Dimethylformamide → Lenalidomide

HRID 514974

Reaction equation

HRID 514974 reaction equation
[N+:1]([C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH2:6][N:7]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[C:8]2=[O:13])([O-:3])=[O:2].CN(C)C=O>C(O)(C)C.C(O)C.CO>[CH:11]1[CH:10]=[C:9]2[C:8](=[O:13])[N:7]([CH:14]3[C:15](=[O:21])[NH:16][C:17](=[O:20])[CH2:18][CH2:19]3)[CH2:6][C:5]2=[C:4]([NH2:1])[CH:12]=1.[N+:1]([C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH2:6][N:7]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[C:8]2=[O:13])([O-:3])=[O:2]

Participants

7

Reactant 2

HCID 6228DimethylformamideHCID 114717813-(4-Nitro-1-oxo-1,3-dihydroisoindol-2-yl)piperidine-2,6-dione

Product 2

HCID 216326LenalidomideHCID 114717813-(4-Nitro-1-oxo-1,3-dihydroisoindol-2-yl)piperidine-2,6-dione

Reagents, catalysts & solvents 3

HCID 702EthanolSolvent2×HCID 887MethanolSolvent2×HCID 3776IsopropanolSolvent2×

Procedure

By catalytic hydrogenation of 3-(4-nitro-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione in solvents such as dimethylformamide, methanol, ethanol, isopropyl alcohol or mixture of these solvents at temperature 50-100.0° C. under pressure or bubbling of hydrogen gas at atmospheric pressure, then filteration of the catalyst followed by distillation under high vacuum Lenalidomide polymorphic form-I is obtained. The polymorphic form-I of Lenalidomide can also be obtained by transfer hydrogenation of 3-(4-nitro-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione using solvents dimethylformamide, methanol, ethanol, isopropyl alcohol or mixture of these solvents at temperature 50-100.0° C. using ammonium formate or formic acid as source of hydrogen. The precious metal catalysts used in the hydrogenation are Raney Nickel, palladium etc., followed by filteration of catalyst and distillation of the solvent under high vacuum.

Workup

  1. custombubbling of hydrogen gas at atmospheric pressure
  2. distillationfilteration of the catalyst followed by distillation under high vacuum Lenalidomide polymorphic form-I
  3. customis obtained

Sources & evidence

ORD record
ord-6a9a9e78f1a6493eb5710f2cb7cb01be
Source dataset
uspto-grants-2015_08
Patent number
US09108945B2

Linked notes

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