Scheme 1.

Synthesis route for target compounds. Reactions and conditions: (a) dimethyl phosphite, 100 °C, 8 h, 62.3%; (b) 2-fluoro-5-formylbenzonitrile, Et₃N, anhydrous THF, 20 °C, 16 h, 92.6%; (c) (i) H₂O, 10mol/l NaOH, 90 °C, 1 h, (ii) NH₂NH₂·H₂O, 70 °C, 18 h, 4 mol/l HCl, 93.7%; (d) propane diacid, NH₄Ac, 85 °C, 5 h, 50.0–80.0%; (e) oxalyl chloride, DMF, 20 °C, 1.5 h; (f) Tert-butoxycarbonylpiperazine, Et₃N, DCM, 20 °C, 12 h, 40.0–70.0%; (g) TFA, DCM, 20 °C, 8 h, 50.0–80.0%; (h) HBTU/DIPEA, DCM, 20 °C, 18 h, 15.7–26.8%;