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In ethyl acetate at 0 - 80℃; |
9
Commercially available p-fluorobenzylamine (0.76 ml, 6.7 mmol) was dissolved in 40 ml of AcOEt and at 0°C triphosgene (1.98 g, lequiv.) was added to the solution. The mixture was warmed at 80°C for 4 hours then evaporated and the residue was dissolved in 20 ml of DMF. The solution of the isocyanate was added dropwise to a solution in DMF (10 ml) of compound la (900 mg, 6 mmol) and the mixture was warmed at 80°C for 8 hours. (TLC AcOEt). The solvent was evaporated and the crude was dissolved in AcOEt (50 ml) and washed with water (1 X 30 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by chromatographic column gave 420 mg of a white solid. Yield = 23% 'HNMR (DMSO, 200 MHz) δ 4.29 (2H, d, J = 6 Hz), 6.62 (1H, dd, J = 7.6Hz, J' = 1.2 Hz), 6.80 (2H, m), 6.95 (1H, dd, J = 8.2 Hz, J' = 1.2 Hz), 7.15 (2H, m), 7.35 (2H, m), 8.23 (1H, bs), 9.96 (1H, bs), 10.59 (1H, bs); [M+1] 301.1 (C15H13FN4O2 requires 300.29). |
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In ethyl acetate at 0 - 80℃; for 4h; |
9
Preparation of 1-(4-fluorobenzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)urea Commercially available p-fluorobenzylamine (0.76 ml, 6.7 mmol) was dissolved in 40 ml of AcOEt and at 0°C triphosgene (1.98 g, lequiv.) was added to the solution. The mixture was warmed at 80°C for 4 hours then evaporated and the residue was dissolved in 20 ml of DMF. The solution of the isocyanate was added dropwise to a solution in DMF (10 ml) of compound 1a (900 mg, 6 mmol) and the mixture was warmed at 80°C for 8 hours. (TLC AcOEt). The solvent was evaporated and the crude was dissolved in AcOEt (50 ml) and washed with water (1 X 30 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by chromatographic column gave 420 mg of a white solid. Yield = 23% 1HNMR (DMSO, 200 MHz) δ 4.29 (2H, d, J = 6 Hz), 6.62 (1H, dd, J = 7.6Hz, J' = 1.2 Hz), 6.80 (2H, m), 6.95 (1H, dd, J = 8.2 Hz, J' = 1.2 Hz), 7.15 (2H, m), 7.35 (2H, m), 8.23 (1H, bs), 9.96 (1H, bs), 10.59 (1H, bs); [M+1] 301.1 (C15H13FN4O2 requires 300.29). |
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In toluene for 4h; Reflux; |
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In toluene Reflux; |
4.2.2 General procedure for the preparation of α-amino acid ureas (3a-3l)
General procedure: A solution of triphosgene (0.15 g, 0.5 mmol) in toluene was dropwise added the amine (1 mmol) at room temperature. After the addition was completed, the reaction suspension was refluxed for 6 h, then toluene was evaporated, and the residue was taken up by CH2Cl2, then added to a solution of the α-amino acid methyl ester hydrochlorides (1.2mmol) with triethylamine (0.17 ml, 1.2 mmol) in CH2Cl2 dropwise at 0 °C. After the addition was completed, the reaction solution was stirred at room temperature for hours. Then CH2Cl2 evaporated, the residue was taken up with ethyl acetate and washed with brine. After being dried with MgSO4 and condensed, α-amino acid ureas (3a-3l) were obtained without further purification. |
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With triethylamine In dichloromethane at 0℃; for 3h; Inert atmosphere; Reflux; |
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In toluene for 4h; Reflux; |
11.1 Preparation of Compound 11:
Step 1, benzylamine (5 mmol, 600 mg) and toluene (10 mL) were added to a 100 mL round bottom flask, and triphosgene (5 mmol, 1.5 g) was added under stirring, and the reaction was refluxed for 4 hours. The solvent was removed by concentration, then dichloromethane (5 mL) was evaporated. |
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