Methanol → Imatinib Mesylate

HRID 59044

Reaction equation

HRID 59044 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[CH:16]=[CH:15][C:14]([CH2:17][N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)=[CH:13][CH:12]=2)=[O:10])=[CH:4][C:3]=1[NH:25][C:26]1[N:31]=[C:30]([C:32]2[CH:37]=[CH:36][CH:35]=[N:34][CH:33]=2)[CH:29]=[CH:28][N:27]=1.CO.ClCCl.[CH3:43][S:44]([OH:47])(=[O:46])=[O:45]>O>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[CH:12]=[CH:13][C:14]([CH2:17][N:18]3[CH2:19][CH2:20][N:21]([CH3:24])[CH2:22][CH2:23]3)=[CH:15][CH:16]=2)=[O:10])=[CH:4][C:3]=1[NH:25][C:26]1[N:27]=[CH:28][CH:29]=[C:30]([C:32]2[CH:37]=[CH:36][CH:35]=[N:34][CH:33]=2)[N:31]=1.[CH3:43][S:44]([OH:47])(=[O:46])=[O:45]

Participants

6

Reactant 4

HCID 887MethanolHCID 5291ImatinibHCID 6344DichloromethaneHCID 6395Methanesulfonic Acid

Product 1

HCID 123596Imatinib Mesylate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

Imatinib free base (90 g), methanol (450 mL) and dichloromethane (270 mL) were stirred at 25° C. in round bottom flask in presence of nitrogen. Methanesulfonic acid (18 g) was slowly added to the reaction mixture at 25° C. Water (27 mL) was added and the reaction mixture was stirred for 2 hours. The reaction mixture was heated at 50° C. and concentrated to remove the solvent mixture. The residue was degassed at 60° C. and cooled to 25° C. Methyl tert-butyl ether (630 mL) was added to the reaction mixture and stirred for 45 minutes. The product was filtered and washed with methyl tert-butyl ether. The product was dried at 60° C. under high vacuum for 10 hours to obtain amorphous imatinib mesylate. Water content 0.90%.

Workup

  1. concentrationconcentrated
  2. customto remove the solvent mixture
  3. customThe residue was degassed at 60° C.
  4. temperaturecooled to 25° C
  5. additionMethyl tert-butyl ether (630 mL) was added to the reaction mixture
  6. stirringstirred for 45 minutes
  7. filtrationThe product was filtered
  8. washwashed with methyl tert-butyl ether
  9. customThe product was dried at 60° C. under high vacuum for 10 hours

Sources & evidence

ORD record
ord-af1762d853804d258e309783c217d2cb
Source dataset
uspto-grants-2016_09
Patent number
US09439903B2

Linked notes

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