Scheme 2.

Routes to linker modified cariprazine analogues^a

^a Reagents and Conditions: (a) NaH, methyl 2-(dimethoxyphosphoryl)acetate, THF, 0 °C to rt; (b) Pd/C, H₂ (50 psi), MeOH, rt; (c) DIBALH, toluene, DCM, −78 °C to rt; (d) DMSO, (COCl)₂, NEt₃, DCM, −78 °C to rt; (e) 1-(2,3-dichlorophenyl)piperazine•HCl, NaBH(OAc)₃, DCE, rt; (f) TFA, DCM, rt; (g) N,N-dimethylcarbamyl chloride, DIPEA, DCM, rt; (h) 3-methoxyproponic acid, HCTU, DIPEA, DCM, rt.