Prodrugs for colon-restricted delivery: Design, synthesis, and in vivo evaluation of colony stimulating factor 1 receptor (CSF1R) inhibitors
Fig 16
Synthesis of secondary alcohol 1.
Reagents and conditions: (a) 4-nitropyrazole, Cs2CO3, DMF, 77% (b) PPTS, acetone/H2O, 88%; (c) NaBH4, EtOH, -5°C; recrystallization from toluene, 59%; (d) Pd/C, H2 (1 atm), MeOH, rt, 98%; (e) 24, DIPEA, DMF, rt, 97%; (f) cyclohex-1-en-1-ylboronic acid, Pd(PPh3)2Cl2, Cs2CO3, 1,4-dioxane/water, 90°C, quant; (g) Pd(OH)2, H2 (1 atm), THF/MeOH/AcOH, rt, 85%.