Methional → 3-(2-Fluoro-4-methylphenyl)-5-(2-(methylthio)ethyl)-4-phenyl-1H-pyrazole

HRID 1471931Notes

Reaction equation

HRID 1471931 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[C:9](=O)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:28][S:29][CH2:30][CH2:31][CH:32]=O.O.[NH2:35][NH2:36]>C1COCC1.CCO>[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:10]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[C:32]([CH2:31][CH2:30][S:29][CH3:28])[NH:36][N:35]=1

Participants

7

Reactant 4

HCID 18635MethionalHCID 24654Hydrazine hydrate (1:1)HCID 2733832Lithium HexamethyldisilazideHCID 673846201-(2-Fluoro-4-methylphenyl)-2-phenylethanone

Product 1

HCID 673847713-(2-Fluoro-4-methylphenyl)-5-(2-(methylthio)ethyl)-4-phenyl-1H-pyrazoleYield 49%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-(2-fluoro-4-methylphenyl)-2-phenylethanone (2.0 g, 8.76 mmol) in THF (10 mL) was added LiHMDS (1.0 M in THF) (17.52 mL, 17.52 mmol) slowly via syringe at 0° C. After stirring for 10 min, 1-0H-benzo[d][1,2,3]triazol-1-yl)-3-(methylthio)propan-1-one (2.327 g, 10.51 mmol) was added in one portion. The reaction was stirred at 0° C. for 30 min before quenched with AcOH (2 mL). To the reaction were added EtOH (30 mL), hydrazine hydrate (1.316 g, 26.3 mmol), and brought to reflux for 2 h. After cooled to room temperature, the reaction was concentrated and extracted with EtOAc/H2O, washed with brine, dried over MgSO4, and purified by column chromatography to give the title compound as a clear oil (1.40 g). LCMS m/z=327.2 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 1.94 (s, 3H), 2.22 (s, 3H), 2.65 (t, J=7.33 Hz, 2H), 2.88 (t, J=7.58 Hz, 2H), 6.71 (d, J=7.83 Hz, 1H), 6.80 (d, J=11.87 Hz, 1H), 6.97 (t, J=7.96 Hz, 1H) 7.09-7.29 (m, 5H), 9.64 (bs, 1H).

Workup

  1. stirringThe reaction was stirred at 0° C. for 30 min
  2. custombefore quenched with AcOH (2 mL)
  3. temperatureto reflux for 2 h
  4. concentrationthe reaction was concentrated
  5. extractionextracted with EtOAc/H2O
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. custompurified by column chromatography

Sources & evidence

ORD record
ord-7ed988ece90e49bfba2a575f165afb08
Source dataset
uspto-grants-2015_04
Patent number
US09012478B2

Reaction notes

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