Pyrazolo pyridine-4,7-diones

Michael-type condensation of cyanoacetohydrazide (NCCH2CONHNH2, CAH) with 1,3-dicarbonyl compounds gave pyrazolo[3,4-b]pyridines under certain conditions. With l,l,l-trifluoropentane-2,4-dione in the presence of piperidine a 1 3 mixture of pyrazolone 92a and the expected aminopyridone 91a was obtained.15 The bicycle was also obtained from hydrazone (90) or by thermal reaction between its two precursors.32 Reaction of CAH and / -keto aldehydes gave good yields of only bicyclic products 92b,20 whereas ethyl benzoylacetate in the presence of piperidine gave bicycle 92c (Ar = Ph)... 

A benzenediazonium salt in pyridine coupled with 2,3-diphenylpyrazolo-[4,3-c]pyridin-4,6-dione in the 7-position.140 Similar treatment of 1,3-disub-stituted pyrazolo[3,4-h]pyrid-4-ones afforded the 5-arylazo products.222... 

Ring opening of 3-(phenylsulfonyloxy)pyrido[3,4-d]pyrimidine-2,4-dione (587) with sodium methoxide, followed by a Lossen rearrangement gave the hydrazinopyridine ester (588) which in refluxing acid yielded 1 //-pyrazolo[3,4-c]pyridin-3-one (589) (Scheme 75) <74JHC163>. 

Using the general method described in Section 7.08.10.2 <74JHC163> 3-(phenylsulfonyloxy) pyrido[4,3-fi ]pyrimidine-2,4-dione (590) ring opens with sodium methoxide and rearranges to a hydrazinopyridine ester, which in refluxing acid yields l//-pyrazolo[4,3-c]pyridin-3-one (591) (Equation (59)). 

Shu-Jiang and co-workers [76] have developed a green approach for the synthesis of biologically important indeno[2,l-c]pyrazolo[5,4-/7]pyridines 36 via a MCR of a suitable aldehyde, 3-methyl-l-phenyl-l//-pyrazol-5-amine and 1,3-indane-dione in water under microwave irradiation without the aid of any catalyst. This protocol has the prominent advantages of being environmentally benign and having... 

The -imtnopyridinium iodide (87J) reacts with either ethoxymethylenecyano-acetate or 3-(ethoxymethylene)pentane-2,4-dione in chloroform containing potassium carbonate to give high yields of the pyrazolo[l,5-a]pyridine. 

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... 

These reactions employ microwave heating and water as the reaction medium at 100 °C for 7-9 min. The mechanism for diastereoselectivity was confirmed by density functional theory (DFT) (B3LYP) calculations. Subsequently, new multicomponent domino reactions of Meldrum s acid 159, aromatic aldehydes 69, and electron-rich heteroaryl-amines 80 have been established for the synthesis of spiro pyrazolo[l,3]dioxanes-pyridine -4,6-diones and spirojisoxazolo [l,3]dioxanes-pyridine -4,6-diones 160 in aqueous solution under microwave irradiation (Scheme 12.64) [88]. A total of 26 examples were examined to show the broad substrate scope and high overall yields (76-93%). A new mechanism was proposed to explain the reaction process and the resulting chemo-, regio-, and stereoselectivity. 

Scheme 12.64 Multicomponent synthesis of spiro pyrazolo[1.3]dioxanes-pyridine)-4,6-diones.

Bazgir et al. (2010) developed a simple, facile, and efficient three-component procedure for the synthesis of spiro[indoline-3,4 -pyrazolo[3,4-fc]pyridine]-2,6 (TFT)-diones (179) by the reaction of 4-hydroxycoumarins (176), isatins (177), and 5-amino-lH-pyrazoles (178) in water as an environmentally benign solvent, using p-toluenesulfonic acid as an inexpensive and readily available catalyst under ultrasonic irradiation (Scheme 8.58). 

Bazgir, A., Ahadi, S., Ghahremanzadeh, R., Khavasi, H. R. and Mirzaei, R 2010. Ultrasound-assisted one-pot, three-component synthesis of spiro[indoline-3,4-pyrazolo[3,4-<>] pyridine]-2,6 (l7/)-diones in water. Ultrason. Sonochem. 17 447—152. 

N. Ma, B. Jiang, G. Zhang, S.-J. Tu, W. Wever, G. Li, Green Chem. 2010, 12, 1357-1361. New multicomponent domino reactions (MDRs) in water highly chemo-, regio- and stereoselective synthesis of spiro [l,3]dioxanopyridine -4,6-diones and pyrazolo[3,4-h]pyridines. 

B. V. Lichitsky, A. N. Komogortsev, A. A. Dudinov, M. M. Krayushkin, Russ. Chem. Bull. 2009, 58, 1504-1508. Three-component condensation of 5-aminopyrazole derivatives with isatins and Meldrum s acid. Synthesis of 1,7-dihydro spiro[pyrazolo[3,4-ii]-pyridine-4,3 indole]-2, 6(l H,5H)-diones. 

In related work, the same researchers described a four-component domino reaction that allows the one-pot synthesis of highly complex spiro systems, i.e. spiro[indoline/acenaphthylene-3,4-pyrazolo[3,4-6]pyridine derivatives 59 and 60 from phertylhydrazine, 3-aminocrotononitrile, isatin or acenaphthylene-1,2-dione and cyclic 1,3-dicarbonyl compoimds, including cyclohexane-l,3-diones and barbituric or thiobaibituric acid, in the presence of ( )-camphor-10-sulphonic acid (CSA) as catalyst (Scheme 1.30). 

Acylation and metallation studies on monomers, dimers, trimers, and tetramers containing linked thiophen, pyridine, pyrimidine, furan, benzofuran, benzothiophen, and indole moieties have been published/ Deuteriation, halogenation, and diazo-coupling reactions of 2-oxo- and 2-thioxo-l,2-dihy-dropyrimidinium salts have been studied and compared with results for 2,2-dialkyl-1,2-dihydropyrimidinium and 2,3-dihydro-1,4-diazepinium salts in order to demonstrate the effect of an adjacent 0x0- or thioxo-group on the properties of a 1,5-diazopentadienium system/ Vilsmeier formylation of, and tautomerism in, 2-hydroxypyrazolo[5,l-h]quinazolone and l-phenylpyrazolo[5,l-A]-quinazoline-2,9-dione have been studied/ The pyrazolo[3,4-c]pyrazole (71) has been methylated and acetylated, the major products being (72)/ ... 

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