Patent ID: 7605257

Claim:
A process for preparing polyethylene glycol conjugates of a rapamycin immunosuppressive macrolide of the following structure: wherein: R 1 is selected from the group consisting of H, and alkyl, alkenyl, aryl, and arylalkyl; R 2 is selected from the group consisting of H, hydroxyl, and —O-alkyl; R 3 is selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, and —C(O)R 31 ; R 31 is selected from the group consisting of H, alkyl, alkenyl, aryl, and arylalkyl; R 4 is selected from the group consisting of H, hydroxyl, and —O-alkyl; R 5 is selected from the group consisting of H, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyaralkyl, and —C(O)R 51 ; and R 51 is selected from the group consisting of hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, and hydroxyaralkyl; the process comprising: (a) reacting an acylating agent with said rapamycin, said rapamycin being regiospecifically acylated at the 42-position; (b) reacting the acylated macrolide with a methoxy poly(ethylene glycol) derivative or thiol-terminated poly(ethylene glycol) derivative in the presence of a base.