1-(chloromethyl)-4-ethylbenzene

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:0.00; pressure:0.00; stir:

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

Procedure: The titled compound (24 mg) as a reddish brown solid was prepared from the compound [4-6] obtained in the process (6) of Example 4 (100 mg) and 4-ethylbenzyl chloride according to the method of the process (7) of Example 4.

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

Procedure: The titled compound (24 mg) as a reddish brown solid was prepared from the compound [4-6] obtained in the process (6) of Example 4 (100 mg) and 4-ethylbenzyl chloride according to the method of the process (7) of Example 4.

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

Procedure: Using 0.16 g of 4-ethylbenzyl chloride, 3 ml of N,N-dimethylformamide, 0.05 g of sodium hydride (60% in oil), and 0.17 g of (3,3,3-trifluoropropyl)malononitrile, and according to the process described in the Production Example 26, there was obtained 0.14 g of 2-(4-ethylbenzyl)-2-(3,3,3-trifluoropropyl)malononitrile (the present compound (31)).

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

Procedure: To a solution of methyl 3-{[5-(methoxymethoxy)-1-(methoxymethyl)-6-oxo-1,6-dihydropyridin-3-yl]sulfanyl}propanoate (Intermediate 16) (290 mg, 0.91 mmol) in THF (5 ml) at −45° C. was added potassium tert-butoxide (113 mg, 1.01 mmol) and the resulting mixture allowed to stir for 20 minutes. 1-(Chloromethyl)-4-ethylbenzene (170 mg, 1.10 mmol) was then added and the reaction mixture allowed to warm to room temperature and stirred for 4 hours before being quenched with water and extracted into dichlormethane. The combined organics were concentrated and subjected to column chromatography (SiO2; 0-10% methanol in dichloromethane) to yield 5-[(4-ethylbenzyl)sulfanyl]-3-(methoxymethoxy)-1-(methoxymethyl)pyridin-2(1H)-one (253 mg, 79%). stirred for 4 hours before being quenched with water extracted into dichlormethane The combined organics were concentrated

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

Procedure: To a solution of indole (4.0 g, 34.1 mmol), potassium hydroxide (2.40 g, 42.6 mmol) in ethanol (200 mL) was added and the mixture solution was stirred at room temperature for two hours. The solvent was distilled under reduced pressure. The residue was dissolved in acetone (200 mL), and 1-chloromethyl-4-ethylbenzene (5.28 g, 34.1 mmol) was added thereto. The reaction mixture was stirred at room temperature a whole day and night, and then subjected to Celite filtration and the filtrate was distilled under reduced pressure. The obtained residue was purified by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:500)] to obtain the title compound (3.8 g, 47%). The solvent was distilled under reduced pressure The residue was dissolved in acetone (200 mL) The reaction mixture was stirred at room temperature a whole day and night subjected to Celite filtration the filtrate was distilled under reduced pressure The obtained residue was purified by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:500)]

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

Procedure: To a solution of indole (4.0 g, 34.1 mmol), potassium hydroxide (2.40 g, 42.6 mmol) in ethanol (200 mL) was added and the mixture solution was stirred at room temperature for two hours. The solvent was distilled under reduced pressure. The residue was dissolved in acetone (200 mL), and 1-chloromethyl-4-ethylbenzene (5.28 g, 34.1 mmol) was added thereto. The reaction mixture was stirred at room temperature a whole day and night, and then subjected to Celite filtration and the filtrate was distilled under reduced pressure. The obtained residue was purified by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:500)] to obtain the title compound (3.8 g, 47%). The solvent was distilled under reduced pressure The residue was dissolved in acetone (200 mL) The reaction mixture was stirred at room temperature a whole day and night subjected to Celite filtration the filtrate was distilled under reduced pressure The obtained residue was purified by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:500)]

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

Procedure: To a solution of the hydrochloride salt of N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl]methanesulfonamide (Preparation 53, 57 mg, 0.19 mmol) in N,N-dimethylformamide (2 ml) was added sodium hydrogen carbonate (630 mg, 7.52 mmol), 1-(chloromethyl)-4-ethylbenzene (32 mg, 0.20 mmol) and sodium iodide (catalytic) and the reaction mixture was heated at 50° C. for 20 h. After cooling, diethyl ether (5 ml) and water (7 ml) were added and the reaction mixture was stirred vigorously for 5 min. The phases were separated and the aqueous layer was further extracted with diethyl ether (2×5 ml). The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. The residual oil was purified by flash column chromatography using a Sep-Pak™ cartridge packed with silica gel (5 g) eluting with dichloromethane:ethanol:0.88 ammonia solution (200:8:1) to afford the title compound as an oil (30 mg, 41%). After cooling The phases were separated the aqueous layer was further extracted with diethyl ether (2×5 ml) The combined organic extracts were dried (Na2SO4) filtered concentrated in vacuo The residual oil was purified by flash column chromatography eluting with dichloromethane