Diacetamide → 1-(2-Bromo-5-fluorophenyl)-3,5-dimethyl-1H-1,2,4-triazole

HRID 1372340Notes

Reaction equation

HRID 1372340 reaction equation
Cl.[Br:2][C:3]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][C:4]=1[NH:10][NH2:11].[CH3:12][C:13]([NH:15][C:16]([CH3:18])=O)=O>N1C=CC=CC=1>[Br:2][C:3]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][C:4]=1[N:10]1[C:16]([CH3:18])=[N:15][C:13]([CH3:12])=[N:11]1

Participants

4

Reactant 2

HCID 12263DiacetamideHCID 21069774(2-Bromo-5-fluorophenyl)hydrazine hydrochloride

Product 1

HCID 210697671-(2-Bromo-5-fluorophenyl)-3,5-dimethyl-1H-1,2,4-triazoleYield 89.6%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A mixture of 1-(2-bromo-5-fluoro-phenyl)-hydrazine hydrochloride (24.15 g, 100 mmol) and diacetamide (10.1 g, 100 mmol; Aldrich) in anhydrous pyridine (100 mL) was stirred in an oil bath heated at 125–130° C. under nitrogen for 2 h. After cooling the mixture was concentrated in vacuo to dryness, and the residue diluted with EtOAc (100 mL) was washed with water (50 mL), and then with brine (30 mL), dried (Na2SO4), filtered and concentrated to obtain 24.2 g of the title compound as a brownish oil: HPLC rt=1.59 min. LC/MS m/z 270/272 (M+H); 1H NMR (CDCl3, 500 MHz) δ ppm 2.30 (3H, s, 9-Me), 2.39 (3H, s, 10-Me), 7.10–7.15 (2H, m, 3,5-CH), 7.67 (1H, dd, J=8.5, 5.5 Hz, 6-H); 13C NMR (CDCl3, 125.8 Hz) δ ppm 12.4 (9-CH3), 13.8 (10-Me), 116.5 (d, J=4 Hz, 1-C), 117.2, (d, J=24 Hz, 3-CH), 118.9 (d, J=22 Hz, 5-CH), 134.7 (d, J=8.5 Hz, 6-CH), 137.8 (d, J=10 Hz, 2-C), 153.9 (7-C), 160.9 (8-C), 161.8 (d, J=251 Hz, 4-CF); HRMS (ESI) calcd for C10H10BrFN3 (M+H) 270.0042. found 270.0048 (δ +2.2 ppm). This triazole was also prepared in 62% yield from 1-(2-bromo-5-fluoro-phenyl)-hydrazine hydrochloride and 2,4,6-trimethyl-s-triazine by refluxing them in EtOH.

Workup

  1. temperatureheated at 125–130° C. under nitrogen for 2 h
  2. temperatureAfter cooling the mixture
  3. concentrationwas concentrated in vacuo to dryness
  4. additionthe residue diluted with EtOAc (100 mL)
  5. washwas washed with water (50 mL)
  6. dry with materialwith brine (30 mL), dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-752b5fc5e93140c9bf3ac1a55fb7d090
Source dataset
uspto-grants-2007_01
Patent number
US07157447B2

Reaction notes

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