Hydrochloric Acid → Nilotinib Hydrochloride Anhydrous

HRID 2046433Notes

Reaction equation

HRID 2046433 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 form A (20 g, 0.04 mol), absolute ethanol (188 ml) and 13.77% HCl solution in absolute ethanol (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, it was maintained at reflux for 1 h, followed by cooling for 2 h to 6° C. At 6° C. absolute ethanol was added (300 ml) and the slurry stirred at 5° C. for 30 minutes, filtered, washed with absolute ethanol, and dried over night at 70° C. in vacuum oven to yield Nilotinib-HCl form T17 (18.4 g, 83% yield).

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, it was maintained
  11. temperatureat reflux for 1 h
  12. temperatureby cooling for 2 h to 6° C
  13. additionAt 6° C. absolute ethanol was added (300 ml)
  14. filtrationfiltered
  15. washwashed with absolute ethanol
  16. customdried over night at 70° C. in vacuum oven

Sources & evidence

ORD record
ord-0acdb535e70646a093643c35b85ea9c1
Source dataset
uspto-grants-2013_11
Patent number
US08592442B2

Reaction notes

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