thietan-3-amine;hydrobromide

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

実験手順: To a solution of 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazin-4-one (500 mg, 1.13 mmol) [prepared according to WO 02/48115, example 2D] in tetrahydrofuran (10 ml) is added triethylamine (0.4 ml, 2.87 mmol) and 3-thietanamine hydrobromide salt [the product of step 2] (250 mg, 1.47 mmol), and the mixture is heated to reflux overnight. The cooled reaction mixture is poured into water, extracted with ethyl acetate, the combined organic layers washed with water and brine, dried (Na2SO4), filtered, and concentrated. The crude product is purified by flash chromatography (ethyl acetate/hexane 1:2) to afford 250 mg (41%) of the title compound as a white solid. the mixture is heated to reflux overnight The cooled reaction mixture extracted with ethyl acetate the combined organic layers washed with water and brine dried (Na2SO4) filtered concentrated The crude product is purified by flash chromatography (ethyl acetate/hexane 1:2)

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

実験手順: To a solution of 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazin-4-one (500 mg, 1.13 mmol) [prepared according to WO 02/48115, example 2D] in tetrahydrofuran (10 ml) is added triethylamine (0.4 ml, 2.87 mmol) and 3-thietanamine hydrobromide salt [the product of step 2] (250 mg, 1.47 mmol), and the mixture is heated to reflux overnight. The cooled reaction mixture is poured into water, extracted with ethyl acetate, the combined organic layers washed with water and brine, dried (Na2SO4), filtered, and concentrated. The crude product is purified by flash chromatography (ethyl acetate/hexane 1:2) to afford 250 mg (41%) of the title compound as a white solid. the mixture is heated to reflux overnight The cooled reaction mixture extracted with ethyl acetate the combined organic layers washed with water and brine dried (Na2SO4) filtered concentrated The crude product is purified by flash chromatography (ethyl acetate/hexane 1:2)

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

実験手順: To a solution of thietan-3-amine hydrobromide in N,N-dimethylformamide, triethylamine was added at 0° C. Then 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (122 mg, 0.53 mmol), 1-hydroxybenzotriazole monohydrate (72 mg, 0.53 mmol), and 2-methyl-4-[3-(3,4,5-trichlorophenyl)-3-(trifluoromethyl)-3,4-dihydro-2H-pyrrol-5-yl]benzoic acid (200 mg, 0.44 mmol) were added to the solution. The reaction mixture was stirred overnight at room temperature and then diluted with t-BuOMe and washed with 2M HCl, and after that with H2O, saturated NaCl aq. and dried over MgSO4. After evaporation, the residue was purified with chromatography (220 mg, 95%). washed with 2M HCl after that with H2O, saturated NaCl aq. and dried over MgSO4 After evaporation the residue was purified with chromatography (220 mg, 95%)

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

実験手順: To the solution of thietan-3-amine hydrobromide (40 mg, 0.23 mmol) in 1,2-dichloromethane was added triethylamine (60 mg, 0.59 mmol) at 0° C. After that 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (54 mg, 0.23 mmol), 1-hydroxybenzotriazole monohydrate (32 mg, 0.23 mmol), and 4-[3-(3,4,5-trichlorophenyl)-3-(trifluoromethyl)-3,4-dihydro-2H-pyrrol-5-yl]-2-(trifluoromethyl)benzoic acid (100 mg, 0.19 mmol) were added to the solution at 0° C. Then the reaction mixture was stirred overnight at room temperature and diluted with t-butylmethylether, and washed with water, and dried over magnesium sulfate anhydrous. After evaporation, the residue was purified with silicagel column chromatography to give 75 mg of N-(thietan-3-yl)-4-[3-(3,4,5-trichlorophenyl)-3-(trifluoromethyl)-3,4-dihydro-2H-pyrrol-5-yl]-2-(trifluoromethyl)benzamide. washed with water dried over magnesium sulfate anhydrous After evaporation the residue was purified with silicagel column chromatography

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

実験手順: To a solution of 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazin-4-one (500 mg, 1.13 mmol) [prepared according to WO 02/48115, example 2D] in tetrahydrofuran (10 ml) is added triethylamine (0.4 ml, 2.87 mmol) and 3-thietanamine hydrobromide salt [the product of step 2] (250 mg, 1.47 mmol), and the mixture is heated to reflux overnight. The cooled reaction mixture is poured into water, extracted with ethyl acetate, the combined organic layers washed with water and brine, dried (Na2SO4), filtered, and concentrated. The crude product is purified by flash chromatography (ethyl acetate/hexane 1:2) to afford 250 mg (41%) of the title compound as a white solid. the mixture is heated to reflux overnight The cooled reaction mixture extracted with ethyl acetate the combined organic layers washed with water and brine dried (Na2SO4) filtered concentrated The crude product is purified by flash chromatography (ethyl acetate/hexane 1:2)