Pyridines carbamoyl

The lUPAC name is [(2R,3R,4S,5S)-2-(6-aminopurin-9-yl)-5-[[[[(2S,3S,4R,5R)-5-(5-carbamoyl-pyridin-l-yl) -3,4-dihydroxy-oxolan-2-yl] methoxy-oxido-phosphoiyl] oxy-hydroxy-phos-phoryl]-ox)methyl]-4-hydroxy-oxolan-3-yl]oxyphosphonic acid. 

Bis(carbamoyl) peroxides of the foUowiag structure were prepared by reaction of the corresponding carbamoyl chlorides and hydrogen peroxide—urea complex in the presence of pyridine (211). 

N-( 1,3-Benzoxazinyl)aminomethylenemalonates (1529 and 1531) were obtained in 70-87% yields when AM 3- and 4-carbamoyl-4- and 3-hydroxy-phenyl)aminomethylenemalonates (1528 and 1530) were first treated with ethyl chloroformate dropwise in a mixture of pyridine and acetonitrile at 0-5°C. After refluxing the mixtures for 2 hr, the low-boiling solvent was removed under reduced pressure and the residues again were refluxed at about 125°C for 1 hr (75IJC1275). 

The bicyclic meso-ionic 3-oxo-l,2,4-triazolo[4,5-a]pyridines (206) have been prepared by the following methods (i) the reaction of the hydrazines (207, X = H) with phosgene, (ii) heating the amide (207, X = CONH2) or the carbamate (207, X = COjEt), and (iii) alkylation or acylation of 3-oxo-l,2,4-triazolo[4,5-a]pyridine (208). The isomeric meso-ionic 2-oxo-l,3,4-triazolo[4,5-a]pyridines (209) are formed from the carbamoyl chlorides (210) and sodium azide. ... 

Free radical acylation of pyridines generally results in predominant or exclusive formation of the 2- and 4-substituted isomers, and carbamoylation, carboxylation and halogenation show similar product distributions. In certain of these reactions, most notably carbamoylation, synthetically significant yields of substitution products can be realized, but in many cases while quoted yields can look impressive, actual conversions can be very low <74AHC(16)123>. 

Acyl radicals obtained by the oxidation of aldehydes or the oxidative decarboxylation of a-keto acids react selectively at the a- or y-position of the protonated heterocyclic nitrogen. Pyridines, quinolines, pyrazines and quinoxalines all react as expected yields are typically 40 to 70%. Similarly, pyridines can be carbamoylated in acid media at C-2 (Scheme 38). 

The introduction of a carbamoyl group to the 5-position of chiral 3-pyridyl alkanol enhances its efficacy as asymmetric autocatalyst. (S)-5-Carbamoyl-3-pyridyl alkanols 61 are automulti-plied with up to 86% ee in the enantioselective addition of i-Pr2Zn to 5-carbamoyl-3-pyridine-carbaldehyde 60 (Scheme 9.32) [60]. The enantioselectivity depends on the structure of the substituent on the nitrogen atom of the amide. A bulky t-Pr substituent is efficient for achieving high enantioselectivity. The amplification of the enantiopurity of 61 to a certain degree is also observed [61]. 

Newcomb and coworkers have very elegantly demonstrated that N-hydroxypyridine-2-thione carbamates lc (PTOC carbamates, X = NR2) are directly analogous to the A-hydroxy-pyridine-2-thione esters la. They can be prepared readily from primary and secondary amines. Reaction of these carbamates in a radical chain process gives carbamoyl radicals that decarboxylate to give aminyl radicals, Scheme 40.66 71 In the... 

In many of the precedent reactions, pyridines are inert, and activation of this fundamental heterocycle remains problematic. To overcome this problem, more powerful activating agents have been tested. For instance, Corey explored the use of triflic anhydride (35) as an efficient method to link a variety of nucleophiles to the pyridine y-position (see 34, Scheme 6) [49]. This reaction in the presence of isocyanides affords a mixture of the a-and y-carbamoylated dihydropyridines 245 and 246 together with the corresponding oxidized products 245 and 246, respectively, in low overall yield (Scheme 36a). A major problem here is the massive degradation of the isocyanide under these rather drastic conditions. Trifiuoroacetic... 

Alternative reaction pathways exploring different synthetic possibilities have been studied. For instance, electron-rich dihydroazines also react with isocyanides in the presence of an electrophile, generating reactive iminium species that can then be trapped by the isocyanide. In this case, coordination of the electrophile with the isocyanide must be kinetically bypassed or reversible, to enable productive processes. Examples of this chemistry include the hydro-, halo- and seleno-carba-moylation of the DHPs 270, as well as analogous reactions of cyclic enol ethers (Scheme 42a) [223, 224]. p-Toluenesulfonic acid (as proton source), bromine and phenylselenyl chloride have reacted as electrophilic inputs, with DHPs and isocyanides to prepare the corresponding a-carbamoyl-(3-substituted tetrahydro-pyridines 272-274 (Scheme 42b). Wanner has recently, implemented a related and useful process that exploits M-silyl DHPs (275) to promote interesting MCRs. These substrates are reacted with a carboxylic acid and an isocyanide in an Ugi-Reissert-type reaction, that forms the polysubstituted tetrahydropyridines 276 with good diasteroselectivity (Scheme 42c) [225]. The mechanism involves initial protiodesilylation to form the dihydropyridinum salt S, which is then attacked by the isocyanide, en route to the final adducts. 

In a study of the synthesis of marine 2-aminoimidazole alkaloids, the aminal C-N bond of bicyclic 898 was cleaved regioselectively to form the allylic amine 899. Deuterium exchange results in H-1, H-2, and H-5, but not H-7 exchange, although the C(6)-C(7) double bond underwent isomerization 901. This is atributed to the assistance of the carbamoyl group that formed the oxazoline 900. Hydrolysis of the carbamate group of 899 under basic conditions affords either pyrrole 902 or pyridine 903 (Scheme 218) <2004OL3933>. 

Some ureido- and thioureidopyrazines have been prepared from aminopyrazines with phenyl isocyanate in pyridine, potassium thiocyanate in acid solution, and with phenyl or isopropyl isothiocyanate in pyridine. Thus 2-amino-3-carbamoyl(and jV-benzylcarbamoyl)-5,6-diphenylpyrazines refluxed with phenyl isocyanate in... 

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