N-methyl-2-pyrrolidone → HCID 86688194, compound

HRID 1528253Notes

Reaction equation

HRID 1528253 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.CN1CCCC1=O.[C:47]([OH:54])(=[O:53])/[CH:48]=[CH:49]\[C:50]([OH:52])=[O:51]>CC(OC)(C)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.[C:47]([O-:54])(=[O:53])/[CH:48]=[CH:49]\[C:50]([O-:52])=[O:51]

Participants

5

Reactant 3

HCID 13387N-methyl-2-pyrrolidone2×HCID 444266Maleic AcidHCID 644241Nilotinib

Product 1

HCID 86688194HCID 86688194, compound

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
40 °C

Procedure

Nilotinib base (3.85 g, 7.27 mmol) was suspended in TFE (19 ml, 5V) and the mixture was heated to 40° C. with stirring. To the resulting cloudy yellow solution, maleic acid (0.84 g, 7.27 mmol) was added in one portion, followed by TFE (19 ml, 5V) at 45-50° C. Dissolution of the solid was achieved after about 5 min stirring at the same temperature. The resulting clear yellow solution was then stirred at 45° C. for about 3 h, and then at room temperature overnight (about 19 h). MTBE (10V) was added with stirring, leading to immediate precipitation. The resulting slurry was stirred for 1 h at room temperature and then the solid was separated from the mother liquors by filtration. The yellow solid was isolated and dried in a vacuum oven (35 mmHg) at 40° C. for 18.5 h to give Nilotinib maleate form IV (3.49 g, 74%) as a pale yellow solid.

Workup

  1. dissolutionDissolution of the solid
  2. stirringstirring at the same temperature
  3. stirringThe resulting clear yellow solution was then stirred at 45° C. for about 3 h
  4. customat room temperature
  5. customovernight (about 19 h)
  6. stirringwith stirring
  7. customleading to immediate precipitation
  8. stirringThe resulting slurry was stirred for 1 h at room temperature
  9. customthe solid was separated from the mother liquors by filtration
  10. customThe yellow solid was isolated
  11. customdried in a vacuum oven (35 mmHg) at 40° C. for 18.5 h

Sources & evidence

ORD record
ord-9ebd37825e4f4b7f98719dd526154f66
Source dataset
uspto-grants-2015_07
Patent number
US09090598B2

Reaction notes

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