* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With hydrogen bromide; bromine; sodium nitrite; In water; at 0 - 35℃; for 12h;
(1) Synthesis of 3-bromo-2-chloro-4-methylpyridine <strong>[133627-45-9]3-amino-2-chloro-4-methylpyridine</strong> (2 g) was added to a mixed solvent of a 48% aqueous hydrogen bromide solution (17 mL) and water (12 mL). Sodium nitrite (2.5 g) was added to the solution at 0 C. Further, bromine (22 mL) was added. The reaction mixture was warmed to room temperature and stirred for 12 hours. The reaction mixture was partitioned by adding a 5 N aqueous sodium hydroxide solution and ethyl acetate. The organic layer was washed with brine and then dried over anhydrous magnesium sulfate. The desiccant was removed by filtration. The filtrate was concentrated under reduced pressure to give the title compound (1.7 g). 1H-NMR (400 MHz, CDCl3) delta (ppm): 2.51 (s, 3H), 7.01-7.24 (m, 1H), 8.06-8.35 (m, 1H).
With sodium methylate; In methanol; N,N-dimethyl-formamide; at 100.0℃; for 12.0h;
(2) Synthesis of 3-bromo-2-methoxy-4-methylpyridine 3-bromo-2-chloro-4-methylpyridine (1 g) was added to DMF (5.6 mL). Sodium methoxide (28% solution in methanol, 4.6 mL) was added to the solution, and the mixture was stirred at 100 C. for 12 hours. The reaction mixture was partitioned by adding ethyl acetate and water. The organic layer was dried over anhydrous magnesium sulfate. The desiccant was removed by filtration, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate/n-heptane, 5% to 30%) to give the title compound (1.1 g). 1H-NMR (400 MHz, CDCl3) delta (ppm): 2.40 (s, 3H), 4.00 (s, 3H), 6.77 (d, J=5.1 Hz, 1H), 7.94 (d, Hz, 1H).
Step 3: In a sealed tube, NaOMe (25% in MeOH, 3.1 mL, 13 mmol) was added to a solution of compound 94 (1.8 g, 8.7 mmol) in MeOH (17 mL). The reaction was heated at 75 C for 3 days. The reaction mixture was cooled to room temperature, diluted with EtOAc, washed with saturated NH4CI and brine, dried over MgS04, filtered and concentrated. The crude product was purified by flash chromatography over silica gel, which was eluted with heptanes/EtOAc (0-15%) to afford compound 95 as a clear oil (991 mg, 56% yield). 1H NMR (400 MHz, DMSO-c/6) delta 8.00 (d, J = 5.0 Hz, 1 H), 6.98 (d, J = 4.8 Hz, 1 H), 3.90 (s, 3 H), 2.35 (s, 3 H).
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
