Pyrimidinylpalladium(II) Complexes in the Synthesis of Alkenylpyrimidines.

Benneche, T.; Oscarson, Stefan; Kvarnström, Ingemar; Niklasson, Annika; Niklasson, Gunilla; Svensson, Susanne; Edwards, J. Vincent

doi:10.3891/acta.chem.scand.44-0927

Cited by 25 publications

(9 citation statements)

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“…Chiral HPLC to determine enantiopurity of precursors of racemic and enantiomers of 11 was performed on an Agilent 1260 Series HPLC using a 0.46 cm × 25 cm Chiralpak AD-H column, with hexanes and 2-propanol (isocratic 10% 2-propanol in hexanes) as the mobile phases, and the flow rate of 0.5 mL/min with UV detection. 4-Chloro-2-methanesulfonyl pyrimidine, 27b 24 , 25 , 26 , 30 40 , 32 65 , 42 and 66 ( 43 ) were synthesized following previously reported procedures. Syntheses of the remaining primary amines are detailed in Supporting Information .…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, the 2-methylthio-4-vinyl pyrimidine ( 40 ) was synthesized by a Stille coupling between commercially available 4-chloro-2-methylthio pyrimidine ( 39 ) and tributylvinyltin in the presence of tetrakistriphenylphosphine Pd(0). 32 A Michael addition between 40 and the particular primary amines gave the corresponding homobenzylic amines ( 41 – 47 ). The primary amines ( 31 – 32 , S3 – S12 (see Supporting Information ), 62 ) were synthesized either from commercially available bromides or carboxylic acids in 2–3 steps, as elaborated in the Supporting Information .…”

Section: Chemistrymentioning

confidence: 99%

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Novel 2,4-Disubstituted Pyrimidines as Potent, Selective, and Cell-Permeable Inhibitors of Neuronal Nitric Oxide Synthase

Mukherjee

Sevrioukova

et al. 2014

J. Med. Chem.

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Selective inhibition of neuronal nitric oxide synthase (nNOS) is an important therapeutic approach to target neurodegenerative disorders. However, the majority of the nNOS inhibitors developed are arginine mimetics and, therefore, suffer from poor bioavailability. We designed a novel strategy to combine a more pharmacokinetically favorable 2-imidazolylpyrimidine head with promising structural components from previous inhibitors. In conjunction with extensive structure–activity studies, several highly potent and selective inhibitors of nNOS were discovered. X-ray crystallographic analysis reveals that these type II inhibitors utilize the same hydrophobic pocket to gain strong inhibitory potency (13), as well as high isoform selectivity. Interestingly, select compounds from this series (9) showed good permeability and low efflux in a Caco-2 assay, suggesting potential oral bioavailability, and exhibited minimal off-target binding to 50 central nervous system receptors. Furthermore, even with heme-coordinating groups in the molecule, modifying other pharmacophoric fragments minimized undesirable inhibition of cytochrome P450s from human liver microsomes.

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Section: Methodsmentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

Novel 2,4-Disubstituted Pyrimidines as Potent, Selective, and Cell-Permeable Inhibitors of Neuronal Nitric Oxide Synthase

Mukherjee

Sevrioukova

et al. 2014

J. Med. Chem.

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“…Polyhalogenated pyrimidines are commonly used substrates in cross-coupling reactions since each substituent could be added sequentially to a pyrimidine ring due to the intrinsic differences in reactivity at different positions [21][22][23][24]. In case of commonly used and commercially available 2,4-dichloropyrimidines, the regioselectivity preference in a Suzuki cross-coupling reaction was observed for C4-position due to the favored oxidative addition of palladium into the C4-chlorine bond [22,24,25]. Some anomalies have been observed, favoring C2 position over C4, mainly due to the steric reasons when additional substituents are present at other positions, i.e., C5 [24].…”

Section: Introductionmentioning

confidence: 99%

Microwave-Assisted Regioselective Suzuki Coupling of 2,4-Dichloropyrimidines with Aryl and Heteroaryl Boronic Acids

2021

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Suzuki coupling reaction has been often used for the preparation of a diverse set of substituted pyrimidines. In this study, the Suzuki coupling of 2,4-dichloropyrimidines with aryl and heteroaryl boronic acids was investigated. A thorough screening of reaction conditions and the use of microwave irradiation led to a very efficient and straightforward synthetic procedure providing C4-substituted pyrimidines in good to excellent yields. Short reaction time (15 min) and extremely low catalyst loading (0.5 mol%) are the main advantages of our tetrakis(triphenylphosphine)palladium(0) catalyzed microwave-assisted procedure, which could be used for quick and low-cost regioselective preparation of substituted pyrimidine rings.

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“…Finally, 3c was treated with different stannanes under the conditions of Method B. 15 It is anticipated that the methodology described here will be useful for the preparation of highly conjugated systems such as 7 (Scheme 2) by a double Stille reaction. Unfortunately, coupling with tributylvinylstannane led to extensive decomposition (Table 1, entry 1) either on using Method A or B.…”

mentioning

confidence: 99%