4-Chloro-2-methoxyphenylboronic acid

Synthesis of Intermediate I-1 10262] 22.1 g (100 mmol) of 2-bromo-5-chioroanisole was dissolved in 500 ml of THF, and stirred in a N2 atmosphere at—78° C. for 10 minutes. Then, 44 mL of 2.5 M n-BuLi was slowly added thereto by using a dropping funnel, and the mixture was additionally stirred for 30 minutes. 10.4 g (110 mmol) of trimethyl borate was slowly and dropwisely added thereto by using a dropping flannel, and the mixture was additionally stirred for 3 hours at room temperature. Next, an organic layer was extracted therefrom once by using 300 ml of 1 M HC1 and three times by using water and diethylether. The organic layer was dried using magnesium sulfate, and a solvent was removed thereform by evaporation. The residue was separated and purified through a silica gel chromatography to obtain 13.61 g of Intermediate 1-1 (73 mmol, yield:73percent). The compound thus obtained was confirmed by usingMS/FAB.10263] C7H8BC103 Cal. 186.40. Found. 186.47.10272] 5.2 g (23.6 mmol) of 2-bromo-5-chloroanisole was dissolved in 100 mE of tetrahydroffiran (THF). 10 mE (25.0 mmol) of n-l3uEi (2.5M in hexane) was slowly added drop- wise thereto at —78° C. The result was stirred at the same temperature for 1 hour. Then, 9.3 mE (50.0 mmol) of trim- ethyl borate was slowly added dropwise thereto, and stirred for 24 hours at room temperature. Once the reaction was complete, 10percent aqueous HC1 solution was added thereto to adjust pH to about 5. Then, an organic layer was extracted three times therefrom by using diethylether. The obtained organic layer was dried by using magnesium sulfate (Mg504). Then, a solvent was removed therefrom by evaporation. The obtained residue was purified by recrystallization, thereby obtaining 3.15 g of Intermediate 1-1 (yield: 50percent).[0836] A mixture tert-butyl (lR, 3s, 5S)-3-((6-chloropyridazin-3-yl)(methyl)amino)-8-azabicyclo[3.2.1]octane-8-carboxylate (300 mg, 0.85 mmol), [0826] A mixture of 6-chloro-N-cyclopropyl-N-(2, 2, 6, 6-tetramethylpiperidin-4-yl)pyridazin-3-amine (160 mg, 0.52 mmol), Synthesis of 3, 5-dichloro-2, 6-bis (4-chloro-2-methoxyphenyl) pyridineIn an argon atmosphere, 2, 3, 5, 6-tetrachloropyridine (2.65 g), (52 mg, 0.27 mmol), compound 2-a (75 mg, 0.23 mmol) and sodium carbonate (73 mg, 0.69 mmol) were suspended in dioxane (1.2 mL) and water (0.3 mL), and [1, 1'-bis (diphenylphosphino)ferrocene]dichloropalladium.dichloromethane (17 mg, 0.02 mmol) was added. The mixture was purged with nitrogen gas for three times and heated at 90 C. under microwave for 1 hour. After cooling to room temperature, the reaction solution was added with water (30 mL) and extracted with dichloromethane (50 mL*2). The combined organic phase was dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel TLC preparative plate (ethyl acetate) to give 6 as a pale yellow solid (30 mg, yield 23%). LC-MS (ESI): m/z=385[M+H]+. 1H NMR (400 MHz, DMSO-d6) delta: 9.43 (s, 1H), 8.95 (s, 1H), 7.657 (s, 1H), 7.19-7.38 (m, 4H), 3.76 (s, 3H), 3.70 (s, 3H), 2.42 (s, 3H) ppm

suzuki reaction

Molecular Weight:186.40
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:186.0255020
Monoisotopic Mass:186.0255020
Topological Polar Surface Area:49.7
Heavy Atom Count:12
Complexity:145
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes