530-62-1/羰基二咪唑 (CDI) 與胺反應(yīng)生成脲

胺也可以先與羰基二咪唑 (CDI)反應(yīng)，形成一個(gè)中間體，然后與另一分子胺反應(yīng)生成脲。本方法適用范圍也很廣，對(duì)那些底物很昂貴、或較難得到的，本方法也很適用。但由于CDI 不穩(wěn)定，放置時(shí)間長(zhǎng)，遇水會(huì)分解，造成加料不準(zhǔn)確，容易生成較難分離的二聚體。因此反應(yīng)前確定CDI 的質(zhì)量尤為關(guān)鍵。

一、羰基二咪唑與芳香伯胺反應(yīng)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、羰基二咪唑與脂肪胺反應(yīng)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 %).