Pyridazine derivatives. Part 38: Efficient Heck alkenylation at position 5 of the 6-phenyl-3(2H)-pyridazinone system

Several 6-phenyl-3(2H)-pyridazinones bearing different alkenyl groups at position 5 have been prepared in the search for novel antiplatelet agents. The target compounds were synthesised by a palladium-catalysed Heck cross-coupling reaction. Variable amounts of 4-phenyl-6-substituted-2-phthalazinones were isolated as by-products during these experiments. The crucial issues for successful Heck coupling in these systems concern the protection of position 2 of the heterocyclic ring and the use of tris(o-tolyl)phosphine as a ligand.     

Pyridazine derivatives 32: Stille-based approaches in the synthesis of 5-substituted-6-phenyl-3(2H)-pyridazinones

A series of 6-phenyl-3(2H)-pyridazinones bearing different substituents in the 5-position of the pyridazinone ring were prepared using Stille-based approaches in the search for new platelet-aggregation inhibitors.     

Pyridazine derivatives. Part 33: Sonogashira approaches in the synthesis of 5-substituted-6-phenyl-3(2H)-pyridazinones

Several 6-phenyl-3(2H)-pyridazinones bearing different alkynyl groups at position 5 have been prepared by a palladium-catalysed Sonogashira cross-coupling reaction. An interesting base-promoted electronically permitted isomerization has been observed during the coupling of 1-phenyl-2-propyn-1-ol. This rearrangement afforded the E-chalcone 6 in excellent yield.     

Pyridazines with heteroatom substituents in position 3 and 5, part 1: 5-Hydroxy-3(2H)-pyridazinone and its derivatives

Summary The synthesis of the title compound7 was achieved starting with mucochloric acidvia the pyridazinones1,2 and6. The electrolytic ionisation constants for7 were found to be 4.81 (±0.03) and –0.3 (±0.3). Crystal structure analyses were performed for7 and its fixed derivatives6 and9.Dedicated to Prof. Dr. Hans Junek on the occasion of his 60th birthday     

Pyrimidines. 24. Analogues and derivatives of 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP)

Preparation of a number of derivatives of 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP) including the 2-dialkylaminoalkylamino-, 2-hydroxyalkylamino-, 2-ethoxycarbonylamino- and 2-alkylaminocarbonyl-amino- groups substituted on the pyrimidine ring as well as preparation of 1-(alkylaminoalkyl)-4,6-dioxo-8-phenyl-2,3,4,6-tetrahydro-1H-pyrimido[1,2-α]pyrimidines and 3,5-dioxo-7-phenyl-1,2,3,5-tetrahydroimidazo-[1,2-α]pyrimidines with or without the bromo-substitution are reported.     

Studies on cardiotonic agents. VI. Synthesis of novel 4,5-dihydro-3(2H)-pyridazinone derivatives carrying some benzoheterocycles at the 6-position

Several benzothiazolyl, imidazobenzothiazolyl, benzothienyl, benzothienopyrimidinyl and quinazolinyl 4,5-dihydro-3(2H)-pyridazinones were synthesized and examined for cardiotonic activity in anesthetized dogs after i.v. administration. Among them, 4-methylamino-7-(2,3,4,5-tetrahydro-5-methyl-3-oxo-6- pyridazinyl)quinazoline (36) showed potent and long-lasting inotropic activity (relative potency = 2.11, milrinone = 1). The activity of 36 was more potent than indolidan (2) (relative potency = 1.53) which is one of the most potent inotropic agents to date.     

2-甲基-6-二乙胺基乙氧基-3(2H)-哒嗪酮的合成及其电子性质

分别利用两种方法合成2－甲基－6－二乙胺基乙氧基－3（2H）－哒嗪酮，用^1H NMR,IR,UV和MS进行结构表征，利用ab initio HF和密度泛函理论（DFT）B3LYP方法，对反应物、中间物、产物及其同分异构体进行几何结构的优化和总能量计算，系统分析前线分子轨道特征和能级分布规律，结果表明，2－甲基－6－二乙胺基乙氧基－3（2H）－哒嗪酮比其同分异构体哒嗪氮烷基化合物的能量低，前比后稳定，与实验事实相符合。     

Synthesis and Electronic Properties of 6-Chloro-2-diethylaminoethyl-3(2H)-pyridazinone

6-Chloro-2-diethylaminoethyl-3(2H)-pyridazinone was synthesized by the reaction of 6-chloro-3(2H)-pyridazinone and 2-diethylamionethyl chloride reaction in methylbenzene.Then the structure was characterized by means of ^1H NMR,IR,UV.By the method of ab initio HF and density functional theory(DFT) BeLYP,the geometric structures of the reagent intermediate,the product and its isomer were optimized and their total energies were calculated,The properties for the frontier molecular orbitals and the rules for energy distribution were analyzed systematically.It was shown that the energy of the nitrogen alkyl compound is lower than that of the oxy alkyl compound and the former is stable than the latter.This result is in accordance with the fact that 6-chloro-2-diethylaminoethyl-3(2H)-pyridazinone is synthesized by the reaction of 6-chloride-2-diethylaminoethyl-3(2H)-pyridazinone and 2-diethylaminoethyl chloride.     

Pyridazine derivatives. Part 39: Reactivity of 5-iodopyridazin-3(2H)-ones in palladium-catalysed reactions

In the search for novel antiplatelet agents, convenient and efficient methods for the preparation of 2,5-disubstituted pyridazin-3(2H)-ones are reported that utilise palladium-catalysed cross-coupling reactions. A post-coupling base-promoted isomerisation has been observed during Sonogashira alkynylation of 5-iodopyridazin-3(2H)-ones (3) with 1-phenyl-2-propyn-1-ol. Variable amounts of phthalazinones were isolated as by-products during the Heck alkenylation of 3. The usefulness of the hydroxymethyl fragment as a protecting group during the synthesis of 5-substituted pyridazin-3(2H)-ones has been validated.     

Pyridazines with heteroatom substituents in positions 3 and 5. 6. SN reactions in position 5 of 2-aryl-5-hydroxypyridazin-3(2H)-ones

The nucleophilic introduction of chloro- ( 2 ), azido- ( 4 ), (substituted) amino ( 3, 6 ), mercapto ( 10 ) and hydrazino-groups ( 13 ) into 2-aryl-5-hydroxypyridazin-3(2H)-ones [3] is described. The 5-aminopyridazin-3(2H)-one ( 6 ) also reacts with activated malonates 8 [4] to give pyrido[2,3-d]pyridazines 9 . Hydrazino compounds 13 can be treated with aldehydes to yield compounds 14 . Iodine can be introduced into position 4 of 5 -amino -(15 ) and 5-hydroxypyridazin-3(2H)-ones ( 17 ) by electrophilic substitution to afford compounds 18 .     

Pyridazine derivatives. Part 40: Reactivity of 5-alkynylpyridazin-3(2H)-ones toward hydrochloric acid

5-Alkynylpyridazin-3(2H)-ones or 5-(2-chloroalkenyl)pyridazin-3(2H)-ones were isolated during the cleavage of the methoxymethyl group in a series of 5-alkynyl-2-methoxymethylpyridazin-3(2H)-ones by treatment with hydrochloric acid. The efficient and selective cleavage of the methoxymethyl group in these compounds can be performed under mild conditions by employing aluminium chloride.     

Infrared matrix isolation and ab initio studies of 3(2H)-pyridazinone and photoproduced 3-hyroxypyridazine

The infrared spectra of 3(2H)-pyridazinone and its rare tautomeric form, 3-hydroxypyridazine, isolated in an argon matrix are reported and discussed. Only the first tautomer was observed after deposition of the matrix. The second form was photochemically produced after ultraviolet irradiation of the matrix (phototautomeric process). This form has never been observed experimentally before. Ab initio 3-21G normal coordinate calculations were carried out for these two forms and on that basis, an assignment of the experimental spectra of both compounds was performed.     

2-甲基-4-羟基-6-苯基嘧啶和2-甲基-4-羟基-5-溴-6-苯基嘧啶的高效液相色谱法分离测定

采用ODS-C18色谱柱和紫外检测器,对2-甲基-4-羟基-6-苯基嘧啶和2-甲基-4-羟基-5-溴-6-苯基嘧啶的含量进行HPLC分离测定.以甲醇水=4555为流动相,紫外检测波长为237 nm,样品线性范围为0.001～0.1 mg/mL.2-甲基-4-羟基-6-苯基嘧啶的RSD为0.5%;2-甲基-4-羟基-5-溴-6-苯基嘧啶的RSD为1.0%.     

Beiträge zur Chemie des Phosphors. 67. Zur Kenntnis der Cyclotriphosphane (PC6H5)3, (PC6H5)2(PC2H5) und (PC6H5)2(PCH3)

Contributions to the Chemistry of Phosphorus. 67. About the Cyclotriphosphanes (PC₆H₅)₃, (PC₆H₅)₂(PC₂H₅), and (PC₆H₅)₂(PCH₃) The reaction of (CH₃)₃Si(C₆H₅)P? P(C₆H₅)Si(CH₃)₃ with RPCl₂ (R = C₆H₅, C₂H₅, CH₃) yields the cyclotriphosphanes (PC₆H₅)₃ 1 , (PC₆H₅)₂(PC₂H₅) 3 , and (PC₆H₅)₂(PCH₃) 4 , respectively. Besides, the corresponding homo- and mixed-substituted cyclotetraphosphanes, cyclopentaphosphanes, and cyclohexaphosphanes are formed. The relative concentrations of the cyclotriphosphanes in the reaction mixtures decrease continuously, whereas those of the cyclopentaphosphanes increase. The reasons for these ring-interconversion reactions of the cyclophosphanes (PR)_n are discussed. The cyclotriphosphanes 1, 3 , and 4 are characterized by ³¹P chemical shifts between +130 and +160 ppm that are at considerable high field compared to open-chain triphosphanes and cyclophosphanes of different ring-size. The substituents R are situated on both sides of the P₃-ring plane, thus giving rise to two diastereomers of 3 that are observed simultaneously in the statistically expected ratio. The ³¹P n.m.r. parameters of 1 and 3 are reported and discussed.     

Synthesis of 6-Alkylthio-5-carbamoyl-3-cyano-4-phenyl-3,4-dihydropyridin-2(1H)-ones

Condensation of ethyl benzylidenecyanoacetate with thiocarbamoylacetamide in the presence of an equimolar amount of piperidine produces piperidinium 5-carbamoyl-3-cyano-2-oxo-4-phenyl-3,4-dihydropyridine-6(1H)-thiolate, which is then used in synthesis of the corresponding 6-alkylthiosubstituted 3,4-dihydropyridin-2(1H)-ones. Dedicated to Professor Henk van der Plas on his 70th birthday. Latvian Institute of Organic Synthesis, Riga LV-1006 Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 506–509, April, 1999.