1,1,1-triethoxypentane

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

Procedure: A solution of tert-butyl 2-{2-[(3-aminoquinolin-4-yl)amino]ethoxy}ethylcarbamate (3.46 g, 10.0 mmol) in 50 mL of toluene was treated with triethylorthovalerate (2.5 mL, 14.5 mmol) and the reaction mixture was heated to reflux. A 25 mg portion of pyridinium hydrochloride was then added and refluxing was continued for 4 h. The reaction was then concentrated to dryness under reduced pressure. The residue was dissolved in 50 mL of CH2Cl2 and washed with saturated NaHCO3, H2O and brine. The organic portion was dried over Na2SO4 and concetrated to give a green oil. The green oil was dissolved in 50 mL of hot MeOH and treated with activated charcoal. The hot solution was filtered and concentrated to give 4.12 g of tert-butyl 2-[2-(2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)ethoxy]ethylcarbamate as a yellow oil. the reaction mixture was heated to reflux refluxing The reaction was then concentrated to dryness under reduced pressure The residue was dissolved in 50 mL of CH2Cl2 washed with saturated NaHCO3, H2O and brine The organic portion was dried over Na2SO4 to give a green oil The hot solution was filtered concentrated

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

Procedure: A solution of tert-butyl 2-{2-[(3-aminoquinolin-4-yl)amino]ethoxy}ethylcarbamate (3.46 g, 10.0 mmol) in 50 mL of toluene was treated with triethylorthovalerate (2.5 mL, 14.5 mmol) and the reaction mixture was heated to reflux. A 25 mg portion of pyridinium hydrochloride was then added and refluxing was continued for 4 h. The reaction was then concentrated to dryness under reduced pressure. The residue was dissolved in 50 mL of CH2Cl2 and washed with saturated NaHCO3, H2O and brine. The organic portion was dried over Na2SO4 and concetrated to give a green oil. The green oil was dissolved in 50 mL of hot MeOH and treated with activated charcoal. The hot solution was filtered and concentrated to give 4.12 g of tert-butyl 2-[2-(2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)ethoxy]ethylcarbamate as a yellow oil. the reaction mixture was heated to reflux refluxing The reaction was then concentrated to dryness under reduced pressure The residue was dissolved in 50 mL of CH2Cl2 washed with saturated NaHCO3, H2O and brine The organic portion was dried over Na2SO4 to give a green oil The hot solution was filtered concentrated

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of aminomalononitrile p-toluenesulfonate (2.0 g, 7.9 mmol, 1.0 equiv) in THF (30 mL) at 25° C. was added NEt3 (1.3 mL, 9.5 mmol, 1.2 equiv) in one portion. The mixture was stirred for 30 min to afford a homogeneous solution. To this solution was added triethyl orthovalerate S3 (2.2 mL, 9.5 mmol, 1.2 equiv) and the solution was heated at reflux for 3 h. TLC indicated the presence of starting material, thus additional triethyl orthovalerate (1.1 mL, 4.7 mmol, 0.6 equiv) was added. The solution was heated at reflux for another 2 h then cooled to 25° C. Next, NEt3 (1.3 mL, 9.5 mmol, 1.2 equiv) and 1-amino-2-methylpropan-2-ol S2 (844 mg, 9.5 mmol, 1.2 equiv) were added sequentially and the reaction was stirred at 25° C. for 15 h. The reaction was concentrated in vacuo and the resulting solid residue was redissolved in CH2Cl2 (100 mL) and washed with saturated aqueous Na2CO3 solution (25 mL). The aqueous layer was extracted with CH2Cl2 (3×20 mL). The combined organic fractions were washed with saturated aqueous NaCl, dried (MgSO4) and concentrated in vacuo. Purification by flash column chromatography on silica gel (CH2Cl2-9/1 MeOH/CH2Cl2, gradient) afforded the title compound (1.55 g, 83%) as an off white solid: 1H NMR (CD3OD, 600 Hz) δ 0.94 (t, J=6.0 Hz, 3H), 1.23 (s, 6H), 1.37 (hex, J=7.8 Hz, 2H), 1.66 (pent, J=6.0 Hz, 2H), 2.60 (t, J=6.0 Hz, 2H), 3.79 (s, 2H); 13C NMR (CD3OD, 150 Hz) δ 12.7, 21.9, 26.0, 26.4, 29.1, 52.9, 71.2, 89.5, 116.2, 145.2, 149.2; MS (ESI+): calcd C12H21N4O [M+H]+ 237.3. found 237.4. to afford a homogeneous solution (2.2 mL, 9.5 mmol, 1.2 equiv) and the solution was heated at reflux for 3 h was added The solution was heated at reflux for another 2 h (844 mg, 9.5 mmol, 1.2 equiv) were added sequentially the reaction was stirred at 25° C. for 15 h The reaction was concentrated in vacuo the resulting solid residue was redissolved in CH2Cl2 (100 mL) washed with saturated aqueous Na2CO3 solution (25 mL) The aqueous layer was extracted with CH2Cl2 (3×20 mL) The combined organic fractions were washed with saturated aqueous NaCl dried (MgSO4) concentrated in vacuo Purification by flash column chromatography on silica gel (CH2Cl2-9/1 MeOH/CH2Cl2, gradient)

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of aminomalononitrile p-toluenesulfonate (2.0 g, 7.9 mmol, 1.0 equiv) in THF (30 mL) at 25° C. was added NEt3 (1.3 mL, 9.5 mmol, 1.2 equiv) in one portion. The mixture was stirred for 30 min to afford a homogeneous solution. To this solution was added triethyl orthovalerate S3 (2.2 mL, 9.5 mmol, 1.2 equiv) and the solution was heated at reflux for 3 h. TLC indicated the presence of starting material, thus additional triethyl orthovalerate (1.1 mL, 4.7 mmol, 0.6 equiv) was added. The solution was heated at reflux for another 2 h then cooled to 25° C. Next, NEt3 (1.3 mL, 9.5 mmol, 1.2 equiv) and 1-amino-2-methylpropan-2-ol S2 (844 mg, 9.5 mmol, 1.2 equiv) were added sequentially and the reaction was stirred at 25° C. for 15 h. The reaction was concentrated in vacuo and the resulting solid residue was redissolved in CH2Cl2 (100 mL) and washed with saturated aqueous Na2CO3 solution (25 mL). The aqueous layer was extracted with CH2Cl2 (3×20 mL). The combined organic fractions were washed with saturated aqueous NaCl, dried (MgSO4) and concentrated in vacuo. Purification by flash column chromatography on silica gel (CH2Cl2-9/1 MeOH/CH2Cl2, gradient) afforded the title compound (1.55 g, 83%) as an off white solid: 1H NMR (CD3OD, 600 Hz) δ 0.94 (t, J=6.0 Hz, 3H), 1.23 (s, 6H), 1.37 (hex, J=7.8 Hz, 2H), 1.66 (pent, J=6.0 Hz, 2H), 2.60 (t, J=6.0 Hz, 2H), 3.79 (s, 2H); 13C NMR (CD3OD, 150 Hz) δ 12.7, 21.9, 26.0, 26.4, 29.1, 52.9, 71.2, 89.5, 116.2, 145.2, 149.2; MS (ESI+): calcd C12H21N4O [M+H]+ 237.3. found 237.4. to afford a homogeneous solution (2.2 mL, 9.5 mmol, 1.2 equiv) and the solution was heated at reflux for 3 h was added The solution was heated at reflux for another 2 h (844 mg, 9.5 mmol, 1.2 equiv) were added sequentially the reaction was stirred at 25° C. for 15 h The reaction was concentrated in vacuo the resulting solid residue was redissolved in CH2Cl2 (100 mL) washed with saturated aqueous Na2CO3 solution (25 mL) The aqueous layer was extracted with CH2Cl2 (3×20 mL) The combined organic fractions were washed with saturated aqueous NaCl dried (MgSO4) concentrated in vacuo Purification by flash column chromatography on silica gel (CH2Cl2-9/1 MeOH/CH2Cl2, gradient)

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

Procedure: A solution of tert-butyl 2-{2-[(3-aminoquinolin-4-yl)amino]ethoxy}ethylcarbamate (3.46 g, 10.0 mmol) in 50 mL of toluene was treated with triethylorthovalerate (2.5 mL, 14.5 mmol) and the reaction mixture was heated to reflux. A 25 mg portion of pyridinium hydrochloride was then added and refluxing was continued for 4 h. The reaction was then concentrated to dryness under reduced pressure. The residue was dissolved in 50 mL of CH2Cl2 and washed with saturated NaHCO3, H2O and brine. The organic portion was dried over Na2SO4 and concetrated to give a green oil. The green oil was dissolved in 50 mL of hot MeOH and treated with activated charcoal. The hot solution was filtered and concentrated to give 4.12 g of tert-butyl 2-[2-(2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)ethoxy]ethylcarbamate as a yellow oil. the reaction mixture was heated to reflux refluxing The reaction was then concentrated to dryness under reduced pressure The residue was dissolved in 50 mL of CH2Cl2 washed with saturated NaHCO3, H2O and brine The organic portion was dried over Na2SO4 to give a green oil The hot solution was filtered concentrated

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

Procedure: A solution of tert-butyl 2-{2-[(3-aminoquinolin-4-yl)amino]ethoxy}ethylcarbamate (3.46 g, 10.0 mmol) in 50 mL of toluene was treated with triethylorthovalerate (2.5 mL, 14.5 mmol) and the reaction mixture was heated to reflux. A 25 mg portion of pyridinium hydrochloride was then added and refluxing was continued for 4 h. The reaction was then concentrated to dryness under reduced pressure. The residue was dissolved in 50 mL of CH2Cl2 and washed with saturated NaHCO3, H2O and brine. The organic portion was dried over Na2SO4 and concetrated to give a green oil. The green oil was dissolved in 50 mL of hot MeOH and treated with activated charcoal. The hot solution was filtered and concentrated to give 4.12 g of tert-butyl 2-[2-(2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)ethoxy]ethylcarbamate as a yellow oil. the reaction mixture was heated to reflux refluxing The reaction was then concentrated to dryness under reduced pressure The residue was dissolved in 50 mL of CH2Cl2 washed with saturated NaHCO3, H2O and brine The organic portion was dried over Na2SO4 to give a green oil The hot solution was filtered concentrated

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

Procedure: A solution of tert-butyl 2-{2-[(3-aminoquinolin-4-yl)amino]ethoxy}ethylcarbamate (3.46 g, 10.0 mmol) in 50 mL of toluene was treated with triethylorthovalerate (2.5 mL, 14.5 mmol) and the reaction mixture was heated to reflux. A 25 mg portion of pyridinium hydrochloride was then added and refluxing was continued for 4 h. The reaction was then concentrated to dryness under reduced pressure. The residue was dissolved in 50 mL of CH2Cl2 and washed with saturated NaHCO3, H2O and brine. The organic portion was dried over Na2SO4 and concetrated to give a green oil. The green oil was dissolved in 50 mL of hot MeOH and treated with activated charcoal. The hot solution was filtered and concentrated to give 4.12 g of tert-butyl 2-[2-(2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)ethoxy]ethylcarbamate as a yellow oil. the reaction mixture was heated to reflux refluxing The reaction was then concentrated to dryness under reduced pressure The residue was dissolved in 50 mL of CH2Cl2 washed with saturated NaHCO3, H2O and brine The organic portion was dried over Na2SO4 to give a green oil The hot solution was filtered concentrated

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

Procedure: A solution of tert-butyl 2-{2-[(3-aminoquinolin-4-yl)amino]ethoxy}ethylcarbamate (3.46 g, 10.0 mmol) in 50 mL of toluene was treated with triethylorthovalerate (2.5 mL, 14.5 mmol) and the reaction mixture was heated to reflux. A 25 mg portion of pyridinium hydrochloride was then added and refluxing was continued for 4 h. The reaction was then concentrated to dryness under reduced pressure. The residue was dissolved in 50 mL of CH2Cl2 and washed with saturated NaHCO3, H2O and brine. The organic portion was dried over Na2SO4 and concetrated to give a green oil. The green oil was dissolved in 50 mL of hot MeOH and treated with activated charcoal. The hot solution was filtered and concentrated to give 4.12 g of tert-butyl 2-[2-(2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)ethoxy]ethylcarbamate as a yellow oil. the reaction mixture was heated to reflux refluxing The reaction was then concentrated to dryness under reduced pressure The residue was dissolved in 50 mL of CH2Cl2 washed with saturated NaHCO3, H2O and brine The organic portion was dried over Na2SO4 to give a green oil The hot solution was filtered concentrated

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

Procedure: A solution of tert-butyl 2-{2-[(3-aminoquinolin-4-yl)amino]ethoxy}ethylcarbamate (3.46 g, 10.0 mmol) in 50 mL of toluene was treated with triethylorthovalerate (2.5 mL, 14.5 mmol) and the reaction mixture was heated to reflux. A 25 mg portion of pyridinium hydrochloride was then added and refluxing was continued for 4 h. The reaction was then concentrated to dryness under reduced pressure. The residue was dissolved in 50 mL of CH2Cl2 and washed with saturated NaHCO3, H2O and brine. The organic portion was dried over Na2SO4 and concetrated to give a green oil. The green oil was dissolved in 50 mL of hot MeOH and treated with activated charcoal. The hot solution was filtered and concentrated to give 4.12 g of tert-butyl 2-[2-(2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)ethoxy]ethylcarbamate as a yellow oil. the reaction mixture was heated to reflux refluxing The reaction was then concentrated to dryness under reduced pressure The residue was dissolved in 50 mL of CH2Cl2 washed with saturated NaHCO3, H2O and brine The organic portion was dried over Na2SO4 to give a green oil The hot solution was filtered concentrated

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

Procedure: A solution of tert-butyl 2-{2-[(3-aminoquinolin-4-yl)amino]ethoxy}ethylcarbamate (3.46 g, 10.0 mmol) in 50 mL of toluene was treated with triethylorthovalerate (2.5 mL, 14.5 mmol) and the reaction mixture was heated to reflux. A 25 mg portion of pyridinium hydrochloride was then added and refluxing was continued for 4 h. The reaction was then concentrated to dryness under reduced pressure. The residue was dissolved in 50 mL of CH2Cl2 and washed with saturated NaHCO3, H2O and brine. The organic portion was dried over Na2SO4 and concetrated to give a green oil. The green oil was dissolved in 50 mL of hot MeOH and treated with activated charcoal. The hot solution was filtered and concentrated to give 4.12 g of tert-butyl 2-[2-(2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)ethoxy]ethylcarbamate as a yellow oil. the reaction mixture was heated to reflux refluxing The reaction was then concentrated to dryness under reduced pressure The residue was dissolved in 50 mL of CH2Cl2 washed with saturated NaHCO3, H2O and brine The organic portion was dried over Na2SO4 to give a green oil The hot solution was filtered concentrated

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

Procedure: A solution of tert-butyl 2-{2-[(3-aminoquinolin-4-yl)amino]ethoxy}ethylcarbamate (3.46 g, 10.0 mmol) in 50 mL of toluene was treated with triethylorthovalerate (2.5 mL, 14.5 mmol) and the reaction mixture was heated to reflux. A 25 mg portion of pyridinium hydrochloride was then added and refluxing was continued for 4 h. The reaction was then concentrated to dryness under reduced pressure. The residue was dissolved in 50 mL of CH2Cl2 and washed with saturated NaHCO3, H2O and brine. The organic portion was dried over Na2SO4 and concetrated to give a green oil. The green oil was dissolved in 50 mL of hot MeOH and treated with activated charcoal. The hot solution was filtered and concentrated to give 4.12 g of tert-butyl 2-[2-(2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)ethoxy]ethylcarbamate as a yellow oil. the reaction mixture was heated to reflux refluxing The reaction was then concentrated to dryness under reduced pressure The residue was dissolved in 50 mL of CH2Cl2 washed with saturated NaHCO3, H2O and brine The organic portion was dried over Na2SO4 to give a green oil The hot solution was filtered concentrated

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

Procedure: A solution of tert-butyl 2-{2-[(3-aminoquinolin-4-yl)amino]ethoxy}ethylcarbamate (3.46 g, 10.0 mmol) in 50 mL of toluene was treated with triethylorthovalerate (2.5 mL, 14.5 mmol) and the reaction mixture was heated to reflux. A 25 mg portion of pyridinium hydrochloride was then added and refluxing was continued for 4 h. The reaction was then concentrated to dryness under reduced pressure. The residue was dissolved in 50 mL of CH2Cl2 and washed with saturated NaHCO3, H2O and brine. The organic portion was dried over Na2SO4 and concetrated to give a green oil. The green oil was dissolved in 50 mL of hot MeOH and treated with activated charcoal. The hot solution was filtered and concentrated to give 4.12 g of tert-butyl 2-[2-(2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)ethoxy]ethylcarbamate as a yellow oil. the reaction mixture was heated to reflux refluxing The reaction was then concentrated to dryness under reduced pressure The residue was dissolved in 50 mL of CH2Cl2 washed with saturated NaHCO3, H2O and brine The organic portion was dried over Na2SO4 to give a green oil The hot solution was filtered concentrated