Tetrahydro-4H-pyran-4-one → 1'-ethyl-6'-(pyridin-4-yl)-2,3,5,6-tetrahydro-1'H-spiro[pyran-4,2'-thieno[3,2-d]pyrimidin]-4'(3'H)-one

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-(ethylamino)-5-(pyridin-4-yl)thiophene-2-carboxamide (0.100 g, 0.400 mmol), tetrahydro-4H-pyran-4-one (1.0 mL), p-toluenesulfonic acid monohydrate (0.0095 g, 0.050 mmol) and acetic acid (2.0 mL) was stirred for 3 h at 100° C. in a sealed tube. The mixture was poured into sat. aqueous sodium hydrogen carbonate (150 mL). Extraction with ethyl acetate/THF (4:1, 100 mL, 50 mL), drying over magnesium sulfate, filtration and concentration at reduced pressure gave an oil. This oil was purified by column chromatography (Combiflash, 12 g silica gel, dichloromethane to 90:10 dichloromethane/methanol), then triturated with ethyl acetate, and the precipitate was collected by filtration to afford the title compound (0.0715 g, 54%) as a yellow solid:

Provenance & Evidence