Pyrrolidine → N-Desethyl Sunitinib

HRID 1246180Notes

Reaction equation

HRID 1246180 reaction equation
[CH2:1]([NH:3][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:18][C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[NH:24][C:23](=[O:28])[CH2:22]2.N1CCCC1>C(O)C>[CH2:1]([NH:3][CH2:4][CH2:5][NH:6][C:7]([C:9]1[C:13]([CH3:14])=[C:12](/[CH:15]=[C:22]2\[C:23](=[O:28])[NH:24][C:25]3[C:21]\2=[CH:20][C:19]([F:18])=[CH:27][CH:26]=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 88048739N-[2-(Ethylamino)ethyl]-5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxamide

Product 1

HCID 10292573N-Desethyl SunitinibYield 95.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

5-Formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-ethylamino-ethyl)-amide (99 g), ethanol (400 mL), 5-fluoro-2-oxindole (32 g) and pyrrolidine (1.5 g) were refluxed for 3 hours with stirring. The mixture was cooled to room temperature and the solids collected by vacuum filtration. The solids were stirred in ethanol at 60° C., cooled to room temperature and collected by vacuum filtration. The product was dried under vacuum to give 5-[5-fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-ethylamino-ethyl)-amide (75 g, 95% yield). 1H-NMR (dimethylsulfoxide-d6) δ 1.03 (t, 3H, CH3), 2.42, 2.44 (2×s, 6H, 2×CH3), 2.56 (q, 2H, CH2), 2.70, 3.30 (2×t, 4H, 2×CH2), 6.85, 6.92, 7.58, 7.72, 7.76 (5×m, 5H, aromatic, vinyl and CONH), 10.90 (br s, 1H, CONH), 13.65 (br s, 1H, pyrrole NH).

Workup

  1. filtrationthe solids collected by vacuum filtration
  2. stirringThe solids were stirred in ethanol at 60° C.
  3. temperaturecooled to room temperature
  4. filtrationcollected by vacuum filtration
  5. customThe product was dried under vacuum

Sources & evidence

ORD record
ord-03c4e626920b497e8c8ade2a375ff576
Source dataset
uspto-grants-2006_10
Patent number
US07125905B2

Reaction notes

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