Pyrazolo pyrimidines reduction

The palladium-catalysed reaction of the pyrazolo-pyrimidine derivative (141) with 3-bromotoluene may result in arylation at the 3-position in the pyrazole ring or at an sp hybridized site in the 7-methyl side-chain depending on the base and ligands used. After initial insertion of the palladium catalyst into the aryl halide bond, palladation of (141) occurs by a concerted metalation-deprotonation pathway and is followed by reductive elimination. Concerted metalation-deprotonation is also likely in the palladium-acetate-catalysed reaction of imidazo[l,2-a]pyridines with aryl bromides to give 3-substituted derivatives such as (142). A careful mechanistic study of the arylation of pyridine A-oxide by bromotoluene, catalysed by palladium acetate and t-butylphosphine, has shown that direct reactions of an aryl palladium complex with... 

Pyrazolo[3,4-, pyrimidines 427 and 428 were synthesized and their antiviral activity was evaluated in a plaque reduction assay. It is very interesting that this class of compounds provide remarkable evidence that they are very specific for human enteroviruses, in particular coxsackie viruses <2004BML2519>. 

Generally pyrazolo[4,3-d]pyrimidines are prepared from pyrazole-5-carboxylic acid derivatives 180 via nitration to yield 181, which on esterification and reduction affords 184 (72CCC2786 78M11 79BCJ208 80MI35 ... 

USP482361). Compound 184 is converted into the pyrazolo[4,3- /]-pyrimidine derivative 185 by formamide. Amines convert 184 into carboxamide 186, which affords 187 upon treatment with formamide (78MI1). Reduction of 181 in the presence of formic acid gives the pyrazole derivative 183, which when treated with DMF affords the pyrazolo[4,3-d]pyrimidine derivative 182 (81USP4822361 83FES369). 

The 4-aminopyrazole (250) reacts under Skraup conditions to give a useful synthesis of the pyrazolo[4,3 6]pyridine (251 19%) (58JCS3259). 1,3-Diketones (252) react with 3-aminopyrazoles e.g. 253) to give simple pyrazolo[l,5-a]pyrimidines (254). If the two R groups are different, mixtures result, but these can be treated with AT-bromosuccinimide to give the 3-bromo derivatives, purified, and the hydrocarbons regenerated by reduction (75JMC460). 

An easy synthesis of 6-aryl-1-methyl-3-propyl-6,7-dihydro-1 W-pyrazolo 4,3-rf pyrimidin-7-one derivatives 79 has been achieved by reduction of l-methyl-3-propyl-4-nitro-5-... 

Cycloaddition and cyclization routes were used to access certain 1,3-diazines. The 4+2 cycloaddition reaction of 4-(N-allyl-N-aryl)amino-l,3-diaza-l,3-butadienes with vinyl-, isopropenyl-, and chloroketene led to pyrimidinone-fused pyrimidinones <97T13841>. Cis-cyclopenta[d]pyrimidines were derived from cis-2-amino-l-cyclopentanecarboxylates by cyclization with KOCN and KSCN <97JHC1211>. 2-Thioxopyrido[3, 2 4,5]thieno[3,2-r/]pyrimidin-4(3//)-ones 19 were prepared by cyclocondensation of 2-carbethoxy-3-amino-4-phenyl-6-substituted-thieno[2,3-/)]pyridines and isothiocyanates <97JHC937>. Thiazolyl-benzimidazoles derived from 2-cyanomethyl-l//-benzimidazole and 2,3-dihydrothiazole-2-(3//)-thiones were cyclized to the corresponding thiazolo[4,5-r/]pyrimidines <97PHA346>. Reductive cyclization of 6-cyanomethyl-5-nitropyrimidines afforded 7-alkyl-5//-pyrrolo[3,2-r/]pyrimidines and 6-amino-7,7-dialkyl-7//-pyrrolo[3,2-rf]pyrimidines <97T391>. 7-Methyl-5-alkyl-2-vinyl-pyrazolo[3,4-r/]pyrimidine-4,6(5//,7//)-diones arose from cyclization and alkylation of... 

TTie synthesis of 2 .3 -dldea7 ucleosides continues to attract attention. The synthon (44) has been used to give p-selective condensation with silylated bases reductive desulphurization then gave 2 ,3 -dideoxy systems.73 Deojqrgenation procedures have been used to prepare 2, 3 -dideoxy- and 2. 3 -dldeojqrdidehydro nucleosides of 2-substituted adeninesJ4.75 pyrrolol2.3-dl pyrimidines (42. R=H),56.71 and further pyrazolo(3.4-d]pyrimidlnes.59 Enzymic... 

Also the NaBH4 reduction of fused pyrazolo[l,5-a]pyrimidines was disclosed in a course of discovery of antitubercular agents and novel structural class of potent calcium-sensing receptor antagonists. The reduction proceeds also in mild condition giving diastereoselectively desired tetrahydropyrazolo[l,5-a]pyrimidines in good preparative yields (Scheme 284) [418,778],... 

Similar intermediates are probably involved in the thionyl-chloride-promoted cyclization of 6-(benzylidene-l-methylhydrazino)-l,3-dimethyl-uracils (246 R = Me R = H) to pyrazolo[3,4-ff]pyrimidinediones (247). Less easily explained is the cyclization of hydrazones (246 R = Me R = H) to the oxazolo [5,4-f/]pyrimidines (245 X = 0) by sodium nitrite in boiling acetic acid. Undoubtedly, nitrosation at the 5-position is the initial step in these reactions, but thereafter events remain unclear. Interestingly, the ketone hydrazones (246 R = H, R = Me), on similar treatment, followed by reduction with sodium dithionite, furnish 6-aryl-l,3-dimethyl-lumazines (248) in low yields (10—15%). ... 

N-acylated esters of (cyclohexa-l,4-dienyl)-L-alanine are ozonized aiming at the synthesis of novel uimatural amino acids. The combined reduction and ozonolysis followed by condensation with a suitable nucleophile results in transformation of the aromatic ring of L-Phe to isooxasolyl, N-phenylpyrazolyl and to bicyclic pyrazolo[l,5-a]pyrimidine groups. The preparation of heterocyclic alanine derivatives is reported [89]. 

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