This research presents a comprehensive study on the synthesis of py2-macrodipa, a second-generation ligand of the alpha therapy chelator macropa, and explores alternative approaches for its large-scale production. Key challenges in the original synthesis, like a problematic debenzylation step and challenging purification were addressed, with a focus on synthesizing the essential intermediate, bis-N-boc-protected diamine. A promising method involved the double tosylation of pyridine-2,6-diyldimethanol, yielding the critical intermediate. Various alternative routes were considered, including O-alkylation and dibromide-based approaches for generating the precursor. Additionally, the synthesis of the picolinate arm, a step necessary for the synthesis of this ligand, was outlined. Several methods for the preparation of macrocyclic derivative py2-macrodipa precursor with two ester groups were proposed. The study additionally aimed to compare these alternative approaches to the previously established method. The double tosylation of pyridine-2,6-diyldimethanol successfully yielded the desired compound after purification. These alternative synthetic routes offer potential solutions to earlier challenges, such as the prolonged reaction time, low yields, and poor purities of the products, opening new avenues for macrocyclic derivative synthesis. Further refinement and evaluation of these methods are required for the optimization of the reaction conditions for the large-scale cost-efficient synthesis of chelating agents.The synthesis began with the preparation of N-Boc aminoethanol and its subsequent reaction with bis-mesylate. An optimized approach resulted in better yield and purity compared to the prior synthetic methods to access this ligand. The key precursor, 2,6-bis(2-aminoethyl)pyridine, was synthesized and reacted with 2,6-diformylpyridine in the presence of Gd(ClO4)3. However, the desired macrocyclic derivative was not obtained using this method. An alternative approach used 2,6-pyridinedicarboxylic acid, leading to a successful synthesis of the target macrocyclic amide. The second part of the work focused on preparing the picolinate arm, a bromomethyl-substituted pyridine carboxylate essential for the macrocycle synthesis. This process involved a NaBH4-mediated monoreduction and subsequent deoxybromination reaction, yielding the desired compound. These steps represent critical progress in obtaining intermediates and precursor materials for the macrocycle synthesis, laying the foundation for further investigations and coordination with the picolinate arm.