Pyrrolidine → N-Desethyl Sunitinib

HRID 1827109Notes

Reaction equation

HRID 1827109 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). MS m/z 369 [M−1].

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-375238b51bd84130a6497c7c5e0d5327
Source dataset
uspto-grants-2006_05
Patent number
US07053114B2

Reaction notes

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