3-trityloxypropanal

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 41.1 g of 3-trityloxy-propionaldehyde in 330 ml of acetone and 120 ml of water were added portionwise, within 90 minutes, 20.65 g of potassium permanganate, the temperature of the mixture being maintained at 20° to 25° C. Stirring was continued for 90 minutes, and then the pH of the mixture was set to 5 by addition of 13 ml of 3N hydrochloric acid. Within 40 minutes, there were added dropwise 200 ml of 38% sodium bisulfite solution at a temperature of 20° to 25° C. The pH was lowered to 2 by the addition of 60 ml of 3N hydrochloric acid, and subsequently the mixture was extracted with 11 of ethyl acetate. The organic layer was washed with water, dried over sodium sulfate, and the solvent was evaporated in vacuo. The residue was crystallized from ethyl acetate/hexane to yield 35.5 g of 3-trityloxy-propionic acid as white solid of m.p. 159°-161° C. Within 40 minutes subsequently the mixture was extracted with 11 of ethyl acetate The organic layer was washed with water dried over sodium sulfate the solvent was evaporated in vacuo The residue was crystallized from ethyl acetate/hexane

反応条件: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 91.4 g of oxalyl chloride in 1.12 1 of methylene chloride, pre-cooled to -70° C., a solution of 123.4 g of dimethylsulfoxide in 0.18 l of methylene chloride was added within 25 minutes. The solution was stirred for 10 minutes at -70° C. Then, a solution of 143.3 g of 3-trityloxy-1-propanol in 0.6 l of methylene chloride was added within 25 minutes, the temperature being maintained at -65° to -70° C. Stirring was continued for another 10 minutes, and then, 182 g of triethylamine were added within 5 minutes at -65° to -70° C. The mixture was stirred for 20 minutes at -70° C. and then allowed to warm up to 10° C. within 1 hour. After the addition of 1.2 1 of water, stirring was continued for 5 minutes. The layers were separated, and the aqueous phase was extracted with 1.2 l of methylene chloride. The organic phases were washed with 1.2 l of water, dried over sodium sulfate, and the solvent was evaporated in vacuo. The residue was crystallized from ethyl acetate/hexane to yield 116.0 g of 3-trityloxypropionaldehyde as white crystals of m.p. 97°-98° C. the temperature being maintained at -65° to -70° C Stirring was continued for another 10 minutes The mixture was stirred for 20 minutes at -70° C. to warm up to 10° C. within 1 hour stirring was continued for 5 minutes The layers were separated the aqueous phase was extracted with 1.2 l of methylene chloride The organic phases were washed with 1.2 l of water dried over sodium sulfate the solvent was evaporated in vacuo The residue was crystallized from ethyl acetate/hexane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-(2-(2-Aminoethoxy)-2-methylpropyl)-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-4-amine (50 mg, 140 μmol) and 3-(triphenylmethoxy)-propanal (CAN 67057-68-5; 44.3 mg, 140 μmol) were combined with ethanol (500 μL) to give a light yellow suspension. The mixture was stirred for 2 hours at room temperature. Afterwards sodium borohydride (5.82 mg, 154 μmol) was added and stirring at room temperature continued overnight. The mixture was stirred with water (2 mL) and ethyl acetate (5 mL), dried by passage through a ChemElut® cartridge and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel-NH2, 0% to 100% ethyl acetate in heptane) followed by another flash chromatography (silica gel, 0 to 10% methanol in ethyl acetate) to give the title compound (10 mg, 11%) as yellowish gum; LC-MS (UV peak area, ESI) 89%, 658.5 (MH+). to give a light yellow suspension stirring at room temperature continued overnight dried by passage through a ChemElut® cartridge concentrated in vacuo The crude material was purified by flash chromatography (silica gel-NH2, 0% to 100% ethyl acetate in heptane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 41.1 g of 3-trityloxy-propionaldehyde in 330 ml of acetone and 120 ml of water were added portionwise, within 90 minutes, 20.65 g of potassium permanganate, the temperature of the mixture being maintained at 20° to 25° C. Stirring was continued for 90 minutes, and then the pH of the mixture was set to 5 by addition of 13 ml of 3N hydrochloric acid. Within 40 minutes, there were added dropwise 200 ml of 38% sodium bisulfite solution at a temperature of 20° to 25° C. The pH was lowered to 2 by the addition of 60 ml of 3N hydrochloric acid, and subsequently the mixture was extracted with 11 of ethyl acetate. The organic layer was washed with water, dried over sodium sulfate, and the solvent was evaporated in vacuo. The residue was crystallized from ethyl acetate/hexane to yield 35.5 g of 3-trityloxy-propionic acid as white solid of m.p. 159°-161° C. Within 40 minutes subsequently the mixture was extracted with 11 of ethyl acetate The organic layer was washed with water dried over sodium sulfate the solvent was evaporated in vacuo The residue was crystallized from ethyl acetate/hexane

反応条件: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 91.4 g of oxalyl chloride in 1.12 1 of methylene chloride, pre-cooled to -70° C., a solution of 123.4 g of dimethylsulfoxide in 0.18 l of methylene chloride was added within 25 minutes. The solution was stirred for 10 minutes at -70° C. Then, a solution of 143.3 g of 3-trityloxy-1-propanol in 0.6 l of methylene chloride was added within 25 minutes, the temperature being maintained at -65° to -70° C. Stirring was continued for another 10 minutes, and then, 182 g of triethylamine were added within 5 minutes at -65° to -70° C. The mixture was stirred for 20 minutes at -70° C. and then allowed to warm up to 10° C. within 1 hour. After the addition of 1.2 1 of water, stirring was continued for 5 minutes. The layers were separated, and the aqueous phase was extracted with 1.2 l of methylene chloride. The organic phases were washed with 1.2 l of water, dried over sodium sulfate, and the solvent was evaporated in vacuo. The residue was crystallized from ethyl acetate/hexane to yield 116.0 g of 3-trityloxypropionaldehyde as white crystals of m.p. 97°-98° C. the temperature being maintained at -65° to -70° C Stirring was continued for another 10 minutes The mixture was stirred for 20 minutes at -70° C. to warm up to 10° C. within 1 hour stirring was continued for 5 minutes The layers were separated the aqueous phase was extracted with 1.2 l of methylene chloride The organic phases were washed with 1.2 l of water dried over sodium sulfate the solvent was evaporated in vacuo The residue was crystallized from ethyl acetate/hexane

反応条件: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 91.4 g of oxalyl chloride in 1.12 1 of methylene chloride, pre-cooled to -70° C., a solution of 123.4 g of dimethylsulfoxide in 0.18 l of methylene chloride was added within 25 minutes. The solution was stirred for 10 minutes at -70° C. Then, a solution of 143.3 g of 3-trityloxy-1-propanol in 0.6 l of methylene chloride was added within 25 minutes, the temperature being maintained at -65° to -70° C. Stirring was continued for another 10 minutes, and then, 182 g of triethylamine were added within 5 minutes at -65° to -70° C. The mixture was stirred for 20 minutes at -70° C. and then allowed to warm up to 10° C. within 1 hour. After the addition of 1.2 1 of water, stirring was continued for 5 minutes. The layers were separated, and the aqueous phase was extracted with 1.2 l of methylene chloride. The organic phases were washed with 1.2 l of water, dried over sodium sulfate, and the solvent was evaporated in vacuo. The residue was crystallized from ethyl acetate/hexane to yield 116.0 g of 3-trityloxypropionaldehyde as white crystals of m.p. 97°-98° C. the temperature being maintained at -65° to -70° C Stirring was continued for another 10 minutes The mixture was stirred for 20 minutes at -70° C. to warm up to 10° C. within 1 hour stirring was continued for 5 minutes The layers were separated the aqueous phase was extracted with 1.2 l of methylene chloride The organic phases were washed with 1.2 l of water dried over sodium sulfate the solvent was evaporated in vacuo The residue was crystallized from ethyl acetate/hexane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-(2-(2-Aminoethoxy)-2-methylpropyl)-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-4-amine (50 mg, 140 μmol) and 3-(triphenylmethoxy)-propanal (CAN 67057-68-5; 44.3 mg, 140 μmol) were combined with ethanol (500 μL) to give a light yellow suspension. The mixture was stirred for 2 hours at room temperature. Afterwards sodium borohydride (5.82 mg, 154 μmol) was added and stirring at room temperature continued overnight. The mixture was stirred with water (2 mL) and ethyl acetate (5 mL), dried by passage through a ChemElut® cartridge and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel-NH2, 0% to 100% ethyl acetate in heptane) followed by another flash chromatography (silica gel, 0 to 10% methanol in ethyl acetate) to give the title compound (10 mg, 11%) as yellowish gum; LC-MS (UV peak area, ESI) 89%, 658.5 (MH+). to give a light yellow suspension stirring at room temperature continued overnight dried by passage through a ChemElut® cartridge concentrated in vacuo The crude material was purified by flash chromatography (silica gel-NH2, 0% to 100% ethyl acetate in heptane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-(2-(2-Aminoethoxy)-2-methylpropyl)-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-4-amine (50 mg, 140 μmol) and 3-(triphenylmethoxy)-propanal (CAN 67057-68-5; 44.3 mg, 140 μmol) were combined with ethanol (500 μL) to give a light yellow suspension. The mixture was stirred for 2 hours at room temperature. Afterwards sodium borohydride (5.82 mg, 154 μmol) was added and stirring at room temperature continued overnight. The mixture was stirred with water (2 mL) and ethyl acetate (5 mL), dried by passage through a ChemElut® cartridge and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel-NH2, 0% to 100% ethyl acetate in heptane) followed by another flash chromatography (silica gel, 0 to 10% methanol in ethyl acetate) to give the title compound (10 mg, 11%) as yellowish gum; LC-MS (UV peak area, ESI) 89%, 658.5 (MH+). to give a light yellow suspension stirring at room temperature continued overnight dried by passage through a ChemElut® cartridge concentrated in vacuo The crude material was purified by flash chromatography (silica gel-NH2, 0% to 100% ethyl acetate in heptane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-(2-(2-Aminoethoxy)-2-methylpropyl)-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-4-amine (50 mg, 140 μmol) and 3-(triphenylmethoxy)-propanal (CAN 67057-68-5; 44.3 mg, 140 μmol) were combined with ethanol (500 μL) to give a light yellow suspension. The mixture was stirred for 2 hours at room temperature. Afterwards sodium borohydride (5.82 mg, 154 μmol) was added and stirring at room temperature continued overnight. The mixture was stirred with water (2 mL) and ethyl acetate (5 mL), dried by passage through a ChemElut® cartridge and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel-NH2, 0% to 100% ethyl acetate in heptane) followed by another flash chromatography (silica gel, 0 to 10% methanol in ethyl acetate) to give the title compound (10 mg, 11%) as yellowish gum; LC-MS (UV peak area, ESI) 89%, 658.5 (MH+). to give a light yellow suspension stirring at room temperature continued overnight dried by passage through a ChemElut® cartridge concentrated in vacuo The crude material was purified by flash chromatography (silica gel-NH2, 0% to 100% ethyl acetate in heptane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 41.1 g of 3-trityloxy-propionaldehyde in 330 ml of acetone and 120 ml of water were added portionwise, within 90 minutes, 20.65 g of potassium permanganate, the temperature of the mixture being maintained at 20° to 25° C. Stirring was continued for 90 minutes, and then the pH of the mixture was set to 5 by addition of 13 ml of 3N hydrochloric acid. Within 40 minutes, there were added dropwise 200 ml of 38% sodium bisulfite solution at a temperature of 20° to 25° C. The pH was lowered to 2 by the addition of 60 ml of 3N hydrochloric acid, and subsequently the mixture was extracted with 11 of ethyl acetate. The organic layer was washed with water, dried over sodium sulfate, and the solvent was evaporated in vacuo. The residue was crystallized from ethyl acetate/hexane to yield 35.5 g of 3-trityloxy-propionic acid as white solid of m.p. 159°-161° C. Within 40 minutes subsequently the mixture was extracted with 11 of ethyl acetate The organic layer was washed with water dried over sodium sulfate the solvent was evaporated in vacuo The residue was crystallized from ethyl acetate/hexane

反応条件: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 91.4 g of oxalyl chloride in 1.12 1 of methylene chloride, pre-cooled to -70° C., a solution of 123.4 g of dimethylsulfoxide in 0.18 l of methylene chloride was added within 25 minutes. The solution was stirred for 10 minutes at -70° C. Then, a solution of 143.3 g of 3-trityloxy-1-propanol in 0.6 l of methylene chloride was added within 25 minutes, the temperature being maintained at -65° to -70° C. Stirring was continued for another 10 minutes, and then, 182 g of triethylamine were added within 5 minutes at -65° to -70° C. The mixture was stirred for 20 minutes at -70° C. and then allowed to warm up to 10° C. within 1 hour. After the addition of 1.2 1 of water, stirring was continued for 5 minutes. The layers were separated, and the aqueous phase was extracted with 1.2 l of methylene chloride. The organic phases were washed with 1.2 l of water, dried over sodium sulfate, and the solvent was evaporated in vacuo. The residue was crystallized from ethyl acetate/hexane to yield 116.0 g of 3-trityloxypropionaldehyde as white crystals of m.p. 97°-98° C. the temperature being maintained at -65° to -70° C Stirring was continued for another 10 minutes The mixture was stirred for 20 minutes at -70° C. to warm up to 10° C. within 1 hour stirring was continued for 5 minutes The layers were separated the aqueous phase was extracted with 1.2 l of methylene chloride The organic phases were washed with 1.2 l of water dried over sodium sulfate the solvent was evaporated in vacuo The residue was crystallized from ethyl acetate/hexane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-(2-(2-Aminoethoxy)-2-methylpropyl)-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-4-amine (50 mg, 140 μmol) and 3-(triphenylmethoxy)-propanal (CAN 67057-68-5; 44.3 mg, 140 μmol) were combined with ethanol (500 μL) to give a light yellow suspension. The mixture was stirred for 2 hours at room temperature. Afterwards sodium borohydride (5.82 mg, 154 μmol) was added and stirring at room temperature continued overnight. The mixture was stirred with water (2 mL) and ethyl acetate (5 mL), dried by passage through a ChemElut® cartridge and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel-NH2, 0% to 100% ethyl acetate in heptane) followed by another flash chromatography (silica gel, 0 to 10% methanol in ethyl acetate) to give the title compound (10 mg, 11%) as yellowish gum; LC-MS (UV peak area, ESI) 89%, 658.5 (MH+). to give a light yellow suspension stirring at room temperature continued overnight dried by passage through a ChemElut® cartridge concentrated in vacuo The crude material was purified by flash chromatography (silica gel-NH2, 0% to 100% ethyl acetate in heptane)