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

HRID 1726669Notes

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

Conditions

Temperature: 127.5 °C

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

temperatureAfter cooling the mixture
concentrationwas concentrated in vacuo to dryness
additionthe residue diluted with EtOAc (100 mL)
washwas washed with water (50 mL)
dry with materialwith brine (30 mL), dried (Na2SO4)
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-8d577fdb8cb04c5a96397a24cb80ab75
Source dataset: uspto-grants-2009_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07491819B1

Reaction notes

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