Pyrazolo 4,3-6 pyridine, 5-methyl

Ring-methylated 1-ethynylpyrazoles were similarly obtained as minor produets in the pyrolysis of 3,5-dimethyl- and a mixture of 3- and 5-methyl- 1-propynoylpyrazoles. Pyrolysis of the 3-methyl derivative gave only pyrazolo[l,5-a]pyridin-5-ol... 

MethyM-cthoxycarbonyl-5-bcnzoyl-hydrazino-l //-pyrazole 274, prepared by reacting benzoyl chloride and 3-methyM-cthoxycarbonyl-5-bcnzoyl-hydrazino-l //-pyrazole hydrochloride 273, in the presence of pyridine in acetonitrile, has been cyclized with phosphoryl chloride in benzene or toluene to give 7-ethoxycarbonyl-6-methyl-3-phenyl-l //-pyrazolo[5,l -/ 1,2,4 triazolc 55. This compound has been also synthesized through cyclization of... 

Stanovnik and co-workers (100,101) systematically investigated the cycloaddition reactions of diazoalkanes with unsaturated nitrogen heterocycles, such as azolo-[l,5-fl]pyridines, pyridazin-3(2/7)-ones, and [fo]-fused azolo- and azinopyridazines. The Stanovnik group have studied the further transformations of the products and reviews of this chemistry are available. In a typical example, the reaction of 6-chlorotetrazolo[l,5-/7]pyridazine (37) with 2-diazopropane yields the NH,NH-dihy-dro-pyrazolo[4,3-(i]tetrazolo[l,5-/7]pyridazine 38 (102) (Scheme 8.11). The latter substrate reacts with acetone to produce an azomethine imine 39 that thermally rearranges to give the fused dihydro-1,2-diazepine 40. The azomethine imine obtained with glucose can be trapped with methyl acrylate to furnish the C-nucleoside 41 (103). 

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>. 

A series of pyrazolo[3,4-, pyridazinones 430 and analogues, potentially useful as peripheral vasodilators, were synthesized and evaluated as inhibitors of PDE5 extracted from human platelets. Several of them showed ICso values in the range 0.14-1.4 pM. A good activity and selectivity profile versus PDE6 was found for compound 430 (6-benzyl-3-methyl-l-isopropyl-4-phenylpyrazolo[3,4-r/]pyridazin-7(6/7)-one). Structure-activity relationship studies demonstrated the essential role played by the benzyl group at position 6 of the pyrazolopyridazine system. Other types of pyridazinones fused with five- and six-membered heterocycles (pyrrole, isoxazole, pyridine, and dihydropyridine), as well as some open-chain models were prepared and evaluated. Besides the pyrazole, the best of the fused systems proved to be isoxazole and pyridine <2002MI227>. 

A mixture of 1- and 2-alkylated products was obtained from reaction of 5-methylpyrazolo[4,3-b]pyridine with methyl iodide in ethanolic sodium hydroxide.111 Methylation of reduced pyrazolo[4,3-c]pyrid-3-ones gave either 1- or 3a-substituted products (Scheme 3).149... 

Pyrazolo[4,3-c]pyridine, 2-benzyl- H NMR, 5, 308 <73T441> Pyrazoio[3,4-b]pyridin-3-one, 6-methyl-4-phenyl-IR, 5, 332 (69M1250)... 

New C-4 fused heterocyclic systems in DHPs, AHC-52 (94) (methyl 2-(N-benzyl-N-methylamino) ethyl-2,6-dimethyl-4-(2-isopropyl-pyrazolo[l,5-a]-pyridine-3-yl)-l,4-dihydropyridine-3,5-dicarboxylate) and its pyridine analog AHC-93 (95) has also been reported to reverse MDR by inhibiting Pgp [123-125]. 

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... 

AT-Iminopyridines (327) react with diketene to give pyrazolo[l,5-a]pyridines (328) and (329) as shown in Scheme 94. Methyl iodide and sodium ethoxide convert (328) into a mixture of its N- (329) and O-methyl (330) derivatives (75CPB452). Similar cyclizations where ester and nitrile groups stabilize the intermediate carbanion are known (78BCJ251). 

MeOOC COOMe (2-Me-l-PhCON)- QH4N+ PhH (r.t.) 1 -Benzoyl-2,3-dicarbomethoxy-3a-methyl-1,3a-dihydro-pyrazolo[l,Sal-pyridine (5), other products 505.516,434... 

Pyrazolo[3,4-Z)]pyridines, the 7-chloro-6-fluoro-2,4-dimethylquinoline and its mercapto-thiadiazolyl or oxadiazolyl quinolines 21 were prepared via Diels-Alder reaction conversion of methyl 2-(3-oxo-3-phenylpropenylamino)benzoate into 3-benzoyl-l.S -quinolin-4-one 22 . A mixture of aniline derivatives and malonic ester gave a variety of 3-aryl-4-hydroxyquinolin-2(l//)-ones 23. Condensation of isatins with ketones afforded quinoline-4-carboxylic acids. 2-Aryl-l,2,3,4-tetrahydro-4-quinolinones 22 and carbazolylquinolone were also prepared. The substitution of 2-chloroquinoline gave the 2-substituted quinolines. Basic alumina has catalyzed the C-C bond formation between 2-hydroxy-1,4-naphthoquinone and 2-chloroquinoline derivative to give 21. Reaction of organic halides with 8-hydroxyquinolines gave the respective ethers. The azodye derivatives of 21 were prepared in the absence of solvent. Silica gel catalyzed the formation of 2-ketomethylquinolines from reaction of 2-methylquinolines with acyl chlorides. 

Synthesis of 3,5-difunctionalized l-methyl-lW-pyrazolo[3,4-fc]pyridines involving palladium mediated coupling reactions has been reported <04TL6633>. A novel synthesis of pyrazolo[3,4-ijjpyridines by condensation of 2-pyrone with 3-aminopyrazolone has been described <04SC2195>. 

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