Novel fluoro-substituted benzo- and benzothieno fused pyrano[2,3-c]pyrazol-4(1H)-ones

A straightforward, two-step synthesis of fluoro substituted chromeno[2,3-c]pyrazol- and [1]benzothieno[2′,3′:5,6]pyrano[2,3-c]pyrazol-4(1H)-ones, respectively, is presented. Hence, treatment of 1-substituted or 1,3-disubstituted 2-pyrazolin-5-ones with fluoro substituted 2-fluorobenzoyl chlorides or 3-chloro-6-fluoro-1-benzothiophene-2-carbonyl chloride using calcium hydroxide in refluxing 1,4-dioxane gave the corresponding 4-aroylpyrazol-5-ols, which were cyclized into the fused ring systems. 5-Fluorochromeno[2,3-c]pyrazol-4(1H)-one was obtained upon treatment of the 1-(4-methoxybenzyl) protected congener with trifluoroacetic acid. Treatment of 5-fluorochromeno[2,3-c]pyrazol-4(1H)-ones with methylhydrazine afforded novel tetracyclic ring systems such as 2-methyl-7-phenyl-2,7-dihydropyrazolo[4′,3′:5,6]pyrano[4,3,2-cd]indazole. Detailed NMR spectroscopic investigations (¹H, ¹³C, ¹⁵N, ¹⁹F) with the obtained compounds were undertaken.     

Thieno[2,3-d]pyrimidin-4-ones 1. Condensation of 2,3-dimethyl- and 2,3-tri-, 2,3-tetra-, and 2,3-pentamethylene-7,8-dihydro-pyrrolo[1,2-a]thieno[2,3-d]pyriminidin-4(6H)-ones with aromatic aldehydes and furfural

2,3-Dimethyl- and 2,3-tri-, 2,3-tetra-, and 2,3-pentamethylene-substituted 8-arylidene-6,7-dihydro-pyrrolo[1,2-a]thieno[2,3-d]pyrimidin-4-ones were synthesized by the reaction of 2,3-dimethyl- and 2,3-tri-, 2,3-tetra-, and 2,3-pentamethylene-7,8-dihydropyrrolo[1,2-a]thieno[2,3-d]pyrimidin-4(6H)-ones with benzaldehyde, its 4-dimethylamino-, 3,4-dimethoxy-, and 3,4-methylenedioxy derivatives and also furfural in the presence of NaOH.     

Single step synthesis of 2,3-dialkyl-6-nitro-quinazolin-4(3H)-imines and 3,5-dialkyl-9-nitro-imidazo[1,2-c]quinazolin-2(3H)-ones

A single step synthesis of 2,3-dialkyl-6-nitro-quinazolin-4(3H)-imines and 3,5-dialkyl-9-nitro-imidazo-[1,2-c]-quinazolin-2(3H)-ones from simple carbonyl compounds, primary amines or amino acid methyl esters and 2-azido-5-nitro-benzonitrile was developed. Key intermediates were N,N′-disubstituted amidines obtained by rearrangement of 4,5-dihydrotriazoles; the new heterocyclic rings were formed by spontaneous intramolecular reaction of the amino and cyano groups which are present in the intermediates.     

Unusual reaction of 2-(trifluoromethyl)-1,2-dihydro-3lambda(6)-thieno- [2,3-c]chromen-3,3,4-triones with hydrazine as a new route to 3-hydrazinopyridazine derivatives

Oxidation of 2-(trifluoromethyl)-1,2-dihydro-4H-thieno[2,3-c]chromen-4-ones 2 with H(2)O(2) in AcOH gives 2-(trifluoromethyl)-1,2-dihydrothieno[2,3-c]chromen-3,3,4-triones 3, which are transformed into 3-hydrazinopyridazine derivatives 4 in high yields by treatment with hydrazine hydrate in ethanol.     

Rearrangement of furo[2,3-c]quinoline-2,4(3aH,5H)-diones to furo[3,4-c]quinoline-3,4(1H,5H)-diones

Thermally assisted base-catalyzed rearrangement of furo[2,3-c]quinoline-2,4(3aH,5H)-diones 1 to the corresponding furo[3,4-c]quinoline-3,4(1H,5H)-diones 2 is reported, and a mechanism of the transformation is proposed.     

Photochemistry of 3H-furo[3,4-c]pyrazoles and 3H-thieno[3,4-c]pyrazoles

The first examples of 3H-furo[3,4-c]pyrazoles and 3H-thieno[3,4-c]pyrazoles were prepared in an attempt to isolate examples of cyclopropane-fused thiophenes and furans. Adducts of acetylenic ketones and 2-diazopropane were reacted with 10-camphorsulfonic acid or phosphorus pentasulfide to produce the title compounds. Photolysis of these compounds did not give the cyclopropane-fused products rather an unreported photochemical fragmentation was observed.     

Gold-catalyzed cyclization of enediynes and arenediynes to 6H-benzo[c]chromen-6-one and dibenzo[c,h]chromen-6-one derivatives

The efficient synthesis of 6H-benzo[c]chromen-6-one and dibenzo[c,h]chromen-6-one derivatives is described. Thus, treatment of arenediynes 1 and enediynes 5 with 5?mol % Ph₃PAuCl and 10?mol % of AgSbF₆ in refluxing toluene gave dibenzo[c,h]chromen-6-ones 4 and 6H-benzo[c]chromen-6-ones 6, in good yields, respectively.     

A new route to pyrazolo[3,4-c] and [4,3-c]pyridinones via heterocyclization of vic-substituted hydroxamic acids of acetylenylpyrazoles

We report in this paper the synthesis of 6-substituted pyrazolo[4,3-c]pyridin-4-ones, 6-substituted 5-hydroxypyrazolo[4,3-c]pyridin-6-ones, 5-substituted pyrazolo[3,4-c]pyridin-7-ones and 5-substituted 6-hydroxypyrazolo[3,4-c]pyridin-7-ones by heterocyclization of vic-acetylenylpyrazol-hydroxamic acids under the influence of copper(I) salt in dimethylformamide or with organic bases in butanol or methanol.     

Antimony trichloride catalyzed three-component reaction of urea, aldehydes and cyclic enol ethers: a novel route to 4-arylhexahydrofuro[2,3-d]pyrimidin-2(3H)-ones

Antimony trichloride efficiently catalyses diastereoselective three-component reaction of urea, aromatic aldehydes and 2,3-dihydrofuran or 3,4-dihydro-2H-pyran leading to 4-arylhexahydrofuro[2,3-d]pyrimidin-2(3H)-ones and 4-arylhexahydro-1H-pyrano[2,3-d]pyrimidin-2(8aH)-ones, respectively in good yield.     

Preparation of 2-aminosubstituted 3H-imidazo[4,5-c]quinolin-4(5H)-ones by palladium-assisted internal biaryl coupling reaction

Representatives of the 3H-imidazo[4,5-c]quinolin-4(5H)-ones have shown interesting biological activity. We have found 2-aminosubstituted 3H-imidazo[4,5-c]quinolin-4(5H)-one as a potent dipeptidyl peptidase 4 inhibitor. However effective synthesis of this nucleus with various substituents at the 6-9-positions has not been reported. We report herein the development of a novel and efficient synthesis of 2-aminosubstituted 3H-imidazo[4,5-c]quinolin-4(5H)-ones by palladium-assisted internal biaryl coupling reaction. Our optimization of the reaction conditions revealed that the most important factors for this reaction are use of silver carbonate as a base and high reaction temperature.     

Substituted chromones in [3+2] cycloadditions with nonstabilized azomethine ylides: synthesis of 1-benzopyrano[2,3-c]pyrrolidines and 1-benzopyrano[2,3-c:3,4-c′]dipyrrolidines

Chromones bearing electron-withdrawing substituents at the 2- or 3-position react with nonstabilized azomethine ylides to produce 1-benzopyrano[2,3-c]pyrrolidines in good yields. Reactions of 3-cyanochromones proceed diastereoselectively to give 1-benzopyrano[2,3-c]pyrrolidines and tetrahydro-1H-spiro[chromeno[2,3-c]pyrrol-9,5′-oxazolidine]-9a-carbonitriles, depending on the reactant ratio, as a result of a 1,3-dipolar cycloaddition of the azomethine ylide at the double bond and carbonyl group of the chromone system. The latter undergoes demethylenation and recyclization into a novel hexahydrochromeno[2,3-c:3,4-c′]dipyrrole tetracyclic system on heating with hydrochloric acid.     

New synthetic methods for 2,3-diarylacridin-9(10H)-one and (E)-2-aryl-4-styrylfuro[3,2-c]quinoline derivatives

Two new synthetic methodologies for 2,3-diarylacridin-9(10H)-ones were developed. The first one involves the Heck reaction of (E)-3-iodo-2-styrylquinolin-4(1H)-ones with styrenes, leading to (E,E)-2,3-distyrylquinolin-4(1H)-ones, which when heated at high temperatures cyclize in two different ways. Electrocyclization and further in situ oxidation leads to 2,3-diarylacridin-9(10H)-ones, while tautomerization, cyclization by nucleophilic addition and further in situ oxidation produces (E)-2-aryl-4-styrylfuro[3,2-c]quinolines as the main compound. The second method gives only 2,3-diaryl-10-methylacridin-9(10H)-ones and involves the Heck reaction of (E)-3-iodo-1-methyl-2-styrylquinolin-4(1H)-ones and styrenes, leading to (E,E)-1-methyl-2,3-distyrylquinolin-4(1H)-ones, which when heated at high temperatures cyclize through electrocyclization and oxidation processes affording the expected compounds. The structures of all new compounds were established by extensive NMR studies.     

Convenient synthesis of linear pyrano[3,2-g]-, [2,3-g]- and angular pyrano[3,2-f]coumarins from 4[(1,1-dimethyl-2-propynyl)oxy]phenol

An easy preparation of new 4-alkoxycarbonyl angular and linear pyranocoumarins starting from 4-[(1,1-dimethyl-2-propynyl)oxy]phenol and their transformation to the known coumarins xanthyletin, 8,8-dimethylpyrano[3,2-f]chromen-3(8H)-one and 7,7-dimethylpyrano[2,3-g]chromen-2(7H)-one is described.     

Regioselective synthesis of 4-chlorophenols, 10-chloro-7-hydroxy-6H-benzo[c]chromen-6-ones, and 4-chloro-1-hydroxy-9H-fluoren-9-ones based on [3+3] cyclizations of 1,3-bis(silyloxy)-1,3-dienes with 2-chloro-3-silyloxy-2-en-1-ones

A variety of 4-chlorophenols, 10-chloro-7-hydroxy-6H-benzo[c]chromen-6-ones, and 4-chloro-1-hydroxy-9H-fluoren-9-ones were prepared by formal [3+3] cyclizations of 1,3-bis(silyloxy)-1,3-dienes with 2-chloro-3-(silyloxy)alk-2-en-1-ones.     

Synthesis of furo[2,3-c]-2,7-naphthyridine derivatives via domino heterocyclization reaction

2-Amino-4-cyanomethyl-6-dialkylamino-3,5-pyridinedicarbonitriles were found to react with substituted oxiranes yielding 5,6-diamino-8-dialkylamino-1,2-dihydrofuro[2,3-c]-2,7-naphthyridine-9-carbonitriles. The oxirane ring was shown to be opened selectively from the unsubstituted side and further cyclization occurred with participation of 3-CN, but not 5-CN of the starting pyridines. The furonaphthyridines obtained were converted into 2-dialkylamino-5-methyl-9,10-dihydro-4H-furo[2,3-c]pyrimido[4,5,6-ij]-2,7-naphthyridine-1-carbonitriles and 2-dialkylamino-5,6,9,10-tetrahydro-4H-spiro{furo[2,3-c]pyrimido[4,5,6-ij]-2,7-naphthyridine-5,1′-cyclohexane}-1-carbonitriles by treatment with acetic anhydride and cyclohexanone, respectively. The structure of prepared compounds was confirmed unambiguously by X-ray crystallographic study.     

A facile route to phenyl, phenylsulfanyl and phenylselanyl substituted pyrano[3,2-c]chromenes

The synthesis of phenyl, phenylsulfanyl and phenylselanyl substituted pyrano[3,2-c]chromenes 4 is accomplished via cyclocondensation of 4-oxo-4H-chromen-3-carbaldehydes 1 with appropriately substituted acetic acids 2 under mild conditions. Further treatment of 4 with alcohol or water led to 5-alkoxy- and 5-hydroxy-2H,5H-pyrano[3,2-c]chromen-2-ones 5 and 6, respectively. Acid and thermal catalysed rearrangement of 4-6 gave 5-hydroxypyrano[2,3-b]chromen-2(10aH)-ones 7 and their subsequent substitution led to 5-alkoxyderivatives 8. Reaction of 4 with amides led to 5-acylamino or 5-phenylsulfonamino substituted 2H,5H-pyrano[3,2-c]chromen-2-ones 9. Reactions were performed under heating or microwave irradiation.     

Reaction of 4-Aryl-1-(4-oxo-3,4-dihydrothieno-[2,3-d]pyrimidin-2-yl)thiosemicarbazides with Dimethyl Acetylenedicarboxylate

4-Aryl-1-(4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-2-yl)thiosemicarbazides react with dimethyl acetylenedicarboxylate in methanol to give the corresponding methyl {3-aryl-4-oxo-2-[(4-oxo-3,4-dihydro-thieno[2,3-d]pyrimidin-2-yl)hydrazono]-1,3-thiazolidin-5-ylidene}acetates, whereas in dioxane methyl 5-aryl-amino-2-methoxycarbonylmethyl-3-(4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-2-yl)-2,3-dihydro-1,3,4-thiadiazole-2-carboxylates are mainly formed.     

Synthesis of 6H-benzo[c]chromen-6-ones by cyclocondensation of 1,3-dicarbonyl compounds with 4-chloro-3-formylcoumarin

6H-benzo[c]chromen-6-ones were prepared by base mediated cyclocondensation of 1,3-dicarbonyl compounds with 4-chloro-3-formylcoumarin.     

Synthesis of furo[2,3-b]pyridin-4(7H)-ones and related quinolinone via Brønsted acid-promoted cyclisation of alkynes

N-Alkyl-4-alkoxy-3-alkynylpyridin-2(1H)-ones readily undergo acid-promoted 5-endo-heteroannulation to furopyridinium intermediates that are dealkylated in situ to provide the corresponding furo[2,3-b]pyridin-4(7H)-ones. The same strategy applies to the formation of furo[2,3-b]quinolin-4(9H)-ones. In the case of Me₃Si-substituted alkynes, hydration of the triple bond was observed.     

Palladium-mediated synthesis of 5-substituted 4-alkynylthieno[2,3-c]pyran-7-ones

We describe here, the first palladium-mediated tandem C-C bond forming reaction between 3-iodothiophene-2-carboxylic acid and terminal alkynes to afford the unexpected 5-substituted 4-alkynylthieno[2,3-c]pyran-7-ones in good yields.