Hydrochloric Acid → Nilotinib Hydrochloride Anhydrous

HRID 2046432Notes

Reaction equation

HRID 2046432 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 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, mild dissolution occurred during the stirring, and the mixture was filtered under reduced pressure. During the filtration precipitation occurred. Absolute ethanol was added (120 ml), and the precipitate was returned to the reactor. The mixture was heated to reflux until dissolution and stirred for 30 minutes, then cooled gradually to 5° C. over 3 h. While cooling, absolute ethanol was added (200 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. dissolutionmild dissolution
  4. filtrationthe mixture was filtered under reduced pressure
  5. filtrationDuring the filtration precipitation
  6. additionAbsolute ethanol was added (120 ml)
  7. temperatureThe mixture was heated
  8. temperatureto reflux until dissolution
  9. temperatureWhile cooling
  10. additionabsolute ethanol was added (200 ml)
  11. stirringthe slurry stirred at 5° C. for 30 minutes
  12. filtrationfiltered
  13. washwashed with absolute ethanol
  14. customdried over night at 70° C. in vacuum oven

Sources & evidence

ORD record
ord-a8bc4ba85f894748b2d3850b20b3404e
Source dataset
uspto-grants-2013_11
Patent number
US08592442B2

Reaction notes

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