2-cyclohexyloxyethanol

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 was prepared from [5-(4-fluorophenylcarbamoyl)pyrimidin-2-yloxy]acetic acid using 2-cyclohexyloxy-ethanol (37 mg, 0.26 mmol) as the coupling partner. Chromatography (1:1 ethyl acetate:dichloromethane) through SiO2 yielded 36 mg (51%) of the titled compound. ESI-MS m/z 418 (MH30 ), 416 (M−H−).

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

Procedure: To a solution of 2-(cyclohexyloxy)-1-ethanol (200 mg, 1.39 mmol) in pyridine (10 mL) at 0° C. was added p-toluenesulfonyl chloride (292 mg, 1.53 mmol) portionwise followed by 4-(dimethylamino)pyridine (a few crystals) and the mixture was stirred at room temperature for 16 hours. The solvent was removed in vacuo to give a crude residue that was partitioned between dichloromethane and 2N aqueous hydrochloric acid. The two layers were separated and the organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to give a yellow oil. This was purified by column chromatography on silica gel, eluting with dichloromethane, to give the title compound (226 mg, 54%) as a yellow oil. The solvent was removed in vacuo to give a crude residue that was partitioned between dichloromethane and 2N aqueous hydrochloric acid The two layers were separated the organic layer was dried over sodium sulfate filtered concentrated in vacuo to give a yellow oil This was purified by column chromatography on silica gel eluting with dichloromethane

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

Procedure: The titled compound was prepared from [5-(4-fluorophenylcarbamoyl)pyrimidin-2-yloxy]acetic acid using 2-cyclohexyloxy-ethanol (37 mg, 0.26 mmol) as the coupling partner. Chromatography (1:1 ethyl acetate:dichloromethane) through SiO2 yielded 36 mg (51%) of the titled compound. ESI-MS m/z 418 (MH30 ), 416 (M−H−).

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

Procedure: The titled compound was prepared from [5-(4-fluorophenylcarbamoyl)pyrimidin-2-yloxy]acetic acid using 2-cyclohexyloxy-ethanol (37 mg, 0.26 mmol) as the coupling partner. Chromatography (1:1 ethyl acetate:dichloromethane) through SiO2 yielded 36 mg (51%) of the titled compound. ESI-MS m/z 418 (MH30 ), 416 (M−H−).

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred mixture of 4-hydroxy-alpha-oxobenzeneacetic acid methyl ester (0.724) in dimethylformamide (10 mL) under argon was treated with 55% sodium hydride (0.175 g), stirred for 15 minutes and treated with the tosylate prepared from 2-(cyclohexyloxy)ethanol (1.49 g). The mixture was heated at 60° C. overnight and worked up as in Example 20. The material from dichloromethane extraction was purified by HPLC (diethyl ether-hexane; 1:1) to provide 0.9 g of pure 4-[[2-(cyclohexyloxy)ethyl]oxy]-alpha-oxobenzeneacetic acid methyl ester as an oil. The material from dichloromethane extraction was purified by HPLC (diethyl ether-hexane; 1:1)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred mixture of 4-hydroxy-alpha-oxobenzeneacetic acid methyl ester (0.724) in dimethylformamide (10 mL) under argon was treated with 55% sodium hydride (0.175 g), stirred for 15 minutes and treated with the tosylate prepared from 2-(cyclohexyloxy)ethanol (1.49 g). The mixture was heated at 60° C. overnight and worked up as in Example 20. The material from dichloromethane extraction was purified by HPLC (diethyl ether-hexane; 1:1) to provide 0.9 g of pure 4-[[2-(cyclohexyloxy)ethyl]oxy]-alpha-oxobenzeneacetic acid methyl ester as an oil. The material from dichloromethane extraction was purified by HPLC (diethyl ether-hexane; 1:1)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred mixture of 4-hydroxy-alpha-oxobenzeneacetic acid methyl ester (0.724) in dimethylformamide (10 mL) under argon was treated with 55% sodium hydride (0.175 g), stirred for 15 minutes and treated with the tosylate prepared from 2-(cyclohexyloxy)ethanol (1.49 g). The mixture was heated at 60° C. overnight and worked up as in Example 20. The material from dichloromethane extraction was purified by HPLC (diethyl ether-hexane; 1:1) to provide 0.9 g of pure 4-[[2-(cyclohexyloxy)ethyl]oxy]-alpha-oxobenzeneacetic acid methyl ester as an oil. The material from dichloromethane extraction was purified by HPLC (diethyl ether-hexane; 1:1)

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

Procedure: To a solution of 2-(cyclohexyloxy)ethanol (63.4 mg, 0.439 mmol, intermediate 38) in THF (5 mL) was added sodium hydride (23.4 mg, 0.586 mmol, 60% dispersion in mineral oil) at 0° C., and the mixture was stirred at room temperature for 30 min. Then a solution of 8-bromo-7-(4-chlorobenzyl)-3-methyl-1-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-1H-purine-2,6(3H,7H)-dione (150 mg, 0.293 mmol, intermediate 14) in THF (1 mL) was added and the resulting mixture was stirred at reflux for 1 h. The reaction was cooled and quenched with ice-water. The mixture was extracted with ethyl acetate. The organic phase was dried and concentrated to give 7-(4-chlorobenzyl)-8-(2-(cyclohexyloxy)ethoxy)-3-methyl-1-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-1H-purine-2,6(3H,7H)-dione (123 mg, 73% yield) as a yellow solid. LCMS retention time 2.064 min; LCMS MH+-THP 491. the resulting mixture was stirred at reflux for 1 h The reaction was cooled quenched with ice-water The mixture was extracted with ethyl acetate The organic phase was dried concentrated

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

Procedure: To the slurry of zirconium tetrachloride (10.65 g, 45.7 mmol) in THF (100 mL) was added sodium borohydride (4.3 g, 114.3 mmol) in small portions at room temperature. A solution of 1,4-dioxaspiro[4.5]decane (6.5 g, 45.7 mmol) in THF (20 mL) was added dropwise and the resulting mixture was stirred at room temperature overnight. The reaction was carefully quenched with 1N HCl and extracted with ethyl acetate. The organic phase was washed with brine, dried and concentrated to give a crude product, which was purified via silica gel chromatography eluting with petroleum ether/ethyl acetate (3:2) to give 2-(cyclohexyloxy)ethanol (3.9 g, 59.2% yield) as light yellow oil. 1H-NMR (CDCl3) δ 3.68-3.70 (t, 2H), 3.53-3.56 (m, 2H), 3.27-3.29 (m, 1H), 2.54 (br, 1H), 1.89-1.93 (m, 2H), 1.70-1.73 (m, 2H), 1.51-1.54 (m, 1H), 1.17-1.28 (m, 5H). The reaction was carefully quenched with 1N HCl extracted with ethyl acetate The organic phase was washed with brine dried concentrated to give a crude product, which was purified via silica gel chromatography eluting with petroleum ether/ethyl acetate (3:2)

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

Procedure: The 2-ethoxyethyl-cyclohexyl-ether was prepared in correspondence with the description of Example 1 from 72 g (0.5 mol) of 2-hydroxyethyl-cyclohexyl-ether and 54 g (0.35 mol) of diethyl sulfate.