imino-methyl-oxo-phenyl-lambda6-sulfane

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred pre-warmed solution of (S)-(+)-S-methyl-S-phenylsulphoximine (3 g, 18.7 mmol) in acetonitrile (2 mL) at 65° C. was added (trimethylsilyl)diethylamine (4.12 g, 21.1 mmol) dropwise via a syringe. The reaction was maintained at 65° C. and stirred for 3 hours. Additional amount of (trimethylsilyl)diethylamine (2 mL, 10.2 mmol) was added and the reaction mixture was stirred at 65° C. overnight. The reaction was then concentrated under reduced pressure and dried under vacuum to give the title compound. This material was used directly in next step of the synthesis without further purification. the reaction mixture was stirred at 65° C. overnight The reaction was then concentrated under reduced pressure dried under vacuum

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-amino-5-bromonicotinic acid (189 mg, 0.87 mmol), N,N-diisopropylethylamine (0.30 mL, 1.7 mmol), and (S)-(+)-S-methyl-S-phenylsulfoximine (162 mg, 1.0 mmol) in 4.0 mL DMF at room temperature was added BOP (423 mg, 0.96 mmol). The solution was stirred 30 minutes, then heated at 60° C. for 30 minutes, and then cooled back to room temperature. After 19 hours, the mixture was dissolved in EtOAc, washed with Na2CO3 solution, H2O, brine, dried with anhydrous Na2SO4 and rotary evaporated. The yellow foam was purified by chromatography (silica gel, CHCl3/EtOAc) to give the title compound as a light yellow solid (260 mg, 84%). cooled back to room temperature After 19 hours washed with Na2CO3 solution, H2O, brine dried with anhydrous Na2SO4 and rotary evaporated The yellow foam was purified by chromatography (silica gel, CHCl3/EtOAc)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 6-amino-5-iodonicotinic acid (330 mg, 1.3 mmol), N,N-diisopropylethylamine (0.44 mL, 2.5 mmol), and (S)-(+)-S-methyl-S-phenylsulfoximine (291 mg, 1.9 mmol) in 7.0 mL DMF at room temperature was added BOP (608 mg, 1.4 mmol). The solution was stirred 10 minutes and then heated at 60° C. for 5 hours. The mixture was dissolved in EtOAc, washed with Na2CO3 solution, H2O, brine, dried with anhydrous Na2SO4 and rotary evaporated. The brown oil was purified by chromatography (silica gel, hexane/acetone). The product containing fractions were purified by chromatography one additional time (silica gel, EtOAc/MeOH). To give the title compound as a white foam (354 mg, 71%). washed with Na2CO3 solution, H2O, brine dried with anhydrous Na2SO4 and rotary evaporated The brown oil was purified by chromatography (silica gel, hexane/acetone) The product containing fractions were purified by chromatography one additional time (silica gel, EtOAc/MeOH)

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

Procedure: To a solution of 5-bromonicotinic acid (1.21 g, 6.0 mmol), N,N-diisopropylethylamine (2.1 mL, 12.0 mmol), and (S)-(+)-S-methyl-S-phenylsulfoximine (931 mg, 6.0 mmol) in DMF (11.0 mL) cooled to 0° C. was treated with 1-benzotriazolyloxytripyrrolidinylphosphonium hexafluorophosphate (PyBOP) (3.43 g, 6.6 mmol). The reaction mixture was stirred 10 minutes, the ice bath removed, and the reaction continued at room temperature for 2 hours. The mixture was taken up in EtOAc and washed with H2O, Na2CO3 solution, brine, AcOH solution, H2O, Na2CO3 solution, brine, dried with anhydrous Na2SO4 and concentrated. The residual brown oil was purified by chromatography (silica gel, hexane/EtOAc). The product containing eluent was concentrated and then triturated with hexane to give the title compound as an off-white solid (1.88 g, 92%). the ice bath removed the reaction continued at room temperature for 2 hours washed with H2O, Na2CO3 solution, brine, AcOH solution, H2O, Na2CO3 solution, brine dried with anhydrous Na2SO4 concentrated The residual brown oil was purified by chromatography (silica gel, hexane/EtOAc) The product containing eluent was concentrated triturated with hexane

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

Procedure: To a slurry of 5-(2-phenyleth-1-ynyl)nicotinic acid (339 mg, 1.5 mmol) in 6.0 mL THF at room temperature was added 1,1′-carbonyldiimidazole (271 mg, 1.7 mmol). After stirring 1.25 hour, a solution of (S)-(+)-S-methyl-S-phenylsulfoximine (260 mg, 1.7 mmol) in 1.5 mL THF was added and the mixture heated at 50° C. for 22 hours. Then an additional 50 mg (0.32 mmol) (S)-(+)-S-methyl-S-phenylsulfoximine was added and heating continued at 60° C. for 3.5 hours. The reaction was quenched with NaHCO3 solution and then extracted into EtOAc. The EtOAc layer was washed with NaHCO3 solution, H2O, brine, dried with anhydrous Na2SO4 and concentrated. The yellow oil obtained was chromatographed eluting with hexane/EtOAc to give N-[methyl(oxo)phenyl-λ6-sulfanylidene]-5-(phenylethynyl)nicotinamide as a white foam (303 mg, 55%). heating continued at 60° C. for 3.5 hours The reaction was quenched with NaHCO3 solution extracted into EtOAc The EtOAc layer was washed with NaHCO3 solution, H2O, brine dried with anhydrous Na2SO4 concentrated The yellow oil obtained was chromatographed eluting with hexane/EtOAc

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

Procedure: To a slurry of 5-(2-phenyleth-1-ynyl)nicotinic acid (339 mg, 1.5 mmol) in 6.0 mL THF at room temperature was added 1,1′-carbonyldiimidazole (271 mg, 1.7 mmol). After stirring 1.25 hour, a solution of (S)-(+)-S-methyl-5-phenylsulfoximine (260 mg, 1.7 mmol) in 1.5 mL THF was added and the mixture heated at 50° C. for 22 hours. Then an additional 50 mg (0.32 mmol) (S)-(+)-S-methyl-S-phenylsulfoximine was added and heating continued at 60° C. for 3.5 hours. The reaction was quenched with NaHCO3 solution and then extracted into EtOAc. The EtOAc layer was washed with NaHCO3 solution, H2O, brine, dried with anhydrous Na2SO4 and concentrated. The yellow oil obtained was chromatographed eluting with hexane/EtOAc to give N-[methyl(oxo)phenyl-λ6-sulfanylidene]-5-(phenylethynyl)nicotinamide as a white foam (303 mg, 55%). heating continued at 60° C. for 3.5 hours The reaction was quenched with NaHCO3 solution extracted into EtOAc The EtOAc layer was washed with NaHCO3 solution, H2O, brine dried with anhydrous Na2SO4 concentrated The yellow oil obtained was chromatographed eluting with hexane/EtOAc

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred pre-warmed solution of (S)-(+)-S-methyl-S-phenylsulphoximine (3 g, 18.7 mmol) in acetonitrile (2 mL) at 65° C. was added (trimethylsilyl)diethylamine (4.12 g, 21.1 mmol) dropwise via a syringe. The reaction was maintained at 65° C. and stirred for 3 hours. Additional amount of (trimethylsilyl)diethylamine (2 mL, 10.2 mmol) was added and the reaction mixture was stirred at 65° C. overnight. The reaction was then concentrated under reduced pressure and dried under vacuum to give the title compound. This material was used directly in next step of the synthesis without further purification. the reaction mixture was stirred at 65° C. overnight The reaction was then concentrated under reduced pressure dried under vacuum

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred pre-warmed solution of (S)-(+)-S-methyl-S-phenylsulphoximine (3 g, 18.7 mmol) in acetonitrile (2 mL) at 65° C. was added (trimethylsilyl)diethylamine (4.12 g, 21.1 mmol) dropwise via a syringe. The reaction was maintained at 65° C. and stirred for 3 hours. Additional amount of (trimethylsilyl)diethylamine (2 mL, 10.2 mmol) was added and the reaction mixture was stirred at 65° C. overnight. The reaction was then concentrated under reduced pressure and dried under vacuum to give the title compound. This material was used directly in next step of the synthesis without further purification. the reaction mixture was stirred at 65° C. overnight The reaction was then concentrated under reduced pressure dried under vacuum

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-amino-5-bromonicotinic acid (189 mg, 0.87 mmol), N,N-diisopropylethylamine (0.30 mL, 1.7 mmol), and (S)-(+)-S-methyl-S-phenylsulfoximine (162 mg, 1.0 mmol) in 4.0 mL DMF at room temperature was added BOP (423 mg, 0.96 mmol). The solution was stirred 30 minutes, then heated at 60° C. for 30 minutes, and then cooled back to room temperature. After 19 hours, the mixture was dissolved in EtOAc, washed with Na2CO3 solution, H2O, brine, dried with anhydrous Na2SO4 and rotary evaporated. The yellow foam was purified by chromatography (silica gel, CHCl3/EtOAc) to give the title compound as a light yellow solid (260 mg, 84%). cooled back to room temperature After 19 hours washed with Na2CO3 solution, H2O, brine dried with anhydrous Na2SO4 and rotary evaporated The yellow foam was purified by chromatography (silica gel, CHCl3/EtOAc)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-amino-5-bromonicotinic acid (189 mg, 0.87 mmol), N,N-diisopropylethylamine (0.30 mL, 1.7 mmol), and (S)-(+)-S-methyl-S-phenylsulfoximine (162 mg, 1.0 mmol) in 4.0 mL DMF at room temperature was added BOP (423 mg, 0.96 mmol). The solution was stirred 30 minutes, then heated at 60° C. for 30 minutes, and then cooled back to room temperature. After 19 hours, the mixture was dissolved in EtOAc, washed with Na2CO3 solution, H2O, brine, dried with anhydrous Na2SO4 and rotary evaporated. The yellow foam was purified by chromatography (silica gel, CHCl3/EtOAc) to give the title compound as a light yellow solid (260 mg, 84%). cooled back to room temperature After 19 hours washed with Na2CO3 solution, H2O, brine dried with anhydrous Na2SO4 and rotary evaporated The yellow foam was purified by chromatography (silica gel, CHCl3/EtOAc)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 6-amino-5-iodonicotinic acid (330 mg, 1.3 mmol), N,N-diisopropylethylamine (0.44 mL, 2.5 mmol), and (S)-(+)-S-methyl-S-phenylsulfoximine (291 mg, 1.9 mmol) in 7.0 mL DMF at room temperature was added BOP (608 mg, 1.4 mmol). The solution was stirred 10 minutes and then heated at 60° C. for 5 hours. The mixture was dissolved in EtOAc, washed with Na2CO3 solution, H2O, brine, dried with anhydrous Na2SO4 and rotary evaporated. The brown oil was purified by chromatography (silica gel, hexane/acetone). The product containing fractions were purified by chromatography one additional time (silica gel, EtOAc/MeOH). To give the title compound as a white foam (354 mg, 71%). washed with Na2CO3 solution, H2O, brine dried with anhydrous Na2SO4 and rotary evaporated The brown oil was purified by chromatography (silica gel, hexane/acetone) The product containing fractions were purified by chromatography one additional time (silica gel, EtOAc/MeOH)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 6-amino-5-iodonicotinic acid (330 mg, 1.3 mmol), N,N-diisopropylethylamine (0.44 mL, 2.5 mmol), and (S)-(+)-S-methyl-S-phenylsulfoximine (291 mg, 1.9 mmol) in 7.0 mL DMF at room temperature was added BOP (608 mg, 1.4 mmol). The solution was stirred 10 minutes and then heated at 60° C. for 5 hours. The mixture was dissolved in EtOAc, washed with Na2CO3 solution, H2O, brine, dried with anhydrous Na2SO4 and rotary evaporated. The brown oil was purified by chromatography (silica gel, hexane/acetone). The product containing fractions were purified by chromatography one additional time (silica gel, EtOAc/MeOH). To give the title compound as a white foam (354 mg, 71%). washed with Na2CO3 solution, H2O, brine dried with anhydrous Na2SO4 and rotary evaporated The brown oil was purified by chromatography (silica gel, hexane/acetone) The product containing fractions were purified by chromatography one additional time (silica gel, EtOAc/MeOH)