Water → Imatinib Mesylate

HRID 1010813Notes

Reaction equation

HRID 1010813 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].CC(OC)(C)C>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

6

Reactant 4

HCID 962WaterHCID 5291Imatinib2×HCID 6395Methanesulfonic AcidHCID 15413tert-Butyl methyl ether

Product 1

HCID 123596Imatinib Mesylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
-5 °C

Procedure

Imatinib base (60 g; 0.1216 mole) was suspended in 1200 ml of Ethanol and stirred. Reactor was kept under flow of nitrogen during all of the experiment (6 liters per hour). Then, 24 ml of water was added to the suspension and the temperature was adjusted at −15° C. An ethanolic solution of methanesulfonic acid (79.8 ml 10% V/V; 0.1213 mole) was added during 2 minutes to the reaction mixture. Temperature of the solution was set at −10° C. during 10 minutes, imatinib base was dissolved and seeding material of form X (2 g) was added. The crystallization process was continued under stirring for 190 minutes and temperature was continuously increased to −5° C. The suspension was stored overnight in a freezer at approx. −27° C. Than, suspension was diluted by 1000 ml TBME, filtered by nitrogen pressure and obtained crystalline portion was washed with 400 ml TBME. The resulted crystalline form X was dried by flow of nitrogen through the filter to remove free ethanol. Ethanol content was about 7.5%. (Yield was 67.95 g; 85%)

Workup

  1. customReactor was kept under flow of nitrogen
  2. customwas adjusted at −15° C
  3. additionwas added
  4. stirringunder stirring for 190 minutes
  5. waitThe suspension was stored overnight in a freezer at approx. −27° C
  6. filtrationfiltered by nitrogen pressure
  7. customobtained crystalline portion
  8. washwas washed with 400 ml TBME
  9. customThe resulted crystalline form X was dried by flow of nitrogen through the
  10. filtrationfilter
  11. customto remove free ethanol

Sources & evidence

ORD record
ord-1a3936cb22fa4105badb6cbd27bb2c8f
Source dataset
uspto-grants-2011_07
Patent number
US07977348B2

Reaction notes

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