Synthesis
N-Protected Hydrazides 2a-l; General Procedure The protected amino acid 1 (2 equiv) and EDAC (2 equiv) were dissolved in the minimum amount of CH2Cl2 at 0 ??C. The mixture was stirred at 0 ??C for 2 h. PhthNNH2 (1 equiv) was added and the mixture was stirred at 0 ??C for 1 h and then at r.t. overnight. Distillation of the solvent under reduced pressure gave a product which was dissolved in EtOAc and washed successively with 1 M KHSO4, sat. aq NaHCO3, and brine. The organic layer was then dried (Na2SO4), filtered, and concentrated in vacuo. The residue was precipitated with Et2O to yield compound 2. If necessary, the residue was purified by column chromatography (silica gel, hexane- EtOAc, 3:7 to 7:3). Compounds 4a-l; General Procedure Aminomethylated polystyrene resin (3 equiv; 1.1 mmol/g, 100-200 mesh) was conditioned for 10 min at r.t. in CH2Cl2. Then 2 (1 equiv) was added, and the mixture was slowly stirred for 24 h at r.t. The mixture was filtered and the solvent was evaporated in vacuo to give product 4. Compound 4h, yield 89%.
References
[1] Tetrahedron Letters, 2016, vol. 57, # 9, p. 990 - 992
[2] Patent: US2004/19215, 2004, A1. Location in patent: Page 6
[3] Journal of Medicinal Chemistry, 2018, vol. 61, # 5, p. 2124 - 2130
[4] Journal of Organic Chemistry, 1995, vol. 60, # 10, p. 3112 - 3120
[5] Combinatorial Chemistry and High Throughput Screening, 2011, vol. 14, # 2, p. 132 - 137
