In conclusion, the synthesis of a highly soluble porous organic cage, CC21, has been achieved through the introduction of additional amines during the cage self-assembly. Investigation of the prominent reaction intermediates and of control reactions found that cage formation was inhibited by the preferred formation of aminal-based species. Computational analysis of these intermediates for four diamines (DMHDA and three cage-forming diamines) found similar qualitative trends in formation energies toward cage formation. However, where possible, the aminal species was found to be more stable than the imine species. We show that DMHDA favours conformations more amenable to aminal formation than the three other diamines. Therefore, we suggest a stronger preference for forming the aminal species for DMHDA compared to the other diamines, which hinders cage formation. From this, we explored reaction conditions and the use of an additional mono-amine to optimise the cageformation reaction, which demonstrated the importance of balancing transamination towards the desired cage species with the formation of distinct self-assembled species containing both DMHDA and the additional amine.