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The Discovery and Development of a Safe, Practical Synthesis of ABT-869

2009; American Chemical Society; Volume: 13; Issue: 6 Linguagem: Inglês

10.1021/op900208y

1520-586X

Albert W. Kruger, Michael J. Rozema, Alexander Chu-Kung, Jorge Gandarilla, Anthony R. Haight, Brian Kotecki, Steven M. Richter, Albert M. Schwartz, Zhe Wang,

Synthetic Organic Chemistry Methods

The discovery, development and implementation of two chemical routes to ABT-869 is reported. Optimization of the first-generation heterocycle formation and Suzuki coupling is briefly described. Key features of the second-generation synthesis include the development of a safe hydrazine condensation by utilizing an inorganic base to increase the onset temperature of exothermic decomposition. The second-generation Suzuki reaction is discussed in detail, culminating in the use of an oxygen monitor as a PAT to maximize reproducibility on scale.