Pyridazine-3-carboxylic acid esters

In the last decade new reactions have been elaborated in which pyridazines can be transformed into a variety of other heterocycles. Esters of pyridazine-carboxylic acids and 1-diethylaminopropyne undergo cycloaddition reactions with inverse electron demand. The orientation of the two reactants depends on the position of the carboxylate group in the pyridazine ring. For example, from methyl pyridazine-4-carboxylate the pyridine derivative 245 was formed via the adduct 244 and subsequent elimination... 

Pyridazine 1-oxide N NMR, 2, 17 <80HCA504) Pyridazino[4,5-d]azonine-7-carboxylic acid, 1,4-dipbenyl-, etbyl ester... 

Pyridazine-3-carboxylic acid, hexahydro-applications, 3, 56 Pyridazine-4-carboxylic acid ethyl ester... 

The construction of a thieno[3,2-Z>]pyridine by pathway M involves the successive formation of the N(l)-C(2) and C(3)-C(4) bonds of the pyridine fragment. Various 3-aminothiophene-2-carboxylic acid derivatives are most often used as the starting reagents with 2C-components, which introduce carbon atoms C(2) and C(3) into the pyridine ring. For example, the reaction of amino ester 155 with dimethyl acetylenedicarboxylate (156) involves intramolecular cyclocondensation followed by hydrazinolysis to give derivatives of the new heterocyclic system thieno[2, 3 5,6] pyrido[2,3-<7]pyridazine (157) (1991JHC205, 1990SPH203). 

The rates of alkaline hydrolysis of methyl pyridazine-3- and -4-carboxylate were correlated with those of pyridinecarboxylates and benzoates. Diethyl pyridazine-4,5-dicarboxylate (214) reacts with 1,3-diphenylguanidine in the presence of sodium hydride to give the spiro compounds 215, the structure of which was determined by X-ray analysis. Related spiro compounds were obtained from the above ester and esters of glutaric or acetonedicar-boxylic acids. 5-Aminopyridazine-4-carboxylic acid is simply synthesized from the 5-carboxamido analog by Hofmann rearrangement. ... 

In a similar fashion, as carboxylic acids or their esters, certain carboxamides possessing an ortho acyl group tnay also cyclocondense with hydrazine. Thus, Ar,/V-dicthyl-3-(2-pyridy car-bonyl)pyridine-2-carboxamide gives the corresponding pyrido[2,3-(i]pyridazin-H(7//)-one 15 in 89% yield, whereas, in contrast, 3-benzoyl-A, Ar-diisopropylpyridine-2-carboxamide and hydrazine give jV,2V-diisopropyl-5-phenylpyrido[2,3-d]pyridazin-8-amine (16) in 42% yield.50... 

The preparation and reactivity of carboxylic acids and esters was outlined in CHEC-I, with particular emphasis on the ease and practical use of decarboxylation of acids (especially pyridazine-... 

The Hammick reaction ipso substitution by an electrophile of a carboxylic group under decarboxylation conditions) with pyridazine-3-carboxylic acid is not very successful, but it is considerably improved by the use of the TMS ester. Thus, trimethylsilyl pyridazine-3-carboxylate reacts with aldehydes to give, probably via an ylide, good yields of TMS protected alcohols (Scheme 50). The trimethylsilyloxy product is readily desilylated, so this process is equivalent to the reaction of a 3-pyridazinyl organometallic reagent with an aldehyde <88T328i>. 

Pyridazine-3-carboxylic acids as methyl esters 267 have been prepared by methyloxy-carbonylation of 3-pyridazinyl triflates in methanol using Pd(OAc)2 and 1,1-bis (diphenylphosphino)ferrocene as the catalyst system together with carbon monoxide at atmospheric pressure in methanol (Scheme 96). 

---