Hydrazine → HCID 178505667, compound

HRID 1993629Notes

Reaction equation

HRID 1993629 reaction equation
[C:1](/[N:9]=[C:10](\SC)/[NH:11][C@:12]([C:27]1[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:30]=[C:29]([F:37])[CH:28]=1)([C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:40][NH2:41]>CC#N.[N+]([O-])([O-])=O.[Ag+]>[F:37][C:29]1[CH:28]=[C:27]([C@@:12]([NH:11][C:10]2[NH:9][C:1]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[N:41][N:40]=2)([C:20]2[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=2)[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:32]=[C:31]([C:33]([F:34])([F:35])[F:36])[CH:30]=1

Participants

5

Reactant 2

HCID 9321HydrazineHCID 178503942HCID 178503942, compound

Product 1

HCID 178505667HCID 178505667, compoundYield 69.2%

Reagents, catalysts & solvents 2

HCID 24470Silver NitrateCatalystHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of (S,Z)-methyl N′-benzoyl-N-(1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)carbamimidothioate (58 mg, 0.1 mmol) and TEA (28 μL, 0.2 mmol) in CH3CN (1 mL) was added drop wise a solution of AgNO3 (26 mg, 0.15 mmol) in CH3CN (1 mL), followed by the addition of NH2NH2 (10 μL, 0.1 mmol). The reaction mixture was heated at 60° C. for 1 h and allowed to cool to room temperature. The solid was removed by filtration and the filtrate was concentrated. The residue was purified by ISCO chromatography (4 g column) using hexanes/EtOAc (0-30%) over 10 min to give (S)-N-(1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-5-phenyl-4H-1,2,4-triazol-3-amine as a white solid (36 mg, 69% yield). LCMS: RT=4.25 min [M+H] 520.97 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm). NMR: 400 MHz 1H (CDCl3) 7.77 ppm, 2H, dd, J=7.83, 1.52 Hz; 7.37 ppm, 4H, m; 7.26 ppm, 4H, m; 7.10 ppm, 3H, m; 6.98 ppm, 2H, m; 6.63 ppm, 2H, d, J=7.33 Hz; 3.97 ppm, 1H, m; 3.85 ppm, 1H, m.

Workup

  1. temperatureto cool to room temperature
  2. customThe solid was removed by filtration
  3. concentrationthe filtrate was concentrated
  4. customThe residue was purified by ISCO chromatography (4 g column)
  5. customover 10 min

Sources & evidence

ORD record
ord-a1b1ba3ce865472bafbbf3ce386419f3
Source dataset
uspto-grants-2010_01
Patent number
US07652023B2

Reaction notes

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