Cycloheptane → Sunitinib

HRID 1258774Notes

Reaction equation

HRID 1258774 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.C1CCCCCC1.N1CCCC1>C1CCCCC1.C1CCCC1>[CH3:2][CH2:1][N:3]([CH2:4][CH2:5][NH:6][C:7]([C:9]1[C:13]([CH3:14])=[C:12](/[CH:15]=[C:24]2/[C:23]3[CH:22]=[C:21]([F:20])[CH:29]=[CH:28][C:27]=3[NH:26][C:25]/2=[O:30])[NH:11][C:10]=1[CH3:17])=[O:8])[CH2:18][CH3:19]

Participants

7

Reactant 4

HCID 9265CycloheptaneHCID 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 5329102Sunitinib

Reagents, catalysts & solvents 2

HCID 8078CyclohexaneSolventHCID 9253CyclopentaneSolvent

Procedure

According to the process of the present invention, 5-Formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)-amide (IX) and 5-Fluoro-1,3-dihydro-indol-2-one (X) in non-polar alicyclic hydrocarbon solvents like cyclopentane, cyclohexane or cycloheptane are reacted in presence of catalytic amount of pyrrolidine as base at reflux temperature for 1-6 hours. The resultant Sunitinib base is again triturated with the same solvent at reflux temperature for 1-2 hours and isolated at a temperature ranging from 20-45° C., preferably at 25-35° and most preferably at 25-30° C. and dried at 60° C. for 5-20 hours to get Sunitinib base (I) as orange crystalline solid.

Workup

  1. temperatureat reflux temperature for 1-6 hours
  2. customThe resultant Sunitinib base is again triturated with the same solvent
  3. temperatureat reflux temperature for 1-2 hours
  4. customisolated at a temperature
  5. customranging from 20-45° C., preferably at 25-35° and most preferably at 25-30° C.
  6. customdried at 60° C. for 5-20 hours

Sources & evidence

ORD record
ord-bd12b5e3fb10416d9a83bf31525df26d
Source dataset
uspto-grants-2013_06
Patent number
US08466190B2

Reaction notes

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