溴二氟甲烷

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Portions of 3-bromo-2-(3-fluoro-phenyl)-6-methoxy-pyrazolo[1,5-b]pyridazine (400 mg, 2.1 g total) were placed in individual Reactivials equipped with a magnetic stirrer bar. Pyridine hydrochloride (10 eq) was added to each vial, the vials sealed, and heated to 200° for 3 hours. The vials were allowed to cool to ˜140° before opening and the contents poured into ice/water. The resulting mixture was extracted into ethyl acetate (3×100 ml) and the combined organic extracts washed with water (7×75 ml), dried (Na2SO4) and evaporated to give the des-bromo phenol as a brown solid (1.0 g, MH+ 230). This solid was dissolved in anhydrous DMF (10 ml) and sodium hydride (60% dispersion in mineral oil, 200 mg) added portionwise. After stirring for 20 minutes at ambient temperature the solution was transferred to a small cooled autoclave and bromodifluoromethane (5 ml, xs, condensed at −30°) added. The autoclave was then sealed, allowed to warm to ambient temperature and stirred for 36 hours. The resulting solution was diluted with ethyl acetate (200 ml), washed with water (10×20 ml), dried (Na2SO4), concentrated and the residual gum purified by flash column chromatography with cyclohexane:ethyl acetate (4:1) as eluant. This gave the title compound as a solid (652 mg, 60%). equipped with a magnetic stirrer bar sealed heated to 200° for 3 hours to cool to ˜140° before opening The resulting mixture was extracted into ethyl acetate (3×100 ml) the combined organic extracts washed with water (7×75 ml) dried (Na2SO4) evaporated to give the des-bromo phenol as a brown solid (1.0 g, MH+ 230) added The autoclave was then sealed to warm to ambient temperature stirred for 36 hours washed with water (10×20 ml) dried (Na2SO4) concentrated the residual gum purified by flash column chromatography with cyclohexane:ethyl acetate (4:1) as eluant

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2-(4-fluoro-phenyl)-3-(4-methanesulfonyl-phenyl)-pyrazolo[1,5-b]pyridazin-6-ol (0.2 g) in anhydrous dimethyl formamide (5 ml) was treated with sodium hydride ( 0.046 g, 60% dispersion in mineral oil), after effervescence ceased a stream of bromodifluoromethane gas was passed through the mixture at ambient temperature for 30 minutes. The reaction mixture was then poured into water (50 ml) and extracted with ethyl acetate (50 ml), the organic extract was washed with water (3×50 ml), dried and concentrated in vacuo. The residue was purified by chromatography to give the title compound as a white solid (0.17 g). extracted with ethyl acetate (50 ml) the organic extract was washed with water (3×50 ml) dried concentrated in vacuo The residue was purified by chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 10.8 g (56 mmol) of 2-hydroxy-6-propylsulfanylbenzonitrile were dissolved in 120 ml of dimethylformamide, and 15.5 g (0.11 mol) of anhydrous potassium carbonate were added. Then, at room temperature, 8.2 g of bromodifluoromethane were passed in, and the mixture was stirred at room temperature for 5 hours. Then 15.5 g (0.11 mol) of anhydrous potassium carbonate and 7.2 g of bromodifluoromethane were added, and the mixture was stirred at room temperature overnight. The reaction mixture was worked up by pouring into water and extracting twice with methyl tert.-butyl ether. The organic phase was separated, washed several times with water and concentrated. The solid has been dried in vacuo at 50° C. Yield: 12.3 g of an oily residue. at room temperature the mixture was stirred at room temperature overnight extracting twice with methyl tert.-butyl ether The organic phase was separated washed several times with water concentrated The solid has been dried in vacuo at 50° C

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 10.8 g (56 mmol) of 2-hydroxy-6-propylsulfanylbenzonitrile were dissolved in 120 ml of dimethylformamide, and 15.5 g (0.11 mol) of anhydrous potassium carbonate were added. Then, at room temperature, 8.2 g of bromodifluoromethane were passed in, and the mixture was stirred at room temperature for 5 hours. Then 15.5 g (0.11 mol) of anhydrous potassium carbonate and 7.2 g of bromodifluoromethane were added, and the mixture was stirred at room temperature overnight. The reaction mixture was worked up by pouring into water and extracting twice with methyl tert.-butyl ether. The organic phase was separated, washed several times with water and concentrated. The solid has been dried in vacuo at 50° C. Yield: 12.3 g of an oily residue. at room temperature the mixture was stirred at room temperature overnight extracting twice with methyl tert.-butyl ether The organic phase was separated washed several times with water concentrated The solid has been dried in vacuo at 50° C

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Portions of 3-bromo-2-(3-fluoro-phenyl )-6-methoxy-pyrazolo[1,5-b]pyridazine (400 mg, 2.1 g total) were placed in individual Reactivials equipped with a magnetic stirrer bar. Pyridine hydrochloride (10 eq) was added to each vial, the vials sealed, and heated to 200° for 3 hours. The vials were allowed to cool to ˜140° before opening and the contents poured into ice/water. The resulting mixture was extracted into ethyl acetate (3×100 ml) and the combined organic extracts washed with water (7×75 ml), dried (Na2SO4) and evaporated to give the des-bromo phenol as a brown solid (1.0 g, MH+230). This solid was dissolved in anhydrous DMF (10 ml) and sodium hydride (60% dispersion in mineral oil, 200 mg) added portionwise. After stirring for 20 minutes at ambient temperature the solution was transferred to a small cooled autoclave and bromodifluoromethane (5 ml, xs, condensed at −30°) added. The autoclave was then sealed, allowed to warm to ambient temperature and stirred for 36 hours. The resulting solution was diluted with ethyl acetate (200 ml), washed with water (10×20 ml), dried (Na2SO4), concentrated and the residual gum purified by flash column chromatography with cyclohexane:ethyl acetate (4:1) as eluant. This gave the title compound as a solid (652 mg, 60%). equipped with a magnetic stirrer bar sealed heated to 200° for 3 hours to cool to ˜140° before opening The resulting mixture was extracted into ethyl acetate (3×100 ml) the combined organic extracts washed with water (7×75 ml) dried (Na2SO4) evaporated to give the des-bromo phenol as a brown solid (1.0 g, MH+230) added The autoclave was then sealed to warm to ambient temperature stirred for 36 hours washed with water (10×20 ml) dried (Na2SO4) concentrated the residual gum purified by flash column chromatography with cyclohexane:ethyl acetate (4:1) as eluant

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2-(4-fluoro-phenyl)-3-(4-methanesulfonyl-phenyl)-pyrazolo[1,5-b]pyridazin-6-ol (0.2 g) in anhydrous dimethyl formamide (5 ml) was treated with sodium hydride ( 0.046 g, 60% dispersion in mineral oil), after effervescence ceased a stream of bromodifluoromethane gas was passed through the mixture at ambient temperature for 30 minutes. The reaction mixture was then poured into water (50 ml) and extracted with ethyl acetate (50 ml), the organic extract was washed with water (3×50 ml), dried and concentrated in vacuo. The residue was purified by chromatography to give the title compound as a white solid (0.17 g). extracted with ethyl acetate (50 ml) the organic extract was washed with water (3×50 ml) dried concentrated in vacuo The residue was purified by chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2-(4-fluoro-phenyl)-3-(4-methanesulfonyl-phenyl)-pyrazolo[1,5-b]pyridazin-6-ol (0.2 g) in anhydrous dimethyl formamide (5 ml) was treated with sodium hydride ( 0.046 g, 60% dispersion in mineral oil), after effervescence ceased a stream of bromodifluoromethane gas was passed through the mixture at ambient temperature for 30 minutes. The reaction mixture was then poured into water (50 ml) and extracted with ethyl acetate (50 ml), the organic extract was washed with water (3×50 ml), dried and concentrated in vacuo. The residue was purified by chromatography to give the title compound as a white solid (0.17 g). extracted with ethyl acetate (50 ml) the organic extract was washed with water (3×50 ml) dried concentrated in vacuo The residue was purified by chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 10.8 g (56 mmol) of 2-hydroxy-6-propylsulfanylbenzonitrile were dissolved in 120 ml of dimethylformamide, and 15.5 g (0.11 mol) of anhydrous potassium carbonate were added. Then, at room temperature, 8.2 g of bromodifluoromethane were passed in, and the mixture was stirred at room temperature for 5 hours. Then 15.5 g (0.11 mol) of anhydrous potassium carbonate and 7.2 g of bromodifluoromethane were added, and the mixture was stirred at room temperature overnight. The reaction mixture was worked up by pouring into water and extracting twice with methyl tert.-butyl ether. The organic phase was separated, washed several times with water and concentrated. The solid has been dried in vacuo at 50° C. Yield: 12.3 g of an oily residue. at room temperature the mixture was stirred at room temperature overnight extracting twice with methyl tert.-butyl ether The organic phase was separated washed several times with water concentrated The solid has been dried in vacuo at 50° C

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Portions of 3-bromo-2-(3-fluoro-phenyl)-6-methoxy-pyrazolo[1,5-b]pyridazine (400 mg, 2.1 g total) were placed in individual Reactivials equipped with a magnetic stirrer bar. Pyridine hydrochloride (10 eq) was added to each vial, the vials sealed, and heated to 2000 for 3 hours. The vials were allowed to cool to ˜140° before opening and the contents poured into ice/water. The resulting mixture was extracted into ethyl acetate (3×100 ml) and the combined organic extracts washed with water (7×75 ml), dried (Na2SO4) and evaporated to give the des-bromo phenol as a brown solid (1.0 g, MH+ 230). This solid was dissolved in anhydrous DMF (10 ml) and sodium hydride (60% dispersion in mineral oil, 200 mg) added portionwise. After stirring for 20 minutes at ambient temperature the solution was transferred to a small cooled autoclave and bromodifluoromethane (5 ml, xs, condensed at −30°) added. The autoclave was then sealed, allowed to warm to ambient temperature and stirred for 36 hours. The resulting solution was diluted with ethyl acetate (200 ml), washed with water (10×20 ml), dried (Na2SO4), concentrated and the residual gum purified by flash column chromatography with cyclohexane:ethyl acetate (4:1) as eluant. This gave the title compound as a solid (652 mg, 60%). equipped with a magnetic stirrer bar sealed heated to 2000 for 3 hours to cool to ˜140° before opening The resulting mixture was extracted into ethyl acetate (3×100 ml) the combined organic extracts washed with water (7×75 ml) dried (Na2SO4) evaporated to give the des-bromo phenol as a brown solid (1.0 g, MH+ 230) added The autoclave was then sealed to warm to ambient temperature stirred for 36 hours washed with water (10×20 ml) dried (Na2SO4) concentrated the residual gum purified by flash column chromatography with cyclohexane:ethyl acetate (4:1) as eluant

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2-(4-fluoro-phenyl)-3-(4-methanesulfonyl-phenyl)-pyrazolo[1,5-b]pyridazin-6-ol (0.2 9) in anhydrous dimethyl formamide (5 ml) was treated with sodium hydride (0.046 g, 60% dispersion in mineral oil), after effervescence ceased a stream of bromodifluoromethane gas was passed through the mixture at ambient temperature for 30 minutes. The reaction mixture was then poured into water (50 ml) and extracted with ethyl acetate (50 ml), the organic extract was washed with water (3×50 ml), dried and concentrated in vacuo. The residue was purified by chromatography to give the title compound as a white solid (0.17 g). extracted with ethyl acetate (50 ml) the organic extract was washed with water (3×50 ml) dried concentrated in vacuo The residue was purified by chromatography