Synthesis
The general procedure for the synthesis of tri-tert-butyl 1,3,8,11-tetraazacyclotetradecane-1,4,8-tricarboxylate from 1,4,8,11-tetraazacyclotetradecane (cyclam) and di-tert-butyl dicarbonate was carried out in the following manner: first, the synthesis of tri-tert-butyl 1,3,8,11-tetraazacyclotetradecane-1,4,8-tricarboxylate was carried out according to the methodology reported by Dessolin et al. (J. Dessolin, P. Galea, P. Vlieghe, J. Chermann, J. Kraus, J. Med. Chem. 1999, 42, 229-241) was synthesized with slight modifications. The procedure was as follows: 1,4,8,11-tetraazacyclotetradecane (1.00 g, 5.00 mmol, 1 eq.) was dissolved in ice-cold dichloromethane (100 mL) under ice-bath conditions, followed by the addition of di-tert-butyl dicarbonate (2.0 g, 9.00 mmol, 1.8 eq.). The reaction mixture was stirred overnight. Upon completion of the reaction, the solvent was removed by evaporation to give the crude product as a light yellow oil. The crude product was purified by fast column chromatography (eluent ratio methanol/dichloromethane 5:95). The first fraction collected was the tri-Boc-protected cyclam (1), i.e., the target product 1,3,8,11-tetraazacyclotetradecane-1,4,8-tricarboxylic acid tri-tert-butyl ester in the form of a thick colorless oil (0.75 g, 30% yield). Mass spectrometry (electrospray) analysis showed a molecular ion peak of 523 (M + Na)+.
References
[1] Molecular Pharmaceutics, 2017, vol. 14, # 5, p. 1395 - 1404
[2] Chemistry (Weinheim an der Bergstrasse, Germany), 2002, vol. 8, # 21, p. 4965 - 4972
[3] Journal of the American Chemical Society, 2006, vol. 128, # 45, p. 14448 - 14449
[4] Chemical Communications, 2018, vol. 54, # 33, p. 4116 - 4119
[5] Bulletin de la Societe Chimique de France, 1996, vol. 133, # 1, p. 65 - 73
