5-BROMO-3-METHOXYPYRIDIN-2-AMINE

As shown in step 2-ii of Scheme 2, to a stirred solution of compound 1002 (15.0 g, 120.8 mmol) in acetic acid (150.0 mL) was added bromine (6.3 mL, 120.8 mmol) dropwise over 30 minutes at ambient temperature. The resulting reaction mixture was stirred for 16 h at ambient temperature. The reaction mixture was concentrated under reduced pressure and the acetic acid removed by the addition and subsequent removal of toluene (2.x.100 mL) under reduced pressure. The residue was cooled to 0° C. and neutralized with sat. aqueous NaHCO[00109] As shown in step 6-ii of Scheme 6, bromine (6.3 mL, 120.8 mmol) was added dropwise to a stirring solution of Compound 1018 (15 g, 120.8 mmol) in acetic acid (150 mL) at RT. The resulting reaction mixture was stirred at RT for 16 h. The reaction mixture was concentrated under reduced pressure, and the acetic acid was removed by azeotropic distillation with toluene (2 x 100 mL) under reduced pressure. The residue was cooled to 0 As shown in step 6-ii of Scheme 6, bromine (6.3 mL, 120.8 mmol) was added dropwise to a stirring solution of Compound 1018 (15 g, 120.8 mmol) in acetic acid (150 mL) at RT. The resulting reaction mixture was stirred at RT for 16 h. The reaction mixture was concentrated under reduced pressure, and the acetic acid was removed by azeotropic distillation with toluene (2 x 100 mL) under reduced pressure. The residue was cooled to 0 To a solution of 3-methoxypyridin-2-amine (5 g, 40.3 mmol) in acetic acid (50 mL) was added bromine (1N in acetic acid, 40 mL, 40.28 mmol) and the mixture stirred at 25°C for 16h. After completion, the reaction mixture was concentrated under vacuum and azeotroped by toluene. The residue thus obtained was neutralized (pH~7) by saturated aqueous sodium bicarbonate solution (70 mL) and extracted with ethyl acetate (2 x 100 mL). The combined organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by chromatography on silica gel to afford the desired product as a yellow solid (5.6 g, 74percent). MS (m/z)=202.8 [M + H]+;A 2000ml Ertenmeyer flask was charged with 10percent sulfuric acid (800ml). At ambient temperature, 2-am.no-3-methoxy~pyr.dine (2, 25.80 grams, 206 mmol) was added with stirring. After a clear solution was obtained, the solution was cooled in an ice/water bath until the solution temperature reached about 3 °C. A mixture of bromine (10.8 ml, 210 mmol) in acetic acid 0C. The solid was collected by filtration and was washed with cold water (2 X 30 ml) and dried to afford 39.0 grams of crude product. The crude was suspended in BtOAc (500 ml) and the resulting dark mixture was stirred vigorously for 0.5 hour and filtered through CeI he. The black solid was washed with EtOAc (2 X) and the combined filtrates were washed with 10percent sodium thiosulfite solυtion(IOO ml), saturated brine and dried (Na^SO*)- Concentration of this mixture afforded 29.0 grams (68, 3percent yield) of 2-amino-3-methoxl-5-bromopyridine (3) as a yellow solid. A 2 L Erlenmeyer flask was charged with 10percent sulfuric acid (800 ml). A 2 L Erlenmeyer flask was charged with 10percent sulfuric acid (800ml). At ambient temperature, 2-amino-3-methoxy-pyridine (25.8 grams, 206 mmol) was added portionwise with stirring. After a clear solution was obtained, the solution was cooled in an ice/water bath until the solution temperature reached 3 To a solution of 3-methoxypyridin-2-amine (1.00 g, 8.06 mmol) in acetic acid (10 mL) was added bromine (0.414 mL, 8.06 mmol) over 30 min. The reaction mixture was then stirred at room temperature for 18 hrs. Acetic acid was evaporated in vacuo and the pH of the residue was adjusted to 7-8 by slow addition of a saturated aqueous solution of sodium bicarbonate. The mixture was extracted with ethyl acetate (2x 50 mL) and the combined organic phases dried (NaA 3-neck I -L flask was fitted with a heating mantle, temperature controller, and an overhead stirrer. To the reaction flask was added 2-nitro-3

Molecular Weight:203.04
XLogP3:1.2
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