octane-1,8-diamine

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:

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium bisulfite was prepared by adding 3.15 g of sodium sulfite and 7.15 g of sodium metabisulfite to 25 ml of water. 1,8-Diaminooctane (7.2 g) was added and the pH was adjusted to 7 with concentrated hydrochloric acid. Calf thymus DNA (Sigma, 139 mg) was dissolved in 20 mL of water and denatured by heating to 100° C. for 30 min followed by rapid cooling in an ice bath. The single stranded DNA was then sonicated for 40 min at 0° C. and added to the sodium bisulfite-diaminooctene solution. This gave a final concentration of 2 M bisulfite and 1 M diaminooctane. The mixture was clarified by centrifugation (4000×g) and then stirred at 60° C. (oil bath) for 42 hrs. The reaction mixture was cooled and filtered (0.2 μm filter) to remove a small amount of particulate material. The product was desalted in two 25 mL portions over a BioRad P-4 column (340×2.6 cm) equilibrated in 0.02 M sodium chloride, 1 mM EDTA, pH 8. After the void volume (60 mL), the product was collected in the next 50 mL fraction and each of these two fractions was separately dialyzed overnight against 4 L of water and lyphilized, yielding together 99.5 mg (72%). Seventy-five percent of the cytosine residues were substituted with DAO, based on alkaline hydrolysis-HPLC. by rapid cooling in an ice bath was then sonicated for 40 min at 0° C.

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium bisulfite was prepared by adding 3.15 g of sodium sulfite and 7.15 g of sodium metabisulfite to 25 ml of water. 1,8-Diaminooctane (7.2 g) was added and the pH was adjusted to 7 with concentrated hydrochloric acid. Calf thymus DNA (Sigma, 139 mg) was dissolved in 20 mL of water and denatured by heating to 100° C. for 30 min followed by rapid cooling in an ice bath. The single stranded DNA was then sonicated for 40 min at 0° C. and added to the sodium bisulfite-diaminooctene solution. This gave a final concentration of 2 M bisulfite and 1 M diaminooctane. The mixture was clarified by centrifugation (4000×g) and then stirred at 60° C. (oil bath) for 42 hrs. The reaction mixture was cooled and filtered (0.2 μm filter) to remove a small amount of particulate material. The product was desalted in two 25 mL portions over a BioRad P-4 column (340×2.6 cm) equilibrated in 0.02 M sodium chloride, 1 mM EDTA, pH 8. After the void volume (60 mL), the product was collected in the next 50 mL fraction and each of these two fractions was separately dialyzed overnight against 4 L of water and lyphilized, yielding together 99.5 mg (72%). Seventy-five percent of the cytosine residues were substituted with DAO, based on alkaline hydrolysis-HPLC. by rapid cooling in an ice bath was then sonicated for 40 min at 0° C.

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

Procedure: Ten mmole of 1,8 diaminooctane is dissolved in 50 ml of pyridine. Five mmole of Ac2O is added to the solution dropwise at 10° C. The organic solvent is then evaporated. Using column chromatography, N-monoacetoamide-1,8-diaminooctane subsequently is separated out. The N-monoacetoamide-1,8-diaminooctane is dissolved in 25 ml 1,2-dichloroethane. To this solution, 6 mmole of LiAlH4 is added. The solution is then stirred under nitrogen gas at room temperature for 1 day. Subsequently, the solution is diluted with 100 ml of ethyl acetate. The resulting solution is washed with 20 ml of saturated sodium chloride solution. The solution is dried over MgSO4 and evaporated to produce a residue of N-monoethyl-1,8-diaminooctane. The obtained N-monoethyl-1,8-diaminooctane is dissolved in 80 ml of 1,2-dichloroethane containing about 15 mmole of 2-methyl-5-nitro-imidazolyl-1-yl-acetaldehyde. This reaction mixture is stirred for 30 minutes and then acidified with 15 mmole of acetic acid. Eighteen mmole of sodium triacetoxyborohydride is added as a reducing agent and the solution is stirred for 48 hours at room temperature. The resulting mixture is diluted with 80 ml of ethyl acetate, and the mixture solution is washed with 100 ml of saturated aqueous NaHCO3 and 50 ml of water. The organic layer is dried over anhydrous MgSO4, and the solvent is evaporated to leave residual oil which solidified at 4° C. for 2 days. The obtained solid is recrystallized from ethyl acetate/hexane to give N, N, N'-tri[2'-(2-methyl-5-nitro-1-imidazolyl) ethyl]-N'-ethyl-1,8-octanediamine. The organic solvent is then evaporated subsequently is separated out The N-monoacetoamide-1,8-diaminooctane is dissolved in 25 ml 1,2-dichloroethane The resulting solution is washed with 20 ml of saturated sodium chloride solution The solution is dried over MgSO4 evaporated

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

Procedure: Ten mmole of 1,8 diaminooctane is dissolved in 50 ml of pyridine. Five mmole of Ac2O is added to the solution dropwise at 10° C. The organic solvent is then evaporated. Using column chromatography, N-monoacetoamide-1,8-diaminooctane subsequently is separated out. The N-monoacetoamide-1,8-diaminooctane is dissolved in 25 ml 1,2-dichloroethane. To this solution, 6 mmole of LiAlH4 is added. The solution is then stirred under nitrogen gas at room temperature for 1 day. Subsequently, the solution is diluted with 100 ml of ethyl acetate. The resulting solution is washed with 20 ml of saturated sodium chloride solution. The solution is dried over MgSO4 and evaporated to produce a residue of N-monoethyl-1,8-diaminooctane. The obtained N-monoethyl-1,8-diaminooctane is dissolved in 80 ml of 1,2-dichloroethane containing about 15 mmole of 2-methyl-5-nitro-imidazolyl-1-yl-acetaldehyde. This reaction mixture is stirred for 30 minutes and then acidified with 15 mmole of acetic acid. Eighteen mmole of sodium triacetoxyborohydride is added as a reducing agent and the solution is stirred for 48 hours at room temperature. The resulting mixture is diluted with 80 ml of ethyl acetate, and the mixture solution is washed with 100 ml of saturated aqueous NaHCO3 and 50 ml of water. The organic layer is dried over anhydrous MGSO4, and the solvent is evaporated to leave residual oil which solidified at 4° C. for 2 days. The obtained solid is recrystallized from ethyl acetate/hexane to give N, N, N'-tri[2'-(2-methyl-5-nitro-1-imidazolyl) ethyl]-N'-ethyl-1,8-octanediamine. The organic solvent is then evaporated subsequently is separated out The N-monoacetoamide-1,8-diaminooctane is dissolved in 25 ml 1,2-dichloroethane The resulting solution is washed with 20 ml of saturated sodium chloride solution The solution is dried over MgSO4 evaporated

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

Procedure: Dissolve 14.4 g (0.1 mol) of 1,8-diaminooctane and 14.5 ml (0.22 mol) of acrylonitrile in 100 ml of ethanol and reflux overnight. Remove the solvent at reduced pressure. Analysis showed the title compound to be >98% pure. reflux overnight Remove the solvent at reduced pressure

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

Procedure: 3-Benzyloxy-2-methyl-4-pyrone (0.066 moles) and 1,8-diaminooctane (0.022 moles) are mixed in 2:1 v/v aqueous methanol (300 ml), solid sodium hydroxide (2 g) is added, and the mixture is heated on a steam bath for 5 hours. The mixture is allowed to cool and an aliquot is taken, acidified to pH 2 with concentrated hydrochloric acid and the solvent removed on the rotary evaporator to give a solid residue. This residue is checked for completion of the reaction through its n.m.r. spectrum, the presence of protons exchangeable at ca δ=8.3 (d6DMSO) showing that the reaction is not complete. If this is the case, refluxing is continued until the solid obtained from an aliquot shows no such protons. On complete reaction being found to have occurred, the mixture is cooled and acidified to pH 2 with concentrated hydrochloric acid, any precipitate formed at this stage being dissolved by the addition of methanol to the mixture. Palladium/carbon catalyst is then added and the solution is hydrogenated at room temperature and atmospheric pressure in order to effect debenzylation. The catalyst is removed by filtration and the solvent by rotary evaporation, the resulting solid then being recrystallised from water to give the title compound(1) in 40% yield as a white solid of m.p. 297°-300° dec; γmax (nujol) 1340 and 1620 cm-1 ; δ(d6DMSO/D2O), 1.5 (m, 12H), 2.5 (s, 6H), 4.3 (m, 4H), 7.1 (d, 2H) and 8.1 (d, 2H); m/e 360. is added the mixture is heated on a steam bath for 5 hours to cool the solvent removed on the rotary evaporator to give a solid residue This residue is checked for completion of the reaction through its n.m.r refluxing obtained from an aliquot On complete reaction the mixture is cooled any precipitate formed at this stage is hydrogenated at room temperature The catalyst is removed by filtration the solvent by rotary evaporation the resulting solid then being recrystallised from water to give the title compound(1) in 40% yield as a white solid of m.p. 297°-300° dec

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step 4) 2,8-Dihydroxy naphthalene-6-sulfonic acid (263 parts), sodium hydrogen sulphite (259 parts), water (900 parts) and 1,8-diaminooctane (400 parts) were stirred at 80° C. for 20 hours and then a further 20 hours at 95° C. The reaction was allowed to cool over night and filtered. The resultant filter cake was stirred in water (500 parts) and 2N sodium hydroxide (750 parts) for 15 minutes. 2N Hydrochloric acid (300 parts) was added and the precipitate filtered. The filter cake was dissolved in water (500 parts) and 2N sodium hydroxide (1000 parts) by heating to 50° C. 2N Hydrochloric acid was added and the precipitate filtered off at 40° C. The filter cake was oven dried at 70° C. to produce a naphthalene intermediate (111 parts). a further 20 hours at 95° C to cool over night filtered The resultant filter cake 2N Hydrochloric acid (300 parts) was added the precipitate filtered The filter cake was dissolved in water (500 parts) 2N Hydrochloric acid was added the precipitate filtered off at 40° C dried at 70° C.

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step 4) 2,8-Dihydroxy naphthalene-6-sulfonic acid (263 parts), sodium hydrogen sulphite (259 parts), water (900 parts) and 1,8-diaminooctane (400 parts) were stirred at 80° C. for 20 hours and then a further 20 hours at 95° C. The reaction was allowed to cool over night and filtered. The resultant filter cake was stirred in water (500 parts) and 2N sodium hydroxide (750 parts) for 15 minutes. 2N Hydrochloric acid (300 parts) was added and the precipitate filtered. The filter cake was dissolved in water (500 parts) and 2N sodium hydroxide (1000 parts) by heating to 50° C. 2N Hydrochloric acid was added and the precipitate filtered off at 40° C. The filter cake was oven dried at 70° C. to produce a naphthalene intermediate (111 parts). a further 20 hours at 95° C to cool over night filtered The resultant filter cake 2N Hydrochloric acid (300 parts) was added the precipitate filtered The filter cake was dissolved in water (500 parts) 2N Hydrochloric acid was added the precipitate filtered off at 40° C dried at 70° C.