4-chloro-3,4-dihydro-2H-chromene

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of sodium hydride (60% dispersion in mineral oil, 0.71 g, 18 mmol) in N,N-dimethylformamide (40 mL) was added a suspension of methyl 4-hydroxy-1,2-dimethyl-1H-benzimidazole-6-carboxylate (3.0 g, 14 mmol, WO 2004054984) in N,N-dimethylformamide (40 mL) dropwise under nitrogen atmosphere at room temperature. After stirring for 20 minutes, a solution of 4-chlorochromane (4.6 g, 27 mmol, WO 2000078751) in N,N-dimethylformamide (10 mL) was added at room temperature. The reaction mixture was warmed to 70° C. for 2.5 hours, cooled to room temperature, and stirred for 18 hours at the same temperature. The reaction mixture was quenched with water and extracted with ethyl acetate (250 mL×2). The combined extracts were washed with sodium hydrogencarbonate aqueous solution, ammonium chloride aqueous solution and brine, dried over sodium sulfate, and concentrated in vacuum. The resulting solid was suspended with ethyl acetate and diethyl ether, and collected by filtration to give the title compound as a white solid (2.95 g, 61%): was added cooled to room temperature stirred for 18 hours at the same temperature The reaction mixture was quenched with water extracted with ethyl acetate (250 mL×2) The combined extracts were washed with sodium hydrogencarbonate aqueous solution, ammonium chloride aqueous solution and brine dried over sodium sulfate concentrated in vacuum collected by filtration

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of sodium hydride (60% dispersion in mineral oil, 0.71 g, 18 mmol) in N,N-dimethylformamide (40 mL) was added a suspension of methyl 4-hydroxy-1,2-dimethyl-1H-benzimidazole-6-carboxylate (3.0 g, 14 mmol, WO 2004054984) in N,N-dimethylformamide (40 mL) dropwise under nitrogen atmosphere at room temperature. After stirring for 20 minutes, a solution of 4-chlorochromane (4.6 g, 27 mmol, WO 2000078751) in N,N-dimethylformamide (10 mL) was added at room temperature. The reaction mixture was warmed to 70° C. for 2.5 hours, cooled to room temperature, and stirred for 18 hours at the same temperature. The reaction mixture was quenched with water and extracted with ethyl acetate (250 mL×2). The combined extracts were washed with sodium hydrogencarbonate aqueous solution, ammonium chloride aqueous solution and brine, dried over sodium sulfate, and concentrated in vacuum. The resulting solid was suspended with ethyl acetate and diethyl ether, and collected by filtration to give the title compound as a white solid (2.95 g, 61%): was added cooled to room temperature stirred for 18 hours at the same temperature The reaction mixture was quenched with water extracted with ethyl acetate (250 mL×2) The combined extracts were washed with sodium hydrogencarbonate aqueous solution, ammonium chloride aqueous solution and brine dried over sodium sulfate concentrated in vacuum collected by filtration

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred suspension of 4-hydroxy-N,N,1,2-tetramethyl-1H-benzimidazole-6-carboxamide (50 mg, 0.21 mmol, WO 2004054984) in N,N-dimethylformamide (2 mL) was added sodium hydride (60% dispersion in mineral oil, 11 mg, 0.27 mmol) at room temperature. After stirring for 20 minutes, a solution of 4-chlorochromane (71 mg, 0.42 mmol, WO 2000078751) in N,N-dimethylformamide (1 mL) was added at room temperature. The reaction mixture was warmed to 70° C., and stirred for 6 hours at the same temperature. The reaction mixture was quenched with sodium hydrogencarbonate aqueous solution, and extracted with ethyl acetate (20 mL×2). The combined extracts were washed with water and brine, dried over magnesium sulfate, and concentrated in vacuum. The residue was purified by column chromatography on silica gel (ethyl acetate:methanol=10:1 as an eluent) to afford the title compound as a white solid (40 mg, 52%): stirred for 6 hours at the same temperature The reaction mixture was quenched with sodium hydrogencarbonate aqueous solution extracted with ethyl acetate (20 mL×2) The combined extracts were washed with water and brine dried over magnesium sulfate concentrated in vacuum The residue was purified by column chromatography on silica gel (ethyl acetate

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred suspension of 4-hydroxy-N,N,1,2-tetramethyl-1H-benzimidazole-6-carboxamide (50 mg, 0.21 mmol, WO 2004054984) in N,N-dimethylformamide (2 mL) was added sodium hydride (60% dispersion in mineral oil, 11 mg, 0.27 mmol) at room temperature. After stirring for 20 minutes, a solution of 4-chlorochromane (71 mg, 0.42 mmol, WO 2000078751) in N,N-dimethylformamide (1 mL) was added at room temperature. The reaction mixture was warmed to 70° C., and stirred for 6 hours at the same temperature. The reaction mixture was quenched with sodium hydrogencarbonate aqueous solution, and extracted with ethyl acetate (20 mL×2). The combined extracts were washed with water and brine, dried over magnesium sulfate, and concentrated in vacuum. The residue was purified by column chromatography on silica gel (ethyl acetate:methanol=10:1 as an eluent) to afford the title compound as a white solid (40 mg, 52%): stirred for 6 hours at the same temperature The reaction mixture was quenched with sodium hydrogencarbonate aqueous solution extracted with ethyl acetate (20 mL×2) The combined extracts were washed with water and brine dried over magnesium sulfate concentrated in vacuum The residue was purified by column chromatography on silica gel (ethyl acetate