Process
AssigneeGenerics [UK] Limited
InventorsVinayak Govind Gore, Vinay Kumar Shukla, Sheryas Bhandari, Suresh Hasbe
Life of this patent
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Abstract
The present invention relates to improved processes for preparing 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione (I) (lenalidomide) and its intermediate 3-(1-oxo-4-nitro-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione. The present invention further relates to improved processes for preparing lenalidomide crystalline form A, use of said crystalline form A as an active pharmaceutical ingredient or as an intermediate in the preparation of further crystalline or amorphous forms of lenalidomide, compositions comprising lenalidomide crystalline form A and their use in the treatment of disease.
Claims40
-80. (canceled)
A process for the preparation of lenalidomide, comprising the catalytic reduction of 3-(1-oxo-4-nitro-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione, comprising:
- (i) mixing the 3-(1-oxo-4-nitro-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione in a solvent system;
- (ii) contacting the resulting mixture from step (i) with a catalyst;
- and
- (iii) contacting the mixture from step (ii) with hydrogen;
- characterised in that the solvent system comprises a mixture of polar solvents.
Lenalidomide having a chemical purity of greater than about 99.5% as measured by HPLC.
A process for the preparation of 3-(1-oxo-4-nitro-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione comprising reacting 3-amino-piperidine-2,6-dione hydrochloride and methyl 2-halomethyl-3-nitro-benzoate in a solvent system, characterised in that the reaction occurs at less than about 60° C.
3-(1-Oxo-4-nitro-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione having a chemical purity of greater than about 99.5% as measured by HPLC.
A process for the preparation of lenalidomide crystalline form A, comprising crystallising lenalidomide from a solvent system comprising a straight or branched chain aliphatic alcohol with 1 to 5 carbon atoms and an aliphatic ester having formula RCOOR′, wherein R comprises 1 to 4 straight or branched chain carbon atoms and R′ comprises 1 to 5 straight or branched chain carbon atoms.
Lenalidomide crystalline form A having a polymorphic purity of greater than about 90%.
Dependencies are inferred from the claim text.