HCID 73297121, compound → Iberdomide

Participants

Reaction Steps

Initially the eeeu was evaluated using (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione freebase and its corresponding anhydrous freebase racemic compound in acetonitrile at 22° C., and was found to be was unfavorably high (94.7%). A hydrated form of (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione freebase was subsequently obtained, and the eeeu of the (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrate with its corresponding hydrate racemic compound at 22° C. remained unfavorably high (89.2%). A THF solvate of (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione was also obtained, and the eeeu of the solvate with its corresponding anhydrate racemic compound at 22° C. was improved (68.5%). However, a THF solvate of (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione is not a suitable drug substance due to the toxicity of THF, and so an alternative approach was sought.

Provenance & Evidence