Hydrochloric Acid → Nilotinib Hydrochloride Anhydrous

HRID 2046434Notes

Reaction equation

HRID 2046434 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). The slurry was heated to reflux, dissolution occurred during the stirring, and the mixture was filtered under reduced pressure. The Filtrate was fed to second reactor and heated back to reflux. At 76.0° C. the solution was seeded with 0.2 g of dry material obtained by the process of example 23. Precipitation was observed. Then, maintained at reflux for 0.5 h, followed by cooling for 2 h to 5° C. During cooling at 20° C. absolute ethanol was added (100 ml) and the slurry stirred till reaching to 5° C., filtered, washed with absolute ethanol, and dried over night at 70° C. in vacuum oven to yield Nilotinib-HCl form T17 (16.3 g, 73% yield).

Workup

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

Sources & evidence

ORD record
ord-5acc48bc49854c16adf5b670fd449567
Source dataset
uspto-grants-2013_11
Patent number
US08592442B2

Reaction notes

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