Hydrochloric Acid → Nilotinib Hydrochloride Anhydrous

HRID 1428322Notes

Reaction equation

HRID 1428322 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 AnhydrousYield 83%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
5 °C

Procedure

To a 1 liter reactor was added Nilotinib-base (20 g, 0.04 mol), absolute ethanol (9.4 vol) and HCl solution (13.77% in ethanol abs., 10 g, 0.04 mol). The resulting slurry was heated to reflux, and dissolution occurred during the stirring. The solution was filtered under reduced pressure. The filtrate was fed back to the reactor and heated back to reflux temperature. At 76.6° C. the solution was seeded with 0.2 g of dry Nilotinib HCl form T17. A solid precipitate was formed, and the mixture was maintained at reflux for 1 hour. The mixture was then cooled over 2 h to 6° C. At 6° C., absolute ethanol (15 vol) was added and the resulting slurry was stirred at 5° C. for 30 minutes. The slurry was then filtered, and the separated solid was washed with absolute ethanol, and dried overnight at 70° C. in a vacuum oven to yield Nilotinib-HCl form T17 (18.4 g, 83% yield)

Workup

  1. temperatureThe resulting slurry was heated
  2. temperatureto reflux
  3. dissolutiondissolution
  4. filtrationThe solution was filtered under reduced pressure
  5. temperatureheated back
  6. temperatureto reflux temperature
  7. customAt 76.6° C.
  8. customA solid precipitate was formed
  9. temperaturethe mixture was maintained
  10. temperatureat reflux for 1 hour
  11. temperatureThe mixture was then cooled over 2 h to 6° C
  12. filtrationThe slurry was then filtered
  13. washthe separated solid was washed with absolute ethanol
  14. customdried overnight at 70° C. in a vacuum oven

Sources & evidence

ORD record
ord-11e49f78b6754096992fb55cc288d1be
Source dataset
uspto-grants-2015_01
Patent number
US08937082B2

Reaction notes

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