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

HRID 388502Notes

Reaction equation

HRID 388502 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.C(OCC)(=O)C>O1CCCC1.C(O)C.O.[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

7

Reactant 2

HCID 8857Ethyl AcetateHCID 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 98%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

1-[2-Fluoro-4-(2-{[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]amino}pyridin-4-yloxy)phenylcarbamoyl]cyclopropanecarboxylic acid benzyl ester (500 mg) was dissolved in a mixed solvent of tetrahydrofuran (2.5 ml), ethanol (2.5 ml) and water (1.5 ml), palladium on carbon (100 mg) was added, and the mixture was stirred at room temperature under a hydrogen atmosphere (0.15 MPa) for 3 hours. The reaction mixture was filtered, and the residue was washed with a 90% aqueous ethanol (1 ml), and the filtrate was concentrated. Addition of ethanol to the residue and subsequent concentration were repeated three times. Ethanol (2.5 ml), tetrahydrofuran (2.5 ml) and the seed crystals obtained in (Method 1) were added to the residue, and the mixture was stirred at room temperature for 1 hour. Ethyl acetate (5 ml) was added, and the mixture was further stirred for 1 hour. The crystals were filtered and dried to give the title compound (420 mg) as white crystals.

Workup

  1. additionwas added
  2. filtrationThe reaction mixture was filtered
  3. washthe residue was washed with a 90% aqueous ethanol (1 ml)
  4. concentrationthe filtrate was concentrated
  5. additionAddition of ethanol
  6. concentrationto the residue and subsequent concentration
  7. customEthanol (2.5 ml), tetrahydrofuran (2.5 ml) and the seed crystals obtained in (Method 1)
  8. additionwere added to the residue
  9. stirringthe mixture was stirred at room temperature for 1 hour
  10. stirringthe mixture was further stirred for 1 hour
  11. filtrationThe crystals were filtered
  12. customdried

Sources & evidence

ORD record
ord-3854a62cc9c4407796577b76aae4df99
Source dataset
uspto-grants-2013_02
Patent number
US08377938B2

Reaction notes

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