6-Chloro-2-methoxy-3-pyridinecarboxaldehyde

To a solution of 2-chloro-6-methoxypyridine (5 g, 34.82 mmol) in THF (100 mL), cooled to −78° C. was added 2, 6-Dichloronicotinaldehyde (1 g, 5.68 mmol) was diluted with sodium methoxide (11.4 mL, 5.68 mmol) (solution in methanol) and heated to 55°C. After stirring for 3 hours, the reaction was loaded directly onto a silica gel column and eluted with 5percent ethyl acetate/hexanes to 50percent ethyl acetate/hexanes to yield 6-chloro-2- methoxynicotinaldehyde (0.695 g, 4.05 mmol, 71.3 percent yield).A solution of 2?, 2?-dichloro-3-(difluoromethoxy)-3?-(4, 4, 5, 5-tetramethyl-l, 3, 2-dioxaborolan-2- yl)-[l, r:3?, l?-terphenyl]-4-carbaldehyde (218 mg, 0.42 mmol), 6-Chloro-2-methoxynicotinaldehyde (36 mg, 0.21 mmol) and (3-bromo-2-chloro-5- fluorophenyl)boronic acid (46 mg, 0.18 mmol) dissolved in l, 4-dioxane (3 mL) were treated with tetrakis(triphenylphosphine)palladium(0) (14 mg, 0.012 mmol) and potassium carbonate (50 mg, 0.36 mmol) dissolved in water. The reaction mixture was heated in the microwave at 110 C for 30 min. (1582) After cooling to room temperature, the reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic layer was dried over sodium sulfate and filtered. The filtrate was concentrated and purified by ISCO silica gel chromatography to give 6-(3-bromo-2-chloro-5- fluorophenyl)-2-methoxynicotinaldehyde.6-Chloro-2-methoxynicotinaldehyde (62 mg, 0.36 mmol) and 2-((6-(2, 2?-dichloro-3?-(4, 4, 5, 5- tetramethyl- 1 , 3 , 2-dioxaborolan-2-yl)-[ 1 , 1' -biphenyl]-3 -yl)-3 -formylpyridin-2-yl)oxy)acetonitrile (130 mg, 0.26 mmol) dissolved in l, 4-dioxane (6 mL) were treated with (1553) tetrakis(triphenylphosphine)palladium(0) (18 mg, 0.016 mmol) and potassium carbonate (70 mg, 0.51 mmol) dissolved in water. The reaction mixture was heated in the microwave at 110 C for 1 h. After cooling to room temperature, the reaction mixture was concentrated. The residue was dissolved in ethyl acetate and washed with water and brine. The organic layer was dried over sodium sulfate and filtered. The filtrate was concentrated and purified by ISCO silica gel chromatography to provide 2-((6-(2, 2?- dichloro-3' -(5 -formyl-6-methoxypyridin-2-yl)- [ 1 , G -biphenyl] -3 -yl)-3 -formylpyridin-2- yl)oxy)acetonitrile .

Molecular Weight:171.58
XLogP3:1.6
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:171.0087061
Monoisotopic Mass:171.0087061
Topological Polar Surface Area:39.2
Heavy Atom Count:11
Complexity:142
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes