imino-dimethyl-oxo-lambda6-sulfane

Conditions: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Bromo-3-iodo-benzene (250 μL, 1.96 mmol), (methylsulfonimidoyl)methane (219.188 mg, 2.353 mmol), cesium carbonate (894.466 mg, 2.745 mmol) and dioxane (12 mL) are purged with argon. (5-diphenylphosphanyl-9,9-dimethyl-xanthen-4-yl)-diphenyl-phosphane (85.098, 0.147 mmol) and tris(dibenzylideneacetone)dipalladium(0) (44.89 mg, 0.049 mmol) are added, purged again with argon and stirred at 105° C. for 3 h. purged again with argon

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

Procedure: from 2-bromopropionic acid, dimethyl sulphoximine and 5-(o-chloro-p-trifluoromethyl-phenoxy)-2-nitrobenzoic acid using sodium methylate as the base and 1,2-dimethoxyethane as the solvent there is obtained N-{2-[5-(o-chloro-p-trifluoromethyl-phenoxy)-2-nitrobenzoyloxy]-propionyl}-S,S-dimethyl-sulphoximine as a yellow resin; 1H-NMR (CDCl3): 8.20-6.90 (m,6H), 5.28 (q,1H), 3.37 (s,6H), 1.62 (d,3H);

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

Procedure: from chloroacetic acid, dimethyl sulphoximine and 5-(o-chloro-p-trifluoromethyl-phenoxy)-2-nitrobenzoic acid using 1,5-diaza-bicyclo[5,4,0]undec-5-ene as the base and toluene as the solvent there is obtained N-{[5-(o-chloro-p-trifluoromethyl-phenoxy)-2-nitrobenzoyloxy]acetyl}-S,S-dimethyl-sulphoximine as a yellow resin; 1H-NMR (CDCl3): 8.23-6.92 (m, 6H), 4.87 (s,2H), 3.37 (s,6H);

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

Procedure: from chloroacetic acid, dimethyl sulphoximine and 5-(o-chloro-p-trifluoromethyl-phenoxy)-2-nitrobenzoic acid using 1,5-diaza-bicyclo[5,4,0]undec-5-ene as the base and toluene as the solvent there is obtained N-{[5-(o-chloro-p-trifluoromethyl-phenoxy)-2-nitrobenzoyloxy]acetyl}-S,S-dimethyl-sulphoximine as a yellow resin; 1H-NMR (CDCl3): 8.23-6.92 (m, 6H), 4.87 (s,2H), 3.37 (s,6H);

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

Procedure: A solution of 2.46 g of 2-chloro-5-(o-chloro-p-trifluoromethyl-phenoxy)-benzoic acid in 20 ml of methylene chloride is added dropwise at room temperature while stirring to a solution of 1.3 g of dicyclohexylcarbodiimide and 0.6 g of dimethyl sulphoximine in 5 ml of methylene chloride, a slight exothermic reaction occurring. After a reaction time of 15 minutes the solvent is removed by evaporation under reduced pressure and the residue is purified by chromatography on silica gel with n-hexane/ethyl acetate (9:1). The white crystalline product is then recrystallized from methylene chloride/n-hexane. There is obtained N-[2-chloro-5-(o-chloro-p-trifluoromethyl-phenoxy)-benzoyl]-S,S-dimethyl-sulphoximine, m.p. 128°-131° C.; mass spectrum: m/e 425/427; 1H-NMR (CDCl3): 7.8-6.9 (m,6H), 3.4 (s,6H). a slight exothermic reaction After a reaction time of 15 minutes the solvent is removed by evaporation under reduced pressure the residue is purified by chromatography on silica gel with n-hexane/ethyl acetate (9:1) The white crystalline product is then recrystallized from methylene chloride/n-hexane

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

Procedure: A solution of 2.46 g of 2-chloro-5-(o-chloro-p-trifluoromethyl-phenoxy)-benzoic acid in 20 ml of methylene chloride is added dropwise at room temperature while stirring to a solution of 1.3 g of dicyclohexylcarbodiimide and 0.6 g of dimethyl sulphoximine in 5 ml of methylene chloride, a slight exothermic reaction occurring. After a reaction time of 15 minutes the solvent is removed by evaporation under reduced pressure and the residue is purified by chromatography on silica gel with n-hexane/ethyl acetate (9:1). The white crystalline product is then recrystallized from methylene chloride/n-hexane. There is obtained N-[2-chloro-5-(o-chloro-p-trifluoromethyl-phenoxy)-benzoyl]-S,S-dimethyl-sulphoximine, m.p. 128°-131° C.; mass spectrum: m/e 425/427; 1H-NMR (CDCl3): 7.8-6.9 (m,6H), 3.4 (s,6H). a slight exothermic reaction After a reaction time of 15 minutes the solvent is removed by evaporation under reduced pressure the residue is purified by chromatography on silica gel with n-hexane/ethyl acetate (9:1) The white crystalline product is then recrystallized from methylene chloride/n-hexane

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

Procedure: 3.1 g (7 mmol) of N-(2-benzyloxy-4-fluoro-phenyl)-7-bromo-5-methyl-quinazolin-4-amine, 0.8 g (8.8 mmol) dimethylsulphoximine (IV.1), 0.4 g (1.4 mmol) 2-(di-t-butylphosphino) biphenyl, 0.5 g (0.5 mmol) Pd2dba3 and 1.0 g (10.2 mmol) sodium tert-butoxide in dioxane are heated to 80° C. for 4.5 h. After cooling to RT the reaction mixture is filtered, diluted with water and extracted with EtOAc. The organic layers are pooled, dried and evaporated. The residue is purified by FC giving rise to N-(2-benzyloxy-4-fluoro-phenyl)-7-[[dimethyl(oxo)-λ6-sulfanylidene]amino]-5-methyl-quinazolin-4-amine. is filtered diluted with water extracted with EtOAc dried evaporated The residue is purified by FC

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

Procedure: 3.1 g (7 mmol) of N-(2-benzyloxy-4-fluoro-phenyl)-7-bromo-5-methyl-quinazolin-4-amine, 0.8 g (8.8 mmol) dimethylsulphoximine (V.1), 0.4 g (1.4 mmol) 2-(di-t-butylphosphino) biphenyl, 0.5 g (0.5 mmol) Pd2dba3 and 1.0 g (10.2 mmol) sodium tert-butoxide in dioxane are heated to 80° C. for 4.5 h. After cooling to RT the reaction mixture is filtered, diluted with water and extracted with EtOAc. The organic layers are pooled dried and evaporated. The residue is purified by FC giving rise to N-(2-benzyloxy-4-fluoro-phenyl)-7-[[dimethyl(oxo)-λ6-sulfanylidene]amino]-5-methyl-quinazolin-4-amine. is filtered diluted with water extracted with EtOAc The organic layers are pooled dried evaporated The residue is purified by FC

Conditions: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Bromo-3-iodo-benzene (250 μL, 1.96 mmol), (methylsulfonimidoyl)methane (219.188 mg, 2.353 mmol), cesium carbonate (894.466 mg, 2.745 mmol) and dioxane (12 mL) are purged with argon. (5-diphenylphosphanyl-9,9-dimethyl-xanthen-4-yl)-diphenyl-phosphane (85.098, 0.147 mmol) and tris(dibenzylideneacetone)dipalladium(0) (44.89 mg, 0.049 mmol) are added, purged again with argon and stirred at 105° C. for 3 h. purged again with argon

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

Procedure: from 2-bromopropionic acid, dimethyl sulphoximine and 5-(o-chloro-p-trifluoromethyl-phenoxy)-2-nitrobenzoic acid using sodium methylate as the base and 1,2-dimethoxyethane as the solvent there is obtained N-{2-[5-(o-chloro-p-trifluoromethyl-phenoxy)-2-nitrobenzoyloxy]-propionyl}-S,S-dimethyl-sulphoximine as a yellow resin; 1H-NMR (CDCl3): 8.20-6.90 (m,6H), 5.28 (q,1H), 3.37 (s,6H), 1.62 (d,3H);

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

Procedure: from chloroacetic acid, dimethyl sulphoximine and 5-(o-chloro-p-trifluoromethyl-phenoxy)-2-nitrobenzoic acid using 1,5-diaza-bicyclo[5,4,0]undec-5-ene as the base and toluene as the solvent there is obtained N-{[5-(o-chloro-p-trifluoromethyl-phenoxy)-2-nitrobenzoyloxy]acetyl}-S,S-dimethyl-sulphoximine as a yellow resin; 1H-NMR (CDCl3): 8.23-6.92 (m, 6H), 4.87 (s,2H), 3.37 (s,6H);

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

Procedure: A solution of 2.46 g of 2-chloro-5-(o-chloro-p-trifluoromethyl-phenoxy)-benzoic acid in 20 ml of methylene chloride is added dropwise at room temperature while stirring to a solution of 1.3 g of dicyclohexylcarbodiimide and 0.6 g of dimethyl sulphoximine in 5 ml of methylene chloride, a slight exothermic reaction occurring. After a reaction time of 15 minutes the solvent is removed by evaporation under reduced pressure and the residue is purified by chromatography on silica gel with n-hexane/ethyl acetate (9:1). The white crystalline product is then recrystallized from methylene chloride/n-hexane. There is obtained N-[2-chloro-5-(o-chloro-p-trifluoromethyl-phenoxy)-benzoyl]-S,S-dimethyl-sulphoximine, m.p. 128°-131° C.; mass spectrum: m/e 425/427; 1H-NMR (CDCl3): 7.8-6.9 (m,6H), 3.4 (s,6H). a slight exothermic reaction After a reaction time of 15 minutes the solvent is removed by evaporation under reduced pressure the residue is purified by chromatography on silica gel with n-hexane/ethyl acetate (9:1) The white crystalline product is then recrystallized from methylene chloride/n-hexane