Ethanethiol → N-methyl-4-(2-(methylthio)quinazolin-6-yloxy)picolinamide

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Reaction Steps

The mixture of 2-chloro-6-methoxyquinazoline (1 eq) and sodiumthiomethoxide (2 eq) in ethanol (0.5 M) was refluxed for 3 hours. The reaction was cooled down to room temperature and evaporated. The mixture was taken in ethyl acetate and washed with water and brine, dried in sodium sulfate and concentrated. The resulting crude was treated with dry methylene chloride and ethane thiol (5 eq) was added to it at room temperature. Aluminium chloride (5 eq) was added carefully at 0° C. The reaction was warmed to room temperature and stirred vigorously over night. The reaction was diluted with methylene chloride and saturated Rochelles's salt solution was added and stirred for about 3 hours until 2 layers separated. The organic layer was separated, washed with Rochelle's salt solution (2×), followed by water and brine, dried and evaporated. The crude 2-methylthioquinazolin-6-ol (1 eq) was taken in DMF (0.5 M) and Potassiumbis(trimethylsilyl)amide (2 eq) was added and stirred for 10 min at room temperature. 4-chloro(2-pyridyl)-N-methylcarboxamide (1.1 eq) was added followed by potassium carbonate (1 eq) and stirred at 85-90° C. for 16 hours. The mixture was diluted with ethyl acetate, washed with water and brine, dried and evaporated. The crude was subjected to column chromatography (4:1 Hexanes in ethyl acetate followed by 2:1 and 1:1 Hexanes in ethyl acetate) to afford the product in 75-85% yield.

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