Pyrrolidine → Sunitinib

HRID 50005

Reaction equation

HRID 50005 reaction equation
[CH2:1]([N:3]([CH2:18][CH3:19])[CH2:4][CH2:5][NH:6][C:7]([C:9]1[C:13]([CH3:14])=[C:12]([CH:15]=O)[NH:11][C:10]=1[CH3:17])=[O:8])[CH3:2].[F:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[NH:26][C:25](=[O:30])[CH2:24]2.N1CCCC1>C(O)C>[CH2:1]([N:3]([CH2:18][CH3:19])[CH2:4][CH2:5][NH:6][C:7]([C:9]1[C:13]([CH3:14])=[C:12](/[CH:15]=[C:24]2\[C:25](=[O:30])[NH:26][C:27]3[C:23]\2=[CH:22][C:21]([F:20])=[CH:29][CH:28]=3)[NH:11][C:10]=1[CH3:17])=[O:8])[CH3:2]

Participants

5

Reactant 3

HCID 31268PyrrolidineHCID 37310125-fluoro-1,3-dihydro-2H-indol-2-oneHCID 20761785N-(2-(diethylamino)ethyl)-5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxamide

Product 1

HCID 5329102SunitinibYield 88%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

5-Formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)-amide (809 g), 5-fluoro-1,3-dihydro-indol-2-one (438 g), ethanol (8000 mL) and pyrrolidine (13 mL) were heated at 78° C. for 3 hours. The mixture was cooled to room temperature and the solids collected by vacuum filtration and washed with ethanol. The solids were stirred with ethanol (5900 mL) at 72° C. for 30 minutes. The mixture was cooled to room temperature. The solids were collected by vacuum filtration, washed with ethanol and dried under vacuum at 54° C. for 130 hours to give 5-[5-fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylamino-ethyl)-amide (1013 g, 88% yield) as an orange solid. 1H-NMR (dimethylsulfoxide-d6) δ0.98 (t, 6H, 2×CH3), 2.43, 2.44 (2×s, 6H, 2×CH3), 2.50 (m, 6H, 3×CH2), 3.28 (q, 2H, CH2), 6.84, 6.92, 7.42, 7.71, 7.50 (5×m, 5H, aromatic, vinyl, CONH), 10.88 (s, 1H, CONH), 13.68 (s, 1H, pyrrole NH). MS m/z 397 [M−1].

Workup

  1. filtrationthe solids collected by vacuum filtration
  2. washwashed with ethanol
  3. temperatureThe mixture was cooled to room temperature
  4. filtrationThe solids were collected by vacuum filtration
  5. washwashed with ethanol
  6. customdried under vacuum at 54° C. for 130 hours

Sources & evidence

ORD record
ord-fe021e7d960e41e1be11ef5b844d1b97
Source dataset
uspto-grants-2004_03
Patent number
US06710067B2

Linked notes

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