title: Design and synthesis of pyrido[2,1-b][1,3,5]thiadiazine library via uncatalyzed Mannich-type reaction.
abstract: This Research Article describes the synthesis of an over 700-member library of (8R/8S)-3-R-8-aryl-6-oxo-3,4,7,8-tetrahydro-2H,6H-pyrido[2,1-b][1,3,5]thiadiazin-9-carbonitriles by uncatalyzed Mannich-type reaction of N-methylmorpholinium (4R/4S)-4-aryl-3-cyano-6-oxo-1,4,5,6-tetrahydropyridin-2-thiolates with a set of primary amines and excessive HCHO. The scope and limitations of the reaction were studied. Starting thiolates were obtained in yields of 53-82% by multicomponent reaction of aromatic aldehydes, cyanothioacetamide, 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum's acid), and N-methylmorpholine, followed by heterocyclization of the resulting Michael adducts.
authors.affiliation: ChemEx Laboratory, Vladimir Dal' East Ukrainian National University , 91034 Lugansk, Ukraine.
authors.forename: Victor V
authors.initials: VV
authors.lastname: Dotsenko
authors.forename: Konstantin A
authors.initials: KA
authors.lastname: Frolov
authors.forename: Tatyana M
authors.initials: TM
authors.lastname: Pekhtereva
authors.forename: Olena S
authors.initials: OS
authors.lastname: Papaianina
authors.forename: Sergey Yu
authors.initials: SY
authors.lastname: Suykov
authors.forename: Sergey G
authors.initials: SG
authors.lastname: Krivokolysko
mesh_terms: D002384:Catalysis; D004146:Dioxanes; D015195:Drug Design; D008352:Mannich Bases / Q000737:chemistry*; D054852:Small Molecule Libraries; D013829:Thiadiazines / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D004146:Dioxanes; D008352:Mannich Bases; D054852:Small Molecule Libraries; D013829:Thiadiazines; C076489:Meldrum's acid; C025223:1,4-dioxane
keywords: Meldrum’s acid; aminomethylation; cyanothioacetamide; pyrido[2,1-b][1,3,5]thiadiazines; tetrahydropyridine-2-thiolates; uncatalyzed Mannich-type reaction