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Chemical Structure| 154105-64-3 Chemical Structure| 154105-64-3

Structure of 154105-64-3

Chemical Structure| 154105-64-3

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Jan Petrovčič ;

Abstract: Piperidine is the most frequently encountered aliphatic heterocycle in medicinal chemistry. Despite its prevalence, there is a constant demand for improvement of ADME (absorption, distribution, metabolism, excretion) properties of piperidine-containing drugs and drug candidates. 2-azabicyclo[2.2.0]hexanes present an exciting class of more rigid and structurally programmable piperidine isosteres. EVA (exit vector analysis) of the most frequently employed piperidine isosteres and 2-azabicyclo[2.2.0]hexanes is presented, and a side-by-side comparison is made. This dissertation describes our endeavors towards the expansion of accessible 2-azabicyclo[2.2.0]hex-5-ene chemical space, our exploration of 2-azabicyclo[2.2.0]hex-5-ene scaffold reactivity in olefin functionalization reactions and installation of synthetically useful handles. The malleability and practicality of 2-azabicyclo[2.2.0]hexane core is demonstrated by preparation of several isosteres of piperidine-containing drugs and lead compounds. A general blueprint for functionalized 2-azabicyclo[2.2.0]hexanes is devised. Special attention is devoted to “pseudoaxial” C5-substituted-2-azabicyclo[2.2.0]hexanes, which could serve as isosteres of piperidines in their thermodynamically unfavorable axial conformations without the need to introduce additional carbon atoms. La piperidina è l’eterociclo alifatico più frequente nella chimica farmaceutica (medicinal chemistry). Nonostante la sua prevalenza, c’è una costante domanda for il miglioramento delle proprietà ADME (assorbimento, distribuzione, metabolismo, escrezione) di farmaci e candidati farmaci contenenti strutture piperidiniche. Gli 2-azabiciclo[2.2.0]esani rappresentano un’interessante classe di isosteri della piperidina più rigidi e programmabili strutturalmente. L’EVA (exit vector analysis, analisi di vettore di uscita) degli isosteri della piperidina più frequentemente utilizzati e di 2-azabiciclo[2.2.0]esani viene mostrata, ed è stata eseguita una comparazione tra loro. Questa tesi descrive i nostri sforzi verso l’espansione di spazio chimico accessibile dei 2-azabiciclo[2.2.0]es-2-eni, la nostra esplorazione della reattività della struttura di tipo 2-azabiciclo[2.2.0]es-2-ene nelle reazioni di funzionalizzazione delle olefine e l’installazione di appigli sinteticamente utili. La malleabilità e praticabilità del nucleo di tipo 2-azabiciclo[2.2.0]es-2-ene è dimostrata dalla preparazione di diversi isosteri di farmaci e composti guida, contenenti strutture piperidiniche. Un progetto generale per la funzionalizzazione di 2-azabiciclo[2.2.0]es-2-eni è stato elaborato. Un’attenzione particolare è stata riservata ai 2-azabiciclo[2.2.0]es-2-eni con sostituenti sul C5 “psuedoassiali”, che possono servire come isosteri di piperidine nella loro conformazione assiale termodinamicamente sfavorevole, senza la necessità di introdurre atomi di carbonio addizionali.

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Product Details of [ 154105-64-3 ]

CAS No. :154105-64-3
Formula : C6H4BrNO
M.W : 186.01
SMILES Code : O=CC1=C(Br)C=CN=C1
MDL No. :MFCD06657803

Safety of [ 154105-64-3 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Application In Synthesis of [ 154105-64-3 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 154105-64-3 ]

[ 154105-64-3 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 154105-64-3 ]
  • [ 197007-87-7 ]
YieldReaction ConditionsOperation in experiment
With sodium tetrahydroborate; In ethanol; at 0℃; for 0.5h; 4-Bromo-pyridine-3-carbaldehycie (240 mg) in ethanol (10 ml_) at 0C was treated with sodium borohydride (139 mg) for 30 min. The reaction mixture was then diluted with ethyl acetate and washed with aqueous ammonium chloride and brine to yield (4-bromo-pyridin-3-yl)-methanol as a white solid.1HNMR (CDCI3, 300 MHz) delta (ppm): 10.4 (s, 1 H), 9.01 (s, 1 H), 8.56 (d, J = 5.1 Hz, 1 H), 7.63 (d, J = 5.1 Hz, 1 H).
With sodium tetrahydroborate; In ethanol; at 0℃; for 0.5h; 4-Bromo-pyridine-3-carbaldehyde (240 mg) in ethanol (10 ml_) at 0C was treated with sodium borohydride (139 mg) for 30 min. The reaction mixture was then diluted with ethyl acetate and washed with aqueous ammonium chloride and brine to yield (4-bromo-pyridin-3-yl)-methanol as a white solid.1HNMR (CDCI3, 300 MHz) delta (ppm): 10.4 (s, 1 H), 9.01 (s, 1 H), 8.56 (d, J = 5.1 Hz, 1 H), 7.63 (d, J = 5.1 Hz, 1 H).
Step A: (4-Bromo-3-pyridyl)methanol 0.2 g of sodium borohydride is added in portions to a solution of 1 g of 4-bromonicotinaldehyde in 50 ml of MeOH at 0 C. The whole is then stirred for 6 hours gradually returning to ambient temperature. The reaction mixture is cooled to 0 C., then hydrolyzed with a saturated NH4Cl solution and extracted with CH2Cl2. The organic phases are then combined, washed with a saturated NaCl solution, dried over magnesium sulphate and then concentrated to dryness. The title compound is obtained in the form of a light brown gel which is used as is in the following Step.
 

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