Diisopropyl Ether → 2,2-Dimethyl-5-((thiophen-3-ylamino)methylene)-1,3-dioxane-4,6-dione

Participants

Reaction Conditions

Reaction Steps

Dimethyl-[1,3]dioxane-4,6-dione (5.0 g, 34.6 mmol) was combined with triethyl orthoformate (205 mL, 138 mmol) and stirred at 30° C. for 1 hour. Thiophen-3-ylamine (2.81 g, 28.3 mmol) was added in small portions at room temperature, at which time a white percipitate. The mixture was heated at 85° C. overnight. The reaction mixture was cooled to room temperature and isopropyl ether was added and the suspension was stirred for one hour. The precipitate was filtered off and washed with isopropyl ether and dried in vacuo. The intermediate was dissolved in methylene chloride and potassium carbonate was added and the suspension was stirred for 30 minutes. The solid was filtered off and the solution was concentrated to give 2,2-dimethyl-5-(thiophen-3-ylaminomethylene)-[1,3]dioxane-4,6-dione as the free base. In a single neck round bottom flask, dowtherm A (15 mL) was heated to 260° C. and 2,2-dimethyl-5-(thiophen-3-ylaminomethylene)-11,3]dioxane-4,6-dione was added in small portions. The mixture heated for 30 minutes and then was cooled to room temperature and isopropyl ether was added and the suspension was stirred for one hour. The precipitate was filtered off and washed with isopropyl ether and dried in vacuo to provide 3.43g (79%) of 4H-thieno[3,2-b]pyridin-7-one. 1H NMR (400 MHz, DMSO) d 7.93 (d, 1H), 7.79 (d, 1H), 7.21 (d, 1H), 5.99 (d, 1H); LC-MS: 152 (MH+); HPLC RT: 1.21.

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