Synthesis of novel acyclonucleosides. Reactions of 1-(2-oxopropyl)pyridazin-6-ones

Multi-substituted-1-(1-bromo-2-oxopropyl)pyridazin-6-ones 3, 4 , multi-substituted-1-(1,1-dibromo-2-oxopropyl)pyridazin-6-ones 7, 8 , and multi-substituted-1-(3-bromo-2-oxopropyl)pyridazin-6-ones 5, 6 were synthesized from the corresponding 1-(2-oxopropyl)pyridazin-6-ones 1, 2 by the selective bromination in acidic or neutral medium. And treatment of 1,1-dibromo-2-oxopropyl derivatives 7, 8 with aqueous potassium carbonate gave the corresponding pyridazin-6-ones 9, 10 by the dealkylation. Reaction of 1 with methanolic potassium cyanide afforded only the corresponding 4-methoxy derivative 11 , whereas reaction of 2 with methanolic potassium cyanide gave 4-methoxy derivative 12 and 2-cyano-2-hydroxypropyl derivative 13 . Reaction of 1 and 2 with hydroxylamine in methanol afforded the corresponding syn-2-hydroxyiminopropyl derivatives 14 and 15 .     

Synthesis and reactions of 1-(2-oxopropyl)pyridazin-6-ones

Oxopropylation of 4,5-dihalopyridazin-6-ones with chloroacetone afforded the corresponding 1-(2-oxo-propyl) derivatives. Reaction of title compound with nucleophiles such as amines, alkoxides were investigated. In addition, selective reduction of 3-nitro-1-(2-oxopropyl)pyridazin-6-ones with iron/ammonium chloride in two phase solutions or zinc in acetic acid gave the corresponding 3-amino or 3-hydroxyimino derivatives.     

Synthesis of (hetero)arylated pyridazin-3(2H)-ones via Negishi reaction involving zincated pyridazin-3(2H)-ones

Zincated pyridazin-3(2H)-ones generated via bromine-magnesium exchange followed by transmetalation using ZnCl(2) or via lactam-directed ortho C4-H zincation with TMPZnCl·LiCl have been synthesized. These in situ created organometallics can be used in Negishi reactions with iodo(hetero)arenes delivering a new approach toward (hetero)arylpyridazin-3(2H)-ones.     

Functionalization of 4,5-dihalopyridazin-6-ones using 1-(1,1-dibromo-2-oxopropyl) derivatives

Functionalization of 4,5-dihalopyridazin-6-ones using 1-(1,1-dibromo-2-oxopropyl)-4,5-dihalopyridazin-6-ones with some nucleophiles gave regioselectively only 5-halo-4-substituted-pyridazin-6-ones.     

Synthesis of 1-(2-furyl)-2-nitropropen-3-ones

1-(2-Furyl)-2-nitropropen-3-ones were synthesized by reaction of nitrogen tetroxide with a number of , -unsaturated furylcarbonyl compounds. The 5-nitrofuryl derivative was obtained from 1-(2-furyl)-3-(4-methoxyphenyl)propen-3-one when the excess amount of N₂O₄ was increased. Replacement of bromine by a nitro group in the furan ring is observed in the case of the 5-bromofuryl derivative.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1604–1606, December, 1977.     

2-Quinazolylguanidines in Heterocyclization Reactions. 3. Synthesis of 2-[(6-R-4-Methyl-2-quinazolyl)amino]pyrimidine-(1H)-ones

We synthesized 2-(6-R-4-methyl-2-quinazolyl)amino-1,4-dihydropyrimid-4-ones by reaction of 6-R-4-methyl-2-quinazolylguanidines with acylacetic esters.     

Synthesis of 4,5-dichloro-1-(4,5-dichloropyridazin-3-yl)pyridazin-6-one

This paper presents the synthesis of 4,5-dichloro-1-(4,5-dichloropyridazin-3-yl)pyridazin-6-one from 4,5-dichloropyridazin-6-one.     

Retro-ene reactions. III. Alkylation of 4,5-dichloro-1-hydroxymethylpyridazin-6-ones: Synthesis of 4,5-dichloro-1-(ω-phthalimido and saccharin-2′-ylalkyl)pyridazin-6-ones

4,5-Dichloro-1-(ω-phthalimido and saccharinyl-2′-ylalkyl)pyridazin-6-ones were synthesized from 4,5-dichloro-1-hydroxymethylpyridazin-6-one and the corresponding N-(ω-haloalkyl)phthalimides and saccharins via a fragmentation of retro-ene type.     

Synthesis of 5-substituted 3-(2-oxopropyl)tetrahydrofuran-2-ones and heterocyclic compounds on their base

Alkylation of ethyl 2-oxotetrahydrofuran-3-carboxylates with 2,3-dichloroprop-1-ene and 3-bromoprop-1-yne gave new 3,5,5-tri- and 3,3,5,5-tetrasubstituted tetrahydrofuran-2-ones which were converted into the corresponding 3-(2-oxopropyl)tetrahydrofuran-2-ones. Reactions of the latter with semicarabazide, thiosemicarbazide, and phenylhydrazine were studied with a view to obtain new heterocyclic lactones.     

Synthesis of functionalized pyridazin-3(2H)-ones via nucleophilic substitution of hydrogen (SNH)

Reaction of 2-benzyl-5-halopyridazin-3(2H)-ones (3) with Grignard reagents followed by quenching with electrophiles unexpectedly yielded 4,5-disubstituted pyridazin-3(2H)-ones instead of 5-substituted pyridazin-3(2H)-ones. These reactions represent the first examples of cine substitution in which the anionic σ(H)-adduct is quenched by electrophiles (other than a proton) before elimination takes place. Insight into the reaction mechanism led to the direct transformation of 2-benzylpyridazin-3(2H)-one (7) and 2-benzyl-6-chloropyridazin-3(2H)-one (9) into the corresponding C-4 alkyl and aryl derivatives (when Br(2) was used as the electrophile).     

6-溴-3-[2-(6-溴-2-甲氧基喹啉-3-基)-1,2-二苯乙基]-2-甲氧基喹啉的合成

以6-溴-3-(氯苯基甲基)-2-甲氧基喹啉(2)为起始原料,经过偶合对接反应合成了新型喹啉类抗结核药物TMC-207的衍生物6-溴-3-[2-(6-溴-2-甲氧基喹啉-3-基)-1,2-二苯乙基]-2-甲氧基喹啉,其结构经1H NMR和HR-MS确证.最佳反应条件:2 10 mmol,Et_3N 5 mL,KI 0.17 g,乙腈150 mL,于80 ℃反应6 h,收率73%.     

Synthesis of Dimethyl 2-(2-Alkyl-1,3-diaryl-3-oxopropyl)malonates and Their Reactions with Amines

Zinc enolates generated from 1-aryl-2-bromoalkanones and zinc react with dimethyl 2-(1-arylmethylene)malonate to form dimethyl 2-(2-alkyl-1,3-diaryl-3-oxopropyl)malonates. The latter react with benzylamine or cyclohexylamine to form the corresponding disubstituted amides, while the reactions with piperidine, morpholine, and p-methoxyaniline provide monosubstituted amides of the corresponding target derivatives.__________Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 4, 2005, pp. 636–641.Original Russian Text Copyright © 2005 by Shchepin, Korzun, Poroshina.     

Synthesis and properties of z-1,3-bis-(aryl)-4-bromo-2-buten-1-ones

Bromination of 1,3-bis(aryl)-2-buten-1-ones by N-bromosuccinimide in anhydrous carbon tetrachloride gives Z-1,3-bis(aryl)-4-bromo-2-buten-1-ones. The effect of the nature of substituent in the benzene ring on the course of a reaction with nucleophiles has been studied. Heating an alcohol solution of these ketones (Ar = 4-MeOC₆H₄, 4-ClC₆H₄) in the presence of acid or in the presence of base (Ar = Ph) gave 2,4-bis(aryl)furans. Treatment of 1,3-bis(aryl)-4-bromo-2-buten-1-ones with thioacetamide gave 2,4-bis(aryl)thiophenes. The oxidation of the halo-substituted dypnones with H₂O₂/NaOH gave (3-bromomethyl-3-aryl-2-oxiranyl)(aryl)methanones. The reaction of halo-substituted dypnones with aryl hydrazines gave 1,3,5-triaryl-1,6-dihydropyridazines or 1,3,5-triarylpyridazinium bromides depending on the structure of the reagents.     

6-甲基-4-(3-三氟甲基苯基)-3(2H)-哒嗪酮的合成与生物活性研究

在对3-三氟甲基-1,1'-联苯类衍生物类化合物进行CoMFA计算的基础上,设计合成了化合物6-甲基-4-(3-三氟甲基苯基)-3(2H)-哒嗪酮(T-1),分别采用小杯法、浮萍法和盆栽法对其除草活性进行了较详细的研究,发现化合物T-1具有很好的白化活性和除草效果.研究了T-1的合成路线,实施了三条完全不同的路线进行合成,比较了三条路线的优缺点.     

Synthesis of 1-(2-oxopropyl)adamantane from 1-bromo(chloro)adamantanes and isopropenyl acetate in the presence of iron and manganese compounds

An efficient procedure has been developed for the synthesis of 1-(2-oxopropyl)adamantane by reaction of 1-bromo(chloro)adamantanes with isopropenyl acetate in the presence of manganese and iron compounds.     

Reactions of 1-aryl-2-bromo-3,4,4-trichlorobut-3-en-1-ones with some nucleophilic reagents

Reactions of 2-bromo-1-phenyl- and 2-bromo-1-(4-methylphenyl)-3,4,4-trichlorobut-3-en-1-ones with morpholine and diethylamine are accompanied by prototropic allylic rearrangement, leading to 3-amino-1-aryl-2-bromo-4,4-dichlorobut-2-en-1-ones as mixtures of E and Z isomers. The title compounds react with hydrazine, hydroxylamine, and thiourea to give the corresponding 5-aroyl-4-methoxypyrazoles, 3-aryl-5-hydroxyiminomethyl-4-methoxyisoxazoles, and 2-amino-4-aryl-5-trichlorovinylthiazoles.