A Facile Route of Synthesis for Making Flibanserin

Yang, Feipu; Wu, Chunhui; Li, Zhiqiang; Tian, Guanghui; Wu, Jianzhong; Zhu, Fuqiang; Zhang, Jian; Yang, He; Shen, Jingshan

doi:10.1021/acs.oprd.6b00108

Cited by 17 publications

(16 citation statements)

References 10 publications

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“…The piperazine functionality is abundant across pharmaceutical products (vide supra). 40 Using established methods, 44 in four synthetic steps we converted aryl-coupled piperazine derivatives 19 , 9 , and 22 to flibanserin ( 39 ) and two flibanserin derivatives ( 40 and 41 , Figure 1B). We note that 40 can also be accessed from 8 , therefore eliminating both Boc protection and deprotection steps.…”

Section: Resultsmentioning

confidence: 99%

C–N Cross-Coupling via Photoexcitation of Nickel–Amine Complexes

2018

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C-N cross-coupling is an important class of reactions with far-reaching impacts across chemistry, materials science, biology, and medicine. Transition metal complexes can elegantly orchestrate diverse aminations but typically require demanding reaction conditions, precious metal catalysts, or oxygen-sensitive procedures. Here, we introduce a mild nickel-catalyzed C-N cross-coupling methodology that operates at room temperature using an inexpensive nickel source (NiBr·3HO), is oxygen tolerant, and proceeds through direct irradiation of the nickel-amine complex. This operationally robust process was employed for the synthesis of diverse C-N-coupled products (40 examples) by irradiating a solution containing an amine, an aryl halide, and a catalytic amount of NiBr·3HO with a commercially available 365 nm LED at room temperature without added photoredox catalyst and the amine substrate serving additional roles as the ligands and base. Density functional theory calculations and kinetic isotope effect experiments were performed to elucidate the observed C-N cross-coupling reactivity.

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Section: Resultsmentioning

confidence: 99%

C–N Cross-Coupling via Photoexcitation of Nickel–Amine Complexes

2018

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“…In literature several batch syntheses have been described with yields ranging from 32-51%. [47][48][49] Greiner and co-workers developed an interrupted one-flow system for the synthesis of flibanserin (44) with a minimal number of manual unit operations. 50 Previous existing batch protocols to flibanserin included protecting group introduction and removal as separate steps which was not considered feasible.…”

Section: Interrupted One-flow Systemsmentioning

confidence: 99%

“…50 Previous existing batch protocols to flibanserin included protecting group introduction and removal as separate steps which was not considered feasible. 49 Alternatively, reported N-alkylations were challenging and required forcing reaction conditions with insoluble bases. 47 The authors therefore devised a novel synthetic route for the synthesis of flibanserin in flow (Fig.…”

Section: Interrupted One-flow Systemsmentioning

confidence: 99%

Continuous one-flow multi-step synthesis of active pharmaceutical ingredients

Bloemendal¹,

Janssen²,

Hest

et al. 2020

React. Chem. Eng.

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“…So, this orbital can be acted as a Lewis acid. To happening reaction between two compounds, the HOMO of one compound must overlap with the LUMO of another molecule [16][17][18][19]. Figure 3 shows the frontier molecular orbitals (the filled HOMO and the empty LUMO) of the active compound 3-(1,3dioxoisoindolin-2-yl) benzyl nitrate.…”

Section: Stability and Reactivity Study Of The Compound 3-(13-dioxoimentioning

confidence: 99%

Molecular Modeling of 3-(1,3-Dioxoisoindolin-2-yl)benzyl Nitrate and its Molecular Docking Study with Phosphodiesterase-5 (PDE5)

Nabati¹,

Bodaghi-Namileh²

2020

Adv. J. Chem. A

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In this study, the electronic properties of the novel medicinal compound 3-(1,3-dioxoisoindolin-2-yl) benzyl nitrate as a treatment of sickle cell disease are obtained using density functional theory (DFT) method. In first step, the molecular structure of the title compound is optimized at B3LYP/6-311++G (d,p) level of theory at room temperature. Then, its stability and reactivity properties are calculated by frontier molecular orbitals (FMOs) energies. The global reactivity indices show this medicinal molecule is a more stable compound and the nitrogen atom of the nitrate group has positive charge. So, the nitrate group can quit nitric oxide molecule in binding to Phosphodiesterase-5 (PDE5) enzyme. On the other hand, the docking analysis of the ligand-enzyme complex shows the steric interactions play the main role in this complex formation. Also, the data shows the PDE5 residues containing Phe [A]

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A Facile Route of Synthesis for Making Flibanserin

Abstract: A novel and efficient route of synthesis for making flibanserin via 2-ethoxy-1H-benzo[d]imidazole (12) was described with excellent yield. This protocol provided a more facile approach to flibanserin.

Cited by 17 publications

References 10 publications

C–N Cross-Coupling via Photoexcitation of Nickel–Amine Complexes

C–N Cross-Coupling via Photoexcitation of Nickel–Amine Complexes

Continuous one-flow multi-step synthesis of active pharmaceutical ingredients

Molecular Modeling of 3-(1,3-Dioxoisoindolin-2-yl)benzyl Nitrate and its Molecular Docking Study with Phosphodiesterase-5 (PDE5)

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