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

HRID 1188343Notes

Reaction equation

HRID 1188343 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].C1N=CN(C(N2C=NC=C2)=O)C=1.[NH2:32][NH2:33]>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:32][NH2:33])=[O:15]

Participants

5

Reactant 3

HCID 9321HydrazineHCID 682631,1'-Carbonyldiimidazole3×HCID 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 CDI (0.030 g, 0.184 mmol). The mixture was stirred at rt for 4 h and additional CDI (0.030 g, 0.184 mmol) was added. After 45 min, additional CDI (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. waitAfter 45 min
  2. waitAfter 5 min
  3. stirringthe mixture was stirred at rt for 30 min
  4. customThe mixture was partitioned between EtOAc and 0.2N NaOH
  5. washThe organic phase was washed with 0.2N NaOH
  6. extractionThe combined aqueous phases were extracted with EtOAc (×2)
  7. washThe second EtOAc phases were washed with sat'd NaHCO3 solution and brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash chromatography (0-10% MeOH—CH2Cl2 gradient)

Sources & evidence

ORD record
ord-2c75c3ae12284d96a8cafbbfd16d230f
Source dataset
uspto-grants-2014_03
Patent number
US08673948B2

Reaction notes

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