Synthesis of 3‐Aminopyrido[2,1‐a]isoquinolin‐4‐one Derivatives via Condensation of Azlactones with 1‐Alkyl‐3,4‐dihydroisoquinolines

Abstract

Reactions of available 1-alkyl-3,4-dihydroisoquinolines with 4-(2,2,2-trifluoroacetyl)-, 4-acetyl-or 4-(ethoxy-methylene)-2-aryloxazol-5(4H)-ones were studied. A series of new 3-amino-6,7dihydro-4H-pyrido[2,1-a]isoquinolin-4-one derivatives was synthesized. The intermediates formed as a result of the addition of azlactone to 1-methyl-3,4-dihydroisoquinoline were isolated. The effect of the nature of the substituents, as well as the reaction conditions on the yield and structure of the title products was revealed.

New one-pot synthesis of 4-arylpyrazolo[3,4-b]pyridin-6-ones based on 5-aminopyrazoles and azlactones

“…One of the rational approaches to the synthesis of fused pyridine derivatives is based on the domino reaction of enamines with azlactones [22][23][24][25][26][27][28][29][30]. We have previously reported a plausible mechanism of such reactions [22,25]. 1H-Pyrazol-5-amines also enter into similar transformations with azlactones in various solvents.…”

Easy Route to New Fused Dihydroisoquinoline-Naphthyridinone Frameworks

“…32,33 At the same time, 2-aryl-substituted 3-amino-6,7-dihydro-4H-pyrido[2,1-a]isoquinolin-4-ones are still obtained in low yield by oxidation of dihydro derivatives 2. 30 In order to study an alternative approach to the synthesis of 2-aryl-3-amino-6,7-dihydro-4H-pyrido[2,1-a]isoquinolin-4-ones 10a-f, we synthesized 3,4-dihydroisoquinolines 8a-e by a three-component condensation of substituted benzenes with isobutyric aldehyde, and acetonitrile, 32,34,35 as well as compound 8f by the Bischler-Napieralski reaction from N- (3,4-dimethoxyphenethyl)acetamide. 36 4-(3-Oxoisobenzofuran-1(3H)-ylidene)oxazol-5(4H)-one (7) was synthesized from hippuric acid and phthalic anhydride by heating in Ac 2 O.…”

“…32 It includes an enamine attack on the activated double bond of azlactone, followed by the closure of the pyridone ring. 32 33 At the same time, 2-aryl-substituted 3-amino-6,7-dihydro-4 H -pyrido[2,1- a ]isoquinolin-4-ones are still obtained in low yield by oxidation of dihydro derivatives 2 . 30…”

“…9,12,14,[26][27][28] The most rational approaches to the synthesis of pyrido[2,1-a]isoquinoline ring system are based on one-pot, tandem, and domino reactions. 29 Among them is the reaction of 1-alkyl-3,4-dihydroisoquinolines with azlactones, 12,[30][31][32] which we have used earlier for the synthesis of 3-amino-6,7-dihydro-4H-pyrido[2,1-a]isoquinolin-4-ones containing a hydrogen atom,…”

“…Among them is the reaction of 1-alkyl-3,4-dihydroisoquinolines with azlactones, 12 , 30 31 32 which we have used earlier for the synthesis of 3-amino-6,7-dihydro-4 H -pyrido[2,1- a ]isoquinolin-4-ones containing a hydrogen atom, an alkyl or trifluoromethyl group in the C-2 position. 32 It includes an enamine attack on the activated double bond of azlactone, followed by the closure of the pyridone ring. 32 33 At the same time, 2-aryl-substituted 3-amino-6,7-dihydro-4 H -pyrido[2,1- a ]isoquinolin-4-ones are still obtained in low yield by oxidation of dihydro derivatives 2 .…”