Regioselective synthesis of 1- and 4-substituted 7-oxopyrazolo[1,5-a]pyrimidine-3-carboxamides

The synthesis of 7-substituted pyrazolo[1,5-a]pyrimidine-3-carboxamides was studied. First, methyl 7-hydroxypyrazolo[1,5-a]pyrimidine-3-carboxylate (5) was prepared in three steps from methyl 5-amino-1H-pyrazole-4-carboxylate (3). Treatment of 5 with POCl₃ gave the highly reactive 7-chloro derivative 10, which was reacted with amines, benzyl alcohol, and phenylboronic acid in the presence of Pd-catalyst to give the corresponding 7-substituted derivatives 11. Hydrolysis of the esters 5 and 11 followed by amidation gave the corresponding carboxamides 16a–h and 15. Regioselectivity of N-alkylation of 7-hydroxypyrazolo[1,5-a]pyrimidine-3-carboxylic acid derivatives 5 and 16 was tunable by the carboxy function. Alkylation of the secondary amides 16a–f furnished the 1-alkyl derivatives 17a–f, whereas the ester 5 and the tertiary amides 16g,h gave the 4-alkyl derivatives 14a–d and 16m,n, selectively.     

Synthesis and structure of hydroxylammonium fluoroaluminate

Abstract  

Hydroxylammonium fluoroaluminate with the formula (NH₃OH)₂AlF₅ was synthesized by the reaction of solid NH₃OHF and an aqueous solution of aluminum in HF, and its structure was determined by single-crystal X-ray diffraction. The structure consists of NH₃OH⁺ cations and centrosymmetrical AlF₆ octahedra, which are formed by sharing two opposite corners connected in polymeric (AlF₅)_n²⁻ anions. Oxygen and nitrogen atoms of hydroxylammonium cations are donors of hydrogen bonds to terminal fluorine atoms of fluoroaluminate chains. The compound crystallizes monoclinic P2/c, with cell parameters a = 10.8675(3) ?, b = 7.3098(2) ?, c = 7.2071(2) ?, and β = 91.080(2)°. The thermal decomposition of the compound was studied by TG, DSC, and X-ray powder diffraction. By controlled heating of (NH₃OH)₂AlF₅, a new compound with the formula (NH₃OH)AlF₄ was obtained, and the final product of the decomposition is γ-AlF₃.     

1,3‐Dipolar Cycloadditions to (5Z)‐1‐Acyl‐5‐(cyanomethylidene)‐ imidazolidine‐2,4‐diones: Synthesis and Transformations of Spirohydantoin Derivatives

Cycloadditions of various 1,3‐dipoles to (5Z)‐1‐acyl‐5‐(cyanomethylidene)‐3‐methylimidazolidine‐2,4‐diones 8 or 9 , prepared in 3 steps from hydantoin ( 1 ) (Schemes 1 and 2), were studied. In all cases, reactions proceeded regio‐ and stereoselectively. The type of product depended on the 1,3‐dipole and/or dipolarophile employed as well as on reaction conditions. Thus, with stable dipoles under neutral conditions, spirohydantoin derivatives 12 – 16 were obtained (Scheme 2), while under basic or acidic conditions, pyrazole‐ or isoxazole‐5‐carboxamides 18 and 23 – 26 and carboxylate 27 were formed via aromatization of the newly formed dihydroazole ring, followed by the simultaneous cleavage of the hydantoin ring (Schemes 3 – 5).     

Crystal structure of ciprofloxacin hydrochloride 1.34-hydrate.

Ciprofloxacin belongs to a family of quinolone antibacterial agents. The crystal structure of ciprofloxacin hydrochloride 1,34-hydrate was determined. Most of the bond lengths and angles of the ciprofloxacin cation are very similar to those of ciprofloxacin hexahydrate, which appears in the zwitterionic form. The exceptions are the carbon-oxygen bond distances in the carboxylic group, since in the title compound this group is not deprotonated. Various inter- and intramolecular hydrogen bonds were found in the molecule and are described.     

N‐(o‐Chloro­phenyl)‐2,5‐di­methyl­pyrrole‐3‐carb­aldehyde

Crystal structure analysis of the title compound, C₁₃H₁₂ClNO, reveals three crystallographically independent mol­ecules in the asymmetric unit. The main conformational difference between these mol­ecules is the orientation of the phenyl rings with respect to the pyrrole rings. The coplanar arrangement of the aldehyde groups attached to the pyrrole rings influences the pyrrole‐ring geometry. The C2—C3 and N1—C5 bonds are noticeably longer than the C4—C5 and N1—C2 bonds. Two independent mol­ecules of the title compound form dimers via intermolecular C—H⃛O hydrogen bonds [D⃛A = 3.400 (3) Å and D—H⃛A = 157°]. The perpendicular orientation of the phenyl and pyrrole rings of one independent mol­ecule and its symmetry‐related mol­ecule allows C—H⃛π interactions, with an H⃛centroid distance of 2.85 Å and a C—H⃛π angle of 155°. The distances between the H atom and the pyrrole‐ring atoms indicate that the C—H bond points towards one of the bonds in the pyrrole ring.     

The synthesis, structure and physical properties of lanthanide(III) complexes with nicotinic acid

This article reports the synthesis of novel, rare-earth coordination complexes with nicotinic acid. Three compounds with the general formula Ln₂[(C₅H₄NCOO)₆(H₂O)₄] (Ln = Yb, 1; Ln = Gd, 2; Ln = Nd, 3) were prepared from relatively cheap and readily available reactants. Their compositions and structure were characterized by IR spectroscopy and single-crystal X-ray diffraction. The magnetic and thermogravimetric properties were also studied. The complexes consist of centrosymetric, dimeric molecules having all six nicotinato ligands coordinated with the central atom in the bidentate mode. The coordination environment of the Ln³⁺ for all three compounds is 8. Here we describe the crystal structure of Yb and Gd complexes with nicotinic acid.      

The synthesis and transformations of some 3-thiocarbamoylthiazolidines

In connection with our studies on potential bioactive compounds some new polysubstituted 3-thiocarbamoylthiazolidines 5, 6, 7, 9 and 10 were prepared in the reaction between 2-(2-methoxy-phenyl)iminothiazolidine (2) and sulfamoylphenyl isothiocyanates 3 and 4a-c. The structures for compounds 2 and 5 were established by X-ray analyses, showing that the reaction is taking place at the endo-cyclic nitrogen atom of thiazolidine ring.     

Synthesis and preliminary biological evaluations of (+)-isocampholenic acid-derived amides

The synthesis of two novel (+)-isocampholenic acid-derived amines has been realized starting from commercially available (1S)-(+)-10-camphorsulfonic acid. The novel amines as well as (+)-isocampholenic acid have been used as building blocks in the construction of a library of amides using various aliphatic, aromatic, and amino acid-derived coupling partners using BPC and CDI as activating agents. Amide derivatives have been assayed against several enzymes that hold potential for the development of new drugs to battle bacterial infections and Alzheimer’s disease. Compounds 20c and 20e showed promising selective sub-micromolar inhibition of human butyrylcholinesterase \((h\hbox {BChE})\) (\(\hbox {IC}_{50}\) values \(0.80\,\pm 0.05\) and \(0.25\,\pm 0.02\,{\upmu }\hbox {M}\), respectively).