Water → 4-{2-[5-(4-Acetylpiperazin-1-yl)pyridin-2-yl]ethyl}benzyl tert-butyl hydrazine-1,2-dicarboxylate

HRID 1465474Notes

Reaction equation

HRID 1465474 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[CH:12][C:13]([CH2:16][CH2:17][C:18]3[CH:23]=[CH:22][C:21]([CH2:24][OH:25])=[CH:20][CH:19]=3)=[N:14][CH:15]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[C:26]([N:33]1C=CN=C1)(N1C=CN=C1)=[O:27].[C:38]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])(=[O:41])[NH:39]N.O>CN(C)C=O>[NH:33]([C:26]([O:25][CH2:24][C:21]1[CH:20]=[CH:19][C:18]([CH2:17][CH2:16][C:13]2[CH:12]=[CH:11][C:10]([N:7]3[CH2:6][CH2:5][N:4]([C:1](=[O:3])[CH3:2])[CH2:9][CH2:8]3)=[CH:15][N:14]=2)=[CH:23][CH:22]=1)=[O:27])[NH:39][C:38]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41]

Participants

6

Reactant 4

HCID 962WaterHCID 682631,1'-CarbonyldiimidazoleHCID 70091tert-Butyl carbazate3×HCID 58181252(4-{2-[5-(4-Acetylpiperazin-1-yl)pyridin-2-yl]ethyl}phenyl)methanol

Product 1

HCID 581813324-{2-[5-(4-Acetylpiperazin-1-yl)pyridin-2-yl]ethyl}benzyl tert-butyl hydrazine-1,2-dicarboxylateYield 87.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of (4-{2-[5-(4-acetylpiperazin-1-yl)pyridin-2-yl]ethyl}phenyl)methanol (115.3 mg, 0.340 mmol) in anhydrous N,N-dimethylformamide (1.5 ml) was added 1,1′-carbonyldiimidazole (83.1 mg, 0.513 mmol), and the mixture was stirred at room temperature for 1.5 hrs. tert-Butyl carbazate (137.5 mg, 1.040 mmol) was added, and the mixture was stirred at room temperature 7 hrs. tert-Butyl carbazate (134.8 mg, 1.020 mmol) was added, and the mixture was stirred at room temperature for 16 hrs. tert-Butyl carbazate (135.7 mg, 1.027 mmol) was further added, and the mixture was stirred at 50° C. for 8 hrs. Water was added, and the mixture was extracted twice with ethyl acetate. The combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was suspended in dichloromethane (15 ml), collected by filtration, washed with dichloromethane and dried under reduced pressure. The residue was purified by silica gel column chromatography (methanol:dichloromethane=1:20). The fraction containing the target product was concentrated and the obtained solid was suspended in a mixture of ethyl acetate (1 ml) and diisopropyl ether (4 ml), collected by filtration and dried under reduced pressure to give 4-{2-[5-(4-acetylpiperazin-1-yl)pyridin-2-yl]ethyl}benzyl tert-butyl hydrazine-1,2-dicarboxylate (148.6 mg, yield 87.9%) as a white solid.

Workup

  1. stirringthe mixture was stirred at room temperature 7 hrs
  2. stirringthe mixture was stirred at room temperature for 16 hrs
  3. stirringthe mixture was stirred at 50° C. for 8 hrs
  4. extractionthe mixture was extracted twice with ethyl acetate
  5. washThe combined organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. filtrationcollected by filtration
  9. washwashed with dichloromethane
  10. customdried under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (methanol:dichloromethane=1:20)
  12. additionThe fraction containing the target product
  13. concentrationwas concentrated
  14. additionthe obtained solid was suspended in a mixture of ethyl acetate (1 ml) and diisopropyl ether (4 ml)
  15. filtrationcollected by filtration
  16. customdried under reduced pressure

Sources & evidence

ORD record
ord-c3c3316a7f804fdeb633ebb9d5e522b2
Source dataset
uspto-grants-2015_04
Patent number
US08999989B2

Reaction notes

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