Dimethyl Sulfoxide → Sunitinib Malate

HRID 2192697Notes

Reaction equation

HRID 2192697 reaction equation
[CH3:1][CH2:2][N:3]([CH2:6][CH2:7][NH:8][C:9]([C:11]1[C:12]([CH3:29])=[C:13](/[CH:17]=[C:18]2/[C:19]3[CH:20]=[C:21]([F:28])[CH:22]=[CH:23][C:24]=3[NH:25][C:26]/2=[O:27])[NH:14][C:15]=1[CH3:16])=[O:10])[CH2:4][CH3:5].[C:30]([OH:38])(=[O:37])[C@H:31]([CH2:33][C:34]([OH:36])=[O:35])[OH:32].CS(C)=O>C(OC)(C)(C)C>[CH3:1][CH2:2][N:3]([CH2:6][CH2:7][NH:8][C:9]([C:11]1[C:12]([CH3:29])=[C:13](/[CH:17]=[C:18]2/[C:19]3[CH:20]=[C:21]([F:28])[CH:22]=[CH:23][C:24]=3[NH:25][C:26]/2=[O:27])[NH:14][C:15]=1[CH3:16])=[O:10])[CH2:4][CH3:5].[CH2:33]([C:34]([OH:36])=[O:35])[C@H:31]([OH:32])[C:30]([OH:38])=[O:37]

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 222656L-Malic AcidHCID 5329102Sunitinib

Product 1

HCID 6456015Sunitinib MalateYield 59.9%

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Procedure

Sunitinib free base (5.0 gm), L-malic acid (1.8 gm) and dimethyl sulfoxide (25 ml) are mixed and the mixture was heated to 80 deg C. to obtain a clear solution, stirred for 30 minutes at 80 deg C. The solution was slowly cooled to room temperature and the solution was added to methyl tert-butyl ether (150 ml), stirred for 15 hours at room temperature. The solid obtained by filtration and the solid was washed with mixture of dimethyl sulfoxide (1 ml) and methyl tert-butyl ether (9 ml), and then dried at 60 deg C. under vacuum to obtain 4 gm of sunitinib malate crystal form I.

Workup

  1. temperaturethe mixture was heated to 80 deg C
  2. customto obtain a clear solution
  3. stirringstirred for 15 hours at room temperature
  4. customThe solid obtained by filtration
  5. washthe solid was washed with mixture of dimethyl sulfoxide (1 ml) and methyl tert-butyl ether (9 ml)
  6. customdried at 60 deg C

Sources & evidence

ORD record
ord-e10b9761e61b4531bebc6264c80cd915
Source dataset
uspto-grants-2012_12
Patent number
US08329740B2

Reaction notes

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