3,5-dibromo-1-oxidopyridin-1-ium

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

実験手順: A mixture of 3,5-dibromopyridine N-oxide (prepared in the above (1)) 2.26 g, trimethylsilylcyanide 1.06 g and dimethylcarbamic acid chloride 1.15 g in methylene chloride 25 ml is refluxed under heating for 1 day. To the mixture are added trimethylsilylcyanide 443 mg and dimethylcarbamic acid chloride 480 mg, and the mixture is refluxed under heating for 20 hours. An aqueous sodium hydrogen carbonate solution is added to the reaction mixture cooled, and the mixture is extracted with methylene chloride. The combined extract is washed, dried and the solvent is removed in vacuo. The residue is purified by silica gel chromatography (solvent; n-hexane:ethyl acetate=1:1) to give 2-cyano-3,5-dibromopyridine 1.38 g. mp 109-112° C. is refluxed under heating for 1 day the mixture is refluxed under heating for 20 hours cooled the mixture is extracted with methylene chloride The combined extract is washed dried the solvent is removed in vacuo The residue is purified by silica gel chromatography (solvent; n-hexane:ethyl acetate=1:1)

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

実験手順: A mixture of 3,5-dibromopyridine N-oxide (prepared in the above (1)) 2.26 g, trimethylsilylcyanide 1.06 g and dimethylcarbamic acid chloride 1.15 g in methylene chloride 25 ml is refluxed under heating for 1 day. To the mixture are added trimethylsilylcyanide 443 mg and dimethylcarbamic acid chloride 480 mg, and the mixture is refluxed under heating for 20 hours. An aqueous sodium hydrogen carbonate solution is added to the reaction mixture cooled, and the mixture is extracted with methylene chloride. The combined extract is washed, dried and the solvent is removed in vacuo. The residue is purified by silica gel chromatography (solvent; n-hexane:ethyl acetate=1:1) to give 2-cyano-3,5-dibromopyridine 1.38 g. mp 109-112° C. is refluxed under heating for 1 day the mixture is refluxed under heating for 20 hours cooled the mixture is extracted with methylene chloride The combined extract is washed dried the solvent is removed in vacuo The residue is purified by silica gel chromatography (solvent; n-hexane:ethyl acetate=1:1)

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

実験手順: 3,5-Dibromopyridine 2.37 g is dissolved in methylene chloride 25 ml and thereto is added m-chloroperbenzoic acid 2.96 g at room temperature under stirring. After stirring for 5 hours at room temperature, additional m-chloroperbenzoic acid 246 mg is added thereto and the mixture is stirred. After 15 hours the solvent is removed in vacuo and the residue is purified by silica gel chromatography (solvent; n-hexane:ethyl acetate=1:1) to give 3,5-dibromopyridine N-oxide as colorless crystals, 2.26 g. mp 140-142° C. After stirring for 5 hours at room temperature the mixture is stirred After 15 hours the solvent is removed in vacuo the residue is purified by silica gel chromatography (solvent; n-hexane:ethyl acetate=1:1)

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

実験手順: A sample of 3,5-dibromopyridine-N-oxide (prepared according to the method of Y. Tamura et al., Heterocycles, 15:871-874 (1981)) is reacted with (S)-(-)-1-methyl-2-pyrrolidinemethanol according to the procedure of Example 3a, and the product is purified by chromatography on silica gel. the product is purified by chromatography on silica gel

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

実験手順: A sample of 3,5-dibromopyridine-N-oxide (prepared according to the method of Y. Tamura et al., Heterocycles, 15:871-874 (1981)) is reacted with (S)-(-)-1-methyl-2-pyrrolidinemethanol according to the procedure of Example 3a, and the product is purified by chromatography on silica gel. the product is purified by chromatography on silica gel

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

実験手順: 3,5-Dibromopyridine (30.5 g, 0.12 mol) was dissolved in dichloromethane (80 mL) and methyltrioxorhenium (150 mg, 0.603 mmol) was added. Hydrogen peroxide (aqueous, 30%, 27 mL) was added slowly over 5 minutes, and the mixture was stirred at ambient temperature for 3 hours. An additional 40 mL of 30% hydrogen peroxide was added, and the reaction was stirred for 16 hours. Manganese dioxide (100 mg) was added, and the suspension was stirred for 40 minutes. The mixture was extracted with dichloromethane, dried (sodium sulfate), filtered and concentrated under reduced pressure. Ethyl acetate was added, and the suspension was refluxed for 30 minutes until solids dissolved, and then the mixture was allowed to cool to ambient temperature and left for 48 hours. 3,5-Dibromopyridine-1-oxide (28.05 g, 79%) was collected by vacuum filtration. MS (LC-MS) m/z 254 (M+H)+. 3,5-Dibromopyridine-1-oxide (25.09 g, 0.099 mol) was then dissolved in acetonitrile (200 mL) and triethylamine (28 mL, 0.198 mol) and trimethylsilylcyanide (40 mL, 0.297 mol) were added. The reaction was stirred for 16 hours, diluted with dichloromethane, aqueous sodium carbonate, water, and then filtered through diatomaceous earth eluting with dichloromethane. The mixture was extracted with dichloromethane and the organics were washed with brine, dried (sodium sulfate), filtered and concentrated under reduced pressure. Purification by silica gel chromatography (30-70% ethyl acetate in hexanes) provided the title compound. MS (LC-MS) m/z 263 (M+H)+. the reaction was stirred for 16 hours the suspension was stirred for 40 minutes The mixture was extracted with dichloromethane dried (sodium sulfate) filtered concentrated under reduced pressure Ethyl acetate was added the suspension was refluxed for 30 minutes until solids dissolved to cool to ambient temperature left for 48 hours 3,5-Dibromopyridine-1-oxide (28.05 g, 79%) was collected by vacuum filtration The reaction was stirred for 16 hours filtered through diatomaceous earth eluting with dichloromethane The mixture was extracted with dichloromethane the organics were washed with brine dried (sodium sulfate) filtered concentrated under reduced pressure Purification by silica gel chromatography (30-70% ethyl acetate in hexanes)

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

実験手順: A sample of 3,5-dibromopyridine-N-oxide (prepared according to the method of Y. Tamura et al., Heterocycles, 15:871-874 (1981)) is reacted with (S)-(-)-1-methyl-2-pyrrolidinemethanol according to the procedure of Example 3a, and the product is purified by chromatography on silica gel. the product is purified by chromatography on silica gel

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

実験手順: A sample of 3,5-dibromopyridine-N-oxide (prepared according to the method of Y. Tamura et al., Heterocycles, 15:871-874 (1981)) is reacted with (S)-(-)-1-methyl-2-pyrrolidinemethanol according to the procedure of Example 3a, and the product is purified by chromatography on silica gel. the product is purified by chromatography on silica gel

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

実験手順: 3,5-dibromopyridine 1-oxide (25.09g, 0.099 mol) was dissolved in acetonitrile (200 mL) and triethylamine (28 mL, 0.198 mol) and trimethylsilylcyanide (40 mL, 0.297 mol) were added. The reaction was stirred 16 hours and then diluted with dichloromethane, aqueous sodium carbonate, water, and then filtered through Celite eluting with dichloromethane. The mixture was extracted with dichloromethane and purified by silica gel chromatography (3:2 hexanes:ethyl acetate gradient elution) to afford 3,5-dibromo-2-pyridinecarbonitrile (18.98 g, 73% yield) as a tan solid. 1H NMR (CDCl3) δ 8.68 (d, J=2 Hz, 1 H), 8.20 (d, J=2 Hz, 1 H); MS m/z 262 M+1). filtered through Celite eluting with dichloromethane The mixture was extracted with dichloromethane purified by silica gel chromatography (3:2 hexanes:ethyl acetate gradient elution)

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

実験手順: 3,5-Dibromopyridine (30.5 g, 0.12 mol) was dissolved in dichloromethane (80 mL) and methlytrioxorhenium (150 mg, 0.603 mmol) was added 30% hydrogen peroxide (27 mL) was added slowly over 5 minutes and the mixture was stirred at ambient temperature for 3 hours. An additional 40 mL of hydrogen peroxide was added and the reaction was stirred 16 hours. Manganese dioxide (100 mg) was added and the suspension was stirred 40 minutes. The mixture was extracted with dichloromethane, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Ethyl acetate was added and the suspension was refluxed for 30 minutes until solids dissolved and then the mixture was allowed to cool to ambient temperature and aged 48 hours. 3,5-dibromopyridine 1-oxide (25.09 g, 82% yield) was collected by vacuum filtration as pale yellow needles. 1H NMR (CDCl3) δ 8.27 (s, 2 H), 7.56 (s, 1 H). was added slowly over 5 minutes the reaction was stirred 16 hours the suspension was stirred 40 minutes The mixture was extracted with dichloromethane dried over sodium sulfate filtered concentrated under reduced pressure Ethyl acetate was added the suspension was refluxed for 30 minutes until solids dissolved to cool to ambient temperature and aged 48 hours

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

実験手順: A mixture of 3,5-dibromopyridine N-oxide (prepared in the above (1)) 2.26 g, trimethylsilylcyanide 1.06 g and dimethylcarbamic acid chloride 1.15 g in methylene chloride 25 ml is refluxed under heating for 1 day. To the mixture are added trimethylsilylcyanide 443 mg and dimethylcarbamic acid chloride 480 mg, and the mixture is refluxed under heating for 20 hours. An aqueous sodium hydrogen carbonate solution is added to the reaction mixture cooled, and the mixture is extracted with methylene chloride. The combined extract is washed, dried and the solvent is removed in vacuo. The residue is purified by silica gel chromatography (solvent; n-hexane:ethyl acetate=1:1) to give 2-cyano-3,5-dibromopyridine 1.38 g. mp 109–112° C. is refluxed under heating for 1 day the mixture is refluxed under heating for 20 hours cooled the mixture is extracted with methylene chloride The combined extract is washed dried the solvent is removed in vacuo The residue is purified by silica gel chromatography (solvent; n-hexane:ethyl acetate=1:1)

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

実験手順: 3,5-Dibromopyridine 2.37 g is dissolved in methylene chloride 25 ml and thereto is added m-chloroperbenzoic acid 2.96 g at room temperature under stirring. After stirring for 5 hours at room temperature, additional m-chloroperbenzoic acid 246 mg is added thereto and the mixture is stirred. After 15 hours the solvent is removed in vacuo and the residue is purified by silica gel chromatography (solvent; n-hexane:ethyl acetate=1:1) to give 3,5-dibromopyridine N-oxide as colorless crystals, 2.26 g. mp 140–142° C. After stirring for 5 hours at room temperature the mixture is stirred After 15 hours the solvent is removed in vacuo the residue is purified by silica gel chromatography (solvent; n-hexane:ethyl acetate=1:1)