lead(2+);diacetate

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

Procedure: The hydrate lead acetate is dissolved in butoxyethanol (BuEtOH) (1) at 60° C. The resulting solution is kept at this temperature for two hours, and is cooled down slowly (2) to thereby form a precipitate of dehydrated lead acetate. The precipitation yield can be promoted by further cooling down the vessel containing said solution in an ice bath.

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

Procedure: On the other hand, 38 g of stannous chloride, 26 g of lead acetate and 200 g of water were charged into a 500 ml beaker equipped with a stirrer and the metal salts were dissolved into the water with stirring. This aqueous solution of the metal salts was added to the aforesaid aqueous solution of potassium naphthenate and a double decomposition reaction was then carried out for 1 hour at 30° C. The reaction mixture was dehydrated, dried and then extracted with toluene. The residue was heated under a reduced pressure of 10 mm Hg to distill off the toluene whereby stannous and lead naphthenates were obtained which had a tin content of 13.2% by weight and a lead content of 9.2% by weight. beaker equipped with a stirrer a double decomposition reaction dried extracted with toluene The residue was heated under a reduced pressure of 10 mm Hg to distill off the toluene whereby stannous

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

Procedure: On the other hand, 38 g of stannous chloride, 26 g of lead acetate and 200 g of water were charged into a 500 ml beaker equipped with a stirrer and the metal salts were dissolved into the water with stirring. This aqueous solution of the metal salts was added to the aforesaid aqueous solution of potassium naphthenate and a double decomposition reaction was then carried out for 1 hour at 30° C. The reaction mixture was dehydrated, dried and then extracted with toluene. The residue was heated under a reduced pressure of 10 mm Hg to distill off the toluene whereby stannous and lead naphthenates were obtained which had a tin content of 13.2% by weight and a lead content of 9.2% by weight. beaker equipped with a stirrer a double decomposition reaction dried extracted with toluene The residue was heated under a reduced pressure of 10 mm Hg to distill off the toluene whereby stannous

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

Procedure: A 500 mL three-necked round-bottom flask was equipped with a magnetic stirrer, a dropping funnel with a pressure-equalizing side arm, a condenser with a dry nitrogen gas inlet tube and an outlet attached to a succession of scrubbers containing 10% aqueous sodium hydroxide and 10% aqueous lead acetate. Into this flask were placed 2,6-bis(1,1-dimethylethyl)-4-methyl-selenopyrylium tetrafluoro-borate (3.0 g, 8.4 mmole, prepared as in Example 1 above, 2,3,4,4-tetrachloro-cyclobut-2-en-1-one (1.7 g, 8.4 mmole) and dichloromethane (150 mL). Stirring was begun and a solution of triethylamine (2.3 mL, 16 mmole) in dichloromethane (50 mL) was added dropwise over a period of 1.5 hours under nitrogen. After the addition of the triethylamine had been completed, the reaction mixture was stirred at room temperature for an additional 1.5 hours, then filtered through a sintered glass funnel containing silica gel (40 g). The silica gel was washed several times with small portions of dichloromethane until the washings were pale orange. The filtrate and washings were combined and evaporated to dryness on a rotary evaporator on a water bath kept at approximately 40° C. The residual green mass was triturated with hexane (60 mL) until maroon crystals formed; these crystals were removed by suction filtration and dried in vacuo at approximately 30° C. to yield 3-[2,6-bis(1,1-dimethylethyl)-(4H-selenopyran-4-ylidene)methyl]-2,4,4-trichlorocyclo-but-2-en-1-one (2.2 g, 60% yield). A 500 mL three-necked round-bottom flask was equipped with a magnetic stirrer, a dropping funnel with a pressure-equalizing side arm, a condenser with a dry nitrogen gas inlet tube and an outlet Into this flask were placed the reaction mixture was stirred at room temperature for an additional 1.5 hours filtered through a sintered glass funnel containing silica gel (40 g) The silica gel was washed several times with small portions of dichloromethane until the washings evaporated to dryness on a rotary evaporator on a water bath kept at approximately 40° C The residual green mass was triturated with hexane (60 mL) until maroon crystals formed these crystals were removed by suction filtration dried in vacuo at approximately 30° C.

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

Procedure: A stirred solution of 5-(2-diethylamino-ethyl)-2-(5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-3-methyl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one (150 mg, 0.37 mmol) obtained from Example 1 in 4 ml of acetic acid was added with lead acetate (160 mg, 0.37 mmol) in an ice-water bath the control the temperature at 15° C. Upon the completion of the addition, the mixture was stirred at room temperature for 3 hours. The reaction mixture was added with 1N sodium hydroxide (60 ml) and extracted with five to one solvent mixture of dichloromethane, methanol (40 ml×4). The combined organic extracts were washed with brine (50 ml) and water (50 ml), dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by HPLC to give 5-(2-diethylamino-ethyl)-2-(5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-3-methyl-1,5-dihydro-pyrrolo[3,2-c]pyridin-4-one (64 mg, 42.6%) as a yellow solid. Upon the completion of the addition extracted with five to one solvent mixture of dichloromethane, methanol (40 ml×4) The combined organic extracts were washed with brine (50 ml) and water (50 ml) dried with anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was purified by HPLC

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

Procedure: A stirred solution of 5-(2-diethylamino-ethyl)-2-(5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-3-methyl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one (150 mg, 0.366 mmol) in acetic acid (3.5 ml) was cooled to 15° C. in an ice-water bath. The mixture was added with lead acetate (130 mg, 0.293 mmol) and stirred for 2.5 hours at room temperature. The mixture was added with 1N aqueous sodium hydroxide solution (60 ml) and extracted with a 5 to 1 solvent mixture of dichloromethane and methanol (40 ml×4). The extracts were combined, washed by brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure and purified by silica gel column chromatography to give 5-(2-diethylamino-ethyl)-2-(5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-3-methyl-1,5-dihydro-pyrrolo[3,2-c]pyridine-4-one (32 mg) as a yellow solid. extracted with a 5 to 1 solvent mixture of dichloromethane and methanol (40 ml×4) washed by brine dried over anhydrous sodium sulfate concentrated under reduced pressure purified by silica gel column chromatography

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

Procedure: A stirred solution of 5-(2-diethylamino-ethyl)-2-(5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-3-methyl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one (150 mg, 0.366 mmol) in acetic acid (3.5 ml) was cooled to 15° C. in an ice-water bath. The mixture was added with lead acetate (130 mg, 0.293 mmol) and stirred for 2.5 hours at room temperature. The mixture was added with 1N aqueous sodium hydroxide solution (60 ml) and extracted with a 5 to 1 solvent mixture of dichloromethane and methanol (40 ml×4). The extracts were combined, washed by brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure and purified by silica gel column chromatography to give 5-(2-diethylamino-ethyl)-2-(5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-3-methyl-1,5-dihydro-pyrrolo[3,2-c]pyridine-4-one (32 mg) as a yellow solid. extracted with a 5 to 1 solvent mixture of dichloromethane and methanol (40 ml×4) washed by brine dried over anhydrous sodium sulfate concentrated under reduced pressure purified by silica gel column chromatography

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

Procedure: A 500 mL three-necked round-bottom flask was equipped with a magnetic stirrer, a dropping funnel with a pressure-equalizing side arm, a condenser with a dry nitrogen gas inlet tube and an outlet attached to a succession of scrubbers containing 10% aqueous sodium hydroxide and 10% aqueous lead acetate. Into this flask were placed 2,6-bis(1,1-dimethylethyl)-4-methyl-selenopyrylium tetrafluoroborate (3.0 g, 8.4 mmole, prepared as in Example 1 above, 2,3,4,4-tetrachlorocyclobut-2-en-1-one (1.7 g, 8.4 mmole) and dichloromethane (150 mL). Stirring was begun and a solution of triethylamine (2.3 mL, 16 mmole) in dichloromethane (50 mL) was added dropwise over a period of 1.5 hours under nitrogen. After the addition of the triethylamine had been completed, the reaction mixture was stirred at room temperature for an additional 1.5 hours, then filtered through a sintered glass funnel containing silica gel (40 g). The silica gel was washed several times with small portions of dichloromethane until the washings were pale orange. The filtrate and washings were combined and evaporated to dryness on a rotary evaporator on a water bath kept at approximately 40° C. The residual green mass was triturated with hexane (60 mL) until maroon crystals formed; these crystals were removed by suction filtration and dried in vacuo at approximately 30° C. to yield 3-[2,6-bis(1,1-dimethylethyl)-(4H-selenopyran-4-ylidene)methyl]-2,4,4-trichlorocyclobut-2-en-1-one (2.2 g, 60% yield). A 500 mL three-necked round-bottom flask was equipped with a magnetic stirrer, a dropping funnel with a pressure-equalizing side arm, a condenser with a dry nitrogen gas inlet tube and an outlet Into this flask were placed the reaction mixture was stirred at room temperature for an additional 1.5 hours filtered through a sintered glass funnel containing silica gel (40 g) The silica gel was washed several times with small portions of dichloromethane until the washings evaporated to dryness on a rotary evaporator on a water bath kept at approximately 40° C The residual green mass was triturated with hexane (60 mL) until maroon crystals formed these crystals were removed by suction filtration dried in vacuo at approximately 30° C.

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

Procedure: A 500 mL three-necked round-bottom flask was equipped with a magnetic stirrer, a dropping funnel with a pressure-equalizing side arm, a condenser with a dry nitrogen gas inlet tube and an outlet attached to a succession of scrubbers containing 10% aqueous sodium hydroxide and 10% aqueous lead acetate. Into this flask were placed 2,6-bis(1,1-dimethylethyl)-4-methyl-selenopyrylium tetrafluoroborate (3.0 g, 8.4 mmole, prepared as in Example 1 above, 2,3,4,4-tetrachlorocyclobut-2-en-1-one (1.7 g, 8.4 mmole) and dichloromethane (150 mL). Stirring was begun and a solution of triethylamine (2.3 mL, 16 mmole) in dichloromethane (50 mL) was added dropwise over a period of 1.5 hours under nitrogen. After the addition of the triethylamine had been completed, the reaction mixture was stirred at room temperature for an additional 1.5 hours, then filtered through a sintered glass funnel containing silica gel (40 g). The silica gel was washed several times with small portions of dichloromethane until the washings were pale orange. The filtrate and washings were combined and evaporated to dryness on a rotary evaporator on a water bath kept at approximately 40° C. The residual green mass was triturated with hexane (60 mL) until maroon crystals formed; these crystals were removed by suction filtration and dried in vacuo at approximately 30° C. to yield 3-[2,6-bis(1,1-dimethylethyl)-(4H-selenopyran-4-ylidene)methyl]-2,4,4-trichlorocyclobut-2-en-1-one (2.2 g, 60% yield). A 500 mL three-necked round-bottom flask was equipped with a magnetic stirrer, a dropping funnel with a pressure-equalizing side arm, a condenser with a dry nitrogen gas inlet tube and an outlet Into this flask were placed the reaction mixture was stirred at room temperature for an additional 1.5 hours filtered through a sintered glass funnel containing silica gel (40 g) The silica gel was washed several times with small portions of dichloromethane until the washings evaporated to dryness on a rotary evaporator on a water bath kept at approximately 40° C The residual green mass was triturated with hexane (60 mL) until maroon crystals formed these crystals were removed by suction filtration dried in vacuo at approximately 30° C.

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

Procedure: A 1 L three-necked flask was fitted with a condenser, which was then vented through an empty flask into a bubbler filled with 1 M KOH. A hydrogen chloride gas generation apparatus was also connected to the reaction flask through a sparging tube. The gas generation apparatus consisted of a 100 mL three-necked flask with an additions funnel and an outlet to a drying tube filled with calcium chloride. A purified nitrogen supply was fed into the top of the additions funnel. Into the reaction flask, 3.073 g (19.3 mmol) of di-(2-aminoisobutyl)amine was placed. This was dissolved in 900 mL of toluene and stirred magnetically. The gas generation apparatus was charged with 18.8 g (322 mmol) of sodium chloride, also stirred magnetically. The system was purged with nitrogen for approximately thirty minutes. Carbon disulfide (1.5 mL, 24.8 mmol) was added to the reaction solution which caused a clouding of the solution. The solution was then stirred at room temperature for four hours and twenty minutes. Production of hydrogen chloride started after 15 mL (280 mmol) of concentrated sulfuric acid was placed in the additions funnel. This was added dropwise to the sodium chloride over the course of ten minutes. The reaction solution was then brought to reflux and heated overnight. The evolution of hydrogen sulfide was followed by the reaction of the effluent gas with lead acetate. The reaction flask was then cooled in an ice bath and filtered to remove the product. The flask was rinsed with approximately 300 mL of methylene chloride to collect any remaining product, this solution was dried and combined with the filtered product. The crude weight was 3.133 g, and this was placed in a vacuum desiccator for several days to remove adsorbed toluene. The dried weight was 2.837 g, giving a yield of 61.8%. NMR (CDCl3) s 1.37 ppm, s 3.47 ppm. The acid salt was neutralized in aqueous potassium hydroxide and the water was then removed by evaporation Extraction of the residue into methyl ethyl ketone yielded the free base but often with many waters of hydration. HRMS calculated 168.1501. found 168.1499. NMR (CD3OD) 2.45 (s, 4H), 1.10 (s, 12H). A 1 L three-necked flask was fitted with a condenser which was then vented through an empty flask into a bubbler The gas generation apparatus consisted of a 100 mL three-necked flask with an additions funnel and an outlet to a drying tube also stirred magnetically The system was purged with nitrogen for approximately thirty minutes The solution was then stirred at room temperature for four hours and twenty minutes to reflux heated overnight The reaction flask was then cooled in an ice bath filtered to remove the product The flask was rinsed with approximately 300 mL of methylene chloride to collect any remaining product this solution was dried this was placed in a vacuum desiccator for several days to remove adsorbed toluene giving a yield of 61.8% the water was then removed by evaporation Extraction of the residue into methyl ethyl ketone yielded the free base

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

Procedure: A 500 mL three-necked round-bottom flask was equipped with a magnetic stirrer, a dropping funnel with a pressure-equalizing side arm, a condenser with a dry nitrogen gas inlet tube and an outlet attached to a succession of scrubbers containing 10% aqueous sodium hydroxide and 10% aqueous lead acetate. Into this flask were placed 2,6-bis(1,1-dimethylethyl)-4-methyl-selenopyrylium tetrafluoroborate (3.0 g, 8.4 mmole, prepared as in Example 4 above, 2,3,4,4-tetrachlorocyclobut-2-en-1-one (1.7 g, 8.4 mmole) and dichloromethane (150 mL). Stirring was begun and a solution of triethylamine (2.3 mL, 16 mmole) in dichloromethane (50 mL) was added dropwise over a period of 1.5 hours under nitrogen. After the addition of the triethylamine had been completed, the reaction mixture was stirred at room temperature for an additional 1.5 hours, then filtered through a sintered glass funnel containing silica gel (40 g). The silica gel was washed several times with small portions of dichloromethane until the washings were pale orange. The filtrate and washings were combined and evaporated to dryness on a rotary evaporator on a water bath kept at approximately 40° C. The residual green mass was triturated with hexane (60 mL) until maroon crystals formed; these crystals were removed by suction filtration and dried in vacuo at approximately 30° C. to yield 3-[2,6-bis(1,1-dimethylethyl)-(4H-selenopyran-4-ylidene)methyl]-2,4,4-trichloro-cyclobut-2-en-1-one (2.2 g, 60% yield). A 500 mL three-necked round-bottom flask was equipped with a magnetic stirrer, a dropping funnel with a pressure-equalizing side arm, a condenser with a dry nitrogen gas inlet tube and an outlet Into this flask were placed the reaction mixture was stirred at room temperature for an additional 1.5 hours filtered through a sintered glass funnel containing silica gel (40 g) The silica gel was washed several times with small portions of dichloromethane until the washings evaporated to dryness on a rotary evaporator on a water bath kept at approximately 40° C The residual green mass was triturated with hexane (60 mL) until maroon crystals formed these crystals were removed by suction filtration dried in vacuo at approximately 30° C.

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

Procedure: A 500 mL three-necked round-bottom flask was equipped with a magnetic stirrer, a dropping funnel with a pressure-equalizing side arm, a condenser with a dry nitrogen gas inlet tube and an outlet attached to a succession of scrubbers containing 10% aqueous sodium hydroxide and 10% aqueous lead acetate. Into this flask were placed 2,6-bis(1,1-dimethylethyl)-4-methyl-selenopyrylium tetrafluoroborate (3.0 g, 8.4 mmole, prepared as in Example 4 above, 2,3,4,4-tetrachlorocyclobut-2-en-1-one (1.7 g, 8.4 mmole) and dichloromethane (150 mL). Stirring was begun and a solution of triethylamine (2.3 mL, 16 mmole) in dichloromethane (50 mL) was added dropwise over a period of 1.5 hours under nitrogen. After the addition of the triethylamine had been completed, the reaction mixture was stirred at room temperature for an additional 1.5 hours, then filtered through a sintered glass funnel containing silica gel (40 g). The silica gel was washed several times with small portions of dichloromethane until the washings were pale orange. The filtrate and washings were combined and evaporated to dryness on a rotary evaporator on a water bath kept at approximately 40° C. The residual green mass was triturated with hexane (60 mL) until maroon crystals formed; these crystals were removed by suction filtration and dried in vacuo at approximately 30° C. to yield 3-[2,6-bis(1,1-dimethylethyl)-(4H-selenopyran-4-ylidene)methyl]-2,4,4-trichloro-cyclobut-2-en-1-one (2.2 g, 60% yield). A 500 mL three-necked round-bottom flask was equipped with a magnetic stirrer, a dropping funnel with a pressure-equalizing side arm, a condenser with a dry nitrogen gas inlet tube and an outlet Into this flask were placed the reaction mixture was stirred at room temperature for an additional 1.5 hours filtered through a sintered glass funnel containing silica gel (40 g) The silica gel was washed several times with small portions of dichloromethane until the washings evaporated to dryness on a rotary evaporator on a water bath kept at approximately 40° C The residual green mass was triturated with hexane (60 mL) until maroon crystals formed these crystals were removed by suction filtration dried in vacuo at approximately 30° C.