1401034-46-5Relevant articles and documents
Multi-kilo delivery of AMG 925 featuring a buchwald-hartwig amination and processing with insoluble synthetic intermediates
Affouard, Caroline,Crockett, Richard D.,Diker, Khalid,Farrell, Robert P.,Gorins, Gilles,Huckins, John R.,Caille, Seb
, p. 476 - 485 (2015/04/14)
The development of a synthetic route to manufacture the drug candidate AMG 925 on kilogram scale is reported herein. The hydrochloride salt of AMG 925 was prepared in 23% overall yield over eight steps from commercially available raw materials, and more than 8 kg of the target molecule were delivered. The synthetic route features a Buchwald-Hartwig amination using BrettPhos as ligand and conducted to afford 12 kg of product in a single batch. In addition, this work highlights the challenges associated with the use of poorly soluble process intermediates in the manufacture of active pharmaceutical ingredients. Creative solutions had to be devised to conduct seemingly routine activities such as salt removal, pH adjustment, and heavy metal scavenging due to the low solubility of the process intermediates. Finally, a slurry-to-slurry amidation protocol was optimized to allow for successful scale-up.
FUSED TRICYCLIC DUAL INHIBITORS OF CDK 4/6 AND FLT3
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, (2012/10/08)
Compounds of Formula I are useful inhibitors of CDK 4, CDK6, and FLT3. Such compounds are useful in treating cancer and various other disease conditions. Compounds of Formula I have the following structure: where R1 is a group of Formula IA, Formula IB, Formula IC, or Formula ID and the definitions of the other variables are provided herein.