Efficient Synthesis of Uracil‐Derived Hexa‐ and Tetrahydropyrido[2,3‐d]pyrimidines

Abstract

A reaction of 6‐amino‐1,3‐dimethyluracil with 3‐(hetero)aroylacrylic acids and their methyl esters leads to hexahydropyrido[2,3‐d]pyrimidine‐5‐carboxylic acids or the corresponding methyl esters in high to excellent yields. One‐pot oxidation of the acid derivatives with CAN is accompanied by decarboxylation to give tetrahydropyrido[2,3‐d]pyrimidines, while oxidation with bromine resulted in the formation of tetrahydropyrido[2,3‐d]pyrimidine‐5‐carboxylic acids. The aromatization of methyl hexahydropyrido[2,3‐d]pyrimidine‐5‐carboxylates was achieved by K2CO3‐mediated air oxidation under ambient conditions.

Type II Kinase Inhibitors Targeting Cys-Gatekeeper Kinases Display Orthogonality with Wild Type and Ala/Gly-Gatekeeper Kinases

“…In combination with a Thr gatekeeper, similar mutations in EphB1 (G703C) and c-Src (S345C), to name a few, are targetable using electrophilic quinazoline-based inhibitors (e.g. AQZ, Figure 1D), but due to the inactivity of these GWL double mutants, we were not able to apply them ( Figure S1F Figure 4A) 9,26 . The resulting compound contained an acrylamide linker bridging the pyrazolopyrimidine moiety with a trifluoromethylbenzoyl group.…”

Divergent Total Syntheses of (−)‐Huperzine Q, (+)‐Lycopladine B, (+)‐Lycopladine C, and (−)‐4‐epi‐Lycopladine D

“…With 6 in hand, we hypothesized that enamine 6 could be oxidized to diiminium ion intermediate 47 , which could then undergo tautomerization to dienamine 41 . Unfortunately, upon treating 6 with various oxidants such as 2,3‐dichloro‐5,6‐dicyanobenzo‐1,4‐quinone (DDQ), 2‐iodoxybenzoic acid (IBX), MnO 2 , Pd(OAc) 2 , and air, desired dienamine 41 was not observed (Table ).…”

Direct Synthesis, Characterization and Theoretical Studies of N‐(6‐Amino‐1,3‐dimethyl‐2,4‐dioxo‐1,2,3,4‐tetrahydropyrimidin‐5‐yl)benzamide Derivatives

“…[11] The rudimentary pyrimidine scaffold and their derivatives can be utilized to synthesize a diverse range of pharmaceutically important analogs. [12][13][14] Such derivatives can be achieved either by using one-pot cycloaddition reaction, using 6-amino uracil scaffolds with aromatic aldehydes and barbituric acid for combing of fused pyrido[2,3-d,6,5-d] pyrimidines using a catalytic amount of (p-TSA). [15] While the fused derivatives can also be synthesized using green chemistry principles i. e. using recyclable catalysts.…”

“…However, under the lights of heterocycles, uracil associates itself as one of the major naturally occurring nucleobases, i. e., forming an integral part of the nucleic acid [11] . The rudimentary pyrimidine scaffold and their derivatives can be utilized to synthesize a diverse range of pharmaceutically important analogs [12–14] . Such derivatives can be achieved either by using one‐pot cycloaddition reaction, using 6‐amino uracil scaffolds with aromatic aldehydes and barbituric acid for combing of fused pyrido[2,3‐d,6,5‐d] pyrimidines using a catalytic amount of (p‐TSA) [15] .…”