Hydrochloric Acid → Nilotinib Hydrochloride Anhydrous

HRID 1428264

Reaction equation

HRID 1428264 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.[ClH:40]>C(O)C>[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.[ClH:40]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 644241Nilotinib

Product 1

HCID 16006490Nilotinib Hydrochloride Anhydrous

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
5 °C

Procedure

Nilotinib HCl form T18 as used in any of the processes described in the present application may be prepared according to WO 2010/054056, examples 33-38, which is incorporated herein by reference. For example: To a 1 Liter reactor was added Nilotinib-base form A (20 g, 0.04 mol), absolute ethanol (188 ml) and 13.77% HCl solution in ethanol abs. (10 g, 0.04 mol). The slurry formed thereby was heated to reflux, and dissolution occurred during the stirring. The solution was then filtered under reduced pressure. The filtrate was fed back to the reactor and heated back to reflux. At 76.6° C. the solution was seeded with 0.2 g of dry material obtained by the process of example 23. Precipitation was observed. Then, the solution was maintained at reflux for 1 h, followed by cooling over 2 h to 6° C. At 6° C. ethanol abs. was added (300 ml) and the slurry was stirred at 5° C. for 30 minutes, filtered, washed with ethanol abs. to yield Nilotinib-HCl, form T18.

Workup

  1. custommay be prepared
  2. customThe slurry formed
  3. temperaturethereby was heated
  4. temperatureto reflux
  5. dissolutiondissolution
  6. filtrationThe solution was then filtered under reduced pressure
  7. temperatureheated back
  8. temperatureto reflux
  9. customAt 76.6° C.
  10. customobtained by the process of example 23
  11. customPrecipitation
  12. temperatureThen, the solution was maintained
  13. temperatureat reflux for 1 h
  14. temperatureby cooling over 2 h to 6° C
  15. customAt 6° C.
  16. additionwas added (300 ml)
  17. filtrationfiltered
  18. washwashed with ethanol abs

Sources & evidence

ORD record
ord-b0fc258ed38946c29f720d665d43e19c
Source dataset
uspto-grants-2015_01
Patent number
US08937082B2

Linked notes

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