Hydrogen Bromide → 1353151-22-0

HRID 1428324Notes

Reaction equation

HRID 1428324 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.[BrH:40]>CN(C)C=O>[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.[BrH:40]

Participants

4

Reactant 2

HCID 260Hydrogen BromideHCID 644241Nilotinib

Product 1

HCID 565926751353151-22-0

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a 250 mL reactor equipped with a reflux condenser and a mechanical stirrer Nilotinib base Form A (15.00 g, 28.3 mmol) was mixed with acetone (150 mL, 10V). The resulting suspension was heated to reflux over 10 min and stirred at reflux for additional 40 min. To the stirred suspension was added HBr (48% aq, 3.30 mL, 29.2 mmol, 1.03 eq) in one portion. Stirring of the resulting mixture was continued at reflux temperature for 1 h. The mixture was then allowed to cool to room temperature over a period of 3 h and maintained at room temperature overnight. The flask containing the mixture was then transferred to the refrigerator where it was kept for about 3 days at a temperature from 2° C. to about 8° C. (in a closed vessel). The mixture was then filtered and the isolated solid was dried in a vacuum oven (25 mmHg) at 70° C. for 22 h to afford Nilotinib HBr form XI as a yellow solid (17.27 g, 99%). Assay determination confirmed the stoichiometry of the salt as monohydrobromide.

Workup

  1. temperatureThe resulting suspension was heated
  2. temperatureto reflux over 10 min
  3. temperatureat reflux for additional 40 min
  4. stirringStirring of the resulting mixture
  5. temperatureat reflux temperature for 1 h
  6. temperaturemaintained at room temperature overnight
  7. additionThe flask containing the mixture
  8. filtrationThe mixture was then filtered
  9. customthe isolated solid was dried in a vacuum oven (25 mmHg) at 70° C. for 22 h

Sources & evidence

ORD record
ord-4816b81590ff480e8b4e0161f4f8a4ee
Source dataset
uspto-grants-2015_01
Patent number
US08937082B2

Reaction notes

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