Sunitinib , synthesis

In summary, sunitinib maleate (1) is a multitargeted receptor tyrosine kinase inhibitor with potent anti-angiogenic and antitumor activity. It is approved for the treatment of advanced renal cell carcinoma and gastrointestinal stromal tumors, and is currently undergoing clinical trials for a number of additional malignancies. The discovery synthesis of 1 along with its process development approaches were described in this chapter. 

The free-base form of sunitinib malate (2) contains a highly substituted pyrrole core bearing an amide side chain at the 3-position and an indolinone substituent at the 5-position. Two routes were originally evaluated for the synthesis of free base 2. These were the early and late amidation routes. In the early amidation route, the pyrrole core is assembled after the amide side chain is installed, and the late amidation route involves amidation after the pyrrole core is assembled. These two approaches are depicted in Figure 4.2. 

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