tert-Butyl methyl ether → Nilotinib L-tartrate

HRID 1428315Notes

Reaction equation

HRID 1428315 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.CC(OC)(C)C.[C:46]([OH:55])(=[O:54])[C@@H:47]([C@H:49]([C:51]([OH:53])=[O:52])[OH:50])[OH:48]>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:51]([C@@H:49]([C@H:47]([C:46]([O-:55])=[O:54])[OH:48])[OH:50])([O-:53])=[O:52]

Participants

5

Reactant 3

HCID 15413tert-Butyl methyl etherHCID 444305L-Tartaric acidHCID 644241Nilotinib

Product 1

HCID 86688187Nilotinib L-tartrate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

Nilotinib base form A (4.00 g, 7.55 mmol) was mixed with ethanol absolute (40 mL, 10V) in a 250 mL reactor equipped with a mechanical stirrer and a reflux condenser to obtain a suspension. The suspension was heated to 80° C. and stirred at the same temperature for 30 min. To the suspension was added a solution of L-tartaric acid (1.25 g, 8.31 mmol, 1.1 mol eq) in ethanol absolute (10 mL, 2.5V) in one portion. The resulting mixture was stirred at 80° C. for 1 hour. Then the heating source was removed and the mixture was allowed to cool to room temperature. The stirring was continued at ambient temperature over a period of 6 h, during which time the mixture became viscous. To the viscous mixture was added another 80 mL ethanol. The mixture was then transferred to the refrigerator and was kept at about 5° C. for 5 days (in a closed vessel) A yellow precipitate formed and was isolated by vacuum filtration to give Nilotinib L-tartrate form IV as indicated by XRD (wet sample). The obtained Nilotinib L-tartrate form IV was dried in a vacuum oven (35 mmHg) at 60° C. for 16 h. The sample was then analyzed by PXRD using a Bruker X-Ray powder diffractometer model D8 and was found to be Nilotinib L-tartrate form IV (4.7 g).

Workup

  1. customequipped with a mechanical stirrer and a reflux condenser
  2. customto obtain a suspension
  3. stirringThe resulting mixture was stirred at 80° C. for 1 hour
  4. customThen the heating source was removed
  5. temperatureto cool to room temperature
  6. waitThe stirring was continued at ambient temperature over a period of 6 h, during which time
  7. additionTo the viscous mixture was added another 80 mL ethanol
  8. waitwas kept at about 5° C. for 5 days
  9. custom(in a closed vessel) A yellow precipitate formed
  10. customwas isolated by vacuum filtration

Sources & evidence

ORD record
ord-5e83c305fe60474ea30053ebf586c12c
Source dataset
uspto-grants-2015_01
Patent number
US08937082B2

Reaction notes

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