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制备有很多方法，一种是酸直接和胺缩合，此类方法有：氯甲酸酯类形成活性酯缩合，DDC和EDC之类的碳二酰亚胺类缩合剂，HATU和BOP等鎓盐类缩合剂，DPP-Cl和DPPA之类的有机磷类缩合剂。第二种是，酰卤和酸酐和胺得到酰胺。

除了以上常规方法下面介绍两种非常规方法。

一、酰基叠氮

酰基叠氮也是一个较为温和的酰化试剂，由于在反应时其不会引起光学活性物质的消旋且对水及其他亲核试剂较为稳定，因而常用于肽及库的合成.但酰基叠氮由于反应活性低，对于位阻大且亲核性低的胺是不适用的。

酰基叠氮实例（J. Med. Chem 2004, vol. 47, No. 10 2599-2610）

To a solution Boc-Tyr-N3(0.65 mmol) in DMF (6 mL) were added 7.3N HCl/dioxane (1.30 mmol) and isopentyl tite (0.78 mmol) under cooling to –15 ℃; The solution was stirred for 10 min at the same temperature, NMM (1.37 mmol) was added to adjust the to 8. This solution was added to a cooled solution of 55 (0.26 mmol) and NMM (0.52 mmol) in DMF (6mL). The mixture was stirred for another 24 h under the same conditions and the pH maintained at 8. After removal of DMF, the residue was dissolved in EA and washed with water, 5% NaHCO3, 10% citric , and saturated brine. The organic layer was dried over Na2SO4 and evaporated. The product was crystallized from ether, and the crystals were collected by filtration (Yield 53.6%).

二、3-酰基-2-硫噻唑啉

3-酰基-2-硫噻唑啉也是一个较为温和的酰化试剂(Tetrahedron lett. 1980,，841； J Org. Chem. 1994, 3506), 其对各类胺的反应选择性较好，同时反应可以用乙醇作溶剂。该反应的一个特点是一般3-酰基-2-硫噻唑啉是黄色的，但反应完2-硫噻唑啉为无色，因此可以通过黄色是否消失来跟踪反应。

1、 3-酰基-2-硫噻唑啉的合成示例（J. Org. Chem., Vol. 57, No. 15,1992. 4243-4249）

A solution of 2-(benzyloxy)propionic acid (2.16 g, 12 mmol) in 2Cl2(50 mL) were added thiozolidine-2-thione (1.93 g, 12 mmol), followed by EDC. HCl(2.42 g, 12.6 mmol) and DMAP (50 mg, 0.41 mmol). After being stirred at RT overnight, the reaction mixture was washed with water and brine, dried, evaporated in vacuo to give an oil residue. The residue was purified by silica gel column chromatography (elution 5:1hexane-AcOEt) to give the desired amide 58 (3.32 g, 86%) as yellow oil.

2 、3-酰基-2-硫噻唑啉的合成酰胺示例（Genin, Michael J.; Allwine, Debra A. ect.; J. Med. Chem., 2000, 5, 953-970）

p-Anisidine (920 mg, 7.47 mmol) was added to a solution of 59 (3.0 g, 6.24 mmol) in CH2Cl2(20 mL) and the solution was stirred at RT overnight. Evaporation of the solvent in vacuo followed by purification of the residue on a silical gel column with 5:1 of hexane-AcOEt gave amide 60 (2.76 g, quantitatively yield) as colorless needles.

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