Three‐Component Reaction for Construction of Spiro[indoline‐3,7′‐thiazolo[3,2‐a]pyridines] and Spiro[benzo[4,5]thiazolo[3,2‐a]pyridine‐3,3′‐indolines]

The three‐component reaction of thiazole (benzothiazole), dialkyl but‐2‐ynedioate, and isatinylidene malononitriles in toluene at 110–120°C in a sealed tube afforded a mixture of cis/trans‐isomers of functionalized diastereoisomeric spiro[indoline‐3,7′‐thiazolo[3,2‐a]pyridines] and spiro[benzo[4,5]thiazolo[3,2‐a]pyridine‐3,3′‐indolines] in good yields. Both cis‐isomers and trans‐isomers were successfully separated out and fully characterized with spectroscopy and single crystal determination. Under similar conditions, the three‐component reaction containing 2‐(1,3‐dioxo‐1H‐inden‐2(3H)‐ylidene)malononitrile resulted in spiro[indene‐2,7′‐thiazolo[3,2‐a]pyridine] derivatives.     

Convenient Synthesis of Spiro[benzo[d]pyrrolo[2,1‐b]thiazole‐3,2′‐indenes] Derivatives via Three‐Component Reaction

The three‐component reaction of N‐phenacylbenzothiazolium bromides, aromatic aldehydes and indane‐1,3‐dione in ethanol at room temperature in the presence of triethylamine as base afforded functionalized spiro[benzo[d]pyrrolo[2,1‐b]thiazole‐3,2′‐indenes] in good yields and with high diastereoselectivity. The ¹H NMR data and single crystal structure clearly indicated that the obtained spiro compounds predominately have one diastereoisomer.     

A Three‐Component Reaction for the Efficient Construction of the 2′,11b′‐Dihydrospiro[indoline‐3,1′‐pyrido[2,1‐a]isoquinoline] Skeleton

The three‐component reactions of isoquinoline, acetylenedicarboxylates, and 3‐phenacylideneoxindoles in ethanol at room temperature resulted in a mixture of two diastereoisomers of 2′,11b′‐dihydrospiro[indoline‐3,1′‐pyrido[2,1‐a]isoquinoline] derivatives, which were successfully separated and characterized. The regioselectivity and diastereoselectivity of this reaction were briefly discussed.     

Catalyst‐Free Convergent Approach for the Synthesis of Spiro[imidazo[2,1‐b][1,3]oxazine‐7,3′‐indoline

Strategies to address mounting environmental concerns with current approaches include an operationally simple and highly efficient one‐pot three‐component approach for the synthesis of spiro[imidazo[2,1‐b][1,3]oxazine‐7,3′‐indoline derivatives, which has been developed via Huisgen zwitter ion intermediate. The significant advantages of this protocol are short reaction time, excellent yields, and facile formation of three new bonds in one operation from easily available starting materials.     

Three‐Component Synthesis of Spiro[indoline‐3,4′‐pyrazolo[3,4‐b]pyridines] under Microwave Irradiation

A domino three‐component strategy with high efficiency for the synthesis of spiro[indoline‐3,4′‐pyrazolo[3,4‐b ]pyridines] from easily available isatins, pyrazol‐5‐amines and β‐ketonitriles under microwave heating. During reaction process, HOAc plays dual roles as reaction media as well as a Brønsted acid‐promoter. Flexible structural modification, broad functional group compatibility and mild reaction conditions make this strategy a useful and attractive process of library generation for drug discovery.     

Synthesis of new functionalized imidazo[2,1‐b]thiazoles and thiazolo[3,2‐a]pyrimidines

5‐Oxo‐5H‐[1,3]thiazolo[3,2‐a]pyrimidine‐6‐carboxylic acid ( 4 ), and 6‐methylimidazo[2,1‐b]thiazole‐5‐carboxylic acid ( 17 ) were reacted with amines 6a‐i by the reaction with oxalyl chloride and N, N‐di methyl‐formamide as a catalyst into primary and secondary amide derivatives 7‐14 and 19‐22. From compound 24 N,N'‐disubstituted ureas 26, 27 and perhydroimidazo[1,5‐c]thiazole 29 derivatives of imidazo[2,1‐b]thiazole were prepared. By nmr analysis of compound 29 , the existence of two stereoisomers resulting from both optical, due to centre of chirality at C7′a, and conformational isomerism, due to restricted C5? N6′ bond rotation were proved.     

One‐pot Three‐component Synthesis of Spiro[pyrazolo[3,4‐b]pyridine‐4,3′‐indoline] Derivatives Catalyzed by Melamine Trisulfonic Acid

Novel spiro[pyrazolo[3,4‐b]pyridine‐4,3′‐indoline] derivatives were prepared by the three‐component reaction of isatins 3‐methyl‐1‐phenyl‐1H‐pyrazol‐5‐amine and Meldrum's acid in the presence of a catalytic amount of melamine trisulfonic acid. This protocol provides a simple one‐step procedure with the advantages of easy work‐up, mild reaction conditions and environmentally benign.     

One‐Pot,Four‐Component Synthesis of Novel Spiro[indeno[2,1‐b]quinoxaline‐11,4′‐pyran]‐2′‐amines

A one‐pot, four‐component reaction for the efficient synthesis of novel spiro[indeno[2,1‐b]quinoxaline‐11,4′‐pyran]‐2′‐amines by using InCl₃ is described. The syntheses are achieved by reacting ninhydrin with 1,2‐diaminobenzenes to give indenoquinoxalines, which are trapped in situ by alkyl malonates and various α‐methylencarbonyl compounds through cyclization, providing multifunctionalized spiro‐substituted indeno[2,1‐b]quinoxaline‐11,4′‐pyran‐2′‐amines.     

A New Four‐Component Reaction for the Synthesis of Spiro[4H‐indeno[1,2‐b]pyridine‐4,3′‐[3H]indoles]

A new four‐component synthesis of spiro[4H‐indeno[1,2‐b]pyridine‐4,3′‐[3H]indoles] and spiro[acenaphthylene‐1(2H),4′‐[4H‐indeno[1,2‐b]pyridines] by the reaction of indane‐1,3‐dione, 1,3‐dicarbonyl compounds, isatins (=1H‐indole‐2,3‐diones) or acenaphthylene‐1,2‐dione, and AcONH₄ in refluxing toluene in the presence of a catalytic amount of pyridine is reported.     

Efficient One‐Pot Synthesis of Spiro[indoline‐3,1′‐pyrazolo[1,2‐b] phthalazine] Derivatives via Three‐Component Reaction

An efficient one‐pot synthesis of spiro[indoline‐3,1′‐pyrazolo[1,2‐b]phthalazine] derivatives via three‐component reaction of phthalhydrazide, isatin, and malononitrile (cyanoacetic ester) is described. This new protocol has the advantages of high efficiency, mild reaction conditions, one‐pot procedure, and convenient operation.     

A Diastereoselective Synthesis of Functionalized Tetrahydroindeno[2′,1′,3,4]pyrido[2,1‐a]isoquinolines

An effective route to alkyl 9a‐(2,3‐dihydro‐1,3‐dioxo‐1H‐inden‐2‐yl)‐9a,14,14a,14b‐tetrahydro‐14‐oxoindeno[2′,1′:3,4]pyrido[2,1‐a]isoquinoline‐9‐carboxylates via a diastereoselective one‐pot four‐component reaction of isoquinoline and alkyl prop‐2‐ynoates with two equivalents of indane‐1,3‐dione, in aqueous MeOH at room temperature, is described.     

Spiro[4H‐pyran‐3,3′‐oxindoles] Derived from 1,2,3,4‐Tetrahydroquinoline

Three‐component reactions of 5,6‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinoline‐1,2‐dione with malononitrile, or ethyl cyanoacetate, and cyclic six‐membered or a five‐membered 1,3‐diketone, produce spiro[4H‐pyran‐3,3′‐oxindoles].     

Spiro[3H‐pyrazole‐3,3′‐oxindoles] Derived from 1,2,3,4‐Tetrahydroquinoline

Aldol condensation of 5,6‐dihydro‐4H‐pyrrolo[3,2,1‐ij ]quinoline‐1,2‐dione with aryl methyl ketones generates 3‐(aroylmethylidene)oxindoles, which react with hydrazine to generate tricyclic spiro[3H‐pyrazole‐3,3′‐oxindoles].     

An Efficient Four‐component Synthesis of Spiro[indoline‐pyrazolo[4′,3′:5,6]pyrido[2,3‐d]pyrimidine]triones

A four‐component reaction in the presence of Alum [KAl(SO₄)₂·12H₂O] as an inexpensive and reusable catalyst using the ionic liquid as an effective green reaction media is reported.     

Three‐Component One‐Pot Synthesis of Indeno[2′,1′:5,6]Pyrido[2,3‐d]Pyrazole Derivatives in Aqueous Media

A series of indeno[2′,1′:5,6]pyrido[2,3‐d]pyrazoles was synthesized by the three‐component reaction of aldehyde, 5‐amino‐3‐methyl‐1‐phenylpyrazole and 1,3‐indenedione in the presence of SDS in aqueous media. The structures were characterized by IR, ¹H NMR, high resolution mass spectra and were further confirmed by X‐ray diffraction analysis.     

Synthesis of Novel Spiro Pyrano[2,3‐d]thiazolo[3,2‐a]pyrimidine via 1,3‐Dipolar Cycloaddition of Azomethine Ylide

The reaction involving 4‐phenyl‐octahydro‐pyrano[2,3‐d]pyrimidine‐2‐thione, ethyl chloroacetate and the appropriate aromatic aldehyde yielded 2‐arylmethylidene‐5‐phenyl‐5a,7,8,9a‐tetrahydro‐5H,6H‐pyrano[2,3‐d][1,3]thiazolo[3,2‐a]pyrimidin‐3(2H)‐ones. The 1,3‐dipolar cycloaddition of 2‐arylmethylidene‐5‐phenyl‐5a,7,8,9a‐tetrahydro‐5H,6H‐pyrano[2,3‐d][1,3]thiazolo[3,2‐a]pyrimidin‐3(2H)‐ones with azomethine ylide generated by a decarboxylative route from sarcosine and acenaphthenequinone afforded 4′‐aryl‐1′‐methyl‐5″‐phenyl‐5a″,7″,8″,9a″‐tetrahydro‐2H,5″H,6″H‐dispiro[acenaphthylene‐1,2′‐pyrrolidine‐3′,2″‐pyrano[2,3‐d][1,3]thiazolo[3,2‐a]pyrimidine]‐2,3″‐diones in moderate yields. The structures of the products were determined and characterized thoroughly by NMR, MS, IR, elemental analysis, and X‐ray crystallographic analysis.     

Preparation of a series of benzothieno[3,2‐b]pyridine‐3‐carbonitriles and benzofuro[3,2‐b]pyridine‐3‐carbonitriles

New and shorter routes to the benzothieno[3,2‐b]pyridine‐3‐carbonitrile and benzofuro[3,2‐b]pyridine‐3‐carbonitrile ring systems are reported. These heterocycles may function as new templates for kinase inhibitors.     

Spiro[4H–pyran‐3,3′‐oxindoles] Derived from 9,10‐dihydroacridine

Reaction 6H‐pyrrolo[3,2,1‐de ]acridine‐1,2‐dione ( 7 ) with cyclic 1,3‐dicarbonyl compounds in the presence of malononitrile or ethyl cyanoacetate generates spiro[4H‐pyran‐3,3′‐oxindoles] 8 .     

Synthesis of pyrido[3′,2′:4,5] thieno[3,2-d]pyrimidine derivatives

Pyrido [3′,2′:4,5]thieno[3,2-d] pyrimidine and several of its derivatives have been synthesized.