5-chloropentylbenzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a stirred solution of 24.0 g (0.131 mole) of 1-chloro-5-phenylpentane (Columbia Organics, Camden, S.C.) in 150 mL of dimethylformamide was added 24.3 g (0.131 mole) of potassium phthalimide (Aldrich) and the reaction mixture was heated at reflux under a nitrogen atmosphere for 15 hr. The solvent was evaporated under reduced pressure to heave a viscous, oily residue. The residue was triturated with 200 mL of water and then the mixture was extracted with four 200-mL portions of methylene chloride. The combined methylene chloride extracts were washed with two 200 mL portions of 2N sodium hydroxide solution, twice with 200 mL portions of water and dried over magnesium sulfate. The solvent was evaporated under reduced pressure to give 35.0 g (91%) of title compound as a viscous oil. A sample of this viscous oil was further purified by high pressure liquid chromatography (Waters Associates Prep LC/System 500A, PrepPak® 500 silica gel; ethyl acetate-hexanes, 1:10). Fractions containing title compound were combined and the solvents were evaporated under reduced pressure to give purified title compound as a colorless, viscous oil. the reaction mixture was heated at reflux under a nitrogen atmosphere for 15 hr The solvent was evaporated under reduced pressure The residue was triturated with 200 mL of water the mixture was extracted with four 200-mL portions of methylene chloride The combined methylene chloride extracts were washed with two 200 mL portions of 2N sodium hydroxide solution, twice with 200 mL portions of water dried over magnesium sulfate The solvent was evaporated under reduced pressure

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

Procedure: To a stirred solution of 24.0 g (0.131 mole) of 1-chloro-5-phenylpentane (Columbia Organics, Camden, S.C.) in 150 mL of dimethylformamide was added 24.3 g (0.131 mole) of potassium phthalimide (Aldrich) and the reaction mixture was heated at reflux under a nitrogen atmosphere for 15 hr. The solvent was evaporated under reduced pressure to heave a viscous, oily residue. The residue was triturated with 200 mL of water and then the mixture was extracted with four 200-mL portions of methylene chloride. The combined methylene chloride extracts were washed with two 200 mL portions of 2N sodium hydroxide solution, twice with 200 mL portions of water and dried over magnesium sulfate. The solvent was evaporated under reduced pressure to give 35.0 g (91%) of title compound as a viscous oil. A sample of this viscous oil was further purified by high pressure liquid chromatography (Waters Associates Prep LC/System 500A, PrepPak® 500 silica gel; ethyl acetate-hexanes, 1:10). Fractions containing title compound were combined and the solvents were evaporated under reduced pressure to give purified title compound as a colorless, viscous oil. the reaction mixture was heated at reflux under a nitrogen atmosphere for 15 hr The solvent was evaporated under reduced pressure The residue was triturated with 200 mL of water the mixture was extracted with four 200-mL portions of methylene chloride The combined methylene chloride extracts were washed with two 200 mL portions of 2N sodium hydroxide solution, twice with 200 mL portions of water dried over magnesium sulfate The solvent was evaporated under reduced pressure

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

Procedure: To a stirred solution of 24.0 g (0.131 mole) of 1-chloro-5-phenylpentane (Columbia Organics, Camden, S.C.) in 150 mL of dimethylformamide was added 24.3 g (0.131 mole) of potassium phthalimide (Aldrich) and the reaction mixture was heated at reflux under a nitrogen atmosphere for 15 hr. The solvent was evaporated under reduced pressure to heave a viscous, oily residue. The residue was triturated with 200 mL of water and then the mixture was extracted with four 200-mL portions of methylene chloride. The combined methylene chloride extracts were washed with two 200 mL portions of 2N sodium hydroxide solution, twice with 200 mL portions of water and dried over magnesium sulfate. The solvent was evaporated under reduced pressure to give 35.0 g (91%) of title compound as a viscous oil. A sample of this viscous oil was further purified by high pressure liquid chromatography (Waters Associates Prep LC/System 500A, PrepPak® 500 silica gel; ethyl acetate-hexanes, 1:10). Fractions containing title compound were combined and the solvents were evaporated under reduced pressure to give purified title compound as a colorless, viscous oil. the reaction mixture was heated at reflux under a nitrogen atmosphere for 15 hr The solvent was evaporated under reduced pressure The residue was triturated with 200 mL of water the mixture was extracted with four 200-mL portions of methylene chloride The combined methylene chloride extracts were washed with two 200 mL portions of 2N sodium hydroxide solution, twice with 200 mL portions of water dried over magnesium sulfate The solvent was evaporated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 18.2 g. of ethyl p-aminobenzoate 10.2 g. of sodium iodide, 10.0 g. of 5-phenylpentyl chloride and 60 ml. of hexamethylphosphoramide is stirred and heated at 110° C. in an oil bath for 20 hours. The mixture is chilled, diluted with 25 ml. of water and 25 ml. of ethanol, chilled and filtered. The solid is washed with 50 ml. of ethanol-water (1:1), with water and once with cold ethanol to give pale yellow crystals, m.p. 63°-64° C. Recrystallization from ethanol gives off-white crystals, m.p. 73°-75° C. A mixture of 18.2 g The mixture is chilled diluted with 25 ml filtered The solid is washed with 50 ml of ethanol-water (1:1), with water and once with cold ethanol to give pale yellow crystals, m.p. 63°-64° C Recrystallization from ethanol gives off-white crystals, m.p. 73°-75° C.

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 18.2 g. of ethyl p-aminobenzoate 10.2 g. of sodium iodide, 10.0 g. of 5-phenylpentyl chloride and 60 ml. of hexamethylphosphoramide is stirred and heated at 110° C. in an oil bath for 20 hours. The mixture is chilled, diluted with 25 ml. of water and 25 ml. of ethanol, chilled and filtered. The solid is washed with 50 ml. of ethanol-water (1:1), with water and once with cold ethanol to give pale yellow crystals, m.p. 63°-64° C. Recrystallization from ethanol gives off-white crystals, m.p. 73°-75° C. A mixture of 18.2 g The mixture is chilled diluted with 25 ml filtered The solid is washed with 50 ml of ethanol-water (1:1), with water and once with cold ethanol to give pale yellow crystals, m.p. 63°-64° C Recrystallization from ethanol gives off-white crystals, m.p. 73°-75° C.

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

Procedure: To dimethylformamide was added 92 mg of 1-chloro-5-phenylpentane and 152 mg of potassium iodide under ice-cooling, the mixture was allowed to warm up to room temperature and stirred for 20 minutes. Then, 200 mg of 5-(3,5-dichlorophenylthio)-4-isopropyl-2-(p-methoxybenzyloxymethyl)-1H-imidazole (101b)was added, followed by addition of 126 mg of potassium carbonate. Then the mixture was warmed up to 50° C. and allowed to react for 6 hours. After completion of the reaction, the mixture was diluted with water, extracted with diethyl ether, the extract was dried over sodium sulfate, and the solvent was distilled off under reduced pressure. To thus-obtained oil were added 10 ml of ethanol and 20 ml of 36% hydrochloric acid, and the mixture was stirred at 90° C. for 2 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, an aqueous sodium hydrogen carbonate solution was added, extracted with ethyl acetate, the extract was dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (hexane:ethyl acetate=1:1)to give 120 mg of Compound I-124 (yield 57%). cooling Then the mixture was warmed up to 50° C. to react for 6 hours After completion of the reaction extracted with diethyl ether the extract was dried over sodium sulfate the solvent was distilled off under reduced pressure To thus-obtained oil the mixture was stirred at 90° C. for 2 hours After completion of the reaction the solvent was distilled off under reduced pressure an aqueous sodium hydrogen carbonate solution was added extracted with ethyl acetate the extract was dried over sodium sulfate the solvent was distilled off under reduced pressure The residue was purified by silica gel chromatography (hexane

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

Procedure: Crude 5-phenylpentyl chloride (1.3 g) was added to a stirred solution of 4-mercapto-1-β-D-ribofuranosylpyrazolo [3,4-d]pyrimidine (2.0 g) and potassium bicarbonate (0.7 g) in N,N-dimethylformamide. The reaction mixture was heated on a steam bath for 25 hours. An additional 0.7 g of potassium bicarbonate was added and after heating for 1 hour more, the mixture was poured into water. The cooled aqueous mixture was extracted with chloroform. The chloroform soluble material was chromatographed on a silica gel column. The fractions containing the compound were combined and evaporated. Trituration with ether gave 0.4 g of crude product. This was dissolved in ethyl acetate and washed with water. The dried ethyl acetate solution was evaporated and purified by reversed phase chromatography in methanol water (80:20 vol/vol) to give 0.28 g of product m.p. 72°-75° C. (indefinite). The reaction mixture was heated on a steam bath for 25 hours after heating for 1 hour more The cooled aqueous mixture was extracted with chloroform The chloroform soluble material was chromatographed on a silica gel column The fractions containing the compound evaporated Trituration with ether gave 0.4 g of crude product washed with water The dried ethyl acetate solution was evaporated purified by reversed phase chromatography in methanol water (80:20 vol/vol)

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

Procedure: To a stirred solution of 24.0 g (0.131 mole) of 1-chloro-5-phenylpentane (Columbia Organics, Camden, S.C.) in 150 mL of dimethylformamide was added 24.3 g (0.131 mole) of potassium phthalimide (Aldrich) and the reaction mixture was heated at reflux under a nitrogen atmosphere for 15 hr. The solvent was evaporated under reduced pressure to heave a viscous, oily residue. The residue was triturated with 200 mL of water and then the mixture was extracted with four 200-mL portions of methylene chloride. The combined methylene chloride extracts were washed with two 200 mL portions of 2N sodium hydroxide solution, twice with 200 mL portions of water and dried over magnesium sulfate. The solvent was evaporated under reduced pressure to give 35.0 g (91%) of title compound as a viscous oil. A sample of this viscous oil was further purified by high pressure liquid chromatography (Waters Associates Prep LC/System 500A, PrepPak® 500 silica gel; ethyl acetate-hexanes, 1:10). Fractions containing title compound were combined and the solvents were evaporated under reduced pressure to give purified title compound as a colorless, viscous oil. the reaction mixture was heated at reflux under a nitrogen atmosphere for 15 hr The solvent was evaporated under reduced pressure The residue was triturated with 200 mL of water the mixture was extracted with four 200-mL portions of methylene chloride The combined methylene chloride extracts were washed with two 200 mL portions of 2N sodium hydroxide solution, twice with 200 mL portions of water dried over magnesium sulfate The solvent was evaporated under reduced pressure