7033-39-8Relevant academic research and scientific papers
Pyrimidine derivatives. XI. Facile carbon-carbon bond-cleavage reaction of 6-bromomethylpyrimidinediones and (2,4-dioxo-1,2,3,4-tetrahydropyrimidin-6-yl)methyl nitrate via 6-formyl derivatives
Kinoshita,Ohishi,Tanimoto
, p. 2073 - 2076 (1993)
The reaction of 5-bromo-6-bromomethyl-1,3-dimethyl- (1a) and 5-bromo-6-bromomethyl-1-(3-bromopropyl)-3-methyl-2,4(1H,3H)-pyrimidined ione (4a) with 1.0 and 2.0 eq of the sodium salt of 2-nitropropane yielded a mixture of 6-formyl (2 and 5a) and carbon-carbon bond-cleavage products (3 and 6a). When a large excess of the sodium salt of 2-nitropropane was used, 3 and 6a were obtained as sole products, respectively. The nitrates [(5-bromo-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-6-yl)methy l nitrate (1b) and the dinitrate of 5-bromo-6-hydroxymethyl-1-(3-hydroxypropyl)-3-methyl-2,4(1H,3H)-pyrimid inedione (4b)] were exclusively converted to 6-formylpyrimidines (2 and 5b) or 6-unsubstituted pyrimidinediones (3 and 6b) by reaction with 1.0 or 2.0 eq of sodium methoxide, respectively. The dinitrate of 5-bromo-1-(2-hydroxyethyl)-6-hydroxymethyl-3-methyl-2,4(1H,3H)-pyrimidi nediones (7) was treated with sodium methoxide to yield 2-(5-bromo-6-formyl-3-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl )ethyl nitrate (8), a 3,4-dihydropyrimido[6,1-c][1,4]oxazine derivative (9) and 2-(5-bromo-3-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)ethyl nitrate (10). A plausible reaction mechanism is presented.
Site-Selective C–H Functionalization of (Hetero)Arenes via Transient, Non-symmetric Iodanes
Fosu, Stacy C.,Hambira, Chido M.,Chen, Andrew D.,Fuchs, James R.,Nagib, David A.
supporting information, p. 417 - 428 (2019/02/14)
Fosu, Hambira, and colleagues describe the direct C–H functionalization of medicinally relevant arenes or heteroarenes. This strategy is enabled by transient generation of reactive, non-symmetric iodanes from anions and PhI(OAc)2. The site-selective incorporation of Cl, Br, OMs, OTs, and OTf to complex molecules, including within medicines and natural products, can be conducted by the operationally simple procedure included herein. A computational model for predicting site selectivity is also included. The discovery of new medicines is a time- and labor-intensive process that frequently requires over a decade to complete. A major bottleneck is the synthesis of drug candidates, wherein each complex molecule must be prepared individually via a multi-step synthesis, frequently requiring a week of effort per molecule for thousands of candidates. As an alternate strategy, direct, post-synthetic functionalization of a lead candidate could enable this diversification in a single operation. In this article, we describe a new method for direct manipulation of drug-like molecules by incorporation of motifs with either known pharmaceutical value (halides) or that permit subsequent conversion (pseudo-halides) to medicinally relevant analogs. This user-friendly strategy is enabled by combining commercial iodine reagents with salts and acids. We expect this simple method for selective, post-synthetic incorporation of molecular diversity will streamline the discovery of new medicines. A strategy for C–H functionalization of arenes and heteroarenes has been developed to allow site-selective incorporation of various anions, including Cl, Br, OMs, OTs, and OTf. This approach is enabled by in situ generation of reactive, non-symmetric iodanes by combining anions and bench-stable PhI(OAc)2. The utility of this mechanism is demonstrated via para-selective chlorination of medicinally relevant arenes, as well as site-selective C–H chlorination of heteroarenes. Spectroscopic, computational, and competition experiments describe the unique nature, reactivity, and selectivity of these transient, unsymmetrical iodanes.
Room-Temperature Gold-Catalysed Arylation of Heteroarenes: Complementarity to Palladium Catalysis
Cresswell, Alexander J.,Lloyd-Jones, Guy C.
supporting information, p. 12641 - 12645 (2016/08/30)
Tailoring of the pre-catalyst, the oxidant and the arylsilane enables the first room-temperature, gold-catalysed, innate C?H arylation of heteroarenes. Regioselectivity is consistently high and, in some cases, distinct from that reported with palladium ca
DERIVATIVES OF TRIAZINES AND URACILS, THEIR PREPARATION AND THEIR APPLICATION IN HUMAN THERAPEUTICS
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Page/Page column 18, (2010/04/03)
The present invention relates to derivatives of general formula I wherein : - W represents nitrogen, - R1 represents: ? a hydrogen or a linear or branched C1-C5 alkyl radical or, ? a C1-C3 alkyl radical substituted with groups such as trifluoromethyl, nitrile, hydroxy, C1-C3 alcoxy, C3-C6 alkoxyalkoxy, indolyl, thiophenyl, oxothiophenyl, C1-C3 N-alkylcarbamoyl groups or, ? a phenyl or pyridyl or naphthyl, or thiophenyl group optionally substituted with one or more groups such as halogen atoms, nitro, nitrile, trifluoromethyl, vinyl, methylsulfanyl, linear branched C1-C4 alkyl, linear or branched C1-C3 alkoxy groups, ? a C6 2-oxocycloalkyl radical - R2 represents a methyl or heptyl, - m, n are equal to 1, - V represents CH2, - X-Y represents -N- (C=O) -, -CH-O-, - Z represents a phenyl group substituted with one or more trifluoromethyl groups, halogen atoms or linear C1-C4 alkyl groups.
Pyrimidine derivatives XII. A convenient preparation of 6-formylpyrimidinedione and 2- and 3-formylpyridine derivatives from corresponding nitrooxymethyl derivatives
Kinoshita,Ohishi
, p. 1599 - 1603 (2007/10/02)
The convenient preparation of 6-formylpyrimipinedione derivatives and 2- and 3-formylpyridine are described. Thus, 5-bromo-1,3-dimethyl- (1a), 5-bromo-3-methyl-1-(2-nitrooxyethyl)- (1b), and 5-bromo-3-methyl-1-(3-nitrooxypropyl)-2,4(1H,3H)-pyrimidine-dione (1c) were converted to the corresponding 6-formyl compounds 2a, 2b, and 2c, respectively, in excellent yields by the reaction with triethylamine and 1,4-diazabicyclo[2.2.2]octane. These 6-formylpyrimidinedione derivatives are key intermediates for the preparation of 6-carbon-carbon substituted compounds, which are expected to be potential antitumor and antiviral agents. Similarly, 2-(and 3-)formylpyridine (9a (and 9b)) were obtained by the reaction of 2-(and 3)nitrooxymethylpyridine (8a (and 8b)) with 1,4-diazabicyclo[2.2.2]octane.
Photochemistry of Uracils in Halogenated Solvents
Moltke-Leth, Claus,Joergensen, Karl Anker
, p. 1487 - 1490 (2007/10/02)
The photochemistry of uracil and 1-substituted and 1,3-disubstituted uracils in CHBr3-CH2Cl2 is investigated.Photolysis of uracil leads to the formation of 5,6-dibromo-5,6-dihydrouracil as the main product, with 5-bromouracil as the by-product.In contrast with this the 5-bromouracils are formed as the main products by the photolysis of 1-substituted and 1,3-disubstituted uracils, with the corresponding 5,6-dihydro- and 5-bromo-5,6-dihydrouracils as the by-products.The kinetics of the bromination reaction have also been investigated and based on these results a free radical mechanism is proposed.
Selective Oxidative Halogenation of Uracils
Moltke-Leth, Claus,Joergensen, Karl Anker
, p. 1117 - 1121 (2007/10/02)
A variety of N-substituted uracils has been selectively brominated to the corresponding 5-bromouracils in high yield by CHBr3-O2.Both oxidative bromination and chlorination of N-substituted uracils can be performed by means of combination of haloalkane solvents with m-chloroperbenzoic acid, magnesium monoperoxyphthalate, tert-butyl hydroperoxide or iodosylbenzene.Intermediates along the reaction path leading to the 5-halouracils have been identified; the intermediates depend on the oxidant used.Mechanistic aspects of the halogenation reactions and the reactive intermediates are discussed.
In-cell Indirect Electrochemical Halogenation of Pyrimidine Bases and their Nucleosides to 5-Haloderivatives
Palmisano, G.,Danieli, B.,Santagostino, M.,Vodopivec, B.,Fiori, G.
, p. 7779 - 7782 (2007/10/02)
Reaction of anodically generated "halonium" species (LiX or Bu4NX, LiClO4, MeCN, Pt/Pt; I2, LiClO4, MeCN) with pyrimidine bases and their nucleosides leads to 5-halo compounds in good yields.
