6-Bromo-2-methoxy-3-pyridinamine

Brown powder

(2)To a mixture of 2-methoxypyridin-3-amine (4.95 g, 39.87 mmol) and DMF (50 mL) was added NBS (7.98 g, 44.84 mmol) at 0°C. After being stirred at 0°C for 1 h, the mixture was quenched with sat. NHSodium methoxide (176.2 g, 3.26 mol) was added in portions to a sol. of 3-amino-2, 6- dibromopyridine (100 g, 939 mmol) in 1, 4-dioxane (1 1) and the r.m. was stirred under reflux for 3 h. After cooling, the r.m. was poured onto a sat. aq. NHSynthesis of 6-bromo-2-methoxypyridin-3-amine [0311] To a stirred solution of 2, 6-dibromopyridin-3 -amine (38 g, 0.15 mol) in 1, 4- dioxane (400 mL) under argon atmosphere was added sodium methoxide (70.55 g, 1.30 mol) and stirred at reflux for 8 h. After consumption of the starting materials (monitored by TLC), the reaction was quenched with ice cold water (200 mL) and extracted with EtOAc (3 x 200 mL). The combined organic extracts were washed with cold water (2 x 100 mL), dried over sodium sulfate and concentrated in vacuo. The crude material was purified through silica gel column chromatography using 10percent EtOAc:hexanes to afford 6-bromo-2-methoxypyridin-3- amine (13 g, 42percent) as an off-white solid. 1H-NMR (CDC1To a stirred solution of 2, 6-dibromopyridin-3-amine (38 g, 0.188 mol) in 1, 4- dioxane (400 mL) under an argon atmosphere was added sodium methoxide (70.55 g, 1.30 mol) at room temperature. The reaction mixture was stirred at reflux for 8 h. After consumption of the starting material (monitored by TLC), the reaction mixture was quenched with ice cold water (200 mL) and extracted with EtOAc (3 x 200 mL). The combined organic extracts were washed with cold water (2 x 100 mL), dried over sodium sulfate and concentrated in vacuo. The crude material was purified by column chromatography using 10percent EtOAc:hexanes to afford 6-bromo-2-methoxypyridin-3-amine (13 g, 42percent) as a brown solid. Synthesis of 6-bromo-2-methoxypyridin-3-amine Sodium methoxide (176.2 g, 3.26 mol) was added in portions to a sol. of 3-amino-2, 6- dibromopyridine (100 g, 939 mmol) in 1, 4-dioxane (1 1) and the r.m. was stirred under reflux for 3 h. After cooling, the r.m. was poured onto a sat. aq. NH4C1 aq. sol (1 1). Additional NH4CI (150 g) and H20 (1 1) were added and the r.m. was stirred at r.t. for 30 min. Et20 (2 1) was added and the r.m. was stirred for 30 min. The layers were separated and the aq. layer was diluted with H20 (1.5 1) and further extracted with Et20 (6 x 0.5 1). The combined o.l. were treated with brine (2 x 0.5 1), dried (MgS04) and cone, under reduced pressure to give a black residue. The residue was purified by flash chromatography over silicagel (glas filter, eluent DCM). The product fractions were combined and cone, under reduced pressure to afford an orange-brownish solid residue. Yield: 67.2 g of intermediate 24 (78.3 %).Synthesis of To a stirred solution of 2, 6-dibromopyridin-3-amine (38 g, 0.188 mol) in 1, 4- dioxane (400 mL) under an argon atmosphere was added sodium methoxide (70.55 g, 1.30 mol) at room temperature. The reaction mixture was stirred at reflux for 8 h. After consumption of the starting material (monitored by TLC), the reaction mixture was quenched with ice cold water (200 mL) and extracted with EtOAc (3 x 200 mL). The combined organic extracts were washed with cold water (2 x 100 mL), dried over sodium sulfate and concentrated in vacuo. The crude material was purified by column chromatography using 10% EtOAc:hexanes to afford Synthesis of Part A: To 3.18 grams (25.6 mmol) of commercially available 5-amino-2-methoxypyridine in a solution of methylene chloride (50 ml) and methanol (20 ml) was added benzyltrimethylammonium tribromide (10 g, 25.6 mmol) and the mixture was stirred at room temperature for 24 hours. The solvent was then stripped and the resulting residue was taken up in water and extracted (3*100 mL) with ethyl acetate. The organic extracts were dried with magnesium sulfate, filtered, and concentrated in vacuo. The crude material was chromatographed on silica using 30% ethyl acetate in hexanes as solvent to afford General procedure: Added in DMF solution (15mL) the -40 of DMF solution (32mL) N- bromosuccinimide of the compound obtained in Reference Example 714(3.25g) (3.31g), 2 hours the reaction mixture at -25 It stirred. An aqueous solution of sodium thiosulfate was added, and the mixture was stirred for10 minutes at room temperature, was extracted twice with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, andconcentrated. The residue was purified by silica gel column chromatography, and purified by (solvent: hexane / ethyl acetate = 95 / 5-60 / 40) to givethe title compound (4.40 g).MS (ESI) M / Z; 271, 273 [M Tasu H] TasuAt room temperature,

Molecular Weight:203.04
XLogP3:1.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:201.97418
Monoisotopic Mass:201.97418
Topological Polar Surface Area:48.1
Heavy Atom Count:10
Complexity:112
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes