N'-benzyl-N,N'-dimethylethane-1,2-diamine

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A mixture of 0.900 gm N-benzyl-N,N'-dimethylethylenediamine, 1.10 gm powdered sodium carbonate and 0.75 ml of 2-phenylethylbromide is refluxed for 5 hours. An additional 0.25 ml of bromide is added during this time. The reaction mixture is then cooled and filtered. The filterate is concentrated in vacuo and the residue chromatographed on silica gel using an eluent of CH2Cl2 /CH3OH/NH4OH (97/3/0.3) to yield 0.875 gm of N-benzyl-N,N'-dimethyl-N'-(2-phenylethyl)ethylenediamine. is refluxed for 5 hours The reaction mixture is then cooled filtered The filterate is concentrated in vacuo the residue chromatographed on silica gel using an eluent of CH2Cl2 /CH3OH/NH4OH (97/3/0.3)

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 4.5 g portion of methyl 2-[methyl(phenylmethyl)amino]ethylamine was added to a stirred slurry of 5.6 g of 2,3-dichloro-1,4-naphthoquinone in 150 ml of absolute ethanol. Stirring was continued for 16 hours, then the mixture was heated at reflux for one hour and filtered while hot. The mixture was then cooled at -10° C. and filtered. This filtrate was diluted with 100 ml of ether and cooled at -10°C. The resulting precipitate was collected, washed with ether and dried in vacuo at 100°C., giving 3,5 g of the desired product as orange crystals, mp 188-190° C. (dec.). the mixture was heated at reflux for one hour filtered while hot filtered This filtrate was diluted with 100 ml of ether cooled at -10°C The resulting precipitate was collected washed with ether dried in vacuo at 100°C.

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

実験手順: To a solution of 3-(4-isopropoxyphenyl)-1-methyl-1H-pyrazole-4-carbaldehyde (82 mg, 0.32 mmol) in methanol (2 mL) was added TEA (129 mg, 1.2 mmol). ZnCl2 (5 mg, 0.05 mmol) and N-benzyl-N,N′-dimethylethane-1,2-diamine (71 mg, 0.38 mmol) were added at rt and stirred for 45 min. NaCNBH3 (87 mg, 1.2 mmol) was added and stirred for 2 h at rt. The reaction was poured into water (100 mL), extracted with EtOAc (50 mL×2). The combined extracts was washed with brine (100 mL), dried and concentrated under vacuum. The residue was purified by SGC using DCM: MeOH (0%-4%) as eluent to obtain N1-benzyl-N2-((3-(4-isopropoxyphenyl)-1-methyl-1H-pyrazol-4-yl)methyl)-N1,N2-dimethylethane-1,2-diamine (62 mg, Yield: 45%). stirred for 2 h at rt extracted with EtOAc (50 mL×2) The combined extracts was washed with brine (100 mL) dried concentrated under vacuum The residue was purified by SGC

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

実験手順: To a solution of 3-(4-isopropoxyphenyl)-1-methyl-1H-pyrazole-4-carbaldehyde (82 mg, 0.32 mmol) in methanol (2 mL) was added TEA (129 mg, 1.2 mmol). ZnCl2 (5 mg, 0.05 mmol) and N-benzyl-N,N′-dimethylethane-1,2-diamine (71 mg, 0.38 mmol) were added at rt and stirred for 45 min. NaCNBH3 (87 mg, 1.2 mmol) was added and stirred for 2 h at rt. The reaction was poured into water (100 mL), extracted with EtOAc (50 mL×2). The combined extracts was washed with brine (100 mL), dried and concentrated under vacuum. The residue was purified by SGC using DCM: MeOH (0%-4%) as eluent to obtain N1-benzyl-N2-((3-(4-isopropoxyphenyl)-1-methyl-1H-pyrazol-4-yl)methyl)-N1,N2-dimethylethane-1,2-diamine (62 mg, Yield: 45%). stirred for 2 h at rt extracted with EtOAc (50 mL×2) The combined extracts was washed with brine (100 mL) dried concentrated under vacuum The residue was purified by SGC

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

実験手順: A mixture of 0.900 gm N-benzyl-N,N'-dimethylethylenediamine, 1.10 gm powdered sodium carbonate and 0.75 ml of 2-phenylethylbromide is refluxed for 5 hours. An additional 0.25 ml of bromide is added during this time. The reaction mixture is then cooled and filtered. The filterate is concentrated in vacuo and the residue chromatographed on silica gel using an eluent of CH2Cl2 /CH3OH/NH4OH (97/3/0.3) to yield 0.875 gm of N-benzyl-N,N'-dimethyl-N'-(2-phenylethyl)ethylenediamine. is refluxed for 5 hours The reaction mixture is then cooled filtered The filterate is concentrated in vacuo the residue chromatographed on silica gel using an eluent of CH2Cl2 /CH3OH/NH4OH (97/3/0.3)

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: According to the procedure of Example 1, Step E above, 48 mg (0.094 sole) of 1-(N,N-diphenylcarbamoyl)-4-(N,N-di-n-pentylcarbamoyl)piperazine-2carboxylic acid, 14 mg (0.104 mmole) of HOBt, 25 mg (0.132 mmole) of EDAC, and 34 mg (0.19 mmole) of N-benzyl-N-methyl-N'-methylethylenediamine after purification by flash chromatography on 16 g of silica gel eluting with 400 mL of 100:4 CH2Cl2 :MeOH provided 49 mg (78%) of an oil. after purification by flash chromatography on 16 g of silica gel eluting with 400 mL of 100:4 CH2Cl2

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

実験手順: According to the procedure of Example 1, Step E above, 48 mg (0.094 sole) of 1-(N,N-diphenylcarbamoyl)-4-(N,N-di-n-pentylcarbamoyl)piperazine-2carboxylic acid, 14 mg (0.104 mmole) of HOBt, 25 mg (0.132 mmole) of EDAC, and 34 mg (0.19 mmole) of N-benzyl-N-methyl-N'-methylethylenediamine after purification by flash chromatography on 16 g of silica gel eluting with 400 mL of 100:4 CH2Cl2 :MeOH provided 49 mg (78%) of an oil. after purification by flash chromatography on 16 g of silica gel eluting with 400 mL of 100:4 CH2Cl2

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

実験手順: According to the procedure of Example 1, Step E above, 48 mg (0.094 sole) of 1-(N,N-diphenylcarbamoyl)-4-(N,N-di-n-pentylcarbamoyl)piperazine-2carboxylic acid, 14 mg (0.104 mmole) of HOBt, 25 mg (0.132 mmole) of EDAC, and 34 mg (0.19 mmole) of N-benzyl-N-methyl-N'-methylethylenediamine after purification by flash chromatography on 16 g of silica gel eluting with 400 mL of 100:4 CH2Cl2 :MeOH provided 49 mg (78%) of an oil. after purification by flash chromatography on 16 g of silica gel eluting with 400 mL of 100:4 CH2Cl2

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

実験手順: A mixture of 2.61 g of 2,3-epoxy-2,3-dihydro-1,4-naphthoquinone, 2.67 g of N-benzyl-N,N'-dimethylethylenediamine and 150 ml of absolute ethanol was stirred for 20 hours, then concentrated to one-half its original volume and refrigerated overnight. The solvent was removed, the residue dissolved in dichloromethane and passed through a pad of hydrous magnesium silicate and silica, eluting first with dichloromethane, then with 1% methanol in dichloromethane. The active fraction was flash chromatographed eluting with dichloromethane followed by 2% methanol in dichloromethane. The active fraction was evaporated and the residue triturated in dichloromethane/hexane giving 900 mg of the desired product, mp 121°-123° C. concentrated to one-half its original volume and refrigerated overnight The solvent was removed the residue dissolved in dichloromethane eluting first with dichloromethane chromatographed eluting with dichloromethane The active fraction was evaporated the residue triturated in dichloromethane/hexane giving 900 mg of the desired product, mp 121°-123° C.