Hydrazine → 2-[4-Chloro-5-cyano-2-(difluoromethyl)-1H-indol-1-yl]acetohydrazide

HRID 2101850Notes

Reaction equation

HRID 2101850 reaction equation
[Cl:1][C:2]1[C:10]([C:11]#[N:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH:17]([F:19])[F:18])[N:6]2[CH2:13][C:14](O)=[O:15].[NH2:20][NH2:21]>C1COCC1>[Cl:1][C:2]1[C:10]([C:11]#[N:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH:17]([F:19])[F:18])[N:6]2[CH2:13][C:14]([NH:20][NH2:21])=[O:15]

Participants

4

Reactant 2

HCID 9321HydrazineHCID 57800318[4-chloro-5-cyano-2-(difluoromethyl)-1H-indol-1-yl]acetic acid

Product 1

HCID 578001332-[4-Chloro-5-cyano-2-(difluoromethyl)-1H-indol-1-yl]acetohydrazideYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [4-chloro-5-cyano-2-(difluoromethyl)-1H-indol-1-yl]acetic acid (0.050 g, 0.175 mmol) in anhydrous THF (2 mL), under N2, was added CDl (0.030 g, 0.184 mmol). The mixture was stirred at rt for 4 h and additional CDl (0.030 g, 0.184 mmol) was added. After 45 min, additional CDl (0.079 g, 0.49 mmol) was added. After 5 min, hydrazine (0.112 g, 3.5 mmol) was added and the mixture was stirred at rt for 30 min. The mixture was partitioned between EtOAc and 0.2N NaOH. The organic phase was washed with 0.2N NaOH and sat'd brine. The combined aqueous phases were extracted with EtOAc (×2). The second EtOAc phases were washed with sat'd NaHCO3 solution and brine. The organic phases were combined, dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (0-10% MeOH—CH2Cl2 gradient) to afford the title compound (0.027 g, 52% yield): MS (ES) m/z 299 (M+1).

Workup

  1. additionadditional CDl (0.030 g, 0.184 mmol) was added
  2. waitAfter 45 min
  3. additionadditional CDl (0.079 g, 0.49 mmol) was added
  4. waitAfter 5 min
  5. stirringthe mixture was stirred at rt for 30 min
  6. customThe mixture was partitioned between EtOAc and 0.2N NaOH
  7. washThe organic phase was washed with 0.2N NaOH
  8. extractionThe combined aqueous phases were extracted with EtOAc (×2)
  9. washThe second EtOAc phases were washed with sat'd NaHCO3 solution and brine
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by flash chromatography (0-10% MeOH—CH2Cl2 gradient)

Sources & evidence

ORD record
ord-926738f418dc417695f494721487e1a8
Source dataset
uspto-grants-2009_08
Patent number
US07572820B2

Reaction notes

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