A new multicomponent reaction (MCR) was found: a sodium acetate-catalyzed transformation of salicylaldehydes, malononitrile and 4-hydroxy-6-methyl-2H-pyran-2-one in ethanol results in the fast (30min) and efficient formation of new 4-pyrano-substituted 2-amino-4H-chromenes in 86–96% yields. The same transformation initiated by grinding in mortar in the presence of sodium acetate or potassium fluoride results in a faster (15min) formation of 4-pyrano-substituted 2-amino-4H-chromenes in 80–90% yields. This novel ‘one-pot’ process opens an effective and convenient way to pyrano-functionalized 2-amino-4H-chromene systems, which are promising compounds for different biomedical applications.