An efficient method for the preparation of thieno[3′,2′:2,3]pyrido[4,5-d]thiazolo[3,2-a] pyrimidin-5-ones 5 is described. The key intermediate, 7-(3-amino-4-cyano-5-phenyl aminothieno-2-yl)-5H-thiazolo-[3,2-a]pyrimidin-5-one (3), was synthesized from 7-chloromethyl-5H-thiazolo[3,2-a]pyrimidin-5-one (1) with potassium-(2,2-dicyano-1-phenylaminoethen-1-yl)thiolate (2) by Thorpe–Ziegler isomerization. Subsequent reaction of the intermediate amine with aromatic aldehydes via Pictet–Spengler reaction provided thieno-pyridine fused thiazolo[3,2-a]pyrimidines under p-TsOH as catalyst in good yields.Download high-res image (51KB)Download full-size imageAn efficient method for the preparation of thieno[3′,2′:2,3]pyrido-[4,5-d]thiazolo[3,2-a]pyrimidin-5-ones 5 is described. The key intermediate, 7-(3-amino-4-cyano-5-phenylaminothieno-2-yl)-5H-thiazolo[3,2-a]pyrimidin-5-one (3), was synthesized from 7-chloro methyl-5H-thiazolo[3,2-a]pyrimidin-5-one (1) with potassium-(2,2-dicyano-1-phenylaminoethen-1-yl)thiolate (2) by Thorpe–Ziegler isomerization. Subsequent reaction of the intermediate amine with aromatic aldehydes via Pictet–Spengler reaction provided thieno-pyridine fused thiazolo[3,2-a]pyrimidines under p-TsOH as catalyst in good yields.

An efficient method for the synthesis of novel benzo[b]pyrimido[4′,5′:5,4]thieno[2,3e]-[1,6]naphthyridine-8-one derivatives via Pictet–Spengler cyclization is reported. The reaction of 4-(3-aminopyrimido[4,5-d]thieno-2-yl)quinoline-2-ones, which could be obtained from Thorpe–Ziegler isomerization of 4-bromomethylquinoline-2-ones and 5-cyano-1,6-dihydro-4-methyl-2-phenyl-6-thioxopyrimidine, with aromatic aldehydes in the presence of BF3·OEt2 gives pyrimidothieno[1,6]naphthyridines in good yields.An efficient method for the synthesis of novel benzo[b]pyrimido[4′,5′:5,4]thieno[2,3-e][1,6]naphthyridine-8-one derivatives via Pictet-Spengler cyclization is reported. The reaction of 4-(3-aminopyrimido[4,5-d]thieno-2-yl)quinoline-2-ones, which could be obtained from Thorpe-Ziegler isomerization of 4-bromomethylquinoline-2-ones and 5-cyano-1,6-dihydro-4-methyl-2-phenyl-6-thioxo pyrimidine, with aromatic aldehydes in the presence of BF3·OEt2 gives pyrimidothieno[1,6]naphthyridines in good yields.

An efficient method for the synthesis of novel pyrido[3″,2″:4′,5′]thieno[3′,2′:2,3]pyrido [4,5:d][1,3]thiazolo[3,2-a]pyrimidine-4-one derivatives (5) has been developed using a Pictet–Spengler reaction between 2-(3-aminothieno[2,3-b]pyridin-2-yl)thiazolo[3,2-a] pyrimidin-5-one (3), which could be obtained from the condensation of 7-(chloromethyl)-5H-thiazolo[3,2-a]pyrimidin-5-one (1) with 3-cyanopyridine-2-thione (2) via Thorpe–Ziegler isomerization, and aromatic aldehydes under NH2SO3H as catalysis in good yields.An efficient method for the synthesis of novel fused thiazolo[3,2-a]pyrimidinones: pyrido[3″,2″:4′,5′]thieno[3′,2′:2,3]pyrido[4,5:d] [1,3]thiazolo[3,2-a]pyrimidine-5-one derivatives (5) has been developed using a Pictet–Spengler reaction between 2-(3-aminothieno [2,3-b]pyridin-2-yl)thiazolo[3,2-a]pyrimidin-4-one (3), which could be obtained from condensation of 7-(chloromethyl)-5H-thiazolo [3,2-a]pyrimidin-5-one (1) with 3-cyanopyridine-2-thione (2) via Thorpe–Ziegler isomerization, and aromatic aldehydes under NH2SO3H as catalysis in good yields.

An efficient method for the synthesis of benzo[b]benzofurano[2,3-e][1,6]naphthyridine-8-one derivatives has been developed via Pictet-Spengler reaction of 4-(3-aminobenzofuran-2-yl)quinoline-2-ones, which could be obtained from alkylation of 4-bromomethylquinoline-2-ones with salicylonitrile and subsequent Thorpe-Ziegler isomerization, with aromatic aldehydes under p-TsOH as catalyst in good yields.An efficient method for the synthesis of benzo[b]benzofurano[2,3-e][1,6]naphthyridine-8-one derivatives has been developed via Pictet-Spengler reaction of 4-(3-aminobenzofuran-2-yl)quinoline-2-ones, which could be obtained from alkylation of 4-bromomethylquino-line-2-ones with salicylonitrile and subsequent Thorpe-Ziegler isomerization, with aromatic aldehydes under p-TsOH as catalyst in good yields.

Ethyl α-(dimethylaminomethylene)-2-cyanomethyl-4-phenylquinoline-3-carboxylate (2) as new synthons directed to 1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carbonitriles was obtained by the condensation of ethyl 2-cyanomethyl-4-phenylquinoline-3-carboxylate (1) and N,N-dimethylformamide dimethyl acetal (DMFDMA). Reaction of this enamine with primary amines (3) in HOAc-DMF at 120 °C then affords 2-substituted 1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carbonitrile derivatives (4) in good yields by a tandem addition–elimination–cyclization reaction.Ethyl α-(dimethylaminomethylene)-2-cyanomethyl-4-phenylquinoline-3-carboxylate (2) as new synthons directed to 1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carbonitriles was obtained by the condensation of ethyl 2-cyanomethyl-4-phenylquinoline-3-carboxylate (1) and N,N-dimethylformamide dimethyl acetal (DMFDMA).

A simple and efficient procedure was developed for the synthesis of 11H(2H)-4-oxothiophene[3′,4′:6,5]pyrido[3,2-a]azulene-10-carboxylates (3) in moderate to good yields via the Gewald reaction of ethyl 1-cyanoacetyl-2-methoxyazulene-3-carboxylate (1) with carbonyl compounds (2) and elemental sulfur utilizing imidazole as catalyst. This reaction provides a new procedure for synthesis of pyridinone-fused azulenes.A simple and efficient procedure was developed for the synthesis of 11H(2H)-4-oxothiophene[3′,4′:6,5]pyrido[3,2-a]azulene-10-carboxylates (3) in moderate to good yields via Gewald reaction of ethyl 1-cyanoacetyl-2-methoxyazulene-3-carboxylate (1) with carbonyl compounds (2) and elemental sulfur utilizing imidazole as catalyst. This reaction provides a new procedure for synthesis of pyridinone-fused azulenes.

An efficient and mild synthesis of 2-(guaiazulen-1-yl)furans, starting from easily accessible 1-(3-aryl-2-cyanopropenoyl)guaiazulenes, tributylphosphine and acyl chlorides, is described. The strategy employs the intramolecular Wittig protocol as a key step to append the crucial furan ring, leading to the highly functional furans in good yields.An efficient and mild synthesis of 2-(guaiazulen-1-yl)furans, starting from readily available 1-(3-aryl-2-cyanopropenoyl)guaiazulenes, tributylphosphine and acyl chlorides, is described. The strategy employs the intramolecular Wittig protocol as a key step to append the crucial furan ring, leading to the highly functional furans in good yields.

A facile, efficient synthesis of 3-(guaiazulen-1-yl)succinimides was developed by Michael-type addition of guaiazulene to maleimides in the presence of p-toluenesulfonic acid under mild reaction conditions.