Scheme 10.
Synthetic scheme for generating NG-(2-methoxyethyl)-l-arginine carboxylate bioisosteres. Reagents and Conditions: (i) CDI, DBU, methanesulfonamide, THF, RT, 7 h, 51%; (ii) HATU, DIPEA, O-methylhydroxylamine hydrochloride, THF, 0 °C-RT, 16 h, 86%; (iii) HATU, DIPEA, O-benzylhydroxylamine, THF, 0 °C-RT, 16 h, 57%; (iv) 4 M HCl/1,4-dioxane, DCM, RT, 30 min, 99%; (v) DIPEA, DCM, RT, 24 h, 43a 42%, 43b 22%, 43c 56%; (vi) TFMSA/TFA, RT, 1 h, 99%. Reproduced in part from [117] with permission of the Royal Society of Chemistry.