Description
tert-Butyl (5-aminopentyl)carbamate can be used as a PROTAC linker in the synthesis of PROTACs. tert-Butyl (5-aminopentyl)carbamate is an alkane chain with terminal amine and Boc-protected amino groups. Amine group is reactive with carboxylic acids, activated NHS esters, carbonyls (ketone, aldehyde) etc. The Boc group can be deprotected under mild acidic conditions to form the free amine.
Synthesis
GENERAL PROCEDURE: A solution of di-tert-butyl dicarbonate (22 g, 100 mmol) was prepared by dissolving it in methanol (20 mL) under ice bath cooling conditions. This solution was slowly added dropwise over 30 minutes to a stirred methanol solution (160 mL) of 1,5-diaminopentane (1.8 g, 20 mmol). After the dropwise addition was completed, the ice bath was removed and the reaction mixture was allowed to continue stirring at room temperature for 4 hours. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure. The resulting residue was purified by silica gel column chromatography with the eluent ratio of chloroform:methanol:ammonia = 10:1:0.1 to give tert-butyl N-(5-aminopentyl)carbamate in 83% yield.
References
[1] European Journal of Organic Chemistry, 1998, # 5, p. 853 - 859
[2] ACS Medicinal Chemistry Letters, 2017, vol. 8, # 6, p. 614 - 617
[3] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 20, p. 7145 - 7155
[4] Journal of Medicinal Chemistry, 2004, vol. 47, # 20, p. 4933 - 4940
[5] Chemical and Pharmaceutical Bulletin, 2015, vol. 63, # 5, p. 326 - 333
