1、芳香伯胺的对硝基苯氧基碳酰胺和脲的合成示例 【WO2004/9558 A2 (2004/01/29)】
To a solution of methyl 3-aminobenzoate (1.0g, 6.5 mmol) and pyridine (1.0 mL) in 100 mL of dichloromethane was added asolution of 4- nitrophenylchloroformate (1.4 g, 6.7 mmol) in 10 mL of dichloromethanedropwise at 0oC under N2 atmosphere. The resultingmixture was stirred at r.t. for 20 h before poured into ice-water. The mixture was extracted withDCM (3 x 100 mL). The combined organic phases were washed with 0.5 Naq. HC1 andbrine, dried over anhydrous Na2SO4 and filtered. Thefiltrate was concentrated to give the crude product, which was purified bycolumn to afford 2.1 g of 3-[3-(4-tert-Butyl-phenyl)-ureido]-benzoic acidmethyl ester (94 %)
2、脂肪伯胺的对硝基苯氧基碳酰胺和脲的合成示例 （J. Org. Chem. 2004, 46-53）
To a solution of 4-nitrophenyl chloroformate(2.3 g, 11 mmol) in 20 mL of CH2Cl2 was added a solution of benzyl glycinate (0.62 g, 3.8mmol) in 4 mL of 1:1 CH2Cl2/ pyridine at 0 °C dropwise. The solution was stirred for30 min and then diluted with 100 mL of CH2Cl2. The reaction mixture was washedwith 1 M NaHSO4 (3 x 50 mL) and brine (3 x 50 mL). The organicphase was concentrated to the crude product, which was purified by columnchromatography to afford 0.81 g of N-(4-nitrophenyloxycarbonyl)benzyl glycinate(65%) as white solid. To thesolution of N-(4-nitrophenyloxycarbonyl)benzyl glycinate (0.79 g,2.4 mmol) in 10 mL of benzene were added 1,6-aminohexanol (0.34 g, 2.9 mmol),DMAP (88 mg, 0.72 mmol) and diisopropylethylamine (0.46 g, 3.6 mmol) at roomtemperature. The reaction mixture was stirred at for 30 min before diluted with50 mL of CH2Cl2. The mixture was washed with 1 M NaHSO4 (3 x 50 mL), 2% Na2CO3 (3 x 50 mL) and brine (3 x50 mL). The organic phase was dried and concentrated to the crude product,which was purified by column chromatography to afford 0.61 g of [3-(6-hydroxyhexyl)ureido]aceticacid benzyl Ester (86%) as white solid..
3、利用氯甲酸对硝基苯酯一锅法合成脲示例（J. Med. Chem. 2001, 1021-1024）
To a solution of 1-(2,6-dichloro-benzyl)-3-pyrrolidin-1-ylmethyl-1H-indazol-6-ylamine(374 mg, 1.0 mmol) and diisopropylethylamine (640 mg, 5.0 mmol) in 100 mL ofDCM was added a solution of 4-nitrophenyl chloroformate (220 mg, 1.1 mmol) in10 mL of DCM at –20 oC under N2 atmosphere. The resultingmixture was stirred for 30 min and then added 3-amino-4-(3,4-difluoro-phenyl)-1-phenyl-butan-2-one(275 mg, 1.0 mmol). After stirred at – 20 oC for 30 min, the mixturewas warmed to room temperature and then stirred for another 6 h before pouredinto water. The reaction mixture was extractedwith DCM (3 x 100 mL). The combined organic phases were washed with brine (3 x50 mL), dried over anhydrous Na2SO4 and filtered. Thefiltrate was concentrated to the crude product, which was purified by columnchromatography to afford 175 mg of 1-[1-(2,6-dichloro-benzyl)-3-pyrrolidin-1-ylmethyl-1H-indazol-6-yl]-3-[1-(3,4-difluoro-benzyl)-2-oxo-3-phenyl-propyl]-urea (26 %)
4、氯甲酸对硝基苯酯用于仲胺的脲合成示例 （J. Med. Chem. 1999, 5254-5265）
To a solution of 5-oxo-5-piperidin-3-yl-3-pyridin-3-yl-pentanoicacid methyl ester (2.9 g, 10 mmol) in DCM (200 mL) wasadded 4-nitrophenylchloroformate (2.0 g, 10 mmol) and NMM (6.0 mL, 30 mmol) at0 oC. The resulting mixture was stirred for 2 h before poured intowater (15 mL). After separated, the organic layer was dried over anhydrous Na2SO4 and evaporatedto oil, which was dissolved in 100 mL of MeCN. The solution was then treated by[4,4′]bipiperidinyl-1-carboxylic acid tert-butyl ester (4.3 g, 15 mmol) and DMAP(1.2 g, 10 mmol), and heated to reflux for 24 h. After removal of the solvent,the residue was dissolved in EtOAc (200 mL). The organic phase was washed with 1N NaOH (3 x 100 mL), brine (3 x 100 mL) and dried over anhydrous Na2SO4. Afterfiltered, the filtrate was concentrated to the crude product, which was purifiedby silica gel chromatography to afford 4.1g of 1′-[3-(4-methoxycarbonyl-3-pyridin-3-yl-butyryl)-piperidine-1-carbonyl]-[4,4′]bipiperidinyl-1-carboxylicacid tert-butyl ester (69 %)