Water → Imatinib Mesylate

HRID 1010814Notes

Reaction equation

HRID 1010814 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([NH:21][C:22]([C:24]2[CH:25]=[CH:26][C:27]([CH2:30][N:31]3[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]3)=[CH:28][CH:29]=2)=[O:23])=[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.O.[CH3:39][S:40]([OH:43])(=[O:42])=[O:41]>C(O)C>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([NH:21][C:22]([C:24]2[CH:29]=[CH:28][C:27]([CH2:30][N:31]3[CH2:32][CH2:33][N:34]([CH3:37])[CH2:35][CH2:36]3)=[CH:26][CH:25]=2)=[O:23])=[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.[CH3:39][S:40]([OH:43])(=[O:42])=[O:41]

Participants

5

Reactant 3

HCID 962WaterHCID 5291ImatinibHCID 6395Methanesulfonic Acid

Product 1

HCID 123596Imatinib Mesylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
-13 °C

Procedure

Imatinib base (1926 g) was suspended in 38.5 liters of ethanol and 2 liters of water was added under stirring. Reactor was kept under flow of nitrogen during all of the experiment. Temperature of the mixture was adjusted at −15° C. and an ethanolic solution of methanesulphonic acid (375 g of methanesolphonic acid in 2278 ml of Ethanol) was added into the suspension. The temperature was increased to about −13° C. In 15 minutes, the product partially dissolved and recrystallized. After 15 minutes the seeding material of Form X (20 g suspended in chilled ethanol) was added. The temperature was slightly increased up to −5° C. in 3 hours and than 32 liters of TBME was added dropwise in 45 minutes. The mixture was stirred for 30 minutes and then filtered and washed with an additional 5 liters of TBME. The resulted crystalline form X was dried on filter by flow of nitrogen through the filter to remove free ethanol. Ethanol content was about 7.5%.

Workup

  1. customReactor was kept under flow of nitrogen
  2. customwas adjusted at −15° C.
  3. dissolutionthe product partially dissolved
  4. customrecrystallized
  5. additionAfter 15 minutes the seeding material of Form X (20 g suspended in chilled ethanol) was added
  6. temperatureThe temperature was slightly increased up to −5° C. in 3 hours and than 32 liters of TBME
  7. additionwas added dropwise in 45 minutes
  8. stirringThe mixture was stirred for 30 minutes
  9. filtrationfiltered
  10. washwashed with an additional 5 liters of TBME
  11. customThe resulted crystalline form X was dried
  12. filtrationon filter by flow of nitrogen through the
  13. filtrationfilter
  14. customto remove free ethanol

Sources & evidence

ORD record
ord-7af64dcb1433477d9e9ffe9eaa5d53c3
Source dataset
uspto-grants-2011_07
Patent number
US07977348B2

Reaction notes

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