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

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 [280] 1H-pyrazol-3-amine (305 mg, 3.671 mmol, 1.0 eq), To a stirred solution of tert-butyl 4-[(2-{[6-(4, 4, 5, 5-tetramethyl- 1 , 3, 2-dioxaborolan-2-yl)-1 Hbenzimidazol-2-yl]am ino}pyridin-4-yl)methyl]piperazine-1 -carboxylate (800 mg, 1.50 mmol) in 1-propanol (17 mL) was added a potassium carbonate solution (2.2 mL, 2.0 M, 4.5 mmol), Example 245. 4-(2-(l-(3-Chloro-2-fluorophenyl)-lH-l, 2, 3-triazole-4-carbonyl)- 5-(l -methyl- 1H- 1 , 2, 4-triazol-5-yl)- 1 , 2, 3 , 4-tetrahydroisoquinoline- 1 -carboxamido) benzoic acid, TFA salt: Intermediate 44 (0.050 g, 0.071 mmol), 5-bromo-l -methyl- 1H- 1, 2, 4-triazole (0.017 g, 0.107 mmol), and Na2C03 (2.0M aq. solution) (0.178 mL, 0.356 mmol) were added to dioxane (1.0 mL) and degassed for 15 min. Tetrakis (triphenylphosphine)palladium(O) (8.23 mg, 7.12 muiotaetaomicron) was added and the mixture was irradiated at 120 C for 15 min. The reaction mixture was poured into EtOAc, washed with saturated aHC03 solution, brine, dried over sodium sulfate, filtered, and concentrated. The /-butyl ester group was removed was treatment with 50% TFA/DCM, concentrated, purified by reverse phase prep. HPLC, and freeze-dried to give the title compound as a white solid (14.3 mg, 27%). NMR (400MHz, DMSO-d6) delta 11.02 (s, 1H), 9.21 - 9.15 (m, 1H), 8.14 - 8.05 (m, 1H), 7.93 - 7.84 (m, 5H), 7.75 (d, J = 8.8 Hz, 2H), 7.54 - 7.45 (m, 3H), 6.05 (s, 1H), 4.51 - 4.40 (m, 1H), 4.19 (ddd, J = 12.7, 8.3, 4.2 Hz, 1H), 3.76 (s, 3H), 3.11 - 3.02 (m, 1H), 2.91 - 2.81 (m, 1H) ppm. MS (ESI) m/z: 601(M+H)+. Analytical HPLC: RT = 6.14 min (Method B).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 Example 249.; Preparation of 3-[3-chloro-4-(2-methyl-2H-[1, 2, 4]triazol-3-yl)-thiophen-2-yl]-8-(1-ethyl- propyl)-2, 6-dimethyl-imidazo[1, 2-b]pyridazine.; To a flask of 3-(4-bromo-3-chloro~thiophen-2-yl)-8-(1-ethyl-propyl)-2, 6- dimethyl-imidazo[1, 2-b]pyridazine (0.20 g, 0.49 mmol) is added 0.5 g/ mL Reike Zn (1.3 mL, 0.97 mmol). The slurry is heated at 65 C for 1 hour, placed in a centrifuge for 5 minutes, and the solution transferred to a flask containing 5-bromo-1-methyl-1H- [1, 2, 4]triazole (0.12 g, 0.73 mmol) and PdCl2(dppf) (0.018 g, 0.024 mmol). The EPO

Molecular Weight:161.99
XLogP3:1
Hydrogen Bond Acceptor Count:2
Exact Mass:160.95886
Monoisotopic Mass:160.95886
Topological Polar Surface Area:30.7
Heavy Atom Count:7
Complexity:67.2
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes