Development of a Practical and Scalable Synthesis of the Side Chain for ASP9726, a Successor of Micafungin

Abstract

Here, we describe a practical and scalable synthesis of 1, which is a useful side chain of ASP9726 (2), a successor of Micafungin. For large-scale synthesis of 1, reaction conditions were optimized to control impurities and increase yield. In particular, we utilized a high-yield thiadiazole ring formation to prepare thiadiazole 12, a step which was improved by optimization of reaction conditions and isolation method. Further, the number of steps was reduced from 10 to 9, and hazardous reactions were also avoided. Consequently, this process was scaled to produce 21.7 kg of 1 with overall yield improvement from 36.7% to 56.6%.