4-BROMO-1,5-DIMETHYL-1H-1,2,3-TRIAZOLE

A mixture of tert-butyl 4-({[2-amino-5-(4, 4, 5, 5-tetramethyl-1 , 3, 2-dioxaborolan-2-yl)pyridin-3-yl]oxy}methyl)piperidine-1 -carboxylate (I-55) (500 mg, 1 .15 mmol), 4-bromo-1 , 5-dimethyl-1 /-/-1 , 2, 3-triazole (203 mg, 1 .15 mmol), Cs2C03 (2 M in water, 1 .15 mL, 2.31 mmol) in toluene (1 mL) and EtOH (3mL) was added Pd(PPh3)4 (20.3 mg, 0.1 15mmol). The mixture was thoroughly degassed before heating under nitrogen at 90 C for 14 hr. The mixture was concentrated under vacuum to dryness, and the residue purified by silica gel chromatography (petroleum ether/ EtOAc = 1 /1 to 0/1) to give the te/ -butyl 4-({[2-amino-5-(1 , 5-dimethyl-1 H-1 , 2, 3-triazol-4-yl)pyridin-3-yl]oxy}methyl)piperidine-1 -carboxylate (I-58) (300 mg, 86%) as a yellow solid, which was use in next step without further purification.Example 161: Preparation of 4-bromo-l, 5-dimethyl-lH-[1.2, 31triazole(A) (B)To a solution of 4, 5-dibromo- 1 -methyl- IH-[1 , 2, 3]triazole and 4, 5-dibromo-2- methyl-2H-[l, 2, 3]triazole (1.5 g, 6.23 mmol) (Example 160) in tetrahydrofuran (25 ml) at -SO0C, was slowly added n-butyl lithium (2.5M in TetaF) (3 ml, 7.48 mmol) followed 20 minutes later by methyl iodide (775 mul, 12.46 mmol). The reaction mixture was stirred at -800C for 2 hours. The reaction mixture was allowed to warm to room temperature and Example 122: Preparation of 4-bromo-l, 5-dimethyl-lH-[l, 2, 3~|triazole(A) (B)To a solution of 4, 5-dibromo-l-methyl-lH-[l, 2, 3]triazole and 4, 5-dibromo-2- methyl-2H-[l, 2, 3]triazole (1.5 g, 6.23 mmol) (Example 121) in tetrahydrofuran (25 ml) at -8CPQ was slowly added n-butyl lithium (2.5M in TetaF) (3 ml, 7.48 mmol) followed 20 minutes later by methyl iodide (775 mul, 12.46 mmol). The reaction mixture was stirred at -8(PC for 2 hours. The reaction mixture was allowed to warm to room temperature and quenched with by addition of aqueous hydrochloric acid (IM). The mixture was extracted with dichloromethane, the organic extract dried over magnesium sulfate and concentrated to give a mixture of 4-bromo-l, 5-dimethyl-lH-[l, 2, 3]triazole (isomer A) and 4-bromo-2, 5-dimethyl-2H-[l, 2, 3]triazole (isomer B) (1.096 g, 89% yield). Isomer A 1H-NMR (400 MHz, CDCl3): 2.30 (s, 3H, Me), 4.00 (s, 3H, Me) ppm. Isomer B 1H-NMR (400 MHz, CDCl3): 2.24 (s, 3H, Me), 4.10 (s, 3H, Me) ppm.Example 123: Preparation of 4-bromo-5-bromomethyl-l-methyl-lH-['l, 2, 3'|triazole and A- bromo-5-bromomethyl-2-methyl-2H-[L2, 3]triazole(A) (B) (C) (D)The mixture of 4-bromo-l, 5-dimethyl- IH-[1, 2, 3]triazole and 4-bromo-2, 5- dimethyl-2H-[l, 2, 3]triazole (Example 122) (950mg, 4.32 mmol) were dissolved in carbon tetrachloride (15ml). N-bromosuccinimide (NBS) (845mg, 4.75 mmol) and 2, 2'-azobis- isobutyronitrile (AIBN) (71 mg, 0.43 mmol) were added under nitrogen. The reaction mixture was stirred and irradiated with a UV lamp. After a short time, the mixture was refluxing with the heat of the lamp. The mixture was filtered, the solid was washed with dichloromethane and the combined filtrates were concentrated. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate / hexane) to give 4-bromo-

Molecular Weight:176.01
XLogP3:1.1
Hydrogen Bond Acceptor Count:2
Exact Mass:174.97451
Monoisotopic Mass:174.97451
Topological Polar Surface Area:30.7
Heavy Atom Count:8
Complexity:87.4
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes