8-BroMo-3-phenyl-[1,2,4]triazolo[4,3-a]pyridine synthesis

Yield:54230-91-0 91%

Reaction Conditions:

with sodium acetate;acetic acid in ethanol at 50; for 3.5 h;

Steps:

8-Bromo-3-phenyl-[1,2,4]triazolo[4,3-a]pyridine (1f)

To a mixture of ethyl benzimidate hydrochloride(5b), 1.00 g, 5.22 mmol, 1 equiv.), 3-bromo-2-hydrazinopyridine(4f), 982 mg, 5.22 mmol,1.00 equiv.) and anhydrous sodium acetate (433 mg, 5.22 mmol, 1.00 equiv) was added absolute ethanol (SDA 3C, 5.00 mL) followed by acetic acid (150 μL, 2.61mmol, 0.50 equiv). The heterogeneous mixture was heated to 50 °C for 3.5 h.The slurry was cooled to room temperature and concentrated in vacuo to afford a yellow residue which was partitioned between dichloromethane (50 mL)and saturated aqueous sodium bicarbonate (25 mL). The layers were separated and the aqueous layer was extracted with dichloromethane (25 mL). The combined organic extracted were dried over sodium sulfate, filtered and concentrated in vacuo to afford a yellow solid. The solid was purified by flash column chromatography over silica gel (0 → 5 % methanol in dichloromethane gradient) to afford 1f as a white solid (1.31 g, 91 %). A duplicate experiment afforded 1.26 g (88 %) of product.¹H NMR (500 MHz, DMSO-d₆, 23 °C): δ 8.56 (d, J = 6.9 Hz, 1H), 7.89 (app dd, J = 7.8, 1.8, 2H), 7.78 (d, J = 7.2 Hz, 1H), 7.59-7.65 (m, 3H), 6.93(t, J = 6.9 Hz, 1H).¹³C NMR (125.8 MHz, DMSO-d₆, 23 °C): δ 148.3, 147.7,130.4, 130.2, 129.2, 128.2, 126.2, 123.6, 114.7, 108.4.FTIR(thin film) (cm^-1):3079(w), 1493 (m), 1303 (w), 1072 (m), 778 (s).HRMS(ESI) (m/z):Calc’dfor C₁₂H₉BrN₃ [M+H]⁺: 273.9974,Found:273.9965.Melting Point:181-182°C.

References:

Schmidt, Michael A.;Qian, Xinhua [Tetrahedron Letters,2013,vol. 54,# 42,p. 5721 - 5726] Location in patent:supporting information