胺也可以先与羰基二咪唑 (CDI)反应，形成一个中间体，然后与另一分子胺反应生成脲。本方法适用范围也很广，对那些底物很昂贵、或较难得到的，本方法也很适用。但由于CDI 不稳定，放置时间长，遇水会分解，造成加料不准确，容易生成较难分离的二聚体。因此反应前确定CDI 的质量尤为关键。
一、羰基二咪唑与芳香伯胺反应生成脲（Tetrahedron, 2003; 5603 – 5608）
To a solution of 3-chloro-4-nitro-phenylamine (1.72 g, 10 mmoL) and triethylamine (1.0 g, 10mmol) in 50 mL of DMF was added CDI (1.61 g, 10 mmol) at room temperature under N2 atmosphere. The mixture was stirred at that temperature for 1 h and then added a solution of aniline (1.0 g, 11 mmol) in 5 mL of DMF. After stirred for another 10 h, the reaction mixture was poured into water (100 mL) and extracted with DCM (3 x 50 mL). The combined organic phases were washed with brine (5 x 100 mL), dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated to give the crude product, which was purified by column to afford 2.0 g of 1-(3-chloro-4-nitro-phenyl)-3- phenyl-urea (68 % yield)
二、羰基二咪唑与脂肪胺反应生成脲（J. Med. Chem. 1992; 2446-2451）
To a solution of 3-(3-piperidin-1-ylmethyl-phenoxy)-propylamine (2.48 g, 10 mmoL) and diisopropylethylamine (1. 4 mL, 10 mmol) in DMF (50 mL) was added CDI (1.61 g, 10 mmol) at room temperature under N2 atmosphere. The mixture was stirred at that temperature for 1h and then a solution of i-BuNH2 (146 mg, 20 mmol) in 5 mL of DMF was added to the mixture. The reaction mixture was stirred at room temperature overnight before poured into water (100 mL). The mixture was extracted with DCM (3 x 50 mL). The combined organic phases were washed with brine (5 x 100 mL), dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated to give the crude product, which was purified by column to afford 2.75 g of 1-isobutyl-3-[3-(3-piperidin-1-ylmethyl-phenoxy)-propyl]-urea (80 %).