Hydrochloric Acid → Nilotinib Hydrochloride Anhydrous

HRID 1428265

Reaction equation

HRID 1428265 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].O>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

5

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 644241Nilotinib

Product 1

HCID 16006490Nilotinib Hydrochloride AnhydrousYield 73%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
20 °C

Procedure

To a 1 Liter reactor was added Nilotinib-base form A (20 g, 0.04 mol), absolute ethanol (200 ml), and HCl 32% solution in water (6.45 g, 0.04 mol). A slurry was formed. The slurry was heated to reflux, dissolution occurred during the stirring, and the solution was then filtered under reduced pressure. The filtrate was fed to a second reactor and heated back to reflux. At 76.0° C. the solution was seeded with 0.2 g of a dry material obtained by the process of example 23. Precipitation was observed. Then, the mixture was maintained at reflux for 0.5 h, followed by cooling over 2 h to 5° C. During cooling at 20° C. absolute ethanol was added (100 ml) and the slurry was stirred till it cooled to 5° C. The cooled slurry was then filtered, and the collected solid was washed with absolute ethanol, and dried over night at 70° C. in a vacuum oven to yield Nilotinib-HCl form T17 (16.3 g, 73% yield).

Workup

  1. customA slurry was formed
  2. temperatureThe slurry was heated
  3. temperatureto reflux
  4. dissolutiondissolution
  5. filtrationthe solution was then filtered under reduced pressure
  6. customThe filtrate was fed to a second reactor
  7. temperatureheated back
  8. temperatureto reflux
  9. customAt 76.0° C.
  10. customobtained by the process of example 23
  11. customPrecipitation
  12. temperatureThen, the mixture was maintained
  13. temperatureat reflux for 0.5 h
  14. temperatureby cooling over 2 h to 5° C
  15. additionwas added (100 ml)
  16. temperaturecooled to 5° C
  17. filtrationThe cooled slurry was then filtered
  18. washthe collected solid was washed with absolute ethanol
  19. customdried over night at 70° C. in a vacuum oven

Sources & evidence

ORD record
ord-4a38b8c5e1964945b6b1313481e1250b
Source dataset
uspto-grants-2015_01
Patent number
US08937082B2

Linked notes

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