Acetamide → 3-bromo-5-fluoro-4-(5-methyl-1H-1,2,4-triazol-1-yl)pyridine

HRID 524922Notes

Reaction equation

HRID 524922 reaction equation
[C:1](N)(=O)C.COC(OC)[N:8]([CH3:10])[CH3:9].[Br:13][C:14]1[CH:15]=[N:16][CH:17]=[C:18]([F:22])[C:19]=1[NH:20][NH2:21].O1CCOCC1CC(O)=O>O1CCOCC1>[Br:13][C:14]1[CH:15]=[N:16][CH:17]=[C:18]([F:22])[C:19]=1[N:20]1[C:10]([CH3:1])=[N:8][CH:9]=[N:21]1

Participants

6

Reactant 4

HCID 178AcetamideHCID 78373Dimethylformamide dimethyl acetalHCID 184692262-(1,4-Dioxan-2-yl)acetic acidHCID 867209763-Bromo-5-fluoro-4-hydrazinylpyridine

Product 1

HCID 867209773-bromo-5-fluoro-4-(5-methyl-1H-1,2,4-triazol-1-yl)pyridine

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

Acetamide (136.7 mg, 2.315 mmol), 1,1-dimethoxy-N,N-dimethyl-methanamine (382.0 mg, 425.9 μL, 3.206 mmol), in dioxane was heated at 45-50° C. under 150 mm Hg vacuum for 2 h. The reaction mixture was concentrated in vacuo. To the residue, (3-bromo-5-fluoro-4-pyridyl)hydrazine (367 mg, 1.781 mmol) and dioxane-acetic acid (1/1) was added and the mixture was heated at 130° C. for 1 h then at 160° C. for 2 h. At RT, the residue was loaded on a SCX column, washed with MeOH/DCM mixture. The filtrate is concentrated in vacuo yielding pure 3-bromo-5-fluoro-4-(5-methyl-1H-1,2,4-triazol-1-yl)pyridine as a dark oil. MS (ES+) 257.0.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customAt RT
  3. washwashed with MeOH/DCM mixture
  4. concentrationThe filtrate is concentrated in vacuo

Sources & evidence

ORD record
ord-e2a40c80f98443f4ab858a9775ce0ca1
Source dataset
uspto-grants-2016_05
Patent number
US09340546B2

Reaction notes

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