The precursor used for this conversion was obtained from the reaction: https://www.chemotion-repository.net/pid/13200 [Dimethylamino(triazolo[4,5-b]pyridin-3-yloxy)methylidene]-dimethylazanium hexafluorophosphate (HATU) (0.75 equiv) was dissolved in 40 mL DMF. In parallel, the linear precursor (2S)-2-((2S)-2-((2R)-1-((2S)-2-amino-3-methylpentanoyl)pyrrolidine-2-carboxamido)-5-(tert-butoxy)-5-oxopentanamido)-3-(4-(tert-butoxy)phenyl)propanoic acid (63.3 mg, 100 μmol, 1.00 equiv) was dissolved in 20 mL of DMF and N-ethyl-N-propan-2-ylpropan-2-amine (19.4 mg, 26.1 μL, 150 μmol, 1.50 equiv) was added. 10 mL of this mixture were added to the HATU solution over a period of 6 h at 21 °C. Afterwards, additional 0.75 equiv. of HATU were added to the reaction mixture in one portion. The remaining 10 mL of the linear precursor mixture were added over another period of 6 h. The reaction was stirred for 12 h and the solvent was removed under reduced pressure. The crude macrocycle tert-butyl 3-((3S,6S,9S,14aR)-6-(4-(tert-butoxy)benzyl)-9-(sec-butyl)-1,4,7,10-tetraoxotetradecahydropyrrolo[1,2-a][1,4,7,10]tetraazacyclododecin-3-yl)propanoate (33.0 mg, 53.7 μmol) was obtained in 54% yield and was deprotected in a further step without purification (see: https://www.chemotion-repository.net/pid/12182).
