Domino Approach for the Synthesis of Pyrrolo[1,2-α]pyrazine from Vinyl Azides

Chen, Wenteng; Hu, Miao; Wu, Jianwei; Zou, Haifeng; Yu, Yongping

doi:10.1021/ol101538x

Cited by 69 publications

(25 citation statements)

References 14 publications

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“…21 Over the past decades, many synthetic methodologies to prepare pyrrolo[1,2-a]pyrazines have been reported. For example, Pd-catalyzed intramolecular cyclization of pyrrole-2-carboxamides, 22 TiCl 4 -catalyzed cyclization of 2-acetyl-N-propargylpyrrole, 23 reaction of pyrrole-2-carbaldehydes and vinyl azides, 24 Curtis reaction in Morita-Baylis-Hillman derivatives, 25 AuCl 3 -catalyzed intermolecular addition of pyrazoles to N-propargylpyrrole, 26 and reaction of propargylamines with pyrazine with subsequent Pd-catalyzed intramolecular cyclization of intermediate propargylpyrazines 10 have been documented. However, most of them require transition metals or are limited by substrate unavailability or complexity.…”

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confidence: 99%

Transition-Metal-Free Synthesis of Pyrrolo[1,2-a]pyrazines via Intramolecular Cyclization of N-Propargyl(pyrrolyl)enaminones

et al. 2017

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A concise transition-metal-free strategy for the synthesis of pyrrolo[1,2-a]pyrazines with enone substituents has been developed. It includes the following key steps: (a) cross-coupling of pyrroles with acyl(bromo)acetylenes in solid alumina at room temperature to give 2-(acylethynyl)pyrroles; (b) addition of propargylamine to the above acetylenes to form the corresponding N-propargylenaminones; and (c) chemo- and stereoselective base-catalyzed (Cs2CO3/DMSO) intramolecular cyclization of the synthesized propargylic derivatives to form (acylmethylidene)pyrrolo[1,2-a]pyrazines of Z-configuration.

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mentioning

confidence: 99%

Transition-Metal-Free Synthesis of Pyrrolo[1,2-a]pyrazines via Intramolecular Cyclization of N-Propargyl(pyrrolyl)enaminones

et al. 2017

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“…Vinyl azides are very reactive species and have been employed as a pivotal three‐atom synthon for the formation of diverse N‐heterocycles 7. We initially selected vinyl azide 1 for our investigations as it can undergo nucleophilic attack7f along with the liberation of N 2 , thus providing an intermediate suitable for the key step. We envisioned that vinyl azides 1 might be attacked by secondary amines 2 to generate tertiary amines 3 , which should form nitrogen‐centered radical cation 5 under a visible‐light‐mediated photoredox catalysis, eventually yielding imidazole derivatives 8 through a series of cascade reactions (Scheme ).…”

Section: Methodsmentioning

confidence: 99%

Visible‐Light/Photoredox‐Mediated sp³ CH Functionalization and Coupling of Secondary Amines with Vinyl Azides in Flow Microreactors

Tiwari

Maurya

Nanubolu

2015

Chemistry A European J

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Structurally diverse imidazole derivatives were synthesized by a visible-light/[Ru(bpy)3 ][(PF6 )2 ]-mediated coupling of vinyl azides and secondary amines in flow microreactors. This operationally simple and atom-economical protocol allows the formation of three new C-N bonds through the functionalization of sp(3) C-H bonds adjacent to the secondary nitrogen atom. In order to get mechanistic insight of the coupling reaction, several control experiments were carried out and discussed.

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“…In this paper, we described a targeted reaction for the synthesis of a series of novel poly functionalized 6-amino-pyrazolo[1,5-a]pyrimidines 3 by Michael-addition-cyclization of α-azidochalcones 1 with 3-aminopyrazoles 2 (Scheme 1). It should be also noted that α-azidochalcones 1 have been applied over the last decade to prepare several valuable nitrogen containing skeletons [64][65][66][67][68][69][70][71][72][73][74][75] . To probe the generality of this strategy, various derivatives of both starting materials were applied under the appropriate reaction condition to afford a large library of corresponding 6-amino-pyrazolo[1,5-a]pyrimidines 3 in 65-92% yields.…”

Section: Chemistrymentioning

confidence: 99%

An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity

Peytam

Adib

Shourgeshty

et al. 2020

Sci Rep

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In an attempt to find novel α-glucosidase inhibitors, an efficient, straightforward reaction to synthesize a library of fully substituted 6-amino-pyrazolo[1,5-a]pyrimidines 3 has been investigated. Heating a mixture of α-azidochalcones 1 and 3-aminopyrazoles 2 under the mild condition afforded desired compounds with a large substrate scope in good to excellent yields. All obtained products were evaluated as α-glucosidase inhibitors and exhibited excellent potency with IC 50 values ranging from 15.2 ± 0.4 µM to 201.3 ± 4.2 µM. Among them, compound 3d was around 50-fold more potent than acarbose (IC 50 = 750.0 ± 1.5 µM) as standard inhibitor. Regarding product structures, kinetic study and molecular docking were carried out for two of the most potent ones. Recently, the world health organization (WHO) has identified the diabetes mellitus (DM) as a critical health challenge in the 21st century. The prevalence of diabetes has been increasing at alarming rate over the past three decades. This metabolic disorder, characterized by chronic hyperglycemia, leads to further severe damages like abnormally great thrust, excessive appetite, overweigh, blindness, excessive urination, cardiovascular complications, as well as renal and neurodegenerative diseases 1-6. There are three main diabetes types among which type 2 or non-insulin dependent (T2DM) is the most common one, mainly treated by controlling the digestive enzyme activities such as α-glucosidase 7-9. α-Glucosidase, found in the brush-border surface membrane of intestinal cells, plays catalyzing role in the carbohydrate digestion process by which the postprandial blood glucose levels increases. Preventing the glucose release in the bloodstream, the α-glucosidase inhibitors control T2DM 10. Additionally, this enzyme has a pivotal role in the biosynthesis of glycoprotein, therefore, its inhibitors have possessed anticancer, antitumor, antiviral, and immunoregulatory properties 11-15. Acrabose, miglitol, voglibose, and deoxynojirimycin have clinically been used to restrict the α-glucosidase activity 16. Considering the side effects and absorption problems associated with these drugs, new scaffolds should be synthesized and evaluated by medicinal chemists to extend the library of compounds 17-25. Pyrazoles are common structural motif in numerous drugs 26 and biologically active compounds showing activities such as anti-cancer 27,28 , anti-inflammatory 29 , anti-hypertensive 30 , cannabinoid receptor antagonist 31 , dopaminergic receptor antagonist 32 , and α-glucosidase inhibitors 33. Pyrazoles have been used to synthesize

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Domino Approach for the Synthesis of Pyrrolo[1,2-α]pyrazine from Vinyl Azides

Abstract: A domino synthesis of pyrrolo[1,2-alpha]pyrazine from 1H-2-pyrrolecarbaldehyde and readily synthesized vinyl azides was developed. This reaction proceeded under relatively mild conditions in the presence of base. Additionally, a possible mechanism for the entire sequence is proposed.

Cited by 69 publications

References 14 publications

Transition-Metal-Free Synthesis of Pyrrolo[1,2-a]pyrazines via Intramolecular Cyclization of N-Propargyl(pyrrolyl)enaminones

Transition-Metal-Free Synthesis of Pyrrolo[1,2-a]pyrazines via Intramolecular Cyclization of N-Propargyl(pyrrolyl)enaminones

Visible‐Light/Photoredox‐Mediated sp³ CH Functionalization and Coupling of Secondary Amines with Vinyl Azides in Flow Microreactors

An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity

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Domino Approach for the Synthesis of Pyrrolo[1,2-α]pyrazine from Vinyl Azides

Abstract: A domino synthesis of pyrrolo[1,2-alpha]pyrazine from 1H-2-pyrrolecarbaldehyde and readily synthesized vinyl azides was developed. This reaction proceeded under relatively mild conditions in the presence of base. Additionally, a possible mechanism for the entire sequence is proposed.

Cited by 69 publications

References 14 publications

Transition-Metal-Free Synthesis of Pyrrolo[1,2-a]pyrazines via Intramolecular Cyclization of N-Propargyl(pyrrolyl)enaminones

Transition-Metal-Free Synthesis of Pyrrolo[1,2-a]pyrazines via Intramolecular Cyclization of N-Propargyl(pyrrolyl)enaminones

Visible‐Light/Photoredox‐Mediated sp3 CH Functionalization and Coupling of Secondary Amines with Vinyl Azides in Flow Microreactors

An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity

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Visible‐Light/Photoredox‐Mediated sp³ CH Functionalization and Coupling of Secondary Amines with Vinyl Azides in Flow Microreactors