A synthesis of 1-substituted 5-[2-(acylamino)ethyl]-1H-pyrazole-4-carboxamides

Kralj, David; Friedrich, Miha; Grošelj, Uroš; Kiraly-Potpara, Sonja; Meden, Anton; Wagger, Jernej; Dahmann, Georg; Stanovnik, B.; Svete, Jurij

doi:10.1016/j.tet.2009.06.021

Cited by 20 publications

(23 citation statements)

References 57 publications

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“…[62,64] The magnitudes of couplings 3 J C(1)ÀH(2') = 7 Hz (trans) and 3 J C(3)ÀH(2') = 5 Hz (cis) confirms the E configuration around the exocyclic C=C double bond. [64] Use of short-and long-range 15 C/ 15 N correlation in the lysine side chain in ubiquitin. [21,65] One of them is the intra-residue 15 N z and 13 C g coupling while the other is between the 15 N z and carbonyl 13 C across a hydrogen bond, as shown in Figure 6 J NzCg values are also calculated from the experimental 3 J NzCg and torsional angles obtained from the crystal structure by employing the empirical Karplus equation.…”

Section: Conformational and Configurational Analysismentioning

confidence: 74%

“…It is also well known that the magnitudes of the coupling constant ( 3 J CH ) between nuclei with cis configuration around the C=C double bond are smaller (2-6 Hz) than those of trans-oriented nuclei (8)(9)(10)(11)(12). [62,64] The magnitudes of couplings 3 J C(1)ÀH(2') = 7 Hz (trans) and 3 J C(3)ÀH(2') = 5 Hz (cis) confirms the E configuration around the exocyclic C=C double bond. [64] Use of short-and long-range 15 C/ 15 N correlation in the lysine side chain in ubiquitin.…”

Section: Conformational and Configurational Analysismentioning

confidence: 99%

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Measurement and Applications of Long‐Range Heteronuclear Scalar Couplings: Recent Experimental and Theoretical Developments

2012

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The use of long-range heteronuclear couplings, in association with (1)H-(1)H scalar couplings and NOE restraints, has acquired growing importance for the determination of the relative stereochemistry, and structural and conformational information of organic and biological molecules. However, the routine use of such couplings is hindered by the inherent difficulties in their measurement. Prior to the advancement in experimental techniques, both long-range homo- and heteronuclear scalar couplings were not easily accessible, especially for very large molecules. The development of a large number of multidimensional NMR experimental methodologies has alleviated the complications associated with the measurement of couplings of smaller strengths. Subsequent application of these methods and the utilization of determined J-couplings for structure calculations have revolutionized this area of research. Problems in organic, inorganic and biophysical chemistry have also been solved by utilizing the short- and long-range heteronuclear couplings. In this minireview, we discuss the advantages and limitations of a number of experimental techniques reported in recent times for the measurement of long-range heteronuclear couplings and a few selected applications of such couplings. This includes the study of medium- to larger-sized molecules in a variety of applications, especially in the study of hydrogen bonding in biological systems. The utilization of these couplings in conjunction with theoretical calculations to arrive at conclusions on the hyperconjugation, configurational analysis and the effect of the electronegativity of the substituents is also discussed.

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Section: Conformational and Configurational Analysismentioning

confidence: 74%

Section: Conformational and Configurational Analysismentioning

confidence: 99%

Measurement and Applications of Long‐Range Heteronuclear Scalar Couplings: Recent Experimental and Theoretical Developments

2012

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“…Following literature procedure, 5 β-keto ester 8 was prepared from 7 by Masamune-Claisen type condensation. 8 Further treatment of the β-keto ester 8 with hydrazine derivatives 9a-g in refluxing methanol gave 1'-substituted tert-butyl 2-(5-hydroxy-1H-pyrazol-3-yl)ethylcarbamates 10a-e and 2-(5-oxo-2,5-dihydro-1H-pyrazol-3-yl)ethylcarbamates 11f,g in 48-83% yields.…”

Section: Resultsmentioning

confidence: 99%

“…2 Recently, a part of our research has been focused on the synthesis of histamine analogues 2-5 based on aminoethyl functionalized pyrazole scaffold. [4][5][6][7] Within this context, syntheses of analogues 2 4 and 3 5 have been developed first, followed by synthesis of conformationally constrained histamine analogues 4 6 and 5 7 . Next, we focused our attention on 3-(2- We found pyrazolols 6 interesting because they are structurally closer analogues of histamine 1 than their known regioisomers 2.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 3-(2-aminoethyl)-5-hydroxy-1H-pyrazole derivatives

Kralj¹,

Wagger²,

Dahmann³

et al. 2011

Arkivoc

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Treatment of β-keto ester 8 with hydrazines 9a-g gave 1'-substituted tert-butyl 2-(5-hydroxy-1H-pyrazol-3-yl)ethylcarbamates 10a-e and 2-(5-oxo-2,5-dihydro-1H-pyrazol-3-yl)ethylcarbamates 11f,g. Acidolytic deprotection of 10b,c afforded the corresponding 3-(2-aminoethyl)-5-hydroxy-1H-pyrazoles 6b,c in good yields. Acylation of 6 gave either the N-acyl compounds 12b,c and 13c, or the N,O-diacyl derivative 14. Next, three N,N-dialkyl analogues 15a,b and 26c were prepared from dimethyl acetone-1,3-dicarboxylate 21 via condensation with hydrazines 9a and 9h followed by hydrolysis of the esters 22a,b, amidation of the carboxylic acids 23a,b, and reduction of the tertiary carboxamides 24a and 25b,c.

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“…In continuation, we reported a ring switching synthesis of 1-substituted 4-(2-aminoethyl)-1H-pyrazol-5-ols 2 [9] as the pyrazole analogs of histamine 1 and, soon after, a one-pot parallel solution-phase synthesis of compounds 2 [10]. Next, the syntheses of 1-substituted 5-(2-aminoethyl)-1H-pyrazol-4-carboxamides 3 [11] and their bicyclic analogs, 1,5-disubstituted 6,7-dihydro-1H-pyrazolo [4,3-c]pyridin-4(5H)-ones 4 [12] have been reported. In continuation of our work in this field, we focused our attention on 5-(2-aminophenyl)-1H-pyrazole derivatives 5 as another type of histamine analogs.…”

mentioning

confidence: 99%

A Simple Synthesis of 5‐(2‐Aminophenyl)‐1H‐pyrazoles

Janjić

Prebil

Grošelj

et al. 2011

Helvetica Chimica Acta

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A four-step synthesis of 1-substituted 5-(2-aminophenyl)-1H-pyrazoles 5 as a novel type of histamine analogs and versatile building blocks for further transformations was developed. The synthesis starts from commercially available 2-nitroacetophenone (12), which is converted into the enamino ketone 13 as the key intermediate. Cyclization of the key intermediate 13 with monosubstituted hydrazines 14a -14l afforded the 5-(2-nitrophenyl)-1H-pyrazoles 17a -17l. Finally, catalytic hydrogenation of the nitro compounds 17a, 17c -17e, and 17g -17j furnished the title compounds 5a, 5c -5e, and 5g -5j, respectively, in good yields. As demonstrated by some further transformations, additional functionalization of compounds 17 and 5 is feasible, either by electrophilic substitution at C(4) of the pyrazole ring, or at the NH 2 group.Introduction. -In biological processes, histamine, tyramine, dopamine, tryptamine, serotonin, and melatonin play a crucial role as chemical messengers. Therefore, preparation of their novel synthetic analogs based on the 2-(heteroaryl)ethylamine scaffold is an important target in medicinal and synthetic organic chemistry [1].Pyrazoles are an important class of heterocyclic compounds. Despite their rare occurrence in nature, numerous pyrazole derivatives have found use in various applications, and a general interest in their chemistry is still continuing (for a review, see [2]). Among numerous synthetic options for the construction of the pyrazole ring, two classical approaches are most frequently employed: a) cyclocondensation of a 1,3-dicarbonyl compound with a hydrazine derivative and b) 1,3-dipolar cycloaddition of a CÀNÀN type 1,3-dipole (diazoalkane, nitrile imine, or azomethine imine) to a C,C multiple bond [2].Recently, a part of our research has been focused on the synthesis of functionalized pyrazoles utilizing the

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A synthesis of 1-substituted 5-[2-(acylamino)ethyl]-1H-pyrazole-4-carboxamides

Cited by 20 publications

References 57 publications

Measurement and Applications of Long‐Range Heteronuclear Scalar Couplings: Recent Experimental and Theoretical Developments

Measurement and Applications of Long‐Range Heteronuclear Scalar Couplings: Recent Experimental and Theoretical Developments

Synthesis of 3-(2-aminoethyl)-5-hydroxy-1H-pyrazole derivatives

A Simple Synthesis of 5‐(2‐Aminophenyl)‐1H‐pyrazoles

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