Scheme 1.

Synthesis of the 2N-824 series of compounds.a

^aReagents and conditions: (a) 4-trifluoromethoxybenzyl bromide, NaH, TBAI, DMF, −78°C to rt, 14 h; (b) TBAF, THF, rt, 30 min; (c) MsCl, DIPEA, CH₂Cl₂, rt, 30 min; (d) NaN₃, DMF, 55°C, 14 h; (e) SH(CH₂)₃SH, Et₃N, rt, 2 h; (f) DIPEA, DMF, µW, 150°C, 30min; (g) HCO₂H, Ac₂O, CH₂Cl₂, rt, 14 h; (h) AcCl, Et₃N, CH₂Cl₂, 0 °C to rt, 2 h; (i) NaI, acetone, reflux, 6 h; (j) 2M MeNH₂ in THF, DIPEA, DMF, µW, 200°C, 20 min.