1-(bromomethyl)-4-(trifluoromethylsulfanyl)benzene

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4-[{N-(2-amino5-chlorobenzoyl)glycyl}aminomethyl]piperidine (16.2 mg, 0.050 mmol), 4-(trifluoromethylthio)benzyl bromide (20.3 mg, 0.075 mmol), piperidinomethylpolystyrene (60 mg), acetonitrile (1.0 mL) and chloroform (0.50 mL) was stirred at 60° C. for 15 h. The reaction mixture was cooled, loaded onto Varian™ SCX column and washed with CH3OH (15 mL). Product was eluted using 2 N NH3 in CH3OH (5 mL) and concentrated to afford 4-[{N-(2-amino-5-chlorobenzoyl)glycyl}aminomethyl]-1-{4-(trifluoromethylthio)benzyl}piperidine (Compound No.1616) (21.9 mg, 85%): The purity was determined by RPLC/MS (96%); ESI/MS m/e 545.2 (M++H, C23H26ClF3N4O2S). The reaction mixture was cooled washed with CH3OH (15 mL) Product was eluted concentrated

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4-[{N-(2-amino5-chlorobenzoyl)glycyl}aminomethyl]piperidine (16.2 mg, 0.050 mmol), 4-(trifluoromethylthio)benzyl bromide (20.3 mg, 0.075 mmol), piperidinomethylpolystyrene (60 mg), acetonitrile (1.0 mL) and chloroform (0.50 mL) was stirred at 60° C. for 15 h. The reaction mixture was cooled, loaded onto Varian™ SCX column and washed with CH3OH (15 mL). Product was eluted using 2 N NH3 in CH3OH (5 mL) and concentrated to afford 4-[{N-(2-amino-5-chlorobenzoyl)glycyl}aminomethyl]-1-{4-(trifluoromethylthio)benzyl}piperidine (Compound No.1616) (21.9 mg, 85%): The purity was determined by RPLC/MS (96%); ESI/MS m/e 545.2 (M++H, C23H26ClF3N4O2S). The reaction mixture was cooled washed with CH3OH (15 mL) Product was eluted concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 166 mg (1.017 mmol) of 5-hydroxy-3,4-dihydroisoquinolin-1(2H)-one, 289 mg (1.068 mmol) of 1-(bromomethyl)-4-[(trifluoromethyl)sulphanyl]benzene and 365 mg (2.645 mmol) were suspended in 3 ml of ethanol and stirred under reflux for 6 h. After cooling, the insoluble constituents were filtered off and the solvent was removed under reduced pressure. The residue was dissolved in chloroform and water. The phases were separated, the organic phase was dried over sodium sulphate and the solvent was removed under reduced pressure. The crude product was purified by chromatography (ethyl acetate:n-heptane 2:1). This gave 200 mg (54% of theory) of the desired 5-({4-[(trifluoromethyl)sulphanyl]benzyl}oxy)-3,4-dihydroisoquinolin-1(2H)-one. 1H-NMR (400 MHz, d6-DMSO δ, ppm) 7.89 (br. s, 1H), 7.52-7.44 (m, 4H), 7.28 (t, 1H), 7.22 (d, 1H), 5.16 (s, 2H), 3.33 (dt, 2H), 2.84 (t, 2H). under reflux for 6 h After cooling the insoluble constituents were filtered off the solvent was removed under reduced pressure The residue was dissolved in chloroform The phases were separated the organic phase was dried over sodium sulphate the solvent was removed under reduced pressure The crude product was purified by chromatography (ethyl acetate:n-heptane 2:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 166 mg (1.017 mmol) of 5-hydroxy-3,4-dihydroisoquinolin-1(2H)-one, 289 mg (1.068 mmol) of 1-(bromomethyl)-4-[(trifluoromethyl)sulphanyl]benzene and 365 mg (2.645 mmol) were suspended in 3 ml of ethanol and stirred under reflux for 6 h. After cooling, the insoluble constituents were filtered off and the solvent was removed under reduced pressure. The residue was dissolved in chloroform and water. The phases were separated, the organic phase was dried over sodium sulphate and the solvent was removed under reduced pressure. The crude product was purified by chromatography (ethyl acetate:n-heptane 2:1). This gave 200 mg (54% of theory) of the desired 5-({4-[(trifluoromethyl)sulphanyl]benzyl}oxy)-3,4-dihydroisoquinolin-1(2H)-one. 1H-NMR (400 MHz, d6-DMSO δ, ppm) 7.89 (br. s, 1H), 7.52-7.44 (m, 4H), 7.28 (t, 1H), 7.22 (d, 1H), 5.16 (s, 2H), 3.33 (dt, 2H), 2.84 (t, 2H). under reflux for 6 h After cooling the insoluble constituents were filtered off the solvent was removed under reduced pressure The residue was dissolved in chloroform The phases were separated the organic phase was dried over sodium sulphate the solvent was removed under reduced pressure The crude product was purified by chromatography (ethyl acetate:n-heptane 2:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Prepared according to the described general procedure 4 (GP4) by reaction of 6-(2,6-dimethoxyphenyl)piperidin-2-one with commercially available (4-(bromomethyl)phenyl)(trifluoromethyl)sulfane. Subsequent purification by preparative HPLC afforded the target compound. LC-MS (conditions E): tR=0.83 min.; [M+H]+: 426.20 g/mol. Prepared Subsequent purification by preparative HPLC afforded the target compound

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 30 mg of 2-phenoxymethyl-1H-indole-5-carboxylic acid methyl ester were dissolved in 1 ml of THF and treated with 5 mg NaH (60%) at 0° C. for 15 min. 1.2 eq. of 1-bromomethyl-4-trifluoromethylsulfanyl-benzene were added and the reaction stirred for 1.5 h. The solvent was evaporated and the product extracted from methylenchloride/water. The product was purified by preparative HPLC. MS(ISP): 472.5 (M+H)+. The solvent was evaporated the product extracted from methylenchloride/water The product was purified by preparative HPLC

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 30 mg of 2-phenoxymethyl-1H-indole-5-carboxylic acid methyl ester were dissolved in 1 ml of THF and treated with 5 mg NaH (60%) at 0° C. for 15 min. 1.2 eq. of 1-bromomethyl-4-trifluoromethylsulfanyl-benzene were added and the reaction stirred for 1.5 h. The solvent was evaporated and the product extracted from methylenchloride/water. The product was purified by preparative HPLC. MS(ISP): 472.5 (M+H)+. The solvent was evaporated the product extracted from methylenchloride/water The product was purified by preparative HPLC

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4-[{N-(2-amino5-chlorobenzoyl)glycyl}aminomethyl]piperidine (16.2 mg, 0.050 mmol), 4-(trifluoromethylthio)benzyl bromide (20.3 mg, 0.075 mmol), piperidinomethylpolystyrene (60 mg), acetonitrile (1.0 mL) and chloroform (0.50 mL) was stirred at 60° C. for 15 h. The reaction mixture was cooled, loaded onto Varian™ SCX column and washed with CH3OH (15 mL). Product was eluted using 2 N NH3 in CH3OH (5 mL) and concentrated to afford 4-[{N-(2-amino-5-chlorobenzoyl)glycyl}aminomethyl]-1-{4-(trifluoromethylthio)benzyl}piperidine (Compound No.1616) (21.9 mg, 85%): The purity was determined by RPLC/MS (96%); ESI/MS m/e 545.2 (M++H, C23H26ClF3N4O2S). The reaction mixture was cooled washed with CH3OH (15 mL) Product was eluted concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 5,6-dichloro-2-(2,2,2-trifluoro-ethyl)-1H-benzimidazole (434 mg) in DMF (5 mL) was added potassium carbonate powder (669 mg) and 4-(trifluoromethylthio) benzyl bromide (596 mg). The resulting mixture was stirred at room temperature overnight. The reaction mixture was quenched with water, extracted with EtOAc, and dried over Na2SO4. The crude product was purified by silica gel chromatography (10%-40% EtOAc/hexanes) to yield the title compound as a brown solid. The reaction mixture was quenched with water extracted with EtOAc dried over Na2SO4 The crude product was purified by silica gel chromatography (10%-40% EtOAc/hexanes)