Pyrimidines reagents

Ai,A/-bis(hydroxymethyl) formamide [6921-98-8] (21), which in solution is in equiUbrium with the monomethylol derivative [13052-19-2] and formaldehyde. With ben2aldehyde in the presence of pyridine, formamide condenses to yield ben2yhdene bisformamide [14328-12-2]. Similar reactions occur with ketones, which, however, requite more drastic reaction conditions. Formamide is a valuable reagent in the synthesis of heterocycHc compounds. Synthetic routes to various types of compounds like imida2oles, oxa2oles, pyrimidines, tria2ines, xanthines, and even complex purine alkaloids, eg, theophylline [58-55-9] theobromine [83-67-0], and caffeine [58-08-2], have been devised (22). 

The aminolysis of esters of pyrimidine occurs normally to yield amides. The reagent is commonly alcoholic ammonia or alcoholic amine, usually at room temperature for 20-24 hours, but occasionally under refiux aqueous amine or even undiluted amine are used sometimes. The process is exemplified in the conversion of methyl pyrimidine-5-carboxylate (193 R = Me) or its 4-isomer by methanolic ammonia at 25 °C into the amide (196) or pyrimidine-4-carboxamide, respectively (60MI21300), and in the butylaminolysis of butyl ttracil-6-carboxylate (butyl orotate) by ethanolic butylamine to give A-butyluracil-5-carboxamide (187) (60JOC1950). Hydrazides are made similarly from esters with ethanolic hydrazine hydrate. 

The direct introduction of an alkythio substituent into the 5-position of uracils and analogous pyrimidines is possible. The reagent, which is usually made quite easily in situ,... 

Note Traces of ammonia left by the mobile phase should be completely removed from the chromatograms before the reagent is applied in order to avoid strong background coloration. The dipping solutions may also be applied as spray solutions. Secondary amines, amides, pyrimidines and purines do not react with the reagent [1]. In the case of benzodiazepines only those substances react which... 

Note Flavonoids react with the reagent even at room temperature [1] mycotoxins, steroids, purines, pyrimidines, cardiac glycosides and lipids only react on heating [2, 4-6]. Zirconyl sulfate can be used to replace the zirconyl chloride in the reagent this is reported to result in an increase in the sensitivity to certain groups of substances (e.g. cholesteryl esters, triglycerides) [4]. 

This is the first synthesis of pyrido[2,3-d]pyrimidines in which both nitrogen atoms of the pyrimidine ring have been supplied by the reagent. In view of the success of similar syntheses of pyrido[4,3-d]-pyrimidines this route would appear to be capable of wide extension. 

Substituted pyrimidine Quaternizing reagent Position of quaternization Principal Subsidiary product product Reference... 

Reagent P-K a 2-Chloro- pyrimidine 2-Chloro- 3-nitro- pyridine 2-Chloro- 5-nitro- pyridine 2,4-Dichloro- phenylamino-s-triazine ... 

These factors are sufficient to produce similar amounts of aminated isomers from 2,4-dichloropyrimidine which gives predominantly 4-alkoxylation products. Thus, a mixture of 2-amino-4-chloro- (302) and 4-amino-2-chloro-pyrimidine (303) is obtained on treatment of 2,4-dichloropyrimidine with alcoholic ammonia (25°, <18 hr), the reagent here being better at hydrogen bonding than piperidine. 

Treatment of 5,7-diamino-l,3,4-thiadiazolo[3,2-n]pyrimidinium ehloride (25) with Vilsmeier reagent gave the 7-formamido-l,2,4-triazolo[l,5-c]pyrimidin-5-one (27) (90JHC851) (Seheme 42). Compound 27 has presumably been formed via rupture of the 1,3,4-thiadiazole ring of 25 and... 

Vilsmeier-Haack formylation of 2-(4-methyl-l-piperazinyl)-4//-pyrido-[l,2-n]pyrimidin-4-one with a mixture of POCI3 and DMF at 95°C gave a 3-formyl derivative (93FES1225) while ethyl 4-oxo-6,7,8, 9-tetrahydro-4//-pyrido[l,2-n]pyrimidine-2-acetate at 50 °C yielded a 9-dimethylaminomethylene-3-formyl derivative (01MI4). 3-Formyl-2-hydroxy-8-[2-(4-isopropyl-l,3-thiazol-2-yl)-l-ethenyl]-4//-pyrido[l,2-n]pyri-midin-4-one was obtained from the 3-unsubstituted derivative with oxalyl chloride-DMF reagent in CH2CI2 at room temperature for 3h (OlMIPl). 

Dehydrogenation of piperidine derivative 329 with Hg(II)-EDTA reagent afforded a mixture of perhydropyrido[l,2-n]pyrimidin-2-one 330 and pyrido[],2-c][],2,5]oxadiazine 331 (99ZN(B)632). 

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