Therefore, multiple try-and-error exercises may be needed to find the balance point. The search of analogue routes for step-1a in the benchmark route, see Fig. , can serve as a good demonstration. As shown in Fig. , we purposefully excluded nitrile and hydroxyl groups of the product in step-1a, otherwise the only analogue route shown in the middle of Fig. The last reaction in the proposed route was found during long-range search, see the second route in Fig. in Appendix.