HCID 73297121, compound → Iberdomide

HRID 626325Notes

Reaction equation

HRID 626325 reaction equation
O.[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:34]=[CH:33][C:12]([CH2:13][O:14][C:15]3[CH:23]=[CH:22][CH:21]=[C:20]4[C:16]=3[CH2:17][N:18]([C@H:25]3[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]3=[O:32])[C:19]4=[O:24])=[CH:11][CH:10]=2)[CH2:4][CH2:3]1>C1COCC1>[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:34]=[CH:33][C:12]([CH2:13][O:14][C:15]3[CH:23]=[CH:22][CH:21]=[C:20]4[C:16]=3[CH2:17][N:18]([C@H:25]3[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]3=[O:32])[C:19]4=[O:24])=[CH:11][CH:10]=2)[CH2:4][CH2:3]1

Participants

3

Reactant 1

HCID 73297121HCID 73297121, compound

Product 1

HCID 67335295Iberdomide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  1. customat 22° C.

Sources & evidence

ORD record
ord-331d320561614a3281f5a718923a7c2b
Source dataset
uspto-grants-2016_04
Patent number
US09309220B2

Reaction notes

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