2,4,5-trifluorobenzenesulfonyl chloride

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of sodium sulfite (153 g, 1214 mmol) in 1000 mL water was added a solution of 2,4,5-trifluorobenzene-1-sulfonyl chloride (40 g, 173 mmol) in dioxane (300 mL) dropwise. After the complete addition of sulfonyl chloride, the reaction was basified to about pH 14 by the addition of 1 N NaOH, and the reaction mixture was stirred overnight. The reaction mixture was cooled in ice bath and acidified using ˜100 mL concentrated H2SO4 to pH about 1. The mixture was extracted with EtOAc and CH2Cl2 and the combined organic layers were dried over Na2SO4, filtered and concentrated to afford 2,4,5-trifluorobenzenesulfinic acid (34 g, 100%). The reaction mixture was cooled in ice bath The mixture was extracted with EtOAc and CH2Cl2 the combined organic layers were dried over Na2SO4 filtered concentrated

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

Procedure: The reaction and aftertreatment were conducted in the same manner as in Example 15a by using the N-(2,4-dimethoxybenzyl)-2-fluoropyrimidin-4-amine (0.20 g, 0.76 mmol) prepared in Example 24a, LiHMDS (1.0 M in THF, 0.91 mL, 0.91 mmol), 2,4,5-trifluorobenzenesulfonyl chloride (0.19 g, 0.84 mmol) and THF (3.0 mL), to yield the title compound (0.22 g, 63%) as a colorless solid. The reaction and aftertreatment

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

Procedure: To a solution of the N-(2,4-dimethoxybenzyl)pyrimidin-4-amine (0.76 g, 3.10 mmol) prepared in Example 14a and 1,4-diazabicyclo[2.2.2]octane (0.70 g, 6.20 mmol) in acetonitrile (20 mL), 2,4,5-trifluorobenzenesulfonyl chloride (1.43 g, 6.20 mmol) was added with cooling on ice, and the reaction solution was stirred at room temperature for 1 hour. The reaction solution was filtered, the filtrate was vacuum concentrated, and the residue was purified with silica gel chromatography (hexane/ethyl acetate=67:33) to yield the title compound (0.72 g, 53%) as a colorless solid. with cooling on ice The reaction solution was filtered concentrated the residue was purified with silica gel chromatography (hexane/ethyl acetate=67:33)

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of sodium sulfite (153 mg, 1.21 mmol) and sodium bicarbonate (306 mg, 3.63 mmol) in water (3 mL) was treated with 2,4,5-trifluorobenzenesulfonyl chloride (280 mg, 1.21 mmol) and heated in a microwave reactor at 150° C. for 400 seconds. The resulting mixture was treated with 3-bromodihydrofuran-2(3H)-one (299 mg, 1.82 mmol) and then heated in a microwave reactor at 150° C. for 500 seconds. The mixture was cooled to 10° C. and the resulting solid filtered off and dried in vacuo to give the title compound (60 mg). heated in a microwave reactor at 150° C. for 500 seconds The mixture was cooled to 10° C. the resulting solid filtered off dried in vacuo

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

Procedure: To a solution of sodium sulfite (153 g, 1214 mmol) in 1000 mL water was added a solution of 2,4,5-trifluorobenzene-1-sulfonyl chloride (40 g, 173 mmol) in dioxane (300 mL) dropwise. After the complete addition of sulfonyl chloride, the reaction was basified to about pH 14 by the addition of 1 N NaOH, and the reaction mixture was stirred overnight. The reaction mixture was cooled in ice bath and acidified using ˜100 mL concentrated H2SO4 to pH about 1. The mixture was extracted with EtOAc and CH2Cl2 and the combined organic layers were dried over Na2SO4, filtered and concentrated to afford 2,4,5-trifluorobenzenesulfinic acid (34 g, 100%). The reaction mixture was cooled in ice bath The mixture was extracted with EtOAc and CH2Cl2 the combined organic layers were dried over Na2SO4 filtered concentrated

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

Procedure: The reaction and aftertreatment were conducted in the same manner as in Example 15a by using the N-(2,4-dimethoxybenzyl)-2-fluoropyrimidin-4-amine (0.20 g, 0.76 mmol) prepared in Example 24a, LiHMDS (1.0 M in THF, 0.91 mL, 0.91 mmol), 2,4,5-trifluorobenzenesulfonyl chloride (0.19 g, 0.84 mmol) and THF (3.0 mL), to yield the title compound (0.22 g, 63%) as a colorless solid. The reaction and aftertreatment

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

Procedure: To a solution of the N-(2,4-dimethoxybenzyl)pyrimidin-4-amine (0.76 g, 3.10 mmol) prepared in Example 14a and 1,4-diazabicyclo[2.2.2]octane (0.70 g, 6.20 mmol) in acetonitrile (20 mL), 2,4,5-trifluorobenzenesulfonyl chloride (1.43 g, 6.20 mmol) was added with cooling on ice, and the reaction solution was stirred at room temperature for 1 hour. The reaction solution was filtered, the filtrate was vacuum concentrated, and the residue was purified with silica gel chromatography (hexane/ethyl acetate=67:33) to yield the title compound (0.72 g, 53%) as a colorless solid. with cooling on ice The reaction solution was filtered concentrated the residue was purified with silica gel chromatography (hexane/ethyl acetate=67:33)

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

Procedure: The above titled compound was prepared from 2,4,5-trifluorobenzenesulfonyl chloride (5.0 g, 0.022 mol) and thiazole-4-yl-carbamic acid tert-butyl ester (Preparation 72, 4.3 g, 0.022 mol) using the method of Preparation 453 to afford the product as a white solid (6.84 g, 80%).

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

Procedure: To a solution of (N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine (Preparation 14, 13 g, 51.73 mmol) in dry tetrahydrofuran (150 ml) at −70° C. under argon atmosphere was added 1 M lithium 1,1,1,3,3,3-hexamethyldisilazan-2-ide in tetrahydrofuran (56.9 ml, 56.9 mmol) dropwise. The reaction mixture was allowed to warm up to room temperature and stirred for 1 h. It was again cooled to −70° C. and a tetrahydrofuran (50 ml) solution of 2,4,5-trifluorobenzenesulfonyl chloride (11.9 g, 51.73 mmol) was added dropwise to it at this temperature. After complete addition, reaction mixture was gradually allowed to warm up to room temperature and stirred for 1 hour. The reaction mixture was quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride solution. Crude product was purified over 100-200 silica gel using 5-15% v/v ethyl acetate in hexane to give 17 g (75%) of the title compound as a white solid. It was again cooled to −70° C. After complete addition, reaction mixture to warm up to room temperature stirred for 1 hour The reaction mixture was quenched with saturated aqueous ammonium chloride solution extracted with ethyl acetate The organic layer was washed with water and saturated aqueous sodium chloride solution Crude product was purified over 100-200 silica gel using 5-15% v/v ethyl acetate in hexane