1196531-35-7

Upstream product

• 96-30-0 chloroacetylmethylamide 
• 1196531-36-8 4-methoxy-3-(4-piperidyloxy)benzonitrile hydrochloride 
• 5415-94-1 2-hydroxy-N-methylacetamide 
• 141699-59-4 1-(tert-butoxycarbonyl)piperidin-4-yl methanesulfonate 
• 1196531-33-5 tert-butyl 4-(5-cyano-2-methoxy-phenoxy)piperidine-1-carboxylate 
• 52805-46-6 2-methoxy-5-cyanophenol 

Downstream Products

• 1196531-37-9 2-[4-(5-cyano-2-methoxy-4-nitro-phenoxy)-1-piperidyl]-N-methylacetamide 
• 848942-61-0 Sapitinib 

Relevant academic research and scientific papers

The Development of a Dimroth Rearrangement Route to AZD8931

Recently, the aminoquinazoline motif has been highly prevalent in anticancer pharmaceutical compounds. Synthetic methods are required to make this structure on a multikilo scale and in high purity. The initial route to aminoquinazoline AZD8931 suffered from the formation of late-stage impurities. To avoid these impurities, a new high-yielding Dimroth rearrangement approach to the aminoquinazoline core of AZD8931 was developed. Assessment of route options on a gram scale demonstrated that the Dimroth rearrangement is a viable approach. The processes were then evolved for large-scale production with learning from a kilo campaign and two plant-scale manufactures. Identification of key process impurities offers an insight into the mechanisms of the Dimroth rearrangement as well as the hydrogenation of a key intermediate. The final processes were operated on a 30 kg scale delivering the target AZD8931 in 41% overall yield.

A Survey of the Borrowing Hydrogen Approach to the Synthesis of some Pharmaceutically Relevant Intermediates

The use of the "borrowing hydrogen strategy" in the synthesis of a number of typical pharmaceutical intermediates has been investigated. The main aim of this work was to investigate the scope and limitations of current methodology using standard laboratory techniques in an industrial context. Some interesting and significant results were achieved across a diverse set of complex substrates; however several drawbacks with this approach were identified, such as the high loading, poor turnover, and susceptibility to substrate inactivation of the catalysts. These are areas which are highlighted for future investigation and improvements.

PROCESS 738

Processes for the preparation of 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[1-(N- methylcarbamoylmethyl)piperidin-4-yl]oxy}quinazoline, salts thereof, and the intermediates used in the process are described.

NOVEL SALT-554

4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[1-(N-methylcarbamoylmethyl)piperidin-4-yl]oxy}quinazoline difumarate, pharmaceutical compositions containing the difumarate, the use of the difumarate in the treatment of hyperproliferative disorders such as canc