N1,N3-Diacyl-3,4-dihydropyrimidin-2(1H)-ones: neutral acyl group transfer reagents

Singh, Kamaljit; Singh, K. Chandramani

doi:10.1016/j.tet.2009.10.037

Cited by 21 publications

(11 citation statements)

References 17 publications

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“…Synthetic methodologies so far described for derivatization of Biginelli products are largely dictated by the intrinsic reactivity of the 3,4-DHPM scaffold, addressing concerns of compatibility with the existing functionalities, namely, the multiple heteroatoms, an α,βunsaturated carbonyl moiety and a reaction-prone alkyl substituent on C6. Specifically, analogues have been reported, resulting from the following processes: N1 or N3 alkylation or acylation [20][21][22][23][24][25]; C6 alkyl substituent elaboration to a functionalized derivative [26,27]; and various intramolecular cyclizations (e.g., N1-C6, C2-N3, C4-C5, C4-C6, C5-C6) [24,26,[28][29][30] depending on the nature of substituents on each position.…”

Section: Introductionmentioning

confidence: 99%

N-Directed Pd-Catalyzed Photoredox-Mediated C–H Arylation for Accessing Phenyl-Extended Analogues of Biginelli/Suzuki-Derived Ethyl 4-Methyl-2,6-diphenylpyrimidine-5-carboxylates

2021

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The availability and application of direct, functional group-compatible C–H activation methods for late-stage modification of small-molecule bioactives and other valuable materials remains an ongoing challenge in organic synthesis. In the current study, we demonstrate that a LED-activated, photoredox-mediated, Pd(OAc)2-catalyzed C–H arylation, employing a phenyldiazonium aryl source and either tris(2,2′-bipyridine)ruthenium(II) or (2,2′-bipyridine)bis[3,5-di-fluoro-2-[5-(trifluoromethyl)-2-pyridinyl-kN][phenyl-kC]iridium(III) as photoredox initiator, may successfully produce unprecedented mono- and bis-phenyl derivatives of functionality-rich 2,6-diphenylpyrimidine substrates at room temperature. The series of 19 substrates employed herein, which share the biologically-relevant 4-methyl-2,6-diphenylpyrimidine-5-carboxylate scaffold, were generated via a synthetic route involving (3-component) Biginelli condensation, oxidative dehydrogenation of the obtained 3,4-dihydropyrimidin-2(1H)-one to 2-hydroxypyrimidine, O-sulfonylation, and Suzuki-Miyaura C–C cross-coupling. Submission of these substrates to pyrimidine-N-atom-directed C–H arylation conditions led to regioselective phenylation at the ortho site(s) of the pyrimidine-C2-connected phenyl ring, revealing substituent-dependent electronic and steric effects. A focused library of 18 mono- and 10 bis-phenyl derivatives was generated. Its members exhibit interesting 3D and peripheral substitution features that render them promising for evaluation in drug discovery efforts.

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Section: Introductionmentioning

confidence: 99%

N-Directed Pd-Catalyzed Photoredox-Mediated C–H Arylation for Accessing Phenyl-Extended Analogues of Biginelli/Suzuki-Derived Ethyl 4-Methyl-2,6-diphenylpyrimidine-5-carboxylates

2021

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“…The reaction of phenylmagnesium bromide with 10 was also very facile and furnished the pyrimidine derivative 12j in 68% yield. While the deprotection of carbamate from N-3 positions of products 12aej using LiAlH 4 in methanol 17 (stirring at 0 C to room temperature and then reflux), NaOMe in refluxing methanol 33 or tetrabutyl ammonium fluoride (TBAF) in THF 34 could not be achieved, the current methodology served the purpose of appending a variety of substituents at the C-2 position, regioselectively and in a synthetically useful manner. The formation of the products 12 and 15 can be visualized to be proceeding through the mechanism shown in Scheme 2.…”

Section: Resultsmentioning

confidence: 99%

Regioselective addition reactions at C-2 of 3,4-dihydropyrimidinones. Synthesis and evaluation of multifunctionalized tetrahydropyrimidines

2010

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a b s t r a c tMultifunctionalized tetrahydropyrimidines derivatives have been synthesized from Biginelli 3,4-dihydropyrimidin-2-(1H)-thiones (DHPMs) efficiently. The transformation includes desulfurization of DHPMs with Raney-Ni and subsequent regioselective C-2 functionalization using a variety of C-nucleophiles with simultaneous activation with ethyl chloroformate. Functionalized pyrimidine derivatives containing bulky substituents at C-2 of the pyrimidine ring are cytostatic.

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“…41 The general procedure A was followed with a total reaction time of 1 hour (including 30 min oxidation with DDQ). 41 The general procedure A was followed with a total reaction time of 1 hour (including 30 min oxidation with DDQ).…”

Section: General Methodsmentioning

confidence: 99%

Oxidative activation of dihydropyridine amides to reactive acyl donors

2015

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Amides of 1,4-dihydropyridine (DHP) are activated by oxidation for acyl transfer to amines, alcohols and thiols. In the reduced form the DHP amide is stable towards reaction with amines at room temperature. However, upon oxidation with DDQ the acyl donor is activated via a proposed pyridinium intermediate. The activated intermediate reacts with various nucleophiles to give amides, esters, and thio-esters in moderate to high yields.

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N1,N3-Diacyl-3,4-dihydropyrimidin-2(1H)-ones: neutral acyl group transfer reagents

Cited by 21 publications

References 17 publications

N-Directed Pd-Catalyzed Photoredox-Mediated C–H Arylation for Accessing Phenyl-Extended Analogues of Biginelli/Suzuki-Derived Ethyl 4-Methyl-2,6-diphenylpyrimidine-5-carboxylates

N-Directed Pd-Catalyzed Photoredox-Mediated C–H Arylation for Accessing Phenyl-Extended Analogues of Biginelli/Suzuki-Derived Ethyl 4-Methyl-2,6-diphenylpyrimidine-5-carboxylates

Regioselective addition reactions at C-2 of 3,4-dihydropyrimidinones. Synthesis and evaluation of multifunctionalized tetrahydropyrimidines

Oxidative activation of dihydropyridine amides to reactive acyl donors

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