5-BROMO-3-METHOXYPYRAZIN-2-YLAMINE

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A 30percent w/w solution of NaOMe in MeOH (8.4 mL, 44.8 mmol) was added to a stirring suspension of 3, 5-dibromo-2-aminopyrazine (10 g, 39.5 mmol) in dry MeOH (40 mL). 5-Bromo-3-methoxypyrazin-2-amine A mixture of 3, 5-dibromo-2-aminopyrazine (750 mg, 2.9 mmol), sodium methoxide (400 mg, 7.4 mmol) and methanol (20 ml) was refluxed for 16 h. The solvent was removed and the residue was purified using column chromatography. Yield: 450 mg 1H NMR (CDCI3): 3.99 (3H, s), 4.76 (2H, s), 7.63 (1H, s)5-Bromo-3-methoxy-pyrazin-2-ylamine (A) (816 mg, 4 mmol) and phenyl boronic acid (732 mg , 6 mmol) in toluene (5 mL), ethanol (5 mL) and Na2CO3 (8 mmol, 1 M aqueous) was purged with nitrogen for 10 minutes, and was added PdCl2(PPh3)2 (140 mg, 0.2 mmol). The reaction mixture was stirred at 85 0C for 4 hours. The reaction mixture was cooled to room temperature and diluted with EtOAc (50 mL). The solution was washed with brine (2 X 5 mL). The organic extracts was dried with MgSO4, then solvent was removed under vacuum. The residue was purified with flash column to give product B (660 mg, 82%) as yellow solid. 1H NMR (400 MHz, CDCl3): delta 8.08 (IH, s), 7.92 (2H, d), 7.46 (3H, m), 4.94 (2H, bs), 4.12 (3H, s); MS: 202 (M + H+).A solution of 3, 5-dibromopyrazin-2-amine X-9a (0.60 g, 2.37 mmol) and NaOMe (0.15 g, 2.78 mmol) in MeOH (15 mL) was heated to reflux for 1 h. Progress of the reaction was monitored by TLC and LCMS. After completion, the reaction mixture was cooled to room temperature. The precipitated solid was purified by column chromatography (silica, 100- 200 mesh, 10% EtOAc in hexane) to afford A 30% w/w solution of NaOMe in MeOH (8.4 mL, 44.8 mmol) was added to a stirring suspension of 3, 5-dibromo-2-aminopyrazine (10 g, 39.5 mmol) in dry MeOH (40 mL). The reaction mixture was heated to reflux and maintained for 3 h. The reaction was allowed to cool to rt and concentrate to 1/3 volume. The reaction was then partitioned between DCM and saturated aqueous NaHCO3 solution. The layers were separated and the organic phase was washed with saturated aqueous NaHCO3 solution (3*). The combined aqueous portions were back extracted with DCM (3*). The combined organic portions were washed with brine, dried (Na2SO4), and concentrated to provide 8.1 g of 5-Bromo-3-methoxypyrazin-2-amine A mixture of 3, 5-dibromo-2-aminopyrazine (750 mg, 2.9 mmol), sodium methoxide (400 mg, 7.4 mmol) and methanol (20 ml) was refluxed for 16 h. The solvent was removed and the residue was purified using column chromatography. Yield: 450 mg 1H NMR (CDCI3): 3.99 (3H, s), 4.76 (2H, s), 7.63 (1H, s)A 30% w/w solution of NaOMe in MeOH (8.4 mL, 44.8 mmol) was added to a stirring suspension of 3, 5-dibromo-2- aminopyrazine (10 g, 39.5 mmol) in dry MeOH (40 mL). The reaction mixture was heated to reflux and maintained for 3 h. The reaction was allowed to cool to rt and concentrate to 1/3 volume. The reaction was then partitioned between DCM and saturated aqueous NaHCO3 solution. The layers were separated and the organic phase was washed with saturated aqueous NaHCO3 solution (3 X). The combined aqueous portions were back extracted with DCM (3 X). The combined organic portions were washed with brine, dried (Na2SO^, and concentrated to provide 8.1 g of 5-bromo-3- methoxypyrazin-2-amine: 1H NMR (300 MHz, CDCl3): 7.64 (s, 1 H), 4.79 (br s, 2 H), 4.01 (s, 3 H).

5-Bromo-3-methoxy-2-pyrazinamine is an intermediate in the preparation of N-pyrazinylbenzenesulfonamides used in treatment of chemokine mediated diseases such as asthma.

Molecular Weight:204.02
XLogP3:0.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:202.96942
Monoisotopic Mass:202.96942
Topological Polar Surface Area:61
Heavy Atom Count:10
Complexity:113
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes