5-Bromo-2,3-dimethoxypyridine

As shown in step 2-iv of Scheme 2, a solution of compound 1004 (13.0 g, 43.8 mmol) and 25 wt percent NaOMe in methanol (95.0 mL, 438.3 mmol) was stirred for 3 hours at 75° C.To a 25ml flask containing (63.8mg, 1.2mmol) of sodium ethoxide was added 3ml dry ethanol. The mixture was stirred for 30min. 2-Chloro-3-methoxy-5-bromopyridine (230mg, 1.04mmol) was added to the mixture and heated to 60°C for 16h. The reaction was allowed to cool and the solvent was removed. Ethyl acetate (50ml) was added to the residue. The ethyl acetate solution was washed with water and then brine. The organic solvent was dried and concentrated under reduced pressure, and purified by ISCO flash chromatography using 10percent ethyl acetate in hexane to give 220mg (97percent yield) of the desired product. 5, 6-Dimethoxynicotinaldehyde (42) To a solution of a. Preparation of Compound To a solution of (d). 5, 6-dimethoxynicotinaldehvde To a solution of 5-Bromo-2, 3-dimethoxy-pyridine (43 g) in THF (500 ml) at -78C was added n- butyllithium (191 mmol). After stirring for 30 minutes at -78C DMF (28.8 g) was added dropwise and the reaction mixture was stirred at -78C for 2 hours. The reaction mixture was quenched with NH4CI (saturated in water, 500 ml). The aqueous layer was extracted with ethyl acetate, the organic phases were washed with brine, dried over Na2S04, filtered and concentrated. The crude product was purified by chromatography on silica eluting with heptane with increasing amounts of ethyl acetate. Yield: 33 gn-BuLi(4.90 mL, 2.0 M in cyclohexanes, 35.2 mmol) was added to a solution of2, 3-dimethoxypyridine (1.04 g, 7.5 mmol) was added to 30 mL of a dichloromethane solution, and then liquid bromine (1.12 g, 7.0 mmol) was added, and the reaction was performed at room temperature for 48 hours. After the reaction is completed, most of the solvent is concentrated and removed, and column chromatography (petroleum ether: ethyl acetate = 10: 1) is used to obtain the product Step 1. 3 -(5 , 6-Dimethoxy-3 -pyridinyl)imidazo [ 1 , 2-a]pyridine; (1) 5-Bromo-2, 3-dimethoxypyridine (41) To a stirring solution of 2, 3-dimethoxypyridine (40, 27.0 g, 194.0 mmol) in dichloromethane (200 mL) was added bromine (9.0 mL, 174.6 mmol). The reaction mixture was stirred at RT overnight. The pH value of the mixture was adjusted to 6 with saturated NaHCO3(aq). The mixture was extracted with dichloromethane (2*300 mL), washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated in vacuo. The residue was purified by flash chromatogram with ethyl acetate/petroleum ether (1:5) to afford 5-bromo-2, 3-dimethoxypyridine (41) as a yellow oil (22.0 g, 52%). ESI-MS, m/z=218 [M+H]+. (7-2)To a solution of 2, 3-dimthoxypyridine (7-1, 2.5 g, 18.0 mmol, 1.0 equiv) in dichloromethane: saturated NaHCO3 (80 mL: 40 mL) at 0 C was added bromine (0.93 itiL, 18.0 mmol, 1.0 equiv) and the reaction mixture was stirred for 2 h at 25 C. The reaction mixture was quenched with solid Na2SO3 (~10 g) and the aqueous phase was extracted with dichloromethane (3 x 100 mL). The organic phase was dried over magnesium sulfate and concentrated. The residue was purified via normal phase chromatography (0 to 20% EtOAc in hexanes, silica) to afford the desired product (7-2) as an oil after concentration. ESI+ MS [M+H]+ C7H8NO2 calc'd 218.0, found 218.0. (1-2)To a solution of 2, 3-dimthoxypyridine (1-1, 2.5 g, 18.0 mmol, 1.0 equiv) in dichloromethane:saturated NaHCO3 (80 mL: 40 mL) at 0 C. was added bromine (0.93 mL, 18.0 mmol, 1.0 equiv) and the reaction mixture was stirred for 2 h at 25 C. The reaction mixture was quenched with solid Na2SO3 (10 g) and the aqueous phase was extracted with dichloromethane (3×100 mL). The organic phase was dried over magnesium sulfate and concentrated. The residue was purified via normal phase chromatography (0 to 20% EtOAc in hexanes, silica) to afford the desired product (1-2) as an oil after concentration. ESI+MS [M+H]+C7H8NO2 calc'd 218.0. found 218.0.5-bromo-2.3-dimethoxypyridine (4-2)To a solution of 2, 3-dimthoxypyridine (41_, 2.5 g, 18.0 mmol, 1.0 equiv) in dichloromethane:saturated NaHCO3 (80 mL: 40 mL) at 00C was added bromine (0.93 mL, 18.0 mmol, 1.0 equiv) and the reaction mixture was stirred for 2 h at 25C. The reaction mixture was quenched with solid Na2SO3 (~10 g) and the aqueous phase was extracted with dichloromethane (3 x 100 mL). The organic phase was dried over magnesium sulfate and concentrated. The residue was purified via normal phase chromatography (0 to 20% EtOAc in hexanes, silica) to afford the desired product (42) as an oil after concentration. ESI+ MS [M+H]+ C7H8NO2 calc'd 218.0, found 218.0.(c). A mixture of

Molecular Weight:218.05
XLogP3:1.8
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:216.97384
Monoisotopic Mass:216.97384
Topological Polar Surface Area:31.4
Heavy Atom Count:11
Complexity:123
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes