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To a stirred solution of compound 208.1 (350 mg) in formic acid (2.2 ml) was added acetic anhydride (1.2 ml) at 0 C and stirred at room temperature for 5 hr. After completion of the starting material (by TLC), the reaction mixture was concentrated under reduced pressure to afford compound 208.2 (250 mg, 64%) of a white solid which was used immediately in the next step without further purification. H-NMR (CDCl3, 500 MHz) delta 9.37 (s, 1H), 8.52 (s, 1H), 7.73 (s, 1H), 7.25 (bs, 1H).
To a stirred solution of compound D.I (500 mg, 1.77 mmol) in AcOH (20 ml), was added iron powder (400 mg, 7.27 mmol). The reaction mixture was heated at 60 °C for 2 hr. After completion of the starting material (by TLC), the reaction mixture was filtered on celite bed and washed with ethyl acetate. The filtrate was concentrated under reduced pressure, and the crude material was diluted with NaHCO3 solution (100 ml) and extracted with ethyl acetate (3x 20 ml). The combined organic extracts was washed with water and dried over anhydrous sodium sulphate, concentrated under reduced pressure to afford compound 208.1 (350 mg, 78.47percent, crude) as brown solid, which was used for the next step any further purification. 1H-NMR (CDCl3, 500 MHz) delta 7.94 (s, 1H), 7.54 (s, H), 7.26 (s, 1H), 3.50 (bs, 2H); LCMS m/z = 259 [M+l]. [00268] Synthesis of Compound 208.2.
N-(4,6-dibromo-3-pyridyl)pyridine-3-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
20.0 g
4,6-Dibromopyridine-3-amine (40.9 g, 164 mmol) was dissolved in CH2C12 (200 ml), and triethylamine (49.3 g, 487 mmol) was added. The mixture was stirred at room temperature for 10 mm, and the solution of the acid chloride was then added slowly. The reaction mixture was stirred at room temperature for 16 h, the solvent was removed under reduced pressure and the residue was separated chromatographically by column chromatography on silica gel (gradient: ethyl acetate/petroleum ether 50:50-75:25). This gave 20.0 g (34% yield) of N-(4,6-dibromo-3-pyridyl)pyridine-3-carboxamide.
With sodium bromate; sulfuric acid; sodium bromide; In water; acetonitrile; at 0 - 5℃; for 1.5h;
At 0-5 C., a solution of sodium bromide (21.87 g, 212.4 mmol) and sodium bromate (63.76 g, 425.0 mmol) in water (400 ml) was added to a solution of pyridine-3-amine (20.0 g, 0.213 mol) in acetonitrile (200 ml). With cooling, sulphuric acid (prepared from concentrated sulphuric acid 20.84 g, 212.5 mmol and 200 ml of water) was then added over 30 mm. The mixture was stirred at 5 C. for 1 h and filtered and the residue was washed with a saturated NaHCO3 solution (200 ml) and water (200 ml) and dried under reduced pressure. This gave 40.0 g (quantitative) of crude product, which was reacted in the next step without further purification.