of 4-Quinazolones

The reaction of quinazolones with POCl3 to form the corresponding chloroquinazolines occurs in two distinct stages, which can be separated through appropriate temperature control. An initial phosphorylation reaction occurs readily under basic conditions (R3N, aq pK a > 9) at t 3 addition. Clean turnover of phosphorylated quinazolones to the corresponding chloroquinazoline is then achieved by heating to 70-90 C. (N)- and (O)-phosphorylated intermediates, involving multiple substitution at phosphorus, have been identified and their reactions monitored using a combination of 1H, 31P, and 19F NMR. Kinetic analysis of the reaction profiles suggest that the various intermediates react with both Cl- and Cl2P(O)O-, but product formation arises exclusively from reaction of (O)-phosphorylated intermediates with Cl-. (O)- and (N)-phosphorylated intermediates equilibrate rapidly on the time scale of the reaction. A minimum of 1 molar equiv of POCl3 is required for efficient conversion of the intermediates to product.

A simplified process for the manufacture of AZD0530, a potent SRC kinase inhibitor

An efficient process for the manufacture of AZD0530 1, a potent SRC kinase inhibitor, has been developed. The key transformation, reaction of monofluoroanilide 7 with alcohol 8, was much simplified between manufacturing campaigns. The development of a robust, efficient, and scalable process for this transformation drew on both a practical and theoretical understanding of the process and is described herein

CHEMICAL PROCESS

The present invention relates to chemical processes useful in the manufacture of the compound 4-(6-chloro-2,3-methylenedioxyanilino)-7-[2-(4-methylpiperazin-1-yl)ethoxy]- 5-tetrahydropyran-4-yloxyquinazoline (the active entity within AZD0530), to intermed

QUINAZOLINE DERIVATIVES AND THEIR USE IN THE TREATMENT OF CANCER

The invention concerns quinazoline derivatives of the formula: (I); wherein X1, Q1, Z, R1, R2, Y, a and m are as defined in the description, which are erbB tyrosine kinase inhibitors, particularly EGFR tyrosine