• Different benzothiazolopyridine derivatives were synthesized using piperidine as catalyst in EtOH. • These compounds were synthesis by ultrasonic irradiation and conventional method. • Ultrasonic afforded several privileges such as shorter reaction time, cleaner reactions and high yields. • Molecular docking with estrogen and progesterone exhibit favorable interaction and inhibitory potential. In this work, a convenient and efficient procedure for the synthesis of 1-amino-2- (benzo [d] thiazol-2-yl)-3-aryl-3-hydro-benzo [ 4 , 5 ] thiazolo [3, 2-a] pyridine-4-carbonitrile derivatives (6a-f) was studied. This synthesis was catalyzed by piperidine in an ethanol medium under ultrasonic irradiation at room temperature. The obtained results were compared with the conventional reflux method. Compared to the reflux method, ultrasonic irradiation provided several privileges such as shorter reaction time, cleaner reactions, and higher yields. By using the ultrasound technique, the reaction time was reduced from 50- 480 min to 80–200 min and the product yields improved from 10 -71% to 30–90% compared to the reflux method. Molecular docking studies of synthetic compounds (ligands) were carried out with some vital targets in the breast cancers, such as estrogen receptor-α (ERα) and progesterone receptors A and B (PRA and PRB). The main aim of this evaluation was to predict the activity of ligands against ERα, PRA, and PRB. The docking results show that all ligands have favorable interactions with receptors in terms of binding free energy.