1,1'-Carbonyldiimidazole → 2-((2S)-1-[(4-fluorophenyl)sulfonyl]-2-piperidylcarbonyl)-1-hydrazinecarbothioamide

HRID 397669Notes

Reaction equation

HRID 397669 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[F:13][C:14]1[CH:19]=[CH:18][C:17]([S:20]([N:23]2[CH2:28][CH2:27][CH2:26][CH2:25][C@H:24]2[C:29]([OH:31])=O)(=[O:22])=[O:21])=[CH:16][CH:15]=1.[NH2:32][NH:33][C:34]([NH2:36])=[S:35]>O1CCCC1.O1CCOCC1>[F:13][C:14]1[CH:19]=[CH:18][C:17]([S:20]([N:23]2[CH2:28][CH2:27][CH2:26][CH2:25][C@H:24]2[C:29]([NH:32][NH:33][C:34](=[S:35])[NH2:36])=[O:31])(=[O:22])=[O:21])=[CH:16][CH:15]=1

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 768662(2S)-1-[(4-fluorophenyl)sulfonyl]-2-piperidinecarboxylic acidHCID 2723789Thiosemicarbazide

Product 1

HCID 572149072-((2S)-1-[(4-fluorophenyl)sulfonyl]-2-piperidylcarbonyl)-1-hydrazinecarbothioamideYield 49.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

1,1′-Carbonyidimidazole (195 mg) was added to a solution of (2S)-1-[(4-fluorophenyl)sulfonyl]-2-piperidinecarboxylic acid (287 mg) [see Preparation 38] in tetrahydrofuran (5 ml). The reaction mixture was stirred and heated under reflux for 1 hour and then evaporated under reduced pressure to afford a yellow gum. The gum was dissolved in 1,4-dioxane (5 ml) and thiosemicarbazide (182 mg) was added. The reaction mixture was heated under reflux for 1.25 hour. After this time the cooled mixture was purified by column chromatography on MCI (trade mark) reverse phase gel eluting with a solvent gradient of 30:70 changing to 70:30, by volume, methanol:water to afford 2-((2S)-1-[(4-fluorophenyl)sulfonyl]-2-piperidylcarbonyl)-1-hydrazinecarbothioamide (178 mg) as a white foam.

Workup

  1. temperatureheated
  2. temperatureunder reflux for 1 hour
  3. customevaporated under reduced pressure
  4. customto afford a yellow gum
  5. temperatureThe reaction mixture was heated
  6. temperatureunder reflux for 1.25 hour
  7. customAfter this time the cooled mixture was purified by column chromatography on MCI (trade mark) reverse phase gel
  8. washeluting with a solvent gradient of 30:70 changing to 70:30, by volume, methanol

Sources & evidence

ORD record
ord-c077697144bc487f873c7115df7b3de4
Source dataset
uspto-grants-2003_08
Patent number
US06610707B1

Reaction notes

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