氨基二苯甲烷 盐酸盐

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (S)-2-[(Azepane-1-carbonyl)-amino]-4-methyl-pentanoic acid (0.51 g, 2.0 mmol, Example 1, Step B) was dissolved in dry DMF (6 mL) under nitrogen atmosphere and cooled to 0° C. in an ice-water bath. To this solution were added, in succession, N,N-diisopropylethylamine (1.0 mL, 5.7 mmol) and solid O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.74 g, 2.0 mmol). The resulting reaction mixture was stirred at that temperature for 30 minutes; aminodiphenylmethane hydrochloride (0.43 g, 2.0 mmol, Aldrich, Milwaukee, Wis.) was then added. After additional 30 minutes stirring at 0° C., reaction mixture was mixed with 60 mL of diethyl ether; the resulting mixture was successively washed with 5% aqueous HCl solution, brine, saturated aqueous NaHCO3 solution, brine, and was dried over Na2SO4. The solution was concentrated in vacuo, a white solid was obtained. Recrystallization from EtOAc-hexanes afforded 0.67 g (82%) of the pure titled compound as a white solid: mp 180-181° C. APCI-MS m/z 422.3 (MH+). The resulting reaction mixture After additional 30 minutes stirring at 0° C. reaction mixture the resulting mixture was successively washed with 5% aqueous HCl solution, brine, saturated aqueous NaHCO3 solution, brine was dried over Na2SO4 The solution was concentrated in vacuo a white solid was obtained Recrystallization from EtOAc-hexanes

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

实验步骤: To a solution of 4-[5-nitro-1H-indol-3-ylmethyl]-3-methoxy-benzoic acid methylester (0.50 grams, 1.47 mmol) and triethylamine (0.62 mL, 4.41 mmol) in methylene chloride (30 mL), at 0° C., was added a solution of phosgene in toluene (1.9 M in toluene, 1.5 mL, 2.9 mmol). The solution was warmed to room temperature and stirred for 1 hour. To this was added aminodiphenylmethane hydrochloride (0.65 grams, 2.94 mmol) and the resulting solution was stirred for 12 hours at room temperature. The solution was concentrated in vacuo and the crude triturated with methanol. The resulting pale yellow solid was collected via filtration to give 4-[1-(benzhydryl-carbamoyl)-5-nitro-1H-indol-3-ylmethyl]-3-methoxy-benzoic acid methylester (0.672 grams, 83% yield). the resulting solution was stirred for 12 hours at room temperature The solution was concentrated in vacuo the crude triturated with methanol The resulting pale yellow solid was collected via filtration

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (S)-2-[(Azepane-1-carbonyl)-amino]-4-methyl-pentanoic acid (0.51 g, 2.0 mmol, Example 1, Step B) was dissolved in dry DMF (6 mL) under nitrogen atmosphere and cooled to 0° C. in an ice-water bath. To this solution were added, in succession, N,N-diisopropylethylamine (1.0 mL, 5.7 mmol) and solid O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.74 g, 2.0 mmol). The resulting reaction mixture was stirred at that temperature for 30 minutes; aminodiphenylmethane hydrochloride (0.43 g, 2.0 mmol, Aldrich, Milwaukee, Wis.) was then added. After additional 30 minutes stirring at 0° C., reaction mixture was mixed with 60 mL of diethyl ether; the resulting mixture was successively washed with 5% aqueous HCl solution, brine, saturated aqueous NaHCO3 solution, brine, and was dried over Na2SO4. The solution was concentrated in vacuo, a white solid was obtained. Recrystallization from EtOAc-hexanes afforded 0.67 g (82%) of the pure titled compound as a white solid: mp 180-181° C. APCI-MS m/z 422.3 (MH+). The resulting reaction mixture After additional 30 minutes stirring at 0° C. reaction mixture the resulting mixture was successively washed with 5% aqueous HCl solution, brine, saturated aqueous NaHCO3 solution, brine was dried over Na2SO4 The solution was concentrated in vacuo a white solid was obtained Recrystallization from EtOAc-hexanes