A concise synthesis of quinazolinone TGF-β RI inhibitor through one-pot three-component Suzuki-Miyaura/etherification and imidate-amide rearrangement reactions

A simple and efficient synthesis of dihydropyrrolopyrazole boronic acid intermediate (5) has been developed. Utilization of a three-component Suzuki-Miyaura/etherification with microwave heating led to advanced compound 11 in high yield and with easy purification. Reaction of compound 11 with methanesulfonyl chloride at room temperature furnished the 1,3 O-N rearranged product (12), which is postulated to proceed via an intramolecular mechanism. The outlined synthesis provides a highly efficient and high-yielding route that is amenable to rapid analog synthesis.