To reveal the advantages and drawbacks of the developed mechanochemical synthesis, the first-pass green chemistry metrics were assessed using the CHEM21 toolkit (Table ). To perform a reliable comparison with the solution-based approaches, we selected the known synthetic routes that rely on the same retrosynthetic disconnection and start from the same building blocks 1, 4, and 7 (Scheme 3). Among them, the shortest route for which the complete data were available for the calculations 91 was an early-stage development described by Liu et al. and an example of kilo-scale preparation patented by Natco Pharma Ltd. Activation of hydroxy acid 1 by its conversion to the corresponding chloride via reaction with SOCl2 was used in both approaches as an additional non-constructive step. a Extended data and calculations for similar routes, for which full experimental details are unavailable are also shown in the ESI (Table ). b The yield is adjusted considering the HPLC purity (95%) of the obtained product. c TMU = tetramethyl urea.