L-Tartaric acid → Nilotinib L-tartrate

HRID 1428316Notes

Reaction equation

HRID 1428316 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.[C:40]([OH:49])(=[O:48])[C@@H:41]([C@H:43]([C:45]([OH:47])=[O:46])[OH:44])[OH:42]>CN(C)C=O>[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:45]([C@@H:43]([C@H:41]([C:40]([O-:49])=[O:48])[OH:42])[OH:44])([O-:47])=[O:46]

Participants

4

Reactant 2

HCID 444305L-Tartaric acidHCID 644241Nilotinib

Product 1

HCID 86688187Nilotinib L-tartrate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
80 °C

Procedure

Nilotinib base Form A (4.00 g, 7.55 mmol) was mixed with dimethylformamide (“DMF”) (40 mL, 10V) to obtain a suspension. The suspension was heated to 80° C. and stirred at the same temperature for 30 min to produce a clear yellow solution. To the solution was added a solution of L-tartaric acid (1.25 g, 8.31 mmol, 1.1 mol eq) in DMF (4 mL, 1V) in one portion. The solution 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 after which time the mixture was transferred to the refrigerator for 16 h. MTBE (400 mL) was added portion-wise to the mixture at room temperature until a light yellow precipitate was formed. The resulting suspension was stirred at room temperature for 6 h and then filtered to give Nilotinib L-tartrate form V as a light-yellow solid.

Workup

  1. customto obtain a suspension
  2. customto produce a clear yellow solution
  3. stirringThe solution 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
  7. waitafter which time the mixture was transferred to the refrigerator for 16 h
  8. additionMTBE (400 mL) was added portion-wise to the mixture at room temperature until a light yellow precipitate
  9. customwas formed
  10. stirringThe resulting suspension was stirred at room temperature for 6 h
  11. filtrationfiltered

Sources & evidence

ORD record
ord-0951895fc0e548c29a8b977ae0d2fbc1
Source dataset
uspto-grants-2015_01
Patent number
US08937082B2

Reaction notes

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