3-(2-甲基-1,3-二氧戊环-2-基)丙-1-胺

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: Seventy-one grams of 5-phthalimido-2-pentanone ethylene ketal (0.26 moles) were suspended into 250 ml of 95% ethanol. Then 13.0 g of NH2 ·NH2 ·H2O (0.26 moles) was added and the reaction mixture was brought to reflux. The stirred mixture was refluxed for 2 hours. Ether (400 ml) was added to the cooled suspension, which was then treated with 40 g of potassium hydroxide in 150 ml of water. The two layers were separated and the aqueous The ether was combined and dried over sodium sulfate. The solvent was then removed under pressure and the remaining liquid that contained crude product was weighed. to reflux The stirred mixture was refluxed for 2 hours The two layers were separated dried over sodium sulfate The solvent was then removed under pressure

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

实验步骤: In a flame dried round-bottomed flask equipped with a magnetic stir bar, a mixture of 2-methyl-2-(3-nitro-propyl)-[1,3]dioxolane (1.80 g, 10.27 mmol) and Pd/C 10% (176 mg) in dry MeOH (35 mL) was stirred at rt under atmospheric H2 for 11 h. The reaction mixture was then filtered and concentrated under reduced pressure to give the title compound as a colorless oil. LC-MS-conditions 02: tR=0.25 min; [M+H]+=146.41. In a flame dried round-bottomed flask equipped with a magnetic stir bar The reaction mixture was then filtered concentrated under reduced pressure

反应条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Place 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (prepared essentially as described in Preparation 1) (3 g, 7.08 mmol) in toluene (60 mL) with 3-(2-methyl-[1,3]dioxolan-2-yl)-propylamine (prepared essentially as described in Preparation 38) (3.08 g, 21.24 mmol), tris(dibenzylideneacetone)dipalladium (1.3 g, 1.42 mmol), racemic 2,2′-bis(diphenylphosphino)-1,1′-binapthyl (1.77 g, 2.84 mmol), and cesium carbonate (3.3 g, 9.91 mmol) and heat for 16 h at 95° C. in a sealed tube. Cool the reaction to RT, dilute with EtOAc (600 mL) and filter. Concentrate the filtrate and purify (silica gel chromatography, eluting with 10:90 to 25:75 EtOAc:hexanes) to give the crude product as an orange oil (1.72 g). Dissolve 7-chloro-3-(2,2,2-trifluoroacetyl)-6-[3-(2-methyl[1,3]dioxolan-2-yl)-propylamino]-2,3,4,5-tetrahydro-1H-benzo[d]azepine (1.72 g, 4.09 mmol) in DCM (20 mL) and add methanol (2 mL) and 2 N HCl in diethyl ether (20 mL) and stir at RT for 3 h. Concentrate and dissolve the residue in acetic acid (30 mL) and add sodium cyanoborohydride (1.28 g, 20.43 mmol). Stir the reaction at RT for 0.5 h then concentrate to remove the acetic acid. Dissolve the residue in DCM (200 mL) and extract with saturated aqueous sodium bicarbonate solution (400 mL), Extract the aqueous layer with DCM (100 mL) and combine the organic fractions, dry (sodium sulfate), concentrate and purify (silica gel chromatography, eluting with 10:90 EtOAc:hexanes) to give the title compound as a foam (1.2 g, 81%). prepared essentially Cool the reaction to RT filter Concentrate the filtrate purify (silica gel chromatography, eluting with 10:90 to 25:75 EtOAc:hexanes) to give the crude product as an orange oil (1.72 g) Concentrate dissolve the residue in acetic acid (30 mL) Stir the reaction at RT for 0.5 h then concentrate to remove the acetic acid Dissolve the residue in DCM (200 mL) extract with saturated aqueous sodium bicarbonate solution (400 mL) Extract the aqueous layer with DCM (100 mL) dry (sodium sulfate) concentrate purify (silica gel chromatography, eluting with 10:90 EtOAc:hexanes)

反应条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Place 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (prepared essentially as described in Preparation 1) (3 g, 7.08 mmol) in toluene (60 mL) with 3-(2-methyl-[1,3]dioxolan-2-yl)-propylamine (prepared essentially as described in Preparation 38) (3.08 g, 21.24 mmol), tris(dibenzylideneacetone)dipalladium (1.3 g, 1.42 mmol), racemic 2,2′-bis(diphenylphosphino)-1,1′-binapthyl (1.77 g, 2.84 mmol), and cesium carbonate (3.3 g, 9.91 mmol) and heat for 16 h at 95° C. in a sealed tube. Cool the reaction to RT, dilute with EtOAc (600 mL) and filter. Concentrate the filtrate and purify (silica gel chromatography, eluting with 10:90 to 25:75 EtOAc:hexanes) to give the crude product as an orange oil (1.72 g). Dissolve 7-chloro-3-(2,2,2-trifluoroacetyl)-6-[3-(2-methyl[1,3]dioxolan-2-yl)-propylamino]-2,3,4,5-tetrahydro-1H-benzo[d]azepine (1.72 g, 4.09 mmol) in DCM (20 mL) and add methanol (2 mL) and 2 N HCl in diethyl ether (20 mL) and stir at RT for 3 h. Concentrate and dissolve the residue in acetic acid (30 mL) and add sodium cyanoborohydride (1.28 g, 20.43 mmol). Stir the reaction at RT for 0.5 h then concentrate to remove the acetic acid. Dissolve the residue in DCM (200 mL) and extract with saturated aqueous sodium bicarbonate solution (400 mL), Extract the aqueous layer with DCM (100 mL) and combine the organic fractions, dry (sodium sulfate), concentrate and purify (silica gel chromatography, eluting with 10:90 EtOAc:hexanes) to give the title compound as a foam (1.2 g, 81%). prepared essentially Cool the reaction to RT filter Concentrate the filtrate purify (silica gel chromatography, eluting with 10:90 to 25:75 EtOAc:hexanes) to give the crude product as an orange oil (1.72 g) Concentrate dissolve the residue in acetic acid (30 mL) Stir the reaction at RT for 0.5 h then concentrate to remove the acetic acid Dissolve the residue in DCM (200 mL) extract with saturated aqueous sodium bicarbonate solution (400 mL) Extract the aqueous layer with DCM (100 mL) dry (sodium sulfate) concentrate purify (silica gel chromatography, eluting with 10:90 EtOAc:hexanes)

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

实验步骤: The general method described in Step 1 of Example 1 was used to react 4-chloro-3-nitroquinoline (45.0 g, 216 mmol), 3-(2-methyl-[1,3]dioxolan-2-yl)propylamine (37.0 g, 255 mmol, prepared as described in PCT Publication WO 01/51486) and triethylamine (37.0 g, 366 mmol) in dichloromethane for 15 hours to provide [3-(2-methyl-[1,3]dioxolan-2-yl)propyl]-(3-nitroquinolin-4-yl)amine (44.1 g) as a yellow solid after recrystallization from a toluene/hexane mixture.

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

实验步骤: The general method described in Step 1 of Example 1 was used to react 4-chloro-3-nitroquinoline (45.0 g, 216 mmol), 3-(2-methyl-[1,3]dioxolan-2-yl)propylamine (37.0 g, 255 mmol, prepared as described in PCT Publication WO 01/51486) and triethylamine (37.0 g, 366 mmol) in dichloromethane for 15 hours to provide [3-(2-methyl-[1,3]dioxolan-2-yl)propyl]-(3-nitroquinolin-4-yl)amine (44.1 g) as a yellow solid after recrystallization from a toluene/hexane mixture.

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

实验步骤: 5-Nitro-2,2-ethylenedioxypentane (103 g) is dissolved in methanol (2.0 l) and initially introduced into a hydrogenation flask. After the thorough flushing of the apparatus with N2, 10% Pd/C (10 g) is added. Hydrogenation is then carried out at RT under normal conditions in a stream of H2 for a total of 11 h with vigorous stirring. After the reaction is complete (TLC dichloromethane/methanol=9:1, staining reagent 1.0% strength ethanolic ninhydrin solution), the flask is flushed with N2 and the mixture is filtered off with suction through kieselguhr. The colorless filtrate is concentrated to dryness at T≦40° C. and p≧30 mbar, the title compound (85 g, quant.) first being obtained as a colorless oil, which solidifies to give a wax. TLC (dichloromethane/methanol=9:1), Rf=0.0-0.22. initially introduced into a hydrogenation flask After the thorough flushing of the apparatus with N2, 10% Pd/C (10 g) is added is then carried out at RT under normal conditions in a stream of H2 for a total of 11 h with vigorous stirring the flask is flushed with N2 the mixture is filtered off with suction through kieselguhr The colorless filtrate is concentrated to dryness at T≦40° C. and p≧30 mbar

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

实验步骤: The general method described in Step 1 of Example 1 was used to react 4-chloro-3-nitroquinoline (45.0 g, 216 mmol), 3-(2-methyl-[1,3]dioxolan-2-yl)propylamine (37.0 g, 255 mmol, prepared as described in PCT Publication WO 01/51486) and triethylamine (37.0 g, 366 mmol) in dichloromethane for 15 hours to provide [3-(2-methyl-[1,3]dioxolan-2-yl)propyl]-(3-nitroquinolin-4-yl)amine (44.1 g) as a yellow solid after recrystallization from a toluene/hexane mixture.

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

实验步骤: The general method described in Step 1 of Example 1 was used to react 4-chloro-3-nitroquinoline (45.0 g, 216 mmol), 3-(2-methyl-[1,3]dioxolan-2-yl)propylamine (37.0 g, 255 mmol, prepared as described in PCT Publication WO 01/51486) and triethylamine (37.0 g, 366 mmol) in dichloromethane for 15 hours to provide [3-(2-methyl-[1,3]dioxolan-2-yl)propyl]-(3-nitroquinolin-4-yl)amine (44.1 g) as a yellow solid after recrystallization from a toluene/hexane mixture.

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

实验步骤: 5-Nitro-2,2-ethylenedioxypentane (103 g) is dissolved in methanol (2.0 l) and initially introduced into a hydrogenation flask. After the thorough flushing of the apparatus with N2, 10% Pd/C (10 g) is added. Hydrogenation is then carried out at RT under normal conditions in a stream of H2 for a total of 11 h with vigorous stirring. After the reaction is complete (TLC dichloromethane/methanol=9:1, staining reagent 1.0% strength ethanolic ninhydrin solution), the flask is flushed with N2 and the mixture is filtered off with suction through kieselguhr. The colorless filtrate is concentrated to dryness at T≦40° C. and p≧30 mbar, the title compound (85 g, quant.) first being obtained as a colorless oil, which solidifies to give a wax. TLC (dichloromethane/methanol=9:1), Rf=0.0 -0.22. initially introduced into a hydrogenation flask After the thorough flushing of the apparatus with N2, 10% Pd/C (10 g) is added is then carried out at RT under normal conditions in a stream of H2 for a total of 11 h with vigorous stirring the flask is flushed with N2 the mixture is filtered off with suction through kieselguhr The colorless filtrate is concentrated to dryness at T≦40° C. and p≧30 mbar

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

实验步骤: The general method described in Part A of Example 28 was used to react 4-chloro-3-nitroquinoline (45.0 g, 216 mmol), 3-(2-methyl-[1,3]dioxolan-2-yl)propylamine (37.0 g, 255 mmol, prepared as described in PCT Publication WO 01/51486) and triethylamine (37.0 g, 366 mmol) in dichloromethane for 15 hours to provide [3-(2-methyl-[1,3]dioxolan-2-yl)propyl]-(3-nitroquinolin-4-yl)amine (44.1 g) as a yellow solid after recrystallization from a toluene/hexane mixture.