Reactions between 2-aminobenzothiazoles and Mannich bases are observed to be selectively controlled by the steric hindrance in the latter. Pyrido[2,1-b][1,3]benzothiazoles 3 are produced with non-sterically hindered Mannich bases such as 3-(dimethylamino)propiophenone hydrochlorides 2, whilst [1,3]benzothiazolo[2,3-b]quinazolines are produced with bulky Mannich bases such as 2-(dimethylaminomethyl)tetralone 4. This is shown by reactions with 2-amino-5-(ethylsulfanyl)thiadiazole, which was previously reported to follow the former reaction pathway with 2, while the reaction with 4 follows the latter reaction pathway. The final structures are established by NMR and X-ray diffraction, thus confirming the cyclization processes.