Pyrazolo pyrimidines, methylation

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... 

Oxidative cyclization of the fully methylated 6-(benzylidenehydrazino)uracils (536) provides a 90% yield of the pyrazolo[3,4-J]pyrimidines (537) (75BCJ1484). 

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... 

CN l-[[3-(4,7-dihydro-l-methyl-7-oxo-3-propyl-l//-pyrazolo [4,3- pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl]-4-methylpiperazine... 

Chloro-3-ethoxy-2-methyl-2//-pyrazolo[4,3-reacted with the sodium salt of dimethyl malonate in DMF to give (pyrazolo[4,3-c/]pyrimidin-7-yl)malonate (499) [88JAP(K)246377]. 

N-( l-Acetyl-3-methyl-5-pyrazolyl)aminomethylenemalonate (1103) was cyclized to pyrazolo[l,5-a]pyrimidine-6-carboxylate (1102, R = 2-Me) in 82% yield by heating in boiling diphenyl ether for 10 min (74AP177). 

Pyrazolo[l,5-a]pyrimidine-6-carboxylates (1402) were prepared in 70% yields in the reaction of 3-aminopyrazoles and diethyl amino(trichloro-methyl)methylenemalonate in boiling ethanol in the presence of sodium ethoxide for 6 hr (78JPR533). 

Methylation of some form of 6-mercaptopurine in man has been established by the identification of 6-(methylsulphinyl)-8-hydroxypurine (LXV), 6-(methylthio)uric acid (LX), and 6-(methylthio)-8-hydroxy-A -glucuronide (LXVll). The oxidation of 6-(methylthio)purine to 6-(methylthio)-8-hydroxy-purine (LXVl) is mediated much more rapidly by rabbit liver aldehyde oxidase than by xanthine oxidase, and the oxidation is not inhibited by 4-hydroxy-pyrazolo [3, 4-d] pyrimidine [269], which is known to be an effective inhibitor of xanthine oxidase, and consequently, of the oxidation of 6-mercaptopurine [12,268]. 

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>. 

X-Ray diffraction studies of l-(4,6-dimethylethylsulfanyl-l-//-pyrazolo[3,4-r/ pyrimidinyl)-3-(5-methyl-6-methyl-sulfanyl-4-oxo-l,5-dihydropyrazolo[3,4-, pyrimidin-l-ylpropane 69, the Leonard trimethylene linker, showed unusual U-moieties formed due to intramolecular 7t—Jt stacking interactions, CH- -N, CH- -S, and S- -S interactions <2006JST106>. 

Reaction of 2-amino-3-phenylazo-5-methyl-6,7-dihydropyrazolo [ 1,5-a] -pyrimidine-7-one (209) with ACOH/H2SO4 gives the pyrazolo[l,5-a]-pyrimidine derivative 210 (77JHC155). This reaction can be looked at as electrophilic substitution of the arylazo function by the proton. Similarly, 4,5,6,7-tetrahydro-2-phenyl-3-phenylazo-5-oxopyrazolo[l,5-a] pyrimidine gives 4,5,6,7-tetrahydro-2-phenyl-5-oxopyrazolo[l,5-a]pyrimidine 212 by the action of acetic/hydrochloric acid (75T63). 

Pyrazolo[l,5-fl]pyrimidine derivative 222, when treated with water, partially changes into 223. This reaction is assumed to proceed via attack of base at C-7 (81CPB1548 81JHC163). The C-6=C-7 double bond in 222 adds a variety of electrophiles (81CPB1548 81JHC163 83H(22)1913). Thus, treatment of 222 with acetic acid and water at 70°C affords 8-carbeth-oxy-3-substituted-7-methyl-6W-pyrazolo[ 1,5-a]-1,3-diazepin-6-one (224). Compound 222 reacts with phenylhydrazine to yield the pyrazolo[3,4-6,7]pyrazolo[l,5-n]pyrimidine derivative 225. The double bond in 222 also adds diazoalkanes to yield the pyrazolo[l,5-a]pyrimidine derivatives 226 (81CPB1548 81JHC163 83H(22)1913). 

Diphenylhydrazine (Ph2NNH2) is converted into indazole (215) by Cl2C = NMe2. Oxidative cyclizations are also known thus, fully methylated 6-(benzylidenehydrazino)uracils (216) on photolysis or in hot AcOH give the pyrazolo[3,4-d]pyrimidines (217) (75BCJ1484,92KGS219). 

Pyrazolo[5,1 -6]pyrimidine HNMR, 5, 307 <75CJC119 Pyrazolo[5,l-6]pyrimidine, 8-methyl-UV, 5, 307 <62CPB620 ... 

Ethoxyphenyl)-l-methyl-3-n-propyl-l,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one (10.0 g, 32.1 mmol) was added portionwise to chlorosulfonic acid (20 ml) at 0°C under a nitrogen atmosphere. After being stirred overnight, the reaction solution was cautiously added to ice-water (150... 

Pyrazophos ethyl 2-[(diethoxyphosphinothioyl)oxy]-5-methyl pyrazolo[1,5-aJ pyrimidine-6-carboxylate Hoe 2873 Afugan Curamil... 

The UV spectra of isomeric pairs of pyrazolo[3,4-d]pyrimidine-4,6-diones and pyrazolo[4,3-<7]pyrimidine-5,7 diones show that the isomers with a [4,3-d] ring fusion absorb at longer wavelengths (red shift) compared to the [3,4-d] isomers <82IJC(B)585>. The />-quinonoid structure of the pyrimidine moiety in compounds (74) and (75) causes a bathochromic shift of 20-25 nm, relative to compounds (53) and (76). The close values of 2max for 7-methyl (77 R = Me) and 2,7-dimethyl allopurinol (74) suggest that the former is present in aqueous solutions as the A(2)-H tautomer <79JCS(Pl)2795>. 

Alkylation of pyrazolo[3,4-triethyl orthoformate gives the N-l ethyl derivative <88KGS914>. Phase-transfer methylation of 4-methoxy-l//-pyrazolo[3,4-d]pyrimidines gives a mixture (2 1) of N-l and N-2 methylated derivatives <85JOC1847>. 

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