4-丙烯酰吗啉

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A thick walled glass vessel, equipped with a stir bar, was charged with a warmed solution of 7-bromo-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine (584 mg, 1.5 mmol) in N,N-dimethylformamide (10 mL). To the solution was added in succession, a solution of palladium acetate (37 mg, 0.15 mmol) and tri-ortho-tolylphosphine (91 mg, 0.3 mmol) in N,N-dimethylformamide (5 mL), triethylamine (0.6 mL), and a solution of 4-acryloylmorpholine (254 mg 1.8 mmol) in N,N-dimethylformamide (2 mL). The reaction mixture was purged with nitrogen. The vessel was sealed and heated at 120° C. for 18 hours. The reaction was cooled to ambient temperature and then concentrated to dryness under reduced pressure. The resulting solid was dissolved in dichloromethane (100 mL) and washed with saturated aqueous potassium carbonate (50 mL). The fractions were separated and the organic fraction was concentrated to dryness under reduced pressure. The resulting solid was purified by chromatography using a HORIZON HPFC system (silica cartridge, 0-15% CMA/chloroform). A final recrystallization from acetonitrile provided 345 mg of 2-ethyl-7-[(1E)-3-morpholin-4-yl-3-oxoprop-1-enyl]-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine as a white crystalline solid, mp>260° C. A thick walled glass vessel, equipped with a stir bar To the solution was added in succession The reaction mixture was purged with nitrogen The vessel was sealed The reaction was cooled to ambient temperature concentrated to dryness under reduced pressure The resulting solid was dissolved in dichloromethane (100 mL) washed with saturated aqueous potassium carbonate (50 mL) The fractions were separated the organic fraction was concentrated to dryness under reduced pressure The resulting solid was purified by chromatography A final recrystallization from acetonitrile

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A thick walled glass vessel, equipped with a stir bar, was charged with a warmed solution of 7-bromo-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine (584 mg, 1.5 mmol) in N,N-dimethylformamide (10 mL). To the solution was added in succession, a solution of palladium acetate (37 mg, 0.15 mmol) and tri-ortho-tolylphosphine (91 mg, 0.3 mmol) in N,N-dimethylformamide (5 mL), triethylamine (0.6 mL), and a solution of 4-acryloylmorpholine (254 mg 1.8 mmol) in N,N-dimethylformamide (2 mL). The reaction mixture was purged with nitrogen. The vessel was sealed and heated at 120° C. for 18 hours. The reaction was cooled to ambient temperature and then concentrated to dryness under reduced pressure. The resulting solid was dissolved in dichloromethane (100 mL) and washed with saturated aqueous potassium carbonate (50 mL). The fractions were separated and the organic fraction was concentrated to dryness under reduced pressure. The resulting solid was purified by chromatography using a HORIZON HPFC system (silica cartridge, 0-15% CMA/chloroform). A final recrystallization from acetonitrile provided 345 mg of 2-ethyl-7-[(1E)-3-morpholin-4-yl-3-oxoprop-1-enyl]-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine as a white crystalline solid, mp>260° C. A thick walled glass vessel, equipped with a stir bar To the solution was added in succession The reaction mixture was purged with nitrogen The vessel was sealed The reaction was cooled to ambient temperature concentrated to dryness under reduced pressure The resulting solid was dissolved in dichloromethane (100 mL) washed with saturated aqueous potassium carbonate (50 mL) The fractions were separated the organic fraction was concentrated to dryness under reduced pressure The resulting solid was purified by chromatography A final recrystallization from acetonitrile

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of tert-butyl 5-(benzyloxy)-3-bromo-1H-indole-1-carboxylate (2.011 g), 1-morpholinoprop-2-en-1-one (0.776 g), palladium acetate (31 mg), tri-o-tolylphosphine (187 mg) and triethylamine (1.14 mL) in N,N-dimethylformamide (14 mL) under nitrogen atmosphere was stirred at 100° C. overnight. The mixture was diluted with ethyl acetate and saturated ammonium chloride. The aqueous layer was extracted with ethyl acetate and the combined organic layers were dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography (80% ethyl acetate-hexane) to give the desired product. The aqueous layer was extracted with ethyl acetate the combined organic layers were dried over MgSO4 filtered concentrated The residue was purified by flash chromatography (80% ethyl acetate-hexane)

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A scintillation vial was charged with palladium acetate (22 mg, 0.10 mmol), tri-o-tolylphosphine (61 mg, 0.20 mmol), anhydrous DMF (1.0 mL) and triethylamine (0.4 mL, 3.0 mmol). The orange homogeneous solution was then added to a solution of (11S)-3-bromo-11-methyl-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinolin-6-amine (333 mg, 1.00 mmol) dissolved in 10 mL of anhydrous DMF followed by the addition of a solution of 4-acryloylmorpholine (169 mg, 1.20 mmol) dissolved in 1.0 mL of anhydrous DMF. The mixture was transferred to a glass vessel and the vessel was purged with N2, sealed and heated to 120° C. for 18 hours. The reaction mixture was cooled and concentrated to dryness under reduced pressure to give a golden solid. The solid was treated with CH2Cl2 and saturated aqueous K2CO3 solution and the layers were separated. The organic layer was concentrated to dryness to give a light-brown solid. Chromatography (SiO2, 0-15% CMA/CHCl3) gave a tan solid that was crystallized from acetonitrile to give 250 mg of the title compound as beige crystals, mp>250° C. The mixture was transferred to a glass vessel the vessel was purged with N2 sealed The reaction mixture was cooled concentrated to dryness under reduced pressure to give a golden solid the layers were separated The organic layer was concentrated to dryness to give a light-brown solid that was crystallized from acetonitrile

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A scintillation vial was charged with palladium acetate (22 mg, 0.10 mmol), tri-o-tolylphosphine (61 mg, 0.20 mmol), anhydrous DMF (1.0 mL) and triethylamine (0.4 mL, 3.0 mmol). The orange homogeneous solution was then added to a solution of (11S)-3-bromo-11-methyl-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinolin-6-amine (333 mg, 1.00 mmol) dissolved in 10 mL of anhydrous DMF followed by the addition of a solution of 4-acryloylmorpholine (169 mg, 1.20 mmol) dissolved in 1.0 mL of anhydrous DMF. The mixture was transferred to a glass vessel and the vessel was purged with N2, sealed and heated to 120° C. for 18 hours. The reaction mixture was cooled and concentrated to dryness under reduced pressure to give a golden solid. The solid was treated with CH2Cl2 and saturated aqueous K2CO3 solution and the layers were separated. The organic layer was concentrated to dryness to give a light-brown solid. Chromatography (SiO2, 0-15% CMA/CHCl3) gave a tan solid that was crystallized from acetonitrile to give 250 mg of the title compound as beige crystals, mp>250° C. The mixture was transferred to a glass vessel the vessel was purged with N2 sealed The reaction mixture was cooled concentrated to dryness under reduced pressure to give a golden solid the layers were separated The organic layer was concentrated to dryness to give a light-brown solid that was crystallized from acetonitrile

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Following the procedure of Example 4, 2,6-bis-(1,1-dimethylethyl)4-mercaptophenol (2.389, 0.01 mole) and (1-oxo-2-propenyl)morpholine (1.41 g, 0.01 mole) in methanol (75 ml) were combined with triethylamine (1.5 ml) and stirred for 12 hours at room temperature. The solvent was evaporated under a nitrogen stream leaving an orange oil which was chromatographed over silica. The product was recrystallized from a mixture of hexane, ethyl ether and methanol and the resulting white solid dried to yield the title compound, m.p. about 136.5°-137.5° C. The solvent was evaporated under a nitrogen stream leaving an orange oil which was chromatographed over silica The product was recrystallized from a mixture of hexane, ethyl ether and methanol the resulting white solid dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of morpholine (8.7 g, 0.1 mole) and triethylamine (15.3 ml, 0.1 mole) in ethyl ether (100 ml) was cooled to +5° C. A solution of acryloyl chloride (9.0 g, 0.10 mole) in 25 ml of ethyl ether was added dropwise over a 30 minute period, resulting in the formation of a white solid. An additional 100 ml of ethyl ether was added and the reaction stirred for 72 hours at room temperature. The white solid was filtered and washed well with ethyl ether. The ethyl ether wash and filtrate were combined and solvent removed, leaving an orange oil which was transferred to a 50 ml Erlenmeyer flask and dried overnight under nitrogen to yield 11.5 g of product. The structure was confirmed by NMR. resulting in the formation of a white solid The white solid was filtered washed well with ethyl ether The ethyl ether wash solvent removed leaving an orange oil which dried overnight under nitrogen

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of morpholine (8.7 g, 0.1 mole) and triethylamine (15.3 ml, 0.1 mole) in ethyl ether (100 ml) was cooled to +5° C. A solution of acryloyl chloride (9.0 g, 0.10 mole) in 25 ml of ethyl ether was added dropwise over a 30 minute period, resulting in the formation of a white solid. An additional 100 ml of ethyl ether was added and the reaction stirred for 72 hours at room temperature. The white solid was filtered and washed well with ethyl ether. The ethyl ether wash and filtrate were combined and solvent removed, leaving an orange oil which was transferred to a 50 ml Erlenmeyer flask and dried overnight under nitrogen to yield 11.5 g of product. The structure was confirmed by NMR. resulting in the formation of a white solid The white solid was filtered washed well with ethyl ether The ethyl ether wash solvent removed leaving an orange oil which dried overnight under nitrogen

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a 300 mL three-necked flask, N-acryloylmorpholine (14.20 g, 0.101 mol), N,N-dimethylacrylamide (DMA, 9.92 g, 0.100 mol), t-amyl alcohol (96.63 g), a polymerization initiator VA-061 (Wako Pure Chemical Industries, Ltd., 0.0310 g, 0.124 mmol), 2-mercaptoethanol (86 μL, 1.23 mmol) were charged, and then equipped with a three-way stop-cock, a reflux condenser tube, a thermometer and a mechanical stirrer. The concentration of the monomer was 20% by weight. After degassing inside the three-necked flask using a vacuum pump and repeating replacement by argon three times, stirring was carried out at 70° C. for 1 hour, followed by temperature rise to 75° C. and further stirring for 4 hours. After completion of the polymerization, the polymerization reaction solution was cooled to room temperature and the solvent was distilled off by an evaporator, and then washed once with each of n-hexane/methanol (=400 mL/30 mL, 500 mL/40 mL, 130 mL/3 mL and 200 mL/7 mL). The solid component was dried overnight by a vacuum drying oven at 60° C. Liquid nitrogen was charged and the solid component was crushed by a spatula, and then dried by a vacuum drying oven at 60° C. for 3 hours. The thus obtained copolymer had a molecular weight of Mn: 4.3 kD, Mw: 17 kD (Mw/Mn=4.1)). equipped with a three-way After degassing inside the three-necked flask followed by temperature rise to 75° C. further stirring for 4 hours After completion of the polymerization the polymerization reaction solution the solvent was distilled off by an evaporator washed once with each of n-hexane/methanol (=400 mL/30 mL, 500 mL/40 mL, 130 mL/3 mL and 200 mL/7 mL) The solid component was dried overnight by a vacuum drying oven at 60° C Liquid nitrogen was charged the solid component was crushed by a spatula dried by a vacuum drying oven at 60° C. for 3 hours

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a 300 mL three-necked flask, N-acryloylmorpholine (14.20 g, 0.101 mol), N,N-dimethylacrylamide (DMA, 9.92 g, 0.100 mol), t-amyl alcohol (96.63 g), a polymerization initiator VA-061 (Wako Pure Chemical Industries, Ltd., 0.0310 g, 0.124 mmol), 2-mercaptoethanol (86 μL, 1.23 mmol) were charged, and then equipped with a three-way stop-cock, a reflux condenser tube, a thermometer and a mechanical stirrer. The concentration of the monomer was 20% by weight. After degassing inside the three-necked flask using a vacuum pump and repeating replacement by argon three times, stirring was carried out at 70° C. for 1 hour, followed by temperature rise to 75° C. and further stirring for 4 hours. After completion of the polymerization, the polymerization reaction solution was cooled to room temperature and the solvent was distilled off by an evaporator, and then washed once with each of n-hexane/methanol (=400 mL/30 mL, 500 mL/40 mL, 130 mL/3 mL and 200 mL/7 mL). The solid component was dried overnight by a vacuum drying oven at 60° C. Liquid nitrogen was charged and the solid component was crushed by a spatula, and then dried by a vacuum drying oven at 60° C. for 3 hours. The thus obtained copolymer had a molecular weight of Mn: 4.3 kD, Mw: 17 kD (Mw/Mn=4.1)). equipped with a three-way After degassing inside the three-necked flask followed by temperature rise to 75° C. further stirring for 4 hours After completion of the polymerization the polymerization reaction solution the solvent was distilled off by an evaporator washed once with each of n-hexane/methanol (=400 mL/30 mL, 500 mL/40 mL, 130 mL/3 mL and 200 mL/7 mL) The solid component was dried overnight by a vacuum drying oven at 60° C Liquid nitrogen was charged the solid component was crushed by a spatula dried by a vacuum drying oven at 60° C. for 3 hours