Pyrazole synthesis from pyrimidine

H-l-Benzopyran-4-ones — see Chromones 4H-l-Benzopyran-4-ones, 2-phenyl — see Flavones Benzopyranopyrazoles synthesis, 5, 317, 341 Benzopyrano[4,3-c]pyrazol-4-one synthesis, 3, 712 Benzopyrano[4,3-f>]pyridine synthesis, 3, 712 Benzopyrano[4,3-d]pyrimidine synthesis, 3, 712 Benzopyrans nomenclature, 1, 23 pyrylium salt synthesis from, 3, 873 reactions... 

Further annelation to pyrimidine ring based on substitution of fluorine at 5-position was used in patent literature. Alantos Pharmaceuticals in a course of matrix metaUoprotease inhibitors development described an efficient pyrazole annelation to pyrimidine. The synthesis of key intermediate - pyrimidine dicarbox-ylic acid 188 was accomplished in 3 step bromination - carbonylation - oxidation sequence from pyrimidinone 185. The acid was converted to the corresponding... 

Cyclopent-2-en-l-one, 2-hydroxy-3-methyl-synthesis, 3, 693 Cyclopentenone, 4-methoxy-formation, 1, 423 Cyclopenthiazide as diuretic, 1, 174 Cyclopent[2,3-d]isoxazol-4-one structure, 6, 975 Cyclophane conformation, 2, 115 photoelectron spectroscopy, 2, 140 [2,2]Cyclophane conformation, 2, 115 Cyclophanes nomenclature, 1, 27 Cyclophosphamide as pharmaceutical, 1, 157 reviews, 1, 496 Cyclopiloselloidin synthesis, 3, 743 Cyclopolymerization heterocycle-forming, 1, 292-293 6H-Cyclopropa[5a,6a]pyrazolo[l,5-a]pyrimidine pyrazoles from, 5, 285 Cydopropabenzopyran synthesis, 3, 700 Cyclopropachromenes synthesis, 3, 671 Cyclopropa[c]dnnolines synthesis, 7, 597 Cyclopropanation by carbenes... 

Although only a few condensed 5 6 or 5 5 aromatic pyrazole derivatives can be isolated from biological sources, the chemistry of condensed pyrazoles has received considerable interest. Condensed pyrazoles with an indene skeleton can be considered as purine analogues and, as such, are expected to have biological activity. The discovery of the xanthene oxidase inhibitory action of pyrazolo[3,4-fiT pyrimidine and the cAMP phos-phodiasterase inhibitory action of pyrazolo[l,5-a]pyrimidines has stimulated considerable interest in the synthesis of analogues of both ring systems. 

New pyrazolo[l,5-a]pyrimidine derivatives have been synthesized. These compounds are potent angiotensin-ll receptor antagonists <99CPB928>. Pyrazolot3,4-ri]dihydropyridazinone derivatives have been obtained by the reaction of 5-methyl-4-methoxycarbonyl-3-acetyl-1-phenylpyrazole with different hydrazines <99TL3891>. A direct synthesis of pyrazolo [3,4-b]pyridines 69 from pyrazole 67 and benzothiazole 68, through a Friendlander condensation, has been described <99SC655>. 

B. Synthesis of PYRAZOLo[3,4-r/]pyrimidine 1. From Pyrazole Intermediates... 

Quiroga et al. have described the synthesis of pyrazole 26c g and pyrimidine 27a,b TB derivatives and suggested the mechanism of their formation from isolated intermediates (02TL5617, 02JCS(P1)1588). In this case, C-alkylation served to initiate... 

Cyclocondensation routes also provide access to pyrimidines. 2,3-Disubstituted pyrido[2,3-/i]-quinazolin-4(3//)-ones are obtained via cyclocondensation of 5-aminoquinoline-6-caiboxylic acid with acid chlorides <02SC235>. 5,6,8-Trialkyl-7-methoxy-2-aminoquinazolines are obtained from 1,3-dimethoxybenzenes via cyclocondensation of intermediate dihydrobenzenes with guanidine carbonate <02TL3295>. Diastereoselective intramolecular hetero Diels-Alder cyclization of a pyrazole carboxaldehyde condensed onto 1,3-dimethylbarbituric acid (101) gave polycyclic heterocycle 102 <02T531>. An efficient one-step synthesis of cyclobutene-annelated pyrimidinones 103 from methyl 2-chloro-2-cyclopropylideneacetate and amidines has been... 

A synthesis of sildenafil, which contains a bicyclic system (a l//-pyrazolo[4,3- f pyrimidine) isomeric with that of a purine, starts with a routine synthesis of a pyrazole (cf. 25.12.1.1) followed by M-methylation and ring nitration. Functional group manipulation provides a pyrazole equivalent to AICA (27.11.1.2) from which the pyrimidone ring is formed via reaction with an aromatic acid chloride. 

The synthesis of pyrazolo[5,1 -6]purin-2-ones 261 started from ethyl 7-amino-pyrazolo[l,5-a]pyrimidine-6-carboxylates 262, following hydrazinolysis and reaction with HN02 gave the corresponding azide and the modified Curtius reaction closed the third pyrazole ring of 261. The final tricyclic 261 can be hydrolyzed to 6,7-diamino-pyrazolo[l, 5-a]purines (68CPB2195) (Scheme 77). 

An extremely simple one-pot synthesis of pyrazoles, pyrimidines, and isoxazoles has been realized by reacting enamino ketones, formed in situ with the appropriate bidentate nucleophile, under the action of microwaves [38]. Another approach to pyrazole from 4-alkoxy-l,l,l-trichloro-3-alken-2-ones and hydrazines, with toluene as solvent, is also possible under microwave conditions [39]. The Ullman coupling of (S)-[l-(3-bromophenyl)ethyl]ethylamine with N-H-containing heteroarenes such as pyrazole in N-methylpyrrolidone afforded the N-arylated compounds in high yields under microwave heating conditions at 198 °C [40]. 

Over the last few decades, a wide range of methodologies have been developed for the preparation and manipulation of pyrimidine derivatives. Recently, a microwave-assisted approach to the synthesis of pyrazolo[l,5-n]pyrimidines was reported (Scheme 2.4). Equimolar amounts of the pyrazole and chromen-4-one were heated for 2 min without added solvent. This afforded pyrimidine derivatives that were fairly pure directly from the reaction vessel. Recrystallization from ethanol gave pure materials in excellent yield (88-93%). Since the chemistry was performed neat, the only solvent used was a small amount of ethanol in the purification step, this representing a very clean and straightforward way to generate these valuable materials. 

Reactions of heterocycles ch29 How to make pyridazines and pyrazoles How to make pyrimidines from 1,3-dicarbonyl compounds and amidines How to make thiazoles How to make isoxazoles and tetrazoles by 1,3-dipolar cycloadditions The Fischer indole synthesis Making drugs Viagra, sumatriptan, ondansetron, indomethacin How to make quinolines and isoquinolines ... 

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