An Efficient Three-Component Synthesis of 3-(1-Hydroxyalkyl)[1,2,4]-triazolo[4,3-c]quinazolines

Adib, Mehdi; Ansari, Sara; Feizi, Shahzad; Bijanzadeh, Hamid Reza

doi:10.1055/s-0029-1219562

Cited by 28 publications

(13 citation statements)

References 6 publications

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“…Carboxylic acids bearing electrophilic substituents including; aldehydes (12), sulfonyl fluorides (13), trifluoromethyl alkenes ( 14), allyl bromides (15), and alkyl bromides ( 16), acted as efficient coupling partners providing products with additional sites for further nucleophilic functionalization. Pivalic acid (17), and an oxalic acid half ester (18) reacted successfully affording acyl α-amino 1,3,4oxadiazoles in 48% and 57% yield, respectively. The late-stage functionalization of two carboxylic acid containing APIs (19,20) was realized, demonstrating the potential application of this methodology in drug discovery programmes.…”

Section: Resultsmentioning

confidence: 99%

General α-Amino 1,3,4-Oxadiazole Synthesis via Late-Stage Reductive Functionalization of Tertiary Amides and Lactams

Matheau‐Raven¹,

Dixon²

2021

Preprint

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An iridium-catalyzed reductive three-component coupling reaction for the synthesis of medicinally relevant α-amino 1,3,4-oxadiazoles from abundant tertiary amides or lactams, carboxylic acids, and (N-isocyanimino) triphenylphosphorane, is described. Proceeding under mild conditions using (<1 mol%) Vaska’s complex (IrCl(CO)(PPh3)2) and tetramethyldisiloxane to access the key reactive iminium ion intermediates, a broad range of structurally complex α-amino 1,3,4-oxadiazole architectures were efficiently accessed from diverse carboxylic acid feedstock coupling partners. Extension to α-amino heterodiazole synthesis was readily achieved by exchanging the carboxylic acid coupling partner for C-, S-, or N-centered Brønsted acids, and provided rapid and modular access to these desirable, yet difficult-to-access, heterocycles. Furthermore, the high chemoselectivity of the catalytic reductive activation step allowed the late-stage functionalization of 10 drug molecules, including the synthesis of novel heterodiazole-fused drug-drug conjugates.

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Section: Resultsmentioning

confidence: 99%

General α-Amino 1,3,4-Oxadiazole Synthesis via Late-Stage Reductive Functionalization of Tertiary Amides and Lactams

Matheau‐Raven¹,

Dixon²

2021

Preprint

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“…As part of our current studies on the development of new efficient strategies for the preparation of interesting bioactive molecules and drug cores, 16 herein, we present a new synthetic method for the construction of 5-amido coumarinyl 2-aminofurans via a one-pot, isocyanide-based MCR involving commercially available starting materials. Thus, a mixture of salicylaldehyde 1a, Meldrum's acid 2, tert-butyl isocyanide 3a (2 equiv) and dimethyl acetylenedicarboxylate (DMAD, 4a) afforded dimethyl 2-(tert-butylamino)-5-{tert-butyl[(2-oxo-2H-chromen-3-yl)carbonyl]amino}-3,4-furandicarboxylate 5a (Scheme 1).…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 2-(alkylamino)-5-{alkyl[(2-oxo-2H-chromen-3-yl)carbonyl]amino}-3,4-furandicarboxylates using a multi-component reaction in water

et al. 2010

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“…The N ‐isocyaniminotriphenylphosphorane (NIITP), which was reported by Fehlhammer and Weinberger in 1980, has been extensively explored as the safe, easy‐to‐handle, and odorless solid . It can be used as a phosphonium ylide for converting the carbon–oxygen double bond of a carbonyl compound into a carbon–nitrogen double bond of an imine group, and it can also be served as a key intermediate in multicomponent reactions (Scheme a) for the synthesis of various heterocycles including 1,3,4‐oxadiazoles, 1,3,4‐oxadiazepines, furo[2,3‐ c ]pyrans, pyrrolidine‐2,5‐diones, and [1,2,4]triazolo[4,3‐ c ]quinazolines . Besides the advances made so far, metals have particularly not been introduced to the NIITP reactions.…”

Section: Introductionmentioning

confidence: 91%

Silver‐Catalyzed Cascade Reaction of N‐Isocyaniminotriphenylphosphorane with Aldehydes: Synthesis of Unsymmetrical Azines

Wang

Zhao

et al. 2019

Eur J Org Chem

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A direct synthesis of azines from the silver catalyzed domino interaction of N-isocyaniminotriphenylphosphorane and aldehydes is reported. The reaction proceeds through a tandem aza-Wittig, insertion, intramolecular cyclization and [a] Typical Synthetic Procedure (with 3a as an example): To a dried Schlenk flask N-Isocyanoiminotriphenylphosphorane 1 (604 mg, 2.0 mmol), 4-chlorobenzaldehyde 2a (70.3 mg, 0.5 mmol) and Ag 2 CO 3 (27.5 mg, 0.10 mmol) were added under air atmosphere. After evacuated and refilled with nitrogen 3 times, 1,4-dioxane (4 mL), DIPEA (41.3 μL, 0.25 mmol) and BF 3 ·Et 2 O (18.5 μL, 0.15 mmol) was added in one portion to the mixture by syringe. The mixture was stirred at 100°C for 12 h until substrate 2a disappeared. After completion, the resulting mixture was concentrated and extract with diethyl ether (3 × 15 mL), washed with brine (3 × Eur.7239 40 mL). Then combined organic layer was dried with MgSO 4 and concentrated. Finally, the crude product was further purified by flash column chromatography and recrystallization with diethyl ether to give pure product 3a as a yellow solid in 77 % yield.

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An Efficient Three-Component Synthesis of 3-(1-Hydroxyalkyl)[1,2,4]-triazolo[4,3-c]quinazolines

Abstract: An Efficient Three-Component Synthesis of 3-(1-Hydroxyalkyl)[1,2,4]triazolo[4,3-c]quinazolines S y n t h e s i s o f 3 -( 1 -H y d r o x y a l k y l ) [ 1 , 2 , 4 ] t r i a z o l o [ 4 , 3c ] q u i n a z o l i n e s

Cited by 28 publications

References 6 publications

General α-Amino 1,3,4-Oxadiazole Synthesis via Late-Stage Reductive Functionalization of Tertiary Amides and Lactams

General α-Amino 1,3,4-Oxadiazole Synthesis via Late-Stage Reductive Functionalization of Tertiary Amides and Lactams

Synthesis of 2-(alkylamino)-5-{alkyl[(2-oxo-2H-chromen-3-yl)carbonyl]amino}-3,4-furandicarboxylates using a multi-component reaction in water

Silver‐Catalyzed Cascade Reaction of N‐Isocyaniminotriphenylphosphorane with Aldehydes: Synthesis of Unsymmetrical Azines

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