Hydrochloric Acid → Nilotinib Hydrochloride Anhydrous

HRID 2046436Notes

Reaction equation

HRID 2046436 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

To 1 Liter reactor was added Nilotinib-base form A (20 g, 0.04 mol), ethanol absolute (188 ml) and 13.77% HCl solution in ethanol abs. (10 g, 0.04 mol). The slurry was heated to reflux, dissolution occurred during the stirring, and the mixture was 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 for 2 h to 6° C. At 6° C. ethanol abs. was added (300 ml) and the slurry stirred at 5° C. for 30 minutes, filtered, washed with ethanol abs. to yield Nilotinib-HCl form T18.

Workup

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

Sources & evidence

ORD record
ord-27e3e9ad5b19432fad931e92a0187dfd
Source dataset
uspto-grants-2013_11
Patent number
US08592442B2

Reaction notes

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