Skip to main content
. 2022 Sep 26;13(10):1648–1654. doi: 10.1021/acsmedchemlett.2c00336

Scheme 2. Synthetic Route for the Substituted Warhead Analogues of 1 and CMA.

Scheme 2

Conditions: (a) Maleic anhydride, toluene, 60 °C, 1 h 30 min. (b) H2SO4, MeOH, 40 °C, 1 h 30 min or alkyl bromide, base, DMF, r.t., 5 h–4 days or phenol, DCC, pyridine, DCM, r.t., 2 h or propargylamine hydrochloride, Oxyma, DIC, DMF, r.t., 2 h. (c) Propargyl bromide or bromoacetonitrile, K2CO3, DMF, 85 °C, 8–15 h. (d) Monomethyl fumarate, Oxyma, DIC, DIPEA, DCM, r.t., 3 h. (e) LiOH (1.4 M), dioxane, r.t., 1 h. (f) R–N3, CuSO4·5H2O, sodium ascorbate, TBTA, THF/H2O, r.t., 17–25 h.