METHYL TETRAHYDRO-4-OXO-2H-THIOPYRAN-3-CARBOXYLATE

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of methyl 4-oxotetrahydro-2H-thiopyran-3-carboxylate (3.00 g, 17.2 mmol) in THF (57 mL) was stirred at 0° C. Sodium borohydride (1.30 g, 34.4 mmol) was added and the resulting mixture was stirred at ambient temperature for 4 hours. The mixture was thermally stabilized with a water bath and carefully quenched with 1N aqueous HCl. The reaction mixture was then diluted with water and extracted with EtOAc (2×). The combined organic extracts were washed with water, brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to afford the title compound. The residue was carried forward without further purification. The mixture was thermally stabilized with a water bath carefully quenched with 1N aqueous HCl The reaction mixture was then diluted with water extracted with EtOAc (2×) The combined organic extracts were washed with water, brine dried over anhydrous Na2SO4 filtered concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of methyl 4-oxotetrahydro-2H-thiopyran-3-carboxylate (3.00 g, 17.2 mmol) in THF (57 mL) was stirred at 0° C. Sodium borohydride (1.30 g, 34.4 mmol) was added and the resulting mixture was stirred at ambient temperature for 4 hours. The mixture was thermally stabilized with a water bath and carefully quenched with 1N aqueous HCl. The reaction mixture was then diluted with water and extracted with EtOAc (2×). The combined organic extracts were washed with water, brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to afford the title compound. The residue was carried forward without further purification. The mixture was thermally stabilized with a water bath carefully quenched with 1N aqueous HCl The reaction mixture was then diluted with water extracted with EtOAc (2×) The combined organic extracts were washed with water, brine dried over anhydrous Na2SO4 filtered concentrated in vacuo

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1H-benzimidazol-2-ylacetonitrile (13 g), methyl 4-oxotetrahydro-2H-thiopyran-3-carboxylate (15.3 g), and ammonium acetate (33 g) was heated and stirred at 140° C. for 1 hour. The reaction mixture was cooled to room temperature, water and acetonitrile were added, and the resulting precipitate was collected by filtration and dried under reduced pressure to obtain 12-oxo-3,4,6,12-tetrahydro-1H-thiopyrano[4′,3′:4,5]pyrido[1,2-a]benzimidazole-5-carbonitrile (16 g). was heated The reaction mixture was cooled to room temperature the resulting precipitate was collected by filtration dried under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5.3 g (25 mmol) of potassium enolate of 4H-2,3,5,6-tetrahydro-3-carbomethoxythiopyran-4-one in 50 ml DMSO, was added 3.47 g (25 mmol) of 2-bromoethyl methyl ether. The solution was stirred under N2 at room temperature for 4 days. The reaction mixture was poured into 500 ml H2O and extracted three times with ethyl acetate. The combined ethyl acetate solution was washed with water; 5% NaOH; H2O and brine; dried over magnesium sulfate, filtered and concentrated in vacuo to give about 5 g crude product. Chromatographed through a pressure column eluting with 10% ethyl acetate-n-hexane to give 2.49 g of the title compound. extracted three times with ethyl acetate The combined ethyl acetate solution was washed with water dried over magnesium sulfate filtered concentrated in vacuo to give about 5 g crude product Chromatographed through a pressure column eluting with 10% ethyl acetate-n-hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of methyl 4-oxotetrahydro-2H-thiopyran-3-carboxylate (3.00 g, 17.2 mmol) in THF (57 mL) was stirred at 0° C. Sodium borohydride (1.30 g, 34.4 mmol) was added and the resulting mixture was stirred at ambient temperature for 4 hours. The mixture was thermally stabilized with a water bath and carefully quenched with 1N aqueous HCl. The reaction mixture was then diluted with water and extracted with EtOAc (2×). The combined organic extracts were washed with water, brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to afford the title compound. The residue was carried forward without further purification. The mixture was thermally stabilized with a water bath carefully quenched with 1N aqueous HCl The reaction mixture was then diluted with water extracted with EtOAc (2×) The combined organic extracts were washed with water, brine dried over anhydrous Na2SO4 filtered concentrated in vacuo