Microwave-assisted synthesis of fused pyrazolo[3,4-b]pyrazines by the reaction of ortho-aminonitrosopyrazoles and cyclic β-diketones

Novel fused pyrazolo[3,4-b]pyrazines 3 were prepared by assisted microwave cyclocondensation reaction of ortho-aminonitrosopyrazoles 1 and cyclic β-diketones 2 in dimethylformamide. This protocol provides a simple procedure for the synthesis of the title compounds with the advantages of easy work-up, mild reaction conditions and good yields.     

Reactiohs with α -thiocarbamoylcinnamonitriles: Synthesis of pyrazolo [1,5-a] pyrimidines

Whereas each of α -thiocarbamoyl- and α -cyanomalononitrile derivatives 1a and 1d reacted with benzamidine (2) hydrochloride to give only 4-amino-6-(4-chlorophenyl)-2-phenyl-5-pyrimidine-carbonitrile (5a), they react with 5-amino-3-phenylpyrazole (6) to yield the two differently substituted pyrazolo[l,5-a]pyrimidines 7 and 8, respectively. Compounds 1a,c reacted also with α -haloketones to produce the substituted thiazoles 10. The structures of the newly synthesized compounds were proved by spectral studies and chemical routes.     

Fluoroalkyl-containing lithium β-diketonates in the synthesis of 1,2,4-triazolo[1,5-a]pyrimidines

Cyclocondensation of fluorine-containing lithium -diketonates with 3-amino-1,2,4-triazoles afforded 7-fluoromethyl-1,2,4-triazolo[1,5-a]pyrimidines.     

Synthesis of (7-polyfluoroalkyl)pyrazolo[1,5-a]pyrimidines based on lithium fluorine-containing β-diketonates

The reactions of Li enolates of fluorine-containing -diketones with 3-aminopyrazoles afforded (7-polyfluoroalkyl)pyrazolo[1,5-a]pyrimidines. The structure of 3-bromo-2-methyl-5-phenyl-7-trifluoromethylpyrazolo[1,5-a]pyrimidine was established by X-ray diffraction analysis.     

Synthesis and antitumor activity of some new pyrazolo[1,5-α]pyrimidines

New series of pyrazolo[1,5-α]pyrimidine derivatives 7a-i,11a-c and Schiff bases 13a-c were synthesized and screened for their in vitro antitumor activity against three human carcinoma cell lines,namely colorectal carcinoma(HCT116),prostate adenocarcinoma(PC-3) and liver carcinoma(HepG-2) using MTT cytotoxicity assay at 100 μg/mL.Some of the tested compounds displayed good anticancer activities against HCT-116 and PC-3 cells.Whereas,compounds 7d and 11 a showed better antitumor activity than the rest of the compounds against both cell lines.A structure-activity relationship(SAR) has been discussed and structures of the newly synthesized compounds were confirmed by different spectral data(MS,IR,~1H NMR and ~(13)C NMR) and elemental analysis.     

Microwave-assisted synthesis of pyrazolo[3,4-b]pyridine-spirocycloalkanediones by three-component reaction of 5-aminopyrazole derivatives, paraformaldehyde and cyclic β-diketones

New pyrazolo[3,4-b]pyridine-5-spirocycloalkanedione derivatives were prepared via three-component reaction between 5-(4-R-benzylamino)pyrazoles, cyclic β-diketones and paraformaldehyde. The use of indandione as β-diketone resulted in the formation of two products, the pyrazolo[3,4-b]pyridine-5-spiroindanediones and 3-tert-butyl-1-phenylindeno[2,3-e]pyrazolo[3,4-b]pyridine. The structures of the pyrazolo[3,4-b]pyridine-5-spirocycloalkanedione were confirmed by single-crystal X-ray diffraction. This protocol provides a simple one-step synthetic methodology with the advantages of easy work-up, mild reaction conditions and environmentally benign.     

Synthesis of New Pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidines and Their Use in the Preparation of Tetraheterocyclic Systems

8,10-Dimethyl-3-(unsubstituted, methyl, ethyl, n-butyl, phenyl)-4-hydroxypyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidin-2(1H)-ones and 3-(2-hydroxyethyl)-2,8,10-trimethylpyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidin-4-ol were synthesized by cyclocondensation of 3-amine-4,6-dimethyl-1H-pyrazolo[3,4-b]pyridine with ethyl malonates and α-acetyl-γ-butyrlolactone. Dichloro- and diazido- derivatives were obtained from the reaction of pyridopyrazlopyrimidine derivatives with POCl₃ followed by NaN₃. The tetrahetrocyclic systems were formed by cyclization of 4-chloro-3-(2-chloroethyl)-2,8,10-trimethylpyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine with the appropriate primary amines. The structures of all compounds were established by NMR and mass spectra.     

Selective synthesis of 4,5-dihydroimidazo- and imidazo[1,5-a]quinoxalines via modified Pictet–Spengler reaction

An efficient tandem approach for the selective synthesis of 4,5-dihydroimidazo[1,5-a]quinoxalines 6a–g and imidazo[1,5-a]quinoxalines 7a–h by the reaction of 2-imidazolyl anilines 4a–c with aryl aldehydes 5a–k under mild reaction conditions is described. Introduction of electron releasing alkyl groups in substrates 4a–b was found to be instrumental for the success of the reaction.     

The first example of a (1R,2S,5R)-(−)-menthyl chiral auxiliary in intramolecular nitrilimine cycloadditions: synthesis of enantiopure pyrazolo[1,5-a][4,1]benzoxazepines and pyrazolo[1,5-a][4,1]benzodiazepines

By using (1R,2S,5R)-(−)-menthyl as a chiral auxiliary, we have developed a synthesis of hydrazonoyl chlorides 2 and 8, treatment of which with silver carbonate promoted the in situ generation of the corresponding nitrilimines 3 and 9. The latter underwent intramolecular cycloaddition giving, respectively, enantiopure pyrazolo[1,5-a][4,1]benzoxazepines 4, 5 and pyrazolo[1,5-a][4,1]benzodiazepines 10.     

Regioselective synthesis of linalyl compounds via addition reaction of geranyl bromide and tin with carbonyl compounds

Linalyl alkyl or aryl carbinols were regioselectively synthesized by the reaction ofgeranyl bromide and powdered tin with aldehydes and ketones.     

Microwave-prompted rapid and efficient synthesis of 3-alkyl substituted imidazo[1,5-a]pyridines

Under regular heating and microwave irradiation, 3-alkyl substituted imidazo[1,5-a] pyridines were synthesized from 2,2＇- pyridil, di-2-pyridyl ketone and aliphatic aldehydes in the presence of ammonium acetate and acetic acid. Compared to the traditional heating condition, the reaction time under microwave irradiation was shorter and 3-alkyl imidazo[1,5-a]pyddines were given in higher yield.     

Regioselective palladium-catalyzed Suzuki–Miyaura coupling reaction of 2,4,6-trihalogenopyrido[2,3-d]pyrimidines

An effective, regioselective, and novel strategy to the access of 2,4,6-trisubstituted pyrido[2,3-d]pyrimidines is developed from the corresponding 2,4,6-trihalogenopyrido[2,3-d]pyrimidine through a Suzuki–Miyaura coupling reaction involving a novel regioselective halogen discrimination.     

Regioselective synthesis of novel imidazo[1,5-b]pyridazine derivatives from diaminoimidazoles and α-acylacrylonitriles

The heterocyclization of 1,2-diamino-4H-phenylimidazole with α-acylacrylonitriles affords cleanly 7-amino-2-R-5- phenylimidazo[1,5-b]pyridazine-3-carbonitriles. The strating α-acylacrylonitriles can be generated in situ from 3-oxo-3-(het)arylpropanenitriles and triethylorthoformate or dimethylformamide dimethyl acetal, and the products can be prepared in one pot.     

An efficient synthesis of pyrazolo[3,4-b]pyridine-4-spiroindolinones by a three-component reaction of 5-aminopyrazoles, isatin, and cyclic β-diketones

Novel pyrazolopyridine-spiroindolinones were prepared by the three-component reaction of 5-aminopyrazoles, isatin, and cyclic β-diketones in aqueous media and catalyzed by p-TSA. This protocol provides a simple one-step procedure with the advantages of easy work-up, mild reaction conditions and environmentally benign.     

3-Aminopyrazolo[4,3-c]pyridine-4,6-dione as a precursor for novel pyrazolo[4,5,1-ij][1,6]naphthyridines and pyrido[4’,3’:3,4]pyrazolo[1,5-a]pyrimidines

The versatile, 3-aminopyrazolo[4,3-c]pyridine-4,6-dione (2) was synthesized and allowed to react with aldehydes, aryldiazonium chlorides, chalcones and enaminones to afford regioselectively the novel pyrazolo[4,3-c]pyridine derivatives 4a-c, pyrazolo[4,5,1-ij][1,6] naphthyridines 9a-d and pyrido[4’,3':3,4]pyrazlo[1,5-a]pyrimidines 19a-i. The structure of all the newly synthesized compounds was assigned from elemental analysis and spectral data. Also, the mechanistic aspects for the formation of the newly synthesized compounds is discussed.     

An efficient and solvent-free one-pot multi-component synthesis of novel highly substituted pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine-3-carbonitrile derivatives catalyzed by tetramethylguanidine

Abstract

An efficient solvent-free access towards highly substituted pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine-3-carbonitrile derivatives has been established through multi-component reaction of 1H‐pyrazolo[3,4‐b]pyridin‐3‐amine, aldehyde, 3-(1H-indol-3-yl)-3-oxopropanenitrile catalyzed by 1,1,3,3-tetramethylguanidine (TMG). The reaction allows the formation of one C?C and two C?N bonds with high yield. The significant features of this solvent-free reaction include mild reaction condition, readily accessible substrates, short reaction time, excellent yield, and broad substrate scopes as well as simple one-pot operation, no column chromatographic purification, which makes this strategy highly attractive.     

Synthesis of 4-aryl(hetaryl)pyrazolo[1,5-a]pyrazines by palladium-catalyzed Suzuki–Miyaura cross coupling

Chemistry of Heterocyclic Compounds - 4-Bromopyrazolo[1,5-a]pyrazines react with aryl(hetaryl)boronic acids in the presence of catalytic amounts of Pd(dppf)Cl2·CH2Cl2 and an excess of Cs2CO3...     

Design of fused systems based on σH-adducts of 6-nitro-1,2,4-triazolo[1,5-a]pyrimidine with π-excessive heteroaromatic compounds

Russian Chemical Bulletin - A new method was developed for the construction of tetra- and pentacyclic fused systems based on σH-adducts of 6-nitro-1,2,4-triazolo[1,5-a]pyrimidine with...     

Synthesis of 2,4-diamino-5-acetyl(ethoxycarbonyl)pyrimidines from β-dicarbonyl compounds and dicyandiamide and their use for building a pyrimido[4,5-d]pyrimidine system

2,4-Diamino-5-acetyl(ethoxycarbonyl)-6-methyl(phenyl)pyrimidines were obtained by the reaction of acetylacetone and -ketocarboxylic acid esters with dicyandiamide in the presence of Ni(OAc)₂. It was shown that annelation of the pyrimidine ring with this compound provides a convenient method for building the pyrimido[4,5-d]-pyrimidine system. New derivatives of 2-aminopyrimido[4,5-d]pyrimidine, 7-amino-3H-pyrimido[4,5-d]-pyrimidin-4-one, and 7-amino-1H,3H-pyrimido[4,5-d]-pyrimidine-2,4-dione were synthesized.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 159–164, January, 1991.