Lithium Chloride → Methyl (4-{4-bromo-3-cyano-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-2-thienyl}pyridin-2-yl)carbamate

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Reaction Conditions

Reaction Steps

A mixture of 2,4-dibromo-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]thiophene-3-carbonitrile (1.27 g, 3.05 mmol), methyl [4-(trimethylstannyl)pyridin-2-yl]carbamate (0.960 g, 3.05 mmol), lithium chloride (0.388 g, 9.14 mmol), copper(I) iodide (0.174 g, 0.914 mmol) and tetrakis(triphenylphosphine)platinum (0) (0.190 g, 0.152 mmol) in anhydrous 1,4-dioxane (45 mL) was degassed by evacuation in vacuum and backfilling with N2 4 times, then heated to 100° C. under N2 for 8 hours, then cooled to room temperature. The suspension was filtered and washed with dioxane. The solid was suspended in 20% MeOH in DCM (300 mL), and washed with water (2×). The organic suspension was concentrated in a rotavapor to give a solid residue. The residue was stirred in DMF/DCM (10 mL/10 mL) at room temperature for 20 min, filtered and washed with DCM to give a solid product (1.16 g, yield 77.8%). LC/MS: (FA) ES+ 489, 491. 1H NMR (400 MHz, d4-MeOH/d-chloroform) δ 8.26-8.35 (m, 3H), 7.34 (m, 1H), 5.48 (m, 1H), 4.00 (m, 1H), 3.73 (s, 3H), 3.64-3.69 (m, 1H), 1.97-2.14 (m, 3H), 1.58-1.68 (m, 3H).

Provenance & Evidence