1,1'-Carbonyldiimidazole → Tert-butyl 2-[(4-{2-[2-(acetylamino)-1,3-thiazol-4-yl]ethyl}benzyl)carbamoyl]hydrazinecarboxylate

HRID 1892518Notes

Reaction equation

HRID 1892518 reaction equation
[C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].[C:13]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])(=[O:16])[NH:14][NH2:15].[NH2:22][CH2:23][C:24]1[CH:29]=[CH:28][C:27]([CH2:30][CH2:31][C:32]2[N:33]=[C:34]([NH:37][C:38](=[O:40])[CH3:39])[S:35][CH:36]=2)=[CH:26][CH:25]=1>O1CCCC1>[C:38]([NH:37][C:34]1[S:35][CH:36]=[C:32]([CH2:31][CH2:30][C:27]2[CH:28]=[CH:29][C:24]([CH2:23][NH:22][C:1]([NH:15][NH:14][C:13]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[O:2])=[CH:25][CH:26]=2)[N:33]=1)(=[O:40])[CH3:39]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 70091tert-Butyl carbazateHCID 21915165N-(4-{2-[4-(aminomethyl)phenyl]ethyl}-1,3-thiazol-2-yl)acetamide

Product 1

HCID 86650019Tert-butyl 2-[(4-{2-[2-(acetylamino)-1,3-thiazol-4-yl]ethyl}benzyl)carbamoyl]hydrazinecarboxylateYield 78.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 1,1′-carbonyldiimidazole (332.1 mg, 2.048 mmol) in anhydrous tetrahydrofuran (1.3 ml) was added tert-butyl carbazate (270.7 mg, 2.048 mmol). After stirring at room temperature for 15 min, N-(4-{2-[4-(aminomethyl)phenyl]ethyl}-1,3-thiazol-2-yl)acetamide (282.6 mg, 1.024 mmol) was added, and the mixture was stirred at room temperature for 6 hr and concentrated under reduced pressure. Ethyl acetate and water were added to the residue, and the mixture was stirred, stood still and then partitioned. The aqueous layer was extracted with ethyl acetate, and the combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (FUJI SILYSIA CHEMICAL LTD. BW-300SP 24 g, dichloromethane:methanol=30:1→20:1). The residue was further purified by silica gel column chromatography (FUJI SILYSIA CHEMICAL LTD. DM-2035 16 g, dichloromethane:methanol=30:1) to give tert-butyl 2-[(4-{2-[2-(acetylamino)-1,3-thiazol-4-yl]ethyl}benzyl)carbamoyl]hydrazinecarboxylate (348.3 mg, 0.803 mmol, yield 78.5%) as a white solid.

Workup

  1. stirringthe mixture was stirred at room temperature for 6 hr
  2. concentrationconcentrated under reduced pressure
  3. additionEthyl acetate and water were added to the residue
  4. stirringthe mixture was stirred
  5. custompartitioned
  6. extractionThe aqueous layer was extracted with ethyl acetate
  7. washthe combined organic layer was washed with saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (FUJI SILYSIA CHEMICAL LTD. BW-300SP 24 g, dichloromethane:methanol=30:1→20:1)
  11. customThe residue was further purified by silica gel column chromatography (FUJI SILYSIA CHEMICAL LTD. DM-2035 16 g, dichloromethane:methanol=30:1)

Sources & evidence

ORD record
ord-ccfaf73112b84f87bb627e6b2ddb9714
Source dataset
uspto-grants-2013_08
Patent number
US08507690B2

Reaction notes

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