Pyrazole ring compounds

At Merck Research Laboratories, the imidazole ring ia losartan (81, K = n — butyl), a novel clinical candidate against hypertension, was replaced with a pyrazole ring (52). Some of the best compounds are represented by formula (82), where K = n — butyl and R = 2,6-dichlorophenyl, 2-chlorophenyl, or... 

Hi) Pyrazole rings containing carbonyl groups In this subsection compounds with a pyrazole C—O bond will be discussed independently of their aromatic character. In solution the tautomers of pyrazolinones, e.g. (78a), (78b) and (78c), are easily identified by their IR spectra (Figure 18) (76AHC(Sl)l). 

The different nucleophilicities of 3,5-dimethyl- and 3,5-bis(trifluoromethyl) pyrazoles are shown by their reactions widi lraas-[Rh(CO)Cl(Ph3P)2]. The dimethyl derivative gives die dinuclear species similar to 111. The less nucleophilic fluorine derivative gives 116, where die pyrazole ring is monodentate. The fluoro compound similar to 111 [L2 = (CO)2l may be obtained in the absence... 

Such an easy isomerization of acetylenylbenzoic acid amides implies the formation of a five-membered nonaromatic ring condensed with the pyrazole ring. However, the pyrazole analog of o-iodobenzamide (amide of 4-iodo-l-methylpyrazole-3-carboxylic acid) formed under heating with CuC=CPh in pyridine for 9 h only the disubstituted acetylene in 71 % yield is identical in all respects to the compound obtained from the corresponding acid by successive action of SOCI2 and NH3 (90IZV2089) (Scheme 126). 

Organic synthesis 72 [OS 72] Pyrazole ring closure from 1,3-dicarbonyl compounds and hydrazines... 

Properties of nickel poly(pyrazol-l-yl)borate complexes such as solubility, coordination geometry, etc., can be controlled by appropriate substituent groups on the pyrazol rings, in particular in the 3- and 5-positions. Typical complexes are those of octahedral C symmetry (192)°02-604 and tetrahedral species (193). In the former case, two different tris(pyrazolyl)borate ligands may be involved to give heteroleptic compounds.602,603 Substituents in the 5-position mainly provide protection of the BH group. Only few representative examples are discussed here. 

Compounds 39 and 40, in which a pyrazole ring is fused to a pyrido[2,3-2,]pyrazinc, are produced as a 3 2 mixture by reaction of pyridine-2,3-diamine with 3-methyl-l-phenylpyrazoline-4,5-dione (Equation 9) <1999T8475>, and the synthesis of compound 41 (Scheme 11) exemplifies a different approach to the same ring system <1997JCM318, 1997JRM2026>. 

Related pyrazole-containing compounds such as 500 and 161 (Figure 33) have shown similar properties in 1 M H2SC>4 using electrochemical methods the choice of these molecules is based on the presence of an electron cloud on the aromatic rings, the presence of 71 electrons of N = N, C = N, C = O, and C = S is expected to affect the corrosion of carbon steel <2003MI1>. 

Only a few reports have dealt with the behavior of tetra-azaindenes toward electrophiles, and the reactions reported involved the pyrazole ring. Thus, alkylation of 336 with alkyl halides affords a mixture of the A-alkylated derivatives 337 and 338. Compound 336 is produced by alkylation of 339. Bromination of 339 (R = H) affords the 7-bromo derivative 340 (82JHC817) (Scheme 34). Nitration of 2-methylpyrazolo[3,4-c] pyridazine occured at pyrazole C-3 (73JAP76893). Bromination of 341 with bromine in acetic acid gives 342 (83AP697). 

With pyrazoles very few ring-expanded compounds are obtained, the main product contains three pyrazole rings attached by a nitrogen atom to a CH.259 A similar reaction occurs with benzimidazole260 (166). 

The acylation of a series of pyrazolo[3,4-c]pyridines has been studied.110 Acetic anhydride in refluxing benzene converted S-substituted derivatives to 1-acyl compounds (101 R2 = H), whereas the 7-methoxy derivative afforded the 2-substituted product 102 (R1 = H, R2 = OMe), attributed to peri interaction. In the absence of solvent, however, the latter reaction gave the 1-acyl isomer as the major product. Furthermore, benzoylation of the 5-chloro bicycle furnished a mixture of 101 and 102 (R1 = Cl, R2 = H). However, products benzoylated mainly at N-6 were obtained following introduction of a nitro group into the pyrazole ring. 

Molecular ions (generally, base peaks in this series of compounds) are often the only peaks reported. The mass spectra of a number of pyrazolo-[l,5-a]pyridines have, however, been analyzed more fully,260-262 with loss of HCN or RCN from the pyrazole ring being the principal fragmentation for each molecular ion. 

Three types of compound are formed depending on the character of the substituents in the pyrazole ring and on the nitrating agent used ... 

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