4-fluoro-2-(trifluoromethyl)benzenesulfonyl Chloride

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

実験手順: Brown solid. MS (ESI): 551.09 (MH+). This example was prepared in analogy to example 1 step C) to D) from 4-(2-methoxy-ethyl)-piperidine-4-carboxylic acid ethyl ester (example 1 step B)), 4-fluoro-2-trifluoromethyl-benzenesulfonyl chloride and methanesulfonic acid 4-amino-phenyl ester.

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

実験手順: Off-white solid. MS (ESI): 539.12 (MH+). This example was prepared in analogy to example 1 step C) to D) from 4-(2-methoxy-ethyl)-piperidine-4-carboxylic acid ethyl ester (example 1 step B)), 4-fluoro-2-trifluoromethyl-benzenesulfonyl chloride and 4-(2,2,2-trifluoroethyl)-aniline.

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

実験手順: Off-white solid. MS (ESI): 485.15 (MH+). This example was prepared in analogy to example 1 step C) to D) from 4-(2-methoxy-ethyl)-piperidine-4-carboxylic acid ethyl ester (example 1 step B)), 4-fluoro-2-trifluoromethyl-benzenesulfonyl chloride and 4-ethyl-aniline.

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

実験手順: Light brown solid. MS (ESI): 497.15 (MH+). This example was prepared in analogy to example 1 step C) to D) from 4-(2-methoxy-ethyl)-piperidine-4-carboxylic acid ethyl ester (example 1 step B)), 4-fluoro-2-trifluoromethyl-benzenesulfonyl chloride and 4-cyclopropyl-aniline.

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Fluoro-2-(trifluoromethyl)benzenesulphonyl chloride (2 g) was dissolved in 1,4-dioxane (12 mL) and water (3 mL) under a nitrogen atmosphere. Tris-(2-carboxylethyl)phosphine hydrochloride (8.73 g) was added and the mixture was stirred under reflux for 6 h. The reaction mixture was cooled to 25° C. and water (20 mL) was added. The product was extracted 3 times with CH2Cl2 (20 mL). The combined organic layers were dried over Na2SO4 filtrated and evaporated to dryness to yield the title compound (1.27 g, 85%) as a colorless liquid. MS (ESI): m/z=194.9 [M−H]−. under reflux for 6 h The product was extracted 3 times with CH2Cl2 (20 mL) The combined organic layers were dried over Na2SO4 filtrated evaporated to dryness

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Fluoro-2-(trifluoromethyl)benzenesulphonyl chloride (2.0 g) was dissolved in dioxane (12 mL) under a N2-atmosphere at ambient temperature. Water (3.0 mL) and tris-(2-carboxylethyl)phosphine hydrochloride (8.73 g) was added afterwards. The reaction mixture is stirred under reflux for 6 h. The reaction mixture is cooled to 25° C. and dissolved with water (30 mL). The product is extracted with CH2Cl2 (100 mL) several times. The combined organic layers are washed with water and dried over Na2SO4. The organic layer is filtrated and evaporated to dryness to yield 1.27 g (85%) of a colorless liquid which is used without further purification. MS (ESI): m/z=194.9 [M−H]−. under reflux for 6 h The product is extracted with CH2Cl2 (100 mL) several times The combined organic layers are washed with water dried over Na2SO4 The organic layer is filtrated evaporated to dryness

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The 2,6-difluoro-N1-(3-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-yl)benzene-1,3-diamine (20 mg, 0.047 mmol) prepared at Step 9 was added and dissolved into dichloromethane solvent. 4-fluoro-2-(trifluoromethyl)benzenesulfonyl chloride (18 mg, 0.07 mmol) and pyridine (8 uL, 0.094 mmol) were added into the reaction solution and stirred at 50° C. for 2 hours. After the reaction, the reactant was washed with 1N aqueous hydrochloric acid solution and salt water. After extraction with dichloromethane, the organic layer was dried with sulfuric anhydride magnesium and vacuum concentrated, and then refined by means of column chromatography, so that 27 mg of the target compound, N-(2,4-difluoro-3-(3-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-ylamino)phenyl)-4-fluoro-2-(trifluoromethyl)benzenesulfonamide (percentage yield: 89%), was obtained. was added After the reaction the reactant was washed with 1N aqueous hydrochloric acid solution and salt water After extraction with dichloromethane the organic layer was dried with sulfuric anhydride magnesium and vacuum concentrated

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

実験手順: The title compound was prepared in analogy to Example 58, Intermediate 1, using 4-fluoro-2-trifluoromethyl-benzene sulfonyl chloride. Colorless liquid. MS (EI): 195.1 (M−H)−.