Hydrogen Bromide → 1353151-22-0

HRID 1428311Notes

Reaction equation

HRID 1428311 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]>CCO>[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 702EthanolSolvent3×

Conditions

Temperature
50 °C

Procedure

Nilotinib base Form A (3.50 g, 6.61 mmol) was suspended in EtOH (70 mL, 20V) and the resulting slurry was heated to 50° C. over 15 min with stirring. To the resulting pale yellow slurry was added HBr (48% aq., 1.23 g, 7.27 mmol, 1.1 eq) followed by another 2V of EtOH (7 mL). This addition led to a colour change to give a neon yellow suspension. The suspension was heated to reflux and another 18V EtOH (63 mL) was added portion-wise with stirring. After 1.5 h the suspension was removed from the heat source and stirred at room temperature overnight. After about 15 h the suspension was subjected to hot filtration (60° C.) under nitrogen. The mother liquors were separated from the solid and the collected solid was dried in a vacuum oven (35 mmHg) at 40° C. for 20 h to give Nilotinib HBr form IV (1.86 g) as a yellow solid.

Workup

  1. additionThis addition
  2. customto give a neon yellow suspension
  3. temperatureThe suspension was heated
  4. temperatureto reflux
  5. stirringwith stirring
  6. customAfter 1.5 h the suspension was removed from the heat source
  7. stirringstirred at room temperature overnight
  8. filtrationAfter about 15 h the suspension was subjected to hot filtration (60° C.) under nitrogen
  9. customThe mother liquors were separated from the solid
  10. customthe collected solid was dried in a vacuum oven (35 mmHg) at 40° C. for 20 h

Sources & evidence

ORD record
ord-a0bfd7966a3e45b986579056d24832b1
Source dataset
uspto-grants-2015_01
Patent number
US08937082B2

Reaction notes

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