Water → 1-[2-Fluoro-4-(2-{[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]amino}pyridin-4-yloxy)phenylcarbamoyl]cyclopropanecarboxylic acid

HRID 388501Notes

Reaction equation

HRID 388501 reaction equation
C([O:8][C:9]([C:11]1([C:14](=[O:46])[NH:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][C:23]3[CH:28]=[CH:27][N:26]=[C:25]([NH:29][C:30]([N:32]4[CH2:37][CH2:36][CH:35]([N:38]5[CH2:43][CH2:42][N:41]([CH3:44])[CH2:40][CH2:39]5)[CH2:34][CH2:33]4)=[O:31])[CH:24]=3)=[CH:18][C:17]=2[F:45])[CH2:13][CH2:12]1)=[O:10])C1C=CC=CC=1.O>O1CCCC1.C(O)C.[Pd]>[F:45][C:17]1[CH:18]=[C:19]([O:22][C:23]2[CH:28]=[CH:27][N:26]=[C:25]([NH:29][C:30]([N:32]3[CH2:37][CH2:36][CH:35]([N:38]4[CH2:39][CH2:40][N:41]([CH3:44])[CH2:42][CH2:43]4)[CH2:34][CH2:33]3)=[O:31])[CH:24]=2)[CH:20]=[CH:21][C:16]=1[NH:15][C:14]([C:11]1([C:9]([OH:10])=[O:8])[CH2:13][CH2:12]1)=[O:46]

Participants

6

Reactant 2

HCID 962WaterHCID 247886941-[2-Fluoro-4-(2-{[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]amino}pyridin-4-yloxy)phenylcarbamoyl]cyclopropanecarboxylic acid benzyl ester

Product 1

HCID 247886301-[2-Fluoro-4-(2-{[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]amino}pyridin-4-yloxy)phenylcarbamoyl]cyclopropanecarboxylic acidYield 80.2%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

1-[2-Fluoro-4-(2-{[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]amino}pyridin-4-yloxy)phenylcarbamoyl]cyclopropanecarboxylic acid benzyl ester (800 mg) was dissolved in a mixed solvent of tetrahydrofuran (4 ml) and ethanol (4 ml), palladium on carbon (400 mg) was added, and the mixture was stirred at room temperature under a hydrogen atmosphere (0.15 MPa) for 4 hours. Water (4 ml) was added to the reaction mixture, which was filtered, and the residue was washed with a 50% aqueous ethanol (8 ml) and water (4 ml), and the filtrate was concentrated. Tetrahydrofuran (8 ml) and ethanol (8 ml) was added to the residue, which was concentrated. Tetrahydrofuran (8 ml), ethyl acetate (8 ml) and ethanol (2 ml) were added to the residue, which was concentrated. Tetrahydrofuran (8 ml) and ethanol (16 ml) were added to the residue, which was concentrated to precipitate crystals. The crystals were suspended in tetrahydrofuran (16 ml), stirred at room temperature for 40 minutes, filtered, and dried to give the title compound (550 mg) as white crystals.

Workup

  1. additionwas added
  2. filtrationwas filtered
  3. washthe residue was washed with a 50% aqueous ethanol (8 ml) and water (4 ml)
  4. concentrationthe filtrate was concentrated
  5. additionTetrahydrofuran (8 ml) and ethanol (8 ml) was added to the residue, which
  6. concentrationwas concentrated
  7. additionTetrahydrofuran (8 ml), ethyl acetate (8 ml) and ethanol (2 ml) were added to the residue, which
  8. concentrationwas concentrated
  9. additionTetrahydrofuran (8 ml) and ethanol (16 ml) were added to the residue, which
  10. concentrationwas concentrated
  11. customto precipitate crystals
  12. stirringstirred at room temperature for 40 minutes
  13. filtrationfiltered
  14. customdried

Sources & evidence

ORD record
ord-8f5519692099400c9a6e9826a229068b
Source dataset
uspto-grants-2013_02
Patent number
US08377938B2

Reaction notes

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