Substituted coumarin amidines: useful building blocks for the preparation of [1]benzopyrano[4,3-b]pyridin-5-one and [1]benzopyrano[4,3-d]pyrimidin-5-one derivatives

The synthesis of [1]benzopyrano[4,3-b]pyridin-5-ones 4a-f and 4g-j starting from 3-formylcoumarin and 3-cyanocoumarin N-functionalized amidines 3a-f and 3g-j, respectively, was reported. The ring-closure reaction mechanism, under basic or acidic media, was proposed. Furthermore, the reaction of 3-formylamidines 3a,c-f with ammonium acetate gave good yields of 2-substituted [1]benzopyrano[4,3-d]pyrimidin-5-ones 7.     

Convenient synthesis of pyrazolo[3,4-b]pyridin-3-ones and pyrazolo[3,4-b]pyridine-5-carbaldehyde using vinamidinium salts

An expedient method for the synthesis of 2-phenyl-5-aryl-2,3-dihydropyrazolo[3,4-b]pyridin-3-ones and 2-phenyl-3-oxo-2,3-dihydropyrazolo[3,4-b]pyridine-5-carbaldehyde in a single-step via condensation of vinamidinium salts with 3-amino-1-phenyl-2-pyrazolin-5-one is described.     

Convenient syntheses of pyrazolo[3,4-b]pyridin-6-ones using either microwave or ultrasound irradiation

An efficient synthesis of 12 pyrazolo[3,4-b]pyridin-6-one derivatives was achieved using either microwave or ultrasound irradiation, resulting in yields of 40-60% and 60-95%, respectively. Under our conditions, these reactions occurred with notably reduced reaction times as compared to literature reports involving traditional heating. Furthermore, these reactions were highly regioselective and produced only one pyrazolo[3,4-b]pyridin-6-one isomer, whose identity was confirmed by NOESY spectroscopy.     

Preparation of novel pyridine-fused tris-heterocycles; pyrido[4,3-e]pyrrolo-/pyrido[4,3-e]furano[2,3-c]pyridazines and pyrido[3,4-b]pyrrolo[3,2-d]pyrrole

Three novel pyrido-fused tris-heterocycles have been prepared based on a Suzuki coupling and subsequent cyclisation approach. Pyrido[4,3-e]pyrrolo[2,3-c]pyridazine (3b, 77%) and pyrido[4,3-e]furano[2,3-c]pyridazine (5b, 76%) were obtained by intramolecular diazocoupling. Successful diazocoupling of furan (5b) is thus reported for the first time by NOBF₄ generation of the diazonium intermediate. N-TIPS-pyrido[3,4-b]pyrrolo[3,2-d]pyrrole (TIPS-4b) was synthesised by thermal cyclisation of pyridyl nitrene in considerably higher yield (71%) than previously experienced from similar cyclisations, due to TIPS-activation.     

An efficient and novel approach to the synthesis of tetrahydrophenanthro[4,3-b]thiophenes

An elegant approach to the synthesis of 2,3,6,7-tetrahydrophenanthro[4,3-b]thiophenes has been described through base catalyzed ring transformation of 4-sec-amino-2-oxo-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles with tetrahydrothiophen-3-one in very good yields.     

Synthesis of dihydrochromeno[4,3-b]pyrrolo[3,2-f]quinolines via intramolecular aza Diels-Alder reaction

An efficient and convenient one-pot intramolecular aza Diels-Alder approach for the synthesis of dihydrochromeno[4,3-b]pyrrolo[3,2-f]quinolines has been reported. Particularly valuable features of this methodology include simple execution, inexpensive catalyst, and good product yields.     

Preparation of new pyrido[3,4-b]thienopyrroles and pyrido[4,3-e]thienopyridazines

Two new types of pyrido-fused tris-heterocycles (1a,b and 2a,b) have been prepared from 3-aminopyridine in five/six steps. A synthetic strategy for the preparation of the novel pyrido[3,4-b]thieno[2,3- and 3,2-d]pyrroles (1a,b) and pyrido[4,3-e]thieno[2,3- and 3,2-c]pyridazines (2a,b) has been studied. The Suzuki cross coupling of the appropriate 2- and 3-thienoboronic acids (3,4) and 4-bromo-3-pyridylpivaloylamide (9) afforded the biaryl coupling products (10,11) in high yields (85%). Diazotization of the hydrolysed (2-thienyl)-coupling product (12) and azide substitution gave the 3-azido-4-(2-thienyl)pyridine intermediate (72%, 14). 3-Azido-4-(3-thienyl)pyridine (15) was prepared by exchanging the previous order of reactions. The desired β-carboline thiophene analogues (1a,b) were obtained via the nitrene by thermal decomposition of the azido precursors (14,15). By optimising conditions for intramolecular diazocoupling, the corresponding pyridazine products (72-83%, 2a,b) were afforded.     

Synthesis of hexahydro[2]benzopyrano[4,3-c]pyridines as serotonin 5-HT2C receptor agonists via intramolecular hetero Diels-Alder reactions

Hexahydro[2]benzopyrano[4,3-c]pyridines were synthesized by an intramolecular hetero Diels-Alder reaction. The reaction was applicable to a range of substrates and the products could be easily converted into serotonin 5-HT_2C receptor agonists.     

Synthesis of new thieno[3,2-b]pyridine derivatives by palladium-catalyzed couplings and intramolecular cyclizations

Two methyl 3-aminothieno[3,2-b]pyridine-2-carboxylates were prepared from 3-fluoro or 3-nitropicolinonitriles and methyl thioglycolate in DMF/KOH(aq). From the unsubstituted precursor in the pyridine ring, di(hetero)arylamines were obtained by C-N Buchwald-Hartwig coupling with bromonitrobenzenes and with 2-bromopyridine. In the latter case a tetracyclic compound was formed by intramolecular cyclization. Using a brominated derivative in the pyridine ring as a coupling component, it was possible to synthesize C-C (Suzuki and Sonogashira) and C-N (Buchwald-Hartwig) coupling products and a tetracyclic compound obtained by bifunctionalization of the thienopyridine system.     

An efficient route to a 5,6-dihydropyrano[3,4-b]pyridin-8-one core in two steps from enaminolactones

A convenient two step conversion of heterocyclic enaminolactones to heterocyclic fused 2-pyran-1-ones is reported. The use of this method can be applied to a wide variety of aromatic and heteroaromatic amines to give potentially biologically active compounds in good yields.     

2-Substituted [1]benzopyrano[4,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidin-5-ones

A new method is reported for the synthesis of 2-R-substituted [1]benzopyrano[4,3-d]pyrimidin-5-ones (R = p-phenyl, p-chlorophenyl-, p-carbamoylphenyl-, 3-pyridinyl-, 4-pyridinyl-, 2-pyrazinyl-, pyrrolidino-,morpholino-, 3,6-dimethyl-1-pyrazolyl-) by the reaction of 4-chloro-3-formylcoumarin with salts of the corresponding amidines RC(=NH)NH₂HX in DMF in the presence of piperidine or triethylamine. 3-Formyl-4-coumarin and 2-aminobenzimidazole give __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 935–940, June, 2007.     

A rapid and convenient synthesis of novel 1-imino-2,3-dihydro-1H-pyrazino[2,1,-b]quinazolin-5-ones

Exploring original approaches for the synthesis of therapeutic agents having a quinazoline part, we discovered that novel 3,4-dihydro-2H-pyrazino[2,1,-b]quinazolines (3) may be rapidly and easily obtained via the chemistry of 4,5-dichloro-1,2,3-dithiazolium chloride (1). Our synthetic approach of this reaction is described with the aim of obtaining a well-controlled access to this very rarely described pyrazino[2,1,-b]quinazoline skeleton.     

A convenient route to functionalized 3-amino-N-methylfuro[3,2-b]pyridine-2-carboxamides

The synthesis of novel functionalized 3-amino-N-methylfuro[3,2-b]pyridine-2-carboxamides is described from cyanopyridine intermediates. Based on the difference in halogen reactivity, ethyl [(5-bromo-2-chloropyridin-3-yl)oxy]acetate was functionalized by a palladium-catalyzed reaction, before the cyclization to the desired furo[3,2-b]pyridines.     

Base-free NIS promoted electrophilic cyclization of alkynes: an efficient synthesis of iodo substituted pyrano[4,3-b]quinolines

A simple and mild procedure for the synthesis of iodo substituted 1H-pyrano[4,3-b]quinolines has been achieved using NIS reagent in the absence of base from 2-alkynylquinoline-3-carboxaldehydes via intramolecular electrophilic cyclization onto alkynes in good to excellent yields in a short duration of time. The reactions proceeded smoothly in a normal solvent in aerobic atmosphere at room temperature. The presence of substituent at either quinoline or alkyne moieties did not show effect on reaction rate of cyclization. The palladium-catalyzed transformations of iodo group to C-C bond are also discussed.     

First construction of 12H-thiochromeno[2,3-b]quinolines and 5H-benzo[7,8]thiocino-[2,3-b]quinolines via intramolecular Friedel-Crafts reaction of Morita-Baylis-Hillman adducts

An acid-promoted intramolecular Friedel-Crafts reaction of the Morita-Baylis-Hillman adducts 3 derived from 2-arylthioquinolin-3-carbaldehydes 2 was investigated. Interestingly, promoted by sulfuric acid, the substrates with electron-donating groups on the aromatic ring gave six-membered fused-ring 12H-thiochromeno[2,3-b]quinolines 4 with good yields, while those with electron-withdrawing groups afforded eight-membered fused-ring 5H-benzo[7,8]thiocino[2,3-b]quinolines 5 in moderate yields. Using triflic acid instead of sulfuric acid, only products 4 could be obtained under the similar condition.     

One pot synthesis of imidazo[2,1-b]thiazoles and benzo[d]thiazolo[3,2-a]imidazoles

A series of imidazo[2,1-b]thiazole and benzo[d]thiazolo[3,2-a]imidazole analogues were synthesized by stirring an equimolar mixture of dibenzoylacetylene with imidazole/thiazole derivatives in toluene or acetonitrile at room temperature. The products were generated in good yields and characterized by standard analytical techniques such as IR, ¹H NMR, ¹³C NMR and mass spectrometry. The structure of products 19, 20, 22, 24 and 25 were also unambiguously confirmed by single crystal X-ray analysis.     

2-Benzyliden-2H-thieto[3,2-b]quinoline: a new heterocycle and its rearrangement to 2-phenylthieno[3,2-b]quinoline

Synthesis of the strained 2H-thieto[3,2-b]quinoline ring system is reported for the first time. Treatment of (Z)-2-benzyliden-2H-thieto[3,2-b]quinoline derivatives of this heterocycle with base, at reflux in ethanol, causes a novel rearrangement to 2-phenylthieno[3,2-b]quinolines. Indeed, the one-pot reaction of 2-aminobenzaldehydes and (Z)-2-benzylidenethietan-3-one in refluxing basic ethanol leads directly to 2-phenylthieno[3,2-b]quinolines in good yields.     

Microwave-assisted Hantzsch thiazole synthesis of N-phenyl-4-(6-phenylimidazo[2,1-b]thiazol-5-yl)thiazol-2-amines from the reaction of 2-chloro-1-(6-phenylimidazo[2,1-b]thiazol-5-yl)ethanones and thioureas

N-Phenyl-4-(6-phenylimidazo[2,1-b]thiazol-5-yl)thiazol-2-amines (6a-q) have been synthesized by the Hantzsch thiazole reaction of 2-chloro-1-(6-phenylimidazo[2,1-b]thiazol-5-yl)ethanones (4a-e) with suitably substituted thioureas using microwave heating. The ethanones (4a-e) were prepared by the reaction of 6-phenylimidazo[2,1-b]thiazoles (3a-e) with chloroacetylchloride in refluxing 1,4-dioxane whereas the thiazoles (3a-e) were synthesized by the reaction of 2-bromo-1-phenylethanones (2a-e) with thiazol-2-amine in refluxing acetone.     

Solid-phase synthesis of fused [2,1-b]quinazolinone alkaloids

Solid-phase synthesis of fused [2,1-b]quinazolinone alkaloids has been developed for the preparation of vasicinone and deoxyvasicinone by two approaches. The derivative of polymer-supported p-nitrophenyl carbonate was attached to anthranilic acid and then coupled with various bromo-lactams. This resin-linked bromo intermediate upon acetylation, hydrolysis and resin cleavage gave the cyclized [2,1-b]quinazolinones (vasicinone). Alternatively, resin-linked azido-benzoic acids were coupled with bromo-substituted lactams followed by cyclization in an aza-Wittig reductive cyclization process giving the bromo-substituted quinazolinone intermediates, with subsequent acetylation, hydrolysis and resin cleavage affording the fused [2,1-b]quinazolinones.     

Water-mediated one-pot synthetic route for pyrazolo[3,4-b]quinolines

First time one-pot water-mediated synthetic route has been developed by carrying condensation of 2-chloro-3-formyl quinolines and hydrazine hydrate/phenyl hydrazine using thermal/microwave energy resources. The route is convenient, eco-friendly, and scalable.