tert-butyl 3-sulfanylazetidine-1-carboxylate

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5-bromo-2-neopentyl-1-(2-(trifluoromethoxy)ethyl)-1H-benzo[d]imidazole (STEP A, 265 mg, 0.700 mmol), tert-butyl 3-mercaptoazetidine-1-carboxylate (STEP D of Example 1, 189 mg, 0.999 mmol), Xantphos (20.2 mg, 0.0350 mmol), tris(dibenzylideneacetone)dipalladium (16.0 mg, 0.0175 mmol) and N,N-diisopropylethylamine (245 microL, 1.40 mmol) in 1,4-dioxane (4 mL) was stirred at 160° C. for 1 h under microwave. The mixture was diluted with ethyl acetate and filtered through a celite. The filtrate was concentrated in vacuo and the residue was purified by silica gel column chromatography (hexane-ethyl acetate, gradient) to give the title compound (278 mg, 81%). filtered through a celite The filtrate was concentrated in vacuo the residue was purified by silica gel column chromatography (hexane-ethyl acetate, gradient)

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5-bromo-2-neopentyl-1-(2-(trifluoromethoxy)ethyl)-1H-benzo[d]imidazole (STEP A, 265 mg, 0.700 mmol), tert-butyl 3-mercaptoazetidine-1-carboxylate (STEP D of Example 1, 189 mg, 0.999 mmol), Xantphos (20.2 mg, 0.0350 mmol), tris(dibenzylideneacetone)dipalladium (16.0 mg, 0.0175 mmol) and N,N-diisopropylethylamine (245 microL, 1.40 mmol) in 1,4-dioxane (4 mL) was stirred at 160° C. for 1 h under microwave. The mixture was diluted with ethyl acetate and filtered through a celite. The filtrate was concentrated in vacuo and the residue was purified by silica gel column chromatography (hexane-ethyl acetate, gradient) to give the title compound (278 mg, 81%). filtered through a celite The filtrate was concentrated in vacuo the residue was purified by silica gel column chromatography (hexane-ethyl acetate, gradient)

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-(5-bromo-2-neopentyl-1H-benzo[d]imidazol-1-yl)-N,N-dimethylethanamine (STEP A, 338 mg, 1.00 mmol), tert-butyl 3-mercaptoazetidine-1-carboxylate (STEP D, 246 mg, 1.30 mmol), Xantphos (28.9 mg, 0.0500 mmol), tris(dibenzylideneacetone)dipalladium (22.3 mg, 0.0250 mmol) and N,N-diisopropylethylamine (262 microL, 1.50 mmol) in 1,4-dioxane (4 mL) was stirred at 160° C. for 1 h under microwave. The mixture was concentrated in vacuo and the residue was purified by amine gel column chromatography (hexane-ethyl acetate, gradient) to give the title compound (442 mg, 99%) as a yellow oil. The mixture was concentrated in vacuo the residue was purified by amine gel column chromatography (hexane-ethyl acetate, gradient)

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-(5-bromo-2-neopentyl-1H-benzo[d]imidazol-1-yl)-N,N-dimethylethanamine (STEP A, 338 mg, 1.00 mmol), tert-butyl 3-mercaptoazetidine-1-carboxylate (STEP D, 246 mg, 1.30 mmol), Xantphos (28.9 mg, 0.0500 mmol), tris(dibenzylideneacetone)dipalladium (22.3 mg, 0.0250 mmol) and N,N-diisopropylethylamine (262 microL, 1.50 mmol) in 1,4-dioxane (4 mL) was stirred at 160° C. for 1 h under microwave. The mixture was concentrated in vacuo and the residue was purified by amine gel column chromatography (hexane-ethyl acetate, gradient) to give the title compound (442 mg, 99%) as a yellow oil. The mixture was concentrated in vacuo the residue was purified by amine gel column chromatography (hexane-ethyl acetate, gradient)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Mixture of tert-butyl 3-(acetylthio)azetidine-1-carboxylate (STEP C, 700 mg, 3.03 mmol), methanol (10 mL) and potassium carbonate (836 mg, 6.05 mol) was stirred at 50° C. for 2 h and cooled to room temperature. To the reaction mixture was added 2 mol/L hydrochloric acid for solution acidified (pH <4). The resulting solution was extracted with diethyl ether (30 mL×2). The organic layer was combined and washed with water (30 mL×2) and brine (30 mL). The extract was dried with magnesium sulfate and concentrated. Resulting crude product (581 mg) was used without further purification. cooled to room temperature The resulting solution was extracted with diethyl ether (30 mL×2) washed with water (30 mL×2) and brine (30 mL) The extract was dried with magnesium sulfate concentrated

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Mixture of tert-butyl 3-(acetylthio)azetidine-1-carboxylate (STEP C, 700 mg, 3.03 mmol), methanol (10 mL) and potassium carbonate (836 mg, 6.05 mol) was stirred at 50° C. for 2 h and cooled to room temperature. To the reaction mixture was added 2 mol/L hydrochloric acid for solution acidified (pH <4). The resulting solution was extracted with diethyl ether (30 mL×2). The organic layer was combined and washed with water (30 mL×2) and brine (30 mL). The extract was dried with magnesium sulfate and concentrated. Resulting crude product (581 mg) was used without further purification. cooled to room temperature The resulting solution was extracted with diethyl ether (30 mL×2) washed with water (30 mL×2) and brine (30 mL) The extract was dried with magnesium sulfate concentrated

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5-bromo-2-neopentyl-1-(2-(trifluoromethoxy)ethyl)-1H-benzo[d]imidazole (STEP A, 265 mg, 0.700 mmol), tert-butyl 3-mercaptoazetidine-1-carboxylate (STEP D of Example 1, 189 mg, 0.999 mmol), Xantphos (20.2 mg, 0.0350 mmol), tris(dibenzylideneacetone)dipalladium (16.0 mg, 0.0175 mmol) and N,N-diisopropylethylamine (245 microL, 1.40 mmol) in 1,4-dioxane (4 mL) was stirred at 160° C. for 1 h under microwave. The mixture was diluted with ethyl acetate and filtered through a celite. The filtrate was concentrated in vacuo and the residue was purified by silica gel column chromatography (hexane-ethyl acetate, gradient) to give the title compound (278 mg, 81%). filtered through a celite The filtrate was concentrated in vacuo the residue was purified by silica gel column chromatography (hexane-ethyl acetate, gradient)

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-(5-bromo-2-neopentyl-1H-benzo[d]imidazol-1-yl)-N,N-dimethylethanamine (STEP A, 338 mg, 1.00 mmol), tert-butyl 3-mercaptoazetidine-1-carboxylate (STEP D, 246 mg, 1.30 mmol), Xantphos (28.9 mg, 0.0500 mmol), tris(dibenzylideneacetone)dipalladium (22.3 mg, 0.0250 mmol) and N,N-diisopropylethylamine (262 microL, 1.50 mmol) in 1,4-dioxane (4 mL) was stirred at 160° C. for 1 h under microwave. The mixture was concentrated in vacuo and the residue was purified by amine gel column chromatography (hexane-ethyl acetate, gradient) to give the title compound (442 mg, 99%) as a yellow oil. The mixture was concentrated in vacuo the residue was purified by amine gel column chromatography (hexane-ethyl acetate, gradient)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Mixture of tert-butyl 3-(acetylthio)azetidine-1-carboxylate (STEP C, 700 mg, 3.03 mmol), methanol (10 mL) and potassium carbonate (836 mg, 6.05 mol) was stirred at 50° C. for 2 h and cooled to room temperature. To the reaction mixture was added 2 mol/L hydrochloric acid for solution acidified (pH <4). The resulting solution was extracted with diethyl ether (30 mL×2). The organic layer was combined and washed with water (30 mL×2) and brine (30 mL). The extract was dried with magnesium sulfate and concentrated. Resulting crude product (581 mg) was used without further purification. cooled to room temperature The resulting solution was extracted with diethyl ether (30 mL×2) washed with water (30 mL×2) and brine (30 mL) The extract was dried with magnesium sulfate concentrated

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5-bromo-2-neopentyl-1-(2-(trifluoromethoxy)ethyl)-1H-benzo[d]imidazole (STEP A, 265 mg, 0.700 mmol), tert-butyl 3-mercaptoazetidine-1-carboxylate (STEP D of Example 1, 189 mg, 0.999 mmol), Xantphos (20.2 mg, 0.0350 mmol), tris(dibenzylideneacetone)dipalladium (16.0 mg, 0.0175 mmol) and N,N-diisopropylethylamine (245 microL, 1.40 mmol) in 1,4-dioxane (4 mL) was stirred at 160° C. for 1 h under microwave. The mixture was diluted with ethyl acetate and filtered through a celite. The filtrate was concentrated in vacuo and the residue was purified by silica gel column chromatography (hexane-ethyl acetate, gradient) to give the title compound (278 mg, 81%). filtered through a celite The filtrate was concentrated in vacuo the residue was purified by silica gel column chromatography (hexane-ethyl acetate, gradient)

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-(5-bromo-2-neopentyl-1H-benzo[d]imidazol-1-yl)-N,N-dimethylethanamine (STEP A, 338 mg, 1.00 mmol), tert-butyl 3-mercaptoazetidine-1-carboxylate (STEP D, 246 mg, 1.30 mmol), Xantphos (28.9 mg, 0.0500 mmol), tris(dibenzylideneacetone)dipalladium (22.3 mg, 0.0250 mmol) and N,N-diisopropylethylamine (262 microL, 1.50 mmol) in 1,4-dioxane (4 mL) was stirred at 160° C. for 1 h under microwave. The mixture was concentrated in vacuo and the residue was purified by amine gel column chromatography (hexane-ethyl acetate, gradient) to give the title compound (442 mg, 99%) as a yellow oil. The mixture was concentrated in vacuo the residue was purified by amine gel column chromatography (hexane-ethyl acetate, gradient)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Mixture of tert-butyl 3-(acetylthio)azetidine-1-carboxylate (STEP C, 700 mg, 3.03 mmol), methanol (10 mL) and potassium carbonate (836 mg, 6.05 mol) was stirred at 50° C. for 2 h and cooled to room temperature. To the reaction mixture was added 2 mol/L hydrochloric acid for solution acidified (pH <4). The resulting solution was extracted with diethyl ether (30 mL×2). The organic layer was combined and washed with water (30 mL×2) and brine (30 mL). The extract was dried with magnesium sulfate and concentrated. Resulting crude product (581 mg) was used without further purification. cooled to room temperature The resulting solution was extracted with diethyl ether (30 mL×2) washed with water (30 mL×2) and brine (30 mL) The extract was dried with magnesium sulfate concentrated