Dimethylformamide → Nilotinib L-tartrate

HRID 1428326Notes

Reaction equation

HRID 1428326 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:21]([NH:23][C:24]2[CH:25]=[C:26]([C:36]([F:39])([F:38])[F:37])[CH:27]=[C:28]([N:30]3[CH:34]=[N:33][C:32]([CH3:35])=[CH:31]3)[CH:29]=2)=[O:22])=[CH:6][C:7]=1[NH:8][C:9]1[N:10]=[CH:11][CH:12]=[C:13]([C:15]2[CH:16]=[CH:17][CH:18]=[N:19][CH:20]=2)[N:14]=1.CN(C)C=O.[C:45]([OH:54])(=[O:53])[C@@H:46]([C@H:48]([C:50]([OH:52])=[O:51])[OH:49])[OH:47]>CCO>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:21]([NH:23][C:24]2[CH:25]=[C:26]([C:36]([F:38])([F:39])[F:37])[CH:27]=[C:28]([N:30]3[CH:34]=[N:33][C:32]([CH3:35])=[CH:31]3)[CH:29]=2)=[O:22])=[CH:6][C:7]=1[NH:8][C:9]1[N:10]=[CH:11][CH:12]=[C:13]([C:15]2[CH:16]=[CH:17][CH:18]=[N:19][CH:20]=2)[N:14]=1.[C:50]([C@@H:48]([C@H:46]([C:45]([O-:54])=[O:53])[OH:47])[OH:49])([O-:52])=[O:51]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 444305L-Tartaric acidHCID 644241Nilotinib

Product 1

HCID 86688187Nilotinib L-tartrate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
80 °C

Procedure

A 250 mL reactor equipped with a reflux condenser and a mechanical stirrer was charged with Nilotinib base Form A (8.00 g, 15.11 mmol) and absolute EtOH (80 mL, 10V). The suspension was heated to 80° C. and stirred for 0.5 h. To the resulting mixture was added a solution of L-tartaric acid (2.49 g, 16.7 mmol, 1.1 eq) in absolute EtOH (20 mL) in one portion, followed by an additional 120 mL of absolute EtOH. The resulting mixture was stirred at 80° C. during 20 min and then cooled to room temperature over 0.5 h with continuous stirring at room temperature for another 16 h. The mixture was then transferred to a refrigerator at 5° C. and kept there for 16 h (in a closed vessel). The solid was isolated by vacuum filtration and dried in a vacuum oven at 70° C. for 24 h to give Nilotinib L-tartrate form IV as a yellow solid (9.10 g, 89%). Mono L-tartrate salt was obtained according to assay determination.

Workup

  1. customA 250 mL reactor equipped with a reflux condenser and a mechanical stirrer
  2. stirringThe resulting mixture was stirred at 80° C. during 20 min
  3. temperaturecooled to room temperature over 0.5 h
  4. stirringwith continuous stirring at room temperature for another 16 h
  5. customwas then transferred to a refrigerator at 5° C.
  6. waitkept there for 16 h
  7. customThe solid was isolated by vacuum filtration
  8. customdried in a vacuum oven at 70° C. for 24 h

Sources & evidence

ORD record
ord-c5dd72d8c3e84528bf8a672c2f963a7a
Source dataset
uspto-grants-2015_01
Patent number
US08937082B2

Reaction notes

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