4-methoxybutan-1-ol

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

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

Procedure: 6.77 g (0.065 mol) of 4-methoxybutanol was dissolved in 60 ml of dimethyl sulfoxide to obtain a solution. 2.6 g (0.065 mol) of 60% sodium hydride was added to this solution at a room temperature in a nitrogen atmosphere. The obtained mixture was heated to 60° C., stirred for one hour and cooled to a room temperature. A solution of 4.66 g (0.032 mol) of 4-chloro-2-methylpyridine 1-oxide in 20 ml of dimethyl sulfoxide was dropwise added to the resulting mixture. The obtained mixture was stirred at 40° C. for one hour. After the completion of the reaction, 5 ml of water was added to the mixture and the obtained mixture was, evaporated to dryness to remove the solvent. 150 ml of water was added to the residue. The obtained mixture was extracted with 200 ml of chloroform four times. The extract was dried over magnesium sulfate and filtered. The filtrate was distilled to remove the solvent. The residue was purified by silica gel column chromatography (ethyl acetate/methanol) to obtain 5.06 g of the title compound as an oil. to obtain a solution cooled to a room temperature The obtained mixture was stirred at 40° C. for one hour was added to the mixture evaporated to dryness to remove the solvent 150 ml of water was added to the residue The obtained mixture was extracted with 200 ml of chloroform four times The extract was dried over magnesium sulfate filtered The filtrate was distilled to remove the solvent The residue was purified by silica gel column chromatography (ethyl acetate/methanol)

Conditions: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 50 mg 2-(3,5-Bis-(4-fluoro-phenyl)-(1,2,4)triazol-1-yl)-1-(4-(6-chloro-pyrimidin-4-yl)-piperazin-1-yl)-ethanone and 53 mg 4-methoxy-1-butanol were added to 14 mg potassiumcarbonate in 2 mL n-methyl-2-pyrrolidinone. The reaction was sonicated for a few minutes and stirred 30 min at 200° C. The reaction was purified by HPLC to give 29 mg desired product. Rt: 1.82 min (method N), (M+H)+: 564 The reaction was sonicated for a few minutes The reaction was purified by HPLC

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

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

Procedure: Mitsunobu reaction of phenol 58 with 4-methoxybutanol gave 2-(3-(3-(4-methoxybutoxy)phenyl)propyl)isoindoline-1,3-dione as yellow oil. Yield (0.840 g, 66%): 1H NMR (400 MHz, CDCl3) δ 7.80-7.85 (m, 2H), 7.68-7.72 (m, 2H), 7.11-7.17 (m, 1H), 6.72-6.79 (m, 2H), 6.65 (dd, J=8.2, 2.4 Hz, 1H), 3.95 (t, J=6.2 Hz, 2H), 3.75 (t, J=6.8 Hz, 2H), 3.44 (t, J=6.4 Hz, 2H), 3.35 (s, 3H), 2.65 (t, J=7.2 Hz, 2H), 1.98-2.06 (m, 2H), 1.70-1.86 (m, 4H).

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

Procedure: Mitsunobu reaction of phenol 58 with 4-methoxybutanol gave 2-(3-(3-(4-methoxybutoxy)phenyl)propyl)isoindoline-1,3-dione as yellow oil. Yield (0.840 g, 66%): 1H NMR (400 MHz, CDCl3) δ 7.80-7.85 (m, 2H), 7.68-7.72 (m, 2H), 7.11-7.17 (m, 1H), 6.72-6.79 (m, 2H), 6.65 (dd, J=8.2, 2.4 Hz, 1H), 3.95 (t, J=6.2 Hz, 2H), 3.75 (t, J=6.8 Hz, 2H), 3.44 (t, J=6.4 Hz, 2H), 3.35 (s, 3H), 2.65 (t, J=7.2 Hz, 2H), 1.98-2.06 (m, 2H), 1.70-1.86 (m, 4H).

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

Procedure: Mitsunobu reaction of phenol 58 with 4-methoxybutanol gave 2-(3-(3-(4-methoxybutoxy)phenyl)propyl)isoindoline-1,3-dione as yellow oil. Yield (0.840 g, 66%): 1H NMR (400 MHz, CDCl3) δ 7.80-7.85 (m, 2H), 7.68-7.72 (m, 2H), 7.11-7.17 (m, 1H), 6.72-6.79 (m, 2H), 6.65 (dd, J=8.2, 2.4 Hz, 1H), 3.95 (t, J=6.2 Hz, 2H), 3.75 (t, J=6.8 Hz, 2H), 3.44 (t, J=6.4 Hz, 2H), 3.35 (s, 3H), 2.65 (t, J=7.2 Hz, 2H), 1.98-2.06 (m, 2H), 1.70-1.86 (m, 4H).

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

Procedure: Triethylamine (2.91 g, 28.86 mmol) was added to the stirred solution of 4-methoxy-1-butanol (1.00 g, 9.62 mmol) in dichloromethane (15 mL) at 0° C. and stirred for 15 min. p-Toluene sulfonyl chloride (1.83 g, 9.62 mmol) was added and the mixture was warmed to ambient temperature and stirred for 2 h. The reaction mixture was quenched with ice-water and the organic layer was separated. The aqueous layer was extracted with dichloromethane (3×5 mL) and the combined organic layers were washed with saturated sodium bicarbonate, water, and brine; dried over anhydrous sodium sulphate and concentrated in vacuo. The crude product was purified by column chromatography over silica gel (60-120 mesh) with 0% to 20% ethyl acetate in petroleum ether as eluent to afford 4-methoxybutyl-4-methylbenzenesulfonate (800 mg, 32%) as a liquid. was added The reaction mixture was quenched with ice-water the organic layer was separated The aqueous layer was extracted with dichloromethane (3×5 mL) the combined organic layers were washed with saturated sodium bicarbonate, water, and brine dried over anhydrous sodium sulphate concentrated in vacuo The crude product was purified by column chromatography over silica gel (60-120 mesh) with 0% to 20% ethyl acetate in petroleum ether as eluent

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

Procedure: Mitsunobu reaction of phenol 58 with 4-methoxybutanol gave 2434344-methoxybutoxy)phenyl)propyl)isoindoline-1,3-dione as yellow oil. Yield (0.840 g, 66%): 1H NMR (400 MHz, CDCl3) δ 7.80-7.85 (m, 2H), 7.68-7.72 (m, 2H), 7.11-7.17 (m, 1H), 6.72-6.79 (m, 2H), 6.65 (dd, J=8.2, 2.4 Hz, 1H), 3.95 (t, J=6.2 Hz, 2H), 3.75 (t, J=6.8 Hz, 2H), 3.44 (t, J=6.4 Hz, 2H), 3.35 (s, 3H), 2.65 (t, J=7.2 Hz, 2H), 1.98-2.06 (m, 2H), 1.70-1.86 (m, 4H).

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

Procedure: 6.77 g (0.065 mol) of 4-methoxybutanol was dissolved in 60 ml of dimethyl sulfoxide to obtain a solution. 2.6 g (0.065 mol) of 60% sodium hydride was added to this solution at a room temperature in a nitrogen atmosphere. The obtained mixture was heated to 60° C., stirred for one hour and cooled to a room temperature. A solution of 4.66 g (0.032 mol) of 4-chloro-2-methylpyridine 1-oxide in 20 ml of dimethyl sulfoxide was dropwise added to the resulting mixture. The obtained mixture was stirred at 40° C. for one hour. After the completion of the reaction, 5 ml of water was added to the mixture and the obtained mixture was evaporated to dryness to remove the solvent. 150 ml of water was added to the residue. The obtained mixture was extracted with 200 ml of chloroform four times. The extract was dried over magnesium sulfate and filtered. The filtrate was distilled to remove the solvent. The residue was purified by silica gel column chromatography (ethyl acetate/methanol) to obtain 5.06 g of the title compound as an oil. to obtain a solution cooled to a room temperature The obtained mixture was stirred at 40° C. for one hour was added to the mixture the obtained mixture was evaporated to dryness to remove the solvent 150 ml of water was added to the residue The obtained mixture was extracted with 200 ml of chloroform four times The extract was dried over magnesium sulfate filtered The filtrate was distilled to remove the solvent The residue was purified by silica gel column chromatography (ethyl acetate/methanol)

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

Procedure: 6.77 g (0.065 mol) of 4-methoxybutanol was dissolved in 60 ml of dimethyl sulfoxide to obtain a solution. 2.6 g (0.065 mol) of 60% sodium hydride was added to this solution at a room temperature in a nitrogen atmosphere. The obtained mixture was heated to 60° C., stirred for one hour and cooled to a room temperature. A solution of 4.66 g (0.032 mol) of 4-chloro-2-methylpyridine 1-oxide in 20 ml of dimethyl sulfoxide was dropwise added to the resulting mixture. The obtained mixture was stirred at 40° C. for one hour. After the completion of the reaction, 5 ml of water was added to the mixture and the obtained mixture was evaporated to dryness to remove the solvent. 150 ml of water was added to the residue. The obtained mixture was extracted with 200 ml of chloroform four times. The extract was dried over magnesium sulfate and filtered. The filtrate was distilled to remove the solvent. The residue was purified by silica gel column chromatography (ethyl acetate/methanol) to obtain 5.06 g of the title compound as an oil. to obtain a solution cooled to a room temperature The obtained mixture was stirred at 40° C. for one hour was added to the mixture the obtained mixture was evaporated to dryness to remove the solvent 150 ml of water was added to the residue The obtained mixture was extracted with 200 ml of chloroform four times The extract was dried over magnesium sulfate filtered The filtrate was distilled to remove the solvent The residue was purified by silica gel column chromatography (ethyl acetate/methanol)

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

Procedure: 6.77 g (0.065 mol) of 4-methoxybutanol was dissolved in 60 ml of dimethyl sulfoxide to obtain a solution. 2.6 g (0.065 mol) of 60% sodium hydride was added to this solution at a room temperature in a nitrogen atmosphere. The obtained mixture was heated to 60° C., stirred for one hour and cooled to a room temperature. A solution of 4.66 g (0.032 mol) of 4-chloro-2-methylpyridine 1-oxide in 20 ml of dimethyl sulfoxide was dropwise added to a resulting mixture. The obtained mixture was stirred at 40° C. for one hour. After the completion of the reaction, 5 ml of water was added to the mixture and the obtained mixture was evaporated to dryness to remove the solvent. 150 ml of water was added to the residue. The obtained mixture was extracted with 200 ml of chloroform four times. The extract was dried over magnesium sulfate and filtered. The filtrate was distilled to remove the solvent. The residue was purified by silica gel column chromatography (ethyl acetate/methanol) to obtain 5.06 g of the title compound as an oil. to obtain a solution cooled to a room temperature The obtained mixture was stirred at 40° C. for one hour was added to the mixture the obtained mixture was evaporated to dryness to remove the solvent 150 ml of water was added to the residue The obtained mixture was extracted with 200 ml of chloroform four times The extract was dried over magnesium sulfate filtered The filtrate was distilled to remove the solvent The residue was purified by silica gel column chromatography (ethyl acetate/methanol)