2-氨基乙醛

反应条件: temp:24.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 3-[(4-Amino-5-chloro-2-methoxyphenyl)methyl]-5-[4-(trifluoromethyl) phenyl]-1,3,4-oxadiazol-2(3H)-one (1.14 g, 2.9 mmol) and triethylamine (1.0 ml, 6.8 mmol) were taken up in anhydrous THF (20 ml) and transferred dropwise by cannula into a 20% solution of phosgene in toluene at 0° C. under N2. The reaction was stirred 2.5 h at 24° C., diluted with diethylether (1 vol), and filtered through a celite plug. Concentrated by rotary evaporation to gave a solid which was dissolved in dichloromethane (50 ml) under N2 and aminoacetaldehyde (0.42 ml, 2.9 mmol) was added. The solution was stirred 3 h and concentrated to remove solvent. The residue was taken up in 25 ml of formic acid (88%) and stirred 18 h at 24° C. The formic acid was removed by rotary evaporation the residue taken up in ethyl acetate, washed with saturated NaHCO3 solution and brine, and dried. Concentration on SiO2, and elution with 45% THF/benzene gave 850 mg (65%). mp 201°-202° C.; IR(KBr, ν=cm-1) 3414, 1792, 1694, 1330, 1236, 1136; 1H NMR (300 MHz, CDCl3) δ3.86 (3H, s), 4.97 (2H, s), 6.38 (2H, br, s), 6.99 (1H, s), 7.40 (1H, s), 7.71 (2H, d, J=8.4 Hz), 7.94 (2H, d, J=8.2 Hz), 10.28 (1H, br, s); MS(ESI)m/z: 465 (M--H-) filtered through a celite plug Concentrated by rotary evaporation to gave a solid which The solution was stirred 3 h concentrated to remove solvent stirred 18 h at 24° C The formic acid was removed by rotary evaporation the residue washed with saturated NaHCO3 solution and brine dried Concentration on SiO2, and elution with 45% THF/benzene gave 850 mg (65%)

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

实验步骤: In the manner given in Preparation 21, α-phenyl-o-toluidine is reacted first with trimethyl orthoformate, the resulting product is reacted with aminoacetaldehyde, dimethyl acetal, and the resulting product of this reaction is heated with titanium tetrachloride in monoglyme to give 1-(α-phenyl-o-tolyl)imidazole.

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

实验步骤: In the manner given in Preparation 21, α-phenyl-o-toluidine is reacted first with trimethyl orthoformate, the resulting product is reacted with aminoacetaldehyde, dimethyl acetal, and the resulting product of this reaction is heated with titanium tetrachloride in monoglyme to give 1-(α-phenyl-o-tolyl)imidazole.

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

实验步骤: In the manner given in Example 1, α-(0-chlorophenyl)-0-toluidine is reacted first with trimethyl orthoformate; the resulting product is reacted with aminoacetaldehyde, dimethyl acetal, and the resulting product of this reaction is heated with titanium tetrachloride in monoglyme to give 1-[α-(0-chlorophenyl)-0-tolyl]imidazole.

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

实验步骤: In the manner given in Example 1, α-(0-chlorophenyl)-0-toluidine is reacted first with trimethyl orthoformate; the resulting product is reacted with aminoacetaldehyde, dimethyl acetal, and the resulting product of this reaction is heated with titanium tetrachloride in monoglyme to give 1-[α-(0-chlorophenyl)-0-tolyl]imidazole.

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

实验步骤: In the manner given in Example 1, α-phenyl-0-toluidine is reacted first with trimethyl orthoformate; the resulting product is reacted with aminoacetaldehyde, dimethyl acetal, and the resulting product of this reaction is heated with titanium tetrachloride in monoglyme to give 1-(α-phenyl-0-tolyl)imidazole.

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

实验步骤: In the manner given in Example 1, α-phenyl-0-toluidine is reacted first with trimethyl orthoformate; the resulting product is reacted with aminoacetaldehyde, dimethyl acetal, and the resulting product of this reaction is heated with titanium tetrachloride in monoglyme to give 1-(α-phenyl-0-tolyl)imidazole.

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

实验步骤: 1-Chloro-3-cyclohexylpropane (11.1 g, 69.0 mmol), 2-aminoacetaldehyde (15.0 mL, 138.0 mmol, 2.0 equiv), and sodium iodide (2.1 g, 14.0 mmol, 0.2 equiv) were combined in anhydrous N,N-dimethylformamide (20 mL). The solution was stirred over solid potassium carbonate (9.66 g, 70 mmol) at 80° C. for 16 hours. The mixture was cooled to room temperature and diluted with water. The solution was extracted with ethyl acetate (2×). The combined organic phase was washed with brine (3×), dried (MgSO4), and concentrated in vacuo to a crude oil. Silica gel chromatography (gradient elution from 50:50 hexane/ethyl acetate to 100% ethyl acetate) yielded the title compound as a yellow oil (12.0 g, 76%). 1H NMR (CDCl3, 300 MHz) δ 4.46 (t, 5.5 Hz, 1H), 3.38 (s, 6H), 2.71 (d, 5.5 Hz, 2H), 2.57 (t, 7.4 Hz, 2H), 1.75-1.60 (m, 3H), 1.47 (m, 2H), 1.17 (m, 8H), 0.86 (m, 2H); Rf=0.27 (50:50 hexane/ethyl acetate). The solution was extracted with ethyl acetate (2×) The combined organic phase was washed with brine (3×) dried (MgSO4) concentrated in vacuo to a crude oil Silica gel chromatography (gradient elution from 50:50 hexane/ethyl acetate to 100% ethyl acetate)

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

实验步骤: 1-Chloro-3-cyclohexylpropane (11.1 g, 69.0 mmol), 2-aminoacetaldehyde (15.0 mL, 138.0 mmol, 2.0 equiv), and sodium iodide (2.1 g, 14.0 mmol, 0.2 equiv) were combined in anhydrous N,N-dimethylformamide (20 mL). The solution was stirred over solid potassium carbonate (9.66 g, 70 mmol) at 80° C. for 16 hours. The mixture was cooled to room temperature and diluted with water. The solution was extracted with ethyl acetate (2×). The combined organic phase was washed with brine (3×), dried (MgSO4), and concentrated in vacuo to a crude oil. Silica gel chromatography (gradient elution from 50:50 hexane/ethyl acetate to 100% ethyl acetate) yielded the title compound as a yellow oil (12.0 g, 76%). 1H NMR (CDCl3, 300 MHz) δ 4.46 (t, 5.5 Hz, 1H), 3.38 (s, 6H), 2.71 (d, 5.5 Hz, 2H), 2.57 (t, 7.4 Hz, 2H), 1.75-1.60 (m, 3H), 1.47 (m, 2H), 1.17 (m, 8H), 0.86 (m, 2H); Rf=0.27 (50:50 hexane/ethyl acetate). The solution was extracted with ethyl acetate (2×) The combined organic phase was washed with brine (3×) dried (MgSO4) concentrated in vacuo to a crude oil Silica gel chromatography (gradient elution from 50:50 hexane/ethyl acetate to 100% ethyl acetate)

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

实验步骤: 1-Chloro-3-cyclohexylpropane (11.1 g, 69.0 mmol), 2-aminoacetaldehyde (15.0 mL, 138.0 mmol, 2.0 equiv), and sodium iodide (2.1 g, 14.0 mmol, 0.2 equiv) were combined in anhydrous N,N-dimethylformamide (20 mL). The solution was stirred over solid potassium carbonate (9.66 g, 70 mmol) at 80° C. for 16 hours. The mixture was cooled to room temperature and diluted with water. The solution was extracted with ethyl acetate (2×). The combined organic phase was washed with brine (3×), dried (MgSO4), and concentrated in vacuo to a crude oil. Silica gel chromatography (gradient elution from 50:50 hexane/ethyl acetate to 100% ethyl acetate) yielded the title compound as a yellow oil (12.0 g, 76%). 1H NMR (CDCl3, 300 MHz) δ 4.46 (t, 5.5 Hz, 1 H), 3.38 (s, 6 H), 2.71 (d, 5.5 Hz, 2 H), 2.57 (t, 7.4 Hz, 2 H), 1.75-1.60 (m, 3 H), 1.47 (m, 2 H), 1.17 (m, 8 H), 0.86 (m, 2 H); Rf =0.27 (50:50 hexane/ethyl acetate). The solution was extracted with ethyl acetate (2×) The combined organic phase was washed with brine (3×) dried (MgSO4) concentrated in vacuo to a crude oil Silica gel chromatography (gradient elution from 50:50 hexane/ethyl acetate to 100% ethyl acetate)

反应条件: temp:24.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 3-[(4-Amino-5-chloro-2-methoxyphenyl)methyl]-5-[4-(trifluoromethyl) phenyl]-1,3,4-oxadiazol-2(3H)-one (1.14 g, 2.9 mmol) and triethylamine (1.0 ml, 6.8 mmol) were taken up in anhydrous THF (20 ml) and transferred dropwise by cannula into a 20% solution of phosgene in toluene at 0° C. under N2. The reaction was stirred 2.5 h at 24° C., diluted with diethylether (1 vol), and filtered through a celite plug. Concentrated by rotary evaporation to gave a solid which was dissolved in dichloromethane (50 ml) under N2 and aminoacetaldehyde (0.42 ml, 2.9 mmol) was added. The solution was stirred 3 h and concentrated to remove solvent. The residue was taken up in 25 ml of formic acid (88%) and stirred 18 h at 24° C. The formic acid was removed by rotary evaporation the residue taken up in ethyl acetate, washed with saturated NaHCO3 solution and brine, and dried. Concentration on SiO2, and elution with 45% THF/benzene gave 850 mg (65%). mp 201°-202° C.; IR(KBr, ν=cm-1) 3414, 1792, 1694, 1330, 1236, 1136; 1H NMR (300 MHz, CDCl3) δ3.86 (3H, s), 4.97 (2H, s), 6.38 (2H, br, s), 6.99 (1H, s), 7.40 (1H, s), 7.71 (2H, d, J=8.4 Hz), 7.94 (2H, d, J=8.2 Hz), 10.28 (1H, br, s); MS(ESI)m/z: 465 (M--H-) filtered through a celite plug Concentrated by rotary evaporation to gave a solid which The solution was stirred 3 h concentrated to remove solvent stirred 18 h at 24° C The formic acid was removed by rotary evaporation the residue washed with saturated NaHCO3 solution and brine dried Concentration on SiO2, and elution with 45% THF/benzene gave 850 mg (65%)

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

实验步骤: In the manner given in Preparation 21, α-phenyl-o-toluidine is reacted first with trimethyl orthoformate, the resulting product is reacted with aminoacetaldehyde, dimethyl acetal, and the resulting product of this reaction is heated with titanium tetrachloride in monoglyme to give 1-(α-phenyl-o-tolyl)imidazole.