反应详情

温度

130 °C

A mixture of 2,4-dibromo-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]thiophene-3-carbonitrile (0.248 g, 0.594 mmol), 4-(tributylstannyl)pyridazine (2.30 mg, 0.624 mmol), copper(I) iodide (34.0 mg, 0.178 mmol), lithium chloride (75.6 mg, 1.78 mmol) and tetrakis(triphenylphosphine)palladium(0) (34.3 mg, 0.0297 mmol) in dry 1,4-dioxane (5.0 mL, 64 mmol) was sonicated under a nitrogen atmosphere for 2 min then heated in a capped vial to 130° C. in microwave machine for 20 mins. The suspension was cooled to rt, diluted with 20% MeOH/DCM (˜100 mL), treated with 12 g of silica gel then rotavaped and dried under high vacuum. The coated silica gel was chromatographed on a silica column eluting with MeOH/DCM (0/100 to 5/95) to afford a solid product (0.143 g, yield 57.7%). LCMS: (AA) ES+, 417, 419. 1H NMR (300 MHz, CDCl3) δ: 9.55 (s, 1H), 9.37-9.39 (m, 1H), 8.40 (s, 1H), 7.69-8.00 (m, 1H), 5.55-5.60 (m, 1H), 4.08-4.13 (m, 1H), 3.73-3.81 (m, 1H), 2.18-2.30 (m, 1H), 2.03-2.16 (m, 2H), 1.68-1.82 (m, 3H).

1. customwas sonicated under a nitrogen atmosphere for 2 min
2. temperatureThe suspension was cooled to rt
3. additiontreated with 12 g of silica gel
4. customdried under high vacuum
5. customThe coated silica gel was chromatographed on a silica column
6. washeluting with MeOH/DCM (0/100 to 5/95)