31217-00-2

Upstream product

• 874-14-6 1,3-dimethyluracil 
• 937-14-4 3-chloro-benzenecarboperoxoic acid 
• 64-19-7 acetic acid 
• 119255-07-1 5,5'-mercuribis(1,3-dimethyluracil) 

Downstream Products

• 110225-42-8 1,3-dimethyl-5-(2,5-dimethylphenyl)uracil 
• 874-14-6 1,3-dimethyluracil 
• 4401-71-2 1,3-dimethylthymine 
• 105202-34-4 1,3-dimethyl-5-o-tolylpyrimidine-2,4(1H,3H)-dione 
• 105202-36-6 1,3-dimethyl-5-p-tolylpyrimidine-2,4(1H,3H)-dione 
• 105202-35-5 1,3-dimethyl-5-(m-tolyl)pyrimidine-2,4(1H,3H)-dione 
• 55377-22-5 1,3-dimethyl-5-phenylpyrimidine-2,4(1H,3H)-dione 
• 136738-87-9 1,3-dimethyl-5,6-dihydro-5-(2,5-xylyl)uracil 
• 136738-88-0 1,3-dimethyl-5,6-dihydro-5-(p-methylbenzyl)-5-(2,5-xylyl)uracil 
• 1420467-03-3 5-chloro-1,3-dimethyl-6-(p-chlorophenyl)uracil 
• 1420467-02-2 5-chloro-1,3-dimethyl-6-(p-methoxyphenyl)uracil 
• 1420467-01-1 5-chloro-1,3-dimethyl-6-(p-tolyl)uracil 
• 1381948-78-2 5-chloro-1,3-dimethyl-6-phenyluracil 
• 129056-81-1 5-Carboxymethyl-1,3-dimethyluracil 

Relevant academic research and scientific papers

Practical halogenations of nucleosides using tetrabutylammonium peroxydisulfate

Direct halogenation of a wide range of acetylated pyrimidine and purine nucleosides was achieved with high regioselectivity in good yields using tetrabutylammonium peroxydisulfate 1. Treatment of protected nucleosides with HCl/DMF or inorganic salts such as LiCl or NaCl in MeCN/AcOH in the presence of 1 gave the corresponding chlorinated nucleosides and bromination was achieved with N-bromosuccinimide in MeCN in the presence of 1.

Site-Selective C–H Functionalization of (Hetero)Arenes via Transient, Non-symmetric Iodanes

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.

BORON-CONTAINING SMALL MOLECULES

Compounds, pharmaceutical formulations, and methods of treating anti-inflammatory conditions and/or helminth-associated diseases are disclosed.

Novel process for generating useful electrophiles from common anions using Selectfluor fluorination agent

In the present work, the electrophile equivalents C1+, Br+, SCN+, and NO2+ are generated from their respective sodium, potassium, and in some cases ammonium salts (M+X-) by reaction with Selectfluor electrophilic fluorination agent in acetonitrile solution at room temperature. These generated electrophilic species subsequently react in situ with a variety of aromatic substrates containing one or more substituent groups including H, F, C1, CH3, COOH, C(O)CH3, NO2, and OR′ and NR′R″ where R′ and R″ are H or CH3. The resulting substitution products are, in most cases, isolable as pure compounds in high yield. Variations in the process include the use of other anions, electrophilic fluorination agents, and solvents.

Process for generating electrophiles from anions by reaction with electrophilic fluorinating agent

A process includes substituting a substituent on a substrate. The process includes reacting a salt of an anionic form of the substituent with an electrophilic fluorination agent to provide an electrophile containing a cationic form of the substituent. The electrophile is then electrophilically substituted on the substrate. In some aspects of the process, the substrate can be an aromatic or a non-aromatic. The process can be used for a variety of reactions having electrophilic mechanisms, including halogenation, thiocyanation and nitration.

Selective Oxidative Halogenation of Uracils

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

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.

Cerium(IV)-Mediated Halogenation at C-5 of Uracil Derivatives

Treatment of protected uracil nucleosides 1 or 2 with elemental iodine or metal halogenides and ceric ammonium nitrate (CAN) at 80 deg C gave the corresponding protected 5-halouracil nucleosides 3a-f in excellent yields.Treatment of the resulting crude 3a-f with 0.1 M NaOMe/MeOH at ambient temperature gave the corresponding 5-halouridines 4a-f in high overall yields from 1 or 2.Further, 5-halouraciles 9a-f were prepared in good yields by treatment of 1,3-dimethyluracil (7) or uracil (8) with elemental iodine, metal halogenides, or hydrochloric acid and CAN.Halouridines 4a-e also were obtained in good yields by treatment of unprotected uracil nucleosides 5 or 6 with halogen sources as above and CAN.

Halo-demercuration Reactions of the 1,3-Dimethyluracil and 1-Methyluracil 5-Substituted Mercurials

Detailed procedures are submitted for direct mercuration (with Hg(II) acetate or chloride) of 1,3-dimethyluracil (I) or 1-methyluracil (VIII) with formation, subsequently, of 5-acetoxymercuri-1,3-dimethyluracil (II), 5-chloromercuri-1,3-dimethyluracil (III) or 5-acetoxymercuri-1-methyluracil (IX) in 52percent, 64percent or 49percent yields, respectively; II with hot solution of NaCl gave III in 45percent yield, whereas from II in hot aq.KI solution 5,5'-mercuribis(1,3-dimethyluracil) (IV) was formed in 89percent yield.The mercurials II, IV or IX were effectively halo-demercurated forming thus: 5-iodo- (V), 5-bromo- (VI) and 5-chloro-1,3-dimethyluracil (VII) or (from IX) 5-bromo-1-methyluracil (X) in the respective yields: 83-88percent, 82-85percent, 74 or 78percent.The structures of I-X are supported chemically, in part analytically as well as by the 1H-NMR spectra (see the Figure).