2-BROMOETHYL PHENYL SULFIDE

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

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Potassium phthalimide (5.43 g, 25 mmol) was added to a DMF (50 ml) solution of [(2-bromoethyl)thio]benzene (5,43 g, 25 mmol) and this stirred mixture under N2 was heated at 90° C. for 2 h. After cooling to room temperature, the reaction was filtered. The solvent was stripped from the filtrate under reduced pressure. The residue, dissolved in CH2Cl2 (100 ml), was filtered, concentrated, and flash chromotographed on a 4 inch column eluting with 1 to 6% EtOAc/toluene to produce 4.9 g of the title product. After cooling to room temperature the reaction was filtered The residue, dissolved in CH2Cl2 (100 ml) was filtered concentrated eluting with 1 to 6% EtOAc/toluene

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

Procedure: This compound was prepared by the condensation procedure 1A. The required intermediate 2-bromoethylphenyl sulphide may be prepared by condensing 1,2-bromoethane and thiophenol in sodium hydroxide solution, in a manner analogous to that used for preparation of the intermediates for compounds of Example Nos. 62-73, but a method which gives better yields uses the scheme: ##STR25## Condensation with ethyl 4-hydroxybenzoate gave 1-(4-ethoxycarbonylphenoxy)-2-phenylthio ethane, m.p. 50°-51° C. This compound was prepared by the condensation procedure 1A 62-73, but a method which gives better yields

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

Procedure: 33 g of thiophenol were dissolved in a solution of 6.9 g of sodium in 120 ml of ethanol and the solution was added dropwise to 129 ml of 1,2-dibromoethane. The mixture was heated under reflux for 1 hour and cooled and 250 ml of ether were added. The salt which had precipitated out was filtered off. The filtrate was concentrated and the evaporation residue was fractionated. 55.4 g of a colourless oil with a boiling point of 125° to 130° C. under 12 mm Hg were obtained. The mixture was heated under reflux for 1 hour cooled The salt which had precipitated out was filtered off The filtrate was concentrated

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Potassium phthalimide (5.43 g, 25 mmol) was added to a DMF (50 ml) solution of [(2-bromoethyl)thio]benzene (5,43 g, 25 mmol) and this stirred mixture under N2 was heated at 90° C. for 2 h. After cooling to room temperature, the reaction was filtered. The solvent was stripped from the filtrate under reduced pressure. The residue, dissolved in CH2Cl2 (100 ml), was filtered, concentrated, and flash chromotographed on a 4 inch column eluting with 1 to 6% EtOAc/toluene to produce 4.9 g of the title product. After cooling to room temperature the reaction was filtered The residue, dissolved in CH2Cl2 (100 ml) was filtered concentrated eluting with 1 to 6% EtOAc/toluene

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

Procedure: A mixture of (2-bromo-ethylsulfanyl)-benzene (273 mg, 1.26 mmol) and 3-chlorobenzenecarboperoxoic acid (650 mg, 3.77 mmol) in methylene chloride (5 mL) were stirred at room temperature for 16 h. A saturated sodium sulfite solution was added and the mixture was extracted with methylene chloride. The organic layers were washed by saturated sodium bicarbonate solution, dried over sodium sulfate, and concentrated in vacuo to provide (2-bromo-ethanesulfonyl)-benzene (0.24 g, 76%). the mixture was extracted with methylene chloride The organic layers were washed by saturated sodium bicarbonate solution dried over sodium sulfate concentrated in vacuo

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Potassium phthalimide (5.43 g, 25 mmol) was added to a DMF (50 ml) solution of [(2-bromoethyl)thio]benzene (5,43 g, 25 mmol) and this stirred mixture under N2 was heated at 90° C. for 2 h. After cooling to room temperature, the reaction was filtered. The solvent was stripped from the filtrate under reduced pressure. The residue, dissolved in CH2Cl2 (100 ml), was filtered, concentrated, and flash chromotographed on a 4 inch column eluting with 1 to 6% EtOAc/toluene to produce 4.9 g of the title product. After cooling to room temperature the reaction was filtered The residue, dissolved in CH2Cl2 (100 ml) was filtered concentrated eluting with 1 to 6% EtOAc/toluene

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 0.2 g (0.93 mmol) of 7-pyridin-4-yl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one in ml of anhydrous N,N-dimethylformamide was added 48.5 mg (1.21 mmol) of sodium hydride (60% suspension in mineral oil) and the resulting mixture was heated at 70° C. during 30 min. There was added 0.32 g (1.49 mmol) of 2-bromoethyl phenyl sulfide and heating was continued at 130° C. during 1 h. Water was added to the cooled mixture and the resulting solution extracted with ethyl acetate. The combined extracts were washed with water and evaporated. The crude product was purified by chromatography on silica gel eluting with a mixture of dichloromethane/methanol/diethylamine in the proportions 98/2/0.2 to obtain pure compound as free base. The compound was converted to the hydrochloride salt by addition of hydrochloric acid to an isopropylic solution of the free base. There is obtained 0.11 g of product as a yellow solid. heating the resulting solution extracted with ethyl acetate The combined extracts were washed with water evaporated The crude product was purified by chromatography on silica gel eluting with a mixture of dichloromethane/methanol/diethylamine in the proportions 98/2/0.2 to obtain pure compound as free base

Conditions: temp:57.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 2.5 mL of an N,N-dimethylformamide solution containing 0.10 g of ethyl 4-(3-(7-methoxy-2-oxoquinolin-1(2H)-yl)propyl)piperidine-4-carboxylate, 74 mg of potassium carbonate and 64 mg of 1-phenylthio-2-bromoethane were added at room temperature, and stirred at 55-60° C. for 4.5 hours. After the reaction mixture was cooled to room temperature, ethyl acetate and water were added. The organic layer was separated, was washed with aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by silica gel column chromatography [eluent; chloroform:methanol=20:1], to give 93 mg of ethyl 4-(3-(7-methoxy-2-oxoquinolin-1(2H)-yl)propyl)-1-(2-(phenylthio)ethyl)piperidine-4-carboxylate as a yellow oil. were added at room temperature After the reaction mixture was cooled to room temperature The organic layer was separated was washed with aqueous saturated sodium chloride solution dried over anhydrous magnesium sulfate the solvent was removed under reduced pressure The residue thus obtained was purified by silica gel column chromatography [eluent; chloroform:methanol=20:1]

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 0.2 g (0.93 mmol) of 7-pyridin-4-yl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one in ml of anhydrous N,N-dimethylformamide was added 48.5 mg (1.21 mmol) of sodium hydride (60% suspension in mineral oil) and the resulting mixture was heated at 70° C. during 30 min. There was added 0.32 g (1.49 mmol) of 2-bromoethyl phenyl sulfide and heating was continued at 130° C. during 1 h. Water was added to the cooled mixture and the resulting solution extracted with ethyl acetate. The combined extracts were washed with water and evaporated. The crude product was purified by chromatography on silica gel eluting with a mixture of dichloromethane/methanol/diethylamine in the proportions 98/2/0.2 to obtain pure compound as free base. The compound was converted to the hydrochloride salt by addition of hydrochloric acid to an isopropylic solution of the free base. There is obtained 0.11 g of product as a yellow solid. heating the resulting solution extracted with ethyl acetate The combined extracts were washed with water evaporated The crude product was purified by chromatography on silica gel eluting with a mixture of dichloromethane/methanol/diethylamine in the proportions 98/2/0.2 to obtain pure compound as free base

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

Conditions: temp:57.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 2.5 mL of an N,N-dimethylformamide solution containing 0.10 g of ethyl 4-(3-(7-methoxy-2-oxoquinolin-1(2H)-yl)propyl)piperidine-4-carboxylate, 74 mg of potassium carbonate and 64 mg of 1-phenylthio-2-bromoethane were added at room temperature, and stirred at 55-60° C. for 4.5 hours. After the reaction mixture was cooled to room temperature, ethyl acetate and water were added. The organic layer was separated, was washed with aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by silica gel column chromatography [eluent; chloroform:methanol=20:1], to give 93 mg of ethyl 4-(3-(7-methoxy-2-oxoquinolin-1(2H)-yl)propyl)-1-(2-(phenylthio)ethyl)piperidine-4-carboxylate as a yellow oil. were added at room temperature After the reaction mixture was cooled to room temperature The organic layer was separated was washed with aqueous saturated sodium chloride solution dried over anhydrous magnesium sulfate the solvent was removed under reduced pressure The residue thus obtained was purified by silica gel column chromatography [eluent; chloroform:methanol=20:1]