tert-butyl N-(3,3-diethoxypropyl)carbamate

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

Procedure: To a stirred solution of tert-butyl (3,3-diethoxypropyl)carbamate (1.0 g, 4.05 mmol) in DMF (15 mL) was added sodium hydride (0.25 g, 6.25 mmol). The reaction mixture was stirred at room temperature for 30 minutes and 3-methoxybenzyl bromide (0.875 mL, 6.25 mmol) added. The reaction mixture was stirred at room temperature for 72 hours. The reaction mixture was diluted with ethyl acetate and washed with water and twice with brine. The organic phase was dried (magnesium sulfate), filtered and the solvent evaporated at reduced pressure. The residue was dissolved in ethanol (10 mL) and 4M hydrogen chloride in dioxane (10 mL) added. The reaction mixture was stirred at room temperature for 2 hours and the solvent evaporated at reduced pressure. The residue was loaded onto an SCX-2 cartridge and eluted with ethanol (4 column volumes) and then 10% triethylamine/ethanol (4 column volumes). The product containing fractions were combined and the solvent evaporated at reduced pressure to afford the title compound (0.543 g, 50%). The reaction mixture was stirred at room temperature for 72 hours washed with water and twice with brine The organic phase was dried (magnesium sulfate) filtered the solvent evaporated at reduced pressure The residue was dissolved in ethanol (10 mL) 4M hydrogen chloride in dioxane (10 mL) added The reaction mixture was stirred at room temperature for 2 hours the solvent evaporated at reduced pressure eluted with ethanol (4 column volumes) The product containing fractions the solvent evaporated at reduced pressure

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

Procedure: To a stirred solution of tert-butyl (3,3-diethoxypropyl)carbamate (1.0 g, 4.05 mmol) in DMF (15 mL) was added sodium hydride (0.25 g, 6.25 mmol). The reaction mixture was stirred at room temperature for 30 minutes and 3-methoxybenzyl bromide (0.875 mL, 6.25 mmol) added. The reaction mixture was stirred at room temperature for 72 hours. The reaction mixture was diluted with ethyl acetate and washed with water and twice with brine. The organic phase was dried (magnesium sulfate), filtered and the solvent evaporated at reduced pressure. The residue was dissolved in ethanol (10 mL) and 4M hydrogen chloride in dioxane (10 mL) added. The reaction mixture was stirred at room temperature for 2 hours and the solvent evaporated at reduced pressure. The residue was loaded onto an SCX-2 cartridge and eluted with ethanol (4 column volumes) and then 10% triethylamine/ethanol (4 column volumes). The product containing fractions were combined and the solvent evaporated at reduced pressure to afford the title compound (0.543 g, 50%). The reaction mixture was stirred at room temperature for 72 hours washed with water and twice with brine The organic phase was dried (magnesium sulfate) filtered the solvent evaporated at reduced pressure The residue was dissolved in ethanol (10 mL) 4M hydrogen chloride in dioxane (10 mL) added The reaction mixture was stirred at room temperature for 2 hours the solvent evaporated at reduced pressure eluted with ethanol (4 column volumes) The product containing fractions the solvent evaporated at reduced pressure

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To (3,3-diethoxypropyl)amine (1.00 equiv) in THF (2 volumes) was charged di-t-butyldicarbonate (1.05 equiv) in THF (3 volumes). The reaction was heated to 45° C. and held for ½ h. Analysis showed the disappearance of starting material, and the resulting solution was heated to 65° C. p-Toluene sulphonic acid (0.1 equiv) and water (5 volumes) were charged over 10 mins, heating continued at 65° C. and held for ½ hour. Analysis showed disappearance of tert-butyl (3,3-diethoxypropyl)carbamate. Toluene (15 volumes) charged, layers separated and washed with water (5 volumes). A fraction of the solution obtained (0.95 equivs) was charged to a solution containing 6-(1-amino-2-methyl-propyl)-5-benzyl-3-methyl-5H-isothiazolo[5,4-d]pyrimidin-4-one (method 30) (1 equiv), toluene (5 volumes) and molecular sieves (1 weight equivalent). The reaction mixture was stirred overnight at room temperature until the reaction was complete. THF (2.5 volumes) were charged followed by sodium acetoxyborohydride (2.0 equiv) and the resulting mixture held overnight until reaction was complete. Aqueous acetic acid (20% v/v, 2.5 volumes) were charged over 10 minutes, stirred at room temperature for 10 minutes, filtered and washed with water (2.5 volumes). The layers were separated and the organic layer was concentrated under vacuo at 50° C. Further toluene was charged (2.5 volumes) and the solvent removed. The product was obtained as an orange oil (typical yield 92%). m/z 486 (MH+). were charged over 10 mins heating continued at 65° C. held for ½ hour layers separated washed with water (5 volumes) A fraction of the solution obtained (0.95 equivs) was charged to a solution the resulting mixture held overnight until reaction stirred at room temperature for 10 minutes filtered washed with water (2.5 volumes) The layers were separated the organic layer was concentrated under vacuo at 50° C Further toluene was charged (2.5 volumes) the solvent removed The product was obtained as an orange oil (typical yield 92%)

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

Procedure: A solution of 2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-amine (1.00 g, 4.13 mmol) in 20 mL of acetonitrile and 5 mL of glacial acetic acid was treated with tert-butyl (3,3-diethoxypropyl)carbamate (2.55 g, 10.3 mmol) and heated to reflux under an atmosphere of nitrogen. After 15 h, the reaction mixture was concentrated under reduced pressure to yield a brown oil. The oil was partitioned between CHCl3 and saturated NaHCO3 solution and the phases were separated. The organic portion was washed with water (2×) and brine, dried over Na2SO4, filtered and concentrated under reduced pressure to yield tert-butyl {3-[(2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)imino]propyl}carbamate (1.64 g) as a dark red/orange oil. heated to reflux under an atmosphere of nitrogen the reaction mixture was concentrated under reduced pressure to yield a brown oil The oil was partitioned between CHCl3 and saturated NaHCO3 solution the phases were separated The organic portion was washed with water (2×) and brine dried over Na2SO4 filtered concentrated under reduced pressure

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

Procedure: To a stirred solution of tert-butyl (3,3-diethoxypropyl)carbamate (1.0 g, 4.05 mmol) in DMF (15 mL) was added sodium hydride (0.25 g, 6.25 mmol). The reaction mixture was stirred at room temperature for 30 minutes and 3-methoxybenzyl bromide (0.875 mL, 6.25 mmol) added. The reaction mixture was stirred at room temperature for 72 hours. The reaction mixture was diluted with ethyl acetate and washed with water and twice with brine. The organic phase was dried (magnesium sulfate), filtered and the solvent evaporated at reduced pressure. The residue was dissolved in ethanol (10 mL) and 4M hydrogen chloride in dioxane (10 mL) added. The reaction mixture was stirred at room temperature for 2 hours and the solvent evaporated at reduced pressure. The residue was loaded onto an SCX-2 cartridge and eluted with ethanol (4 column volumes) and then 10% triethylamine/ethanol (4 column volumes). The product containing fractions were combined and the solvent evaporated at reduced pressure to afford the title compound (0.543 g, 50%). The reaction mixture was stirred at room temperature for 72 hours washed with water and twice with brine The organic phase was dried (magnesium sulfate) filtered the solvent evaporated at reduced pressure The residue was dissolved in ethanol (10 mL) 4M hydrogen chloride in dioxane (10 mL) added The reaction mixture was stirred at room temperature for 2 hours the solvent evaporated at reduced pressure eluted with ethanol (4 column volumes) The product containing fractions the solvent evaporated at reduced pressure