5-bromo-1-methyl-1,2,4-triazole synthesis

Yield: 64%

Reaction Conditions:

Stage #1:1-methyl-1H-1,2,4-triazole with n-butyllithium in tetrahydrofuran at -78; for 0.75 h;
Stage #2: with 1,2-dibromo-1,1,2,2-tetrafluoroethane in tetrahydrofuran at 20; for 2 h;
Stage #3: with water;ethyl acetatemore than 3 stages;

Steps:

133.A; 133.C
Example 133.; Preparation of 8-(1-ethyl-propyl)-3-[3-methoxy-5-(2-methyl-2H-[1,2,4]triazol-3-yl)- thiophen-2-yl]-2,6-dimethyl-imidazo[1,2-b]pyridazine.; A. 5-Bromo-1-methyl-1H-[1,2,4]triazole.; EPO To a -78 °C solution of l-methyl-1H-[1,2,4]triazole (1.0 mL, 13.20 mmol) and TΗF (100 mL) is added 1.6 M n-BuLi (8.70 mL, 13.86 mmol). After 45 minutes 1,2- dibromo-l,1,2,2-tetrafluoro-ethane (1.76 mL, 14.52 mmol) is added, the solution is warmed to ambient temperature and stirred for 2 hours. The solution is diluted with EtOAc (200 mL), washed with water (150 mL), brine (150 mL), dried over MgSO₄, filtered and concentrated to furnish the title compound (1.37 g, 8.46 mmol, 64%). ¹H NMR (CDCl₃) δ 3.82 (s, 3H), 7.78 (s, 1H). LC/MS (m/z): calcd. for C₃H₄BrN₃ (M+H)⁺: 162.0; found: 161.9.

References:

ELI LILLY AND COMPANY WO2006/102194, 2006, A1 Location in patent:Page/Page column 117-118