3,5-DICHLOROPHENYLTHIOUREA

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

実験手順: To a mixture of 4 liters of acetone and 110 g (1.5 moles) of ammonium thiocyanate are added dropwise 173 g (1.23 moles) of benzoyl chloride. The reaction mixture is then heated for a further 15 minutes. Next, 200 g (1.23 moles) of 3,5-dichlorophenyl aniline dissolved in 200 ml of acetone are added. The mixture is then heated for a further 30 minutes, cooled and poured into 4 liters of water. The precipitate is collected and rinsed with 1 liter of water. The crystals are mixed with 2 liters of water containing 50 g of sodium hydroxide. The mixture is heated for 30 minutes and then cooled. The precipitate is collected to give 238 g (88%) of N-[3,5-dichlorophenyl]thiourea, m.p. 180° C. The reaction mixture is then heated for a further 15 minutes are added The mixture is then heated for a further 30 minutes cooled The precipitate is collected rinsed with 1 liter of water The crystals are mixed with 2 liters of water containing 50 g of sodium hydroxide The mixture is heated for 30 minutes cooled The precipitate is collected

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

実験手順: To a solution of 2-bromo-1-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)ethanone (Example 26, Step 2) (0.312, 0.841 mmol) in ethanol (10 mL) in a 25 mL round bottom flask was added N-(3,5-dichlorophenyl)thiourea (0.195 g, 0.882 mmol). The solution was heated to reflux (14 hours) and the reaction was cooled to room temperature. The resulting suspension was concentrated in vacuo, suspended in ethyl acetate (100 mL) and washed with sodium carbonate solution (10%, 3×20 mL), brine (1×20 mL), dried over sodium sulfate, filtered and concentrated, yielding a powdery solid. This solid was dissolved in ethyl acetate/methylene chloride. Addition of isooctane resulted in the precipitation of 4-(4-fluorophenyl)-5-(4-methylsulfonylphenyl)-2-(3,5-dichlorophenylamino)thiazole (0.261 g, 63%) as a pale yellow powder: mp 287°-288° C.; 1HNMR (DMSO d6) 400 mHz 10.84 (s, 1 H), 7.86 (d, J=8.79 Hz, 2 H), 7.73 (s, 2 H), 7.54-7.45 (m, 4 H), 7.22 (t, J=8.79 Hz, 2 H), 7.15 (s, 1 H), 3.22 (s, 3 H); MS m/z 492 (M+). HRMS Δ=4.8 mmu. The solution was heated to reflux (14 hours) The resulting suspension was concentrated in vacuo washed with sodium carbonate solution (10%, 3×20 mL), brine (1×20 mL) dried over sodium sulfate filtered concentrated yielding a powdery solid

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

実験手順: To a mixture of 4 liters of acetone and 110 g (1.5 moles) of ammonium thiocyanate are added dropwise 173 g (1.23 moles) of benzoyl chloride. The reaction mixture is then heated for a further 15 minutes. Next, 200 g (1.23 moles) of 3,5-dichlorophenyl aniline dissolved in 200 ml of acetone are added. The mixture is then heated for a further 30 minutes, cooled and poured into 4 liters of water. The precipitate is collected and rinsed with 1 liter of water. The crystals are mixed with 2 liters of water containing 50 g of sodium hydroxide. The mixture is heated for 30 minutes and then cooled. The precipitate is collected to give 238 g (88%) of N-[3,5-dichlorophenyl]thiourea, m.p. 180° C. The reaction mixture is then heated for a further 15 minutes are added The mixture is then heated for a further 30 minutes cooled The precipitate is collected rinsed with 1 liter of water The crystals are mixed with 2 liters of water containing 50 g of sodium hydroxide The mixture is heated for 30 minutes cooled The precipitate is collected