Hydrazine → 6-bromo-N-methyl-1H-indazol-3-amine

HRID 537178Notes

Reaction equation

HRID 537178 reaction equation
[NH2:1][NH2:2].[Br:3][C:4]1[CH:13]=[CH:12][C:7]([C:8](=S)[NH:9][CH3:10])=[C:6](F)[CH:5]=1>CS(C)=O.C(OCC)(=O)C.O>[Br:3][C:4]1[CH:5]=[C:6]2[C:7]([C:8]([NH:9][CH3:10])=[N:1][NH:2]2)=[CH:12][CH:13]=1

Participants

6

Reactant 2

HCID 9321HydrazineHCID 866646184-bromo-2-fluoro-N-methylbenzothioamide

Product 1

HCID 589553326-bromo-N-methyl-1H-indazol-3-amineYield 54.2%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

Anhydrous hydrazine (0.25 mL, 8.1 mmol) was added to a solution of 4-bromo-2-fluoro-N-methylbenzothioamide (200 mg, 0.8 mmol) in dimethylsulfoxide (2.5 mL). The reaction was heated to 100° C. and stirred for 2 hours. The reaction was cooled to room temperature and diluted with ethyl acetate and water. The layers were separated and the aqueous was extracted with ethyl acetate (3×). The combined organics were washed with saturated aqueous sodium carbonate and brine, dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography (20-100% ethyl acetate/heptanes) gave the title compound (98 mg, 54%) as a white solid. +ESI (M+H+1) 228.0; 1H NMR (400 MHz, CD3OD, δ): 7.52 (d, J=8.58 Hz, 1H), 7.43 (s, 1H), 7.04 (d, J=8.39 Hz, 1H), 2.94 (s, 3H).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customThe layers were separated
  3. extractionthe aqueous was extracted with ethyl acetate (3×)
  4. washThe combined organics were washed with saturated aqueous sodium carbonate and brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by flash column chromatography (20-100% ethyl acetate/heptanes)

Sources & evidence

ORD record
ord-b005fbbd64db4740966e0fcf60cbc778
Source dataset
uspto-grants-2014_10
Patent number
US08859773B2

Reaction notes

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