Реакция #74521

Уравнение реакции

dichloromethane methanol acetic acid

1-(ethoxymethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

3-cyano-N-(1,2,4-thiadiazol-5-yl)-4-[2-iodo-4-(trifluoromethoxy)phenoxy]benzenesulfonamide

1-(ethoxymethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

sodium carbonate

→

title compound

Выход 46.9%

3-cyano-4-[2-(1H-pyrazol-5-yl)-4-(trifluoromethoxy)phenoxy]-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide

Выход 46.9%

Растворители

water

1,4-dioxane

HCl

1,4-dioxane

Условия реакции

Обработка

1. 1
   ДругоеThe reaction was quenched by the addition of ethyl acetate (20 mL) and saturated aqueous brine solution (20 mL)
2. 2
   ДругоеThe organic layer was collected
3. 3
   Сушкаdried over sodium sulphate
4. 4
   Концентрированиеconcentrated in vacuo before purification
5. 5
   Другоеto afford a white solid
6. 6
   workup.STIRRINGstirred at room temperature for 4 hours before concentration in vacuo and purification
7. 7
   Другоеto afford a residue that
8. 8
   Другоеwas triturated in dichloromethane (5 mL)

Методика

3-cyano-N-(1,2,4-thiadiazol-5-yl)-4-[2-iodo-4-(trifluoromethoxy)phenoxy]benzenesulfonamide (Preparation 760, 500 mg, 0.88 mmol), 1-(ethoxymethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (Preparation 337, 600 mg, 1.4 mmol), palladium (0) tetrakis triphenylphosphine (78 mg, 0.067 mmol) and sodium carbonate (420 mg, 3.963 mmol) were dissolved in a mixture of water (4 mL) and 1,4-dioxane (12 mL) and heated to 85° C. under N2 for 7 hours. Further 1-(ethoxymethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (100 mg 0.23 mmol) and palladium (0) tetrakis triphenylphosphine (10 mg, 0.008 mmol) were added and the reaction stirred at 85° C. under N2 for 18 hours. The reaction was quenched by the addition of ethyl acetate (20 mL) and saturated aqueous brine solution (20 mL). The organic layer was collected, dried over sodium sulphate and concentrated in vacuo before purification using silica gel column chromatography (v/v/v dichloromethane:methanol:acetic acid v/v/v 100:0:0 to 95:5:0.5) to afford a white solid. This was dissolved in 4M HCl in 1,4-dioxane (5 mL) and stirred at room temperature for 4 hours before concentration in vacuo and purification using silica gel column chromatography (v/v/v dichloromethane:methanol:acetic acid 100:0:0 to 90:10:1 to afford a residue that was triturated in dichloromethane (5 mL) to afford 210 mg of the title compound as a white solid as the HCl salt.

Источник