Scheme 1.

General synthetic pathway to generate PROTACs. Reaction conditions: (a) K₂CO₃, BnBr, DMF, 0–20 °C; (b) AcOH, NaOAc, Br₂, 20 °C; (c) NaH, MeI, DMF, 0–20 °C; (d) Fe, AcOH, 65 °C; (e) NaNO₂, 10% aq. H₂SO₄; (f) t-butyl acrylate, DIPEA, P(o-tolyl)₃, Pd(OAc)₂, DMF, 95 °C; (g) [RhCl(cod)]₂, (3-(hydroxymethyl)-4- methylphenyl)boronic acid, Et₃N, dioxane, H₂O, 95 °C; (h) PPh₃, DIAD, THF, 0–20 °C; (i) Pd/C, H₂, MeOH, 20 °C; (j) K₂CO₃, alkyl halide, DMF, 80 °C; (k) Pd/C, H₂, MeOH; (l) 40, HATU, DIPEA, DCM, 20 °C; (m) TFA, DCM, 20 °C; (n) 41, DIPEA, DMF 80 °C.