Analogues of α‐Campholenal (= (1R)‐2,2,3‐Trimethylcyclopent‐3‐ene‐1‐acetaldehyde) as Building Blocks for (+)‐β‐Necrodol (= (1S,3S)‐2,2,3‐Trimethyl‐4‐methylenecyclopentanemethanol) and Sandalwood‐like Alcohols

To complete our panorama in structure–activity relationships (SARs) of sandalwood‐like alcohols derived from analogues of α‐campholenal (= (1R)‐2,2,3‐trimethylcyclopent‐3‐ene‐1‐acetaldehyde), we isomerized the epoxy‐isopropyl‐apopinene (?)‐ 2d to the corresponding unreported α‐campholenal analogue (+)‐ 4d (Scheme 1). Derived from the known 3‐demethyl‐α‐campholenal (+)‐ 4a , we prepared the saturated analogue (+)‐ 5a by hydrogenation, while the heterocyclic aldehyde (+)‐ 5b was obtained via a Bayer‐Villiger reaction from the known methyl ketone (+)‐ 6 . Oxidative hydroboration of the known α‐campholenal acetal (?)‐ 8b allowed, after subsequent oxidation of alcohol (+)‐ 9b to ketone (+)‐ 10 , and appropriate alkyl Grignard reaction, access to the 3,4‐disubstituted analogues (+)‐ 4f,g following dehydration and deprotection. (Scheme 2). Epoxidation of either (+)‐ 4b or its methyl ketone (+)‐ 4h , afforded stereoselectively the trans‐epoxy derivatives 11a,b , while the minor cis‐stereoisomer (+)‐ 12a was isolated by chromatography (trans/cis of the epoxy moiety relative to the C₂ or C₃ side chain). Alternatively, the corresponding trans‐epoxy alcohol or acetate 13a,b was obtained either by reduction/esterification from trans‐epoxy aldehyde (+)‐ 11a or by stereoselective epoxidation of the α‐campholenol (+)‐ 15a or of its acetate (?)‐ 15b , respectively. Their cis‐analogues were prepared starting from (+)‐ 12a . Either (+)‐ 4h or (?)‐ 11b , was submitted to a Bayer‐Villiger oxidation to afford acetate (?)‐ 16a . Since isomerizations of (?)‐ 16 lead preferentially to β‐campholene isomers, we followed a known procedure for the isomerization of (?)‐epoxyverbenone (?)‐ 2e to the norcampholenal analogue (+)‐ 19a . Reduction and subsequent protection afforded the silyl ether (?)‐ 19c , which was stereoselectively hydroborated under oxidative condition to afford the secondary alcohol (+)‐ 20c . Further oxidation and epimerization furnished the trans‐ketone (?)‐ 17a , a known intermediate of either (+)‐β‐necrodol (= (+)‐(1S,3S)‐2,2,3‐trimethyl‐4‐methylenecyclopentanemethanol; 17c ) or (+)‐(Z)‐lancifolol (= (1S,3R,4Z)‐2,2,3‐trimethyl‐4‐(4‐methylpent‐3‐enylidene)cyclopentanemethanol). Finally, hydrogenation of (+)‐ 4b gave the saturated cis‐aldehyde (+)‐ 21 , readily reduced to its corresponding alcohol (+)‐ 22a . Similarly, hydrogenation of β‐campholenol (= 2,3,3‐trimethylcyclopent‐1‐ene‐1‐ethanol) gave access via the cis‐alcohol rac‐ 23a , to the cis‐aldehyde rac‐ 24 .     

A series of (E)‐5‐(arylideneamino)‐1‐tert‐butyl‐1H‐pyrrole‐3‐carbonitriles and their reduction products to secondary amines: syntheses and X‐ray structural studies

An efficent access to a series of N‐(pyrrol‐2‐yl)amines, namely (E)‐1‐tert‐butyl‐5‐[(4‐chlorobenzylidene)amino]‐1H‐pyrrole‐3‐carbonitrile, C₁₆H₁₆ClN₃, (7a), (E)‐1‐tert‐butyl‐5‐[(2,4‐dichlorobenzylidene)amino]‐1H‐pyrrole‐3‐carbonitrile, C₁₆H₁₅Cl₂N₃, (7b), (E)‐1‐tert‐butyl‐5‐[(pyridin‐4‐ylmethylene)amino]‐1H‐pyrrole‐3‐carbonitrile, C₁₅H₁₆N₄, (7c), 1‐tert‐butyl‐5‐[(4‐chlorobenzyl)amino]‐1H‐pyrrole‐3‐carbonitrile, C₁₆H₁₈ClN₃, (8a), and 1‐tert‐butyl‐5‐[(2,4‐dichlorobenzyl)amino]‐1H‐pyrrole‐3‐carbonitrile, C₁₆H₁₇Cl₂N₃, (8b), by a two‐step synthesis sequence (solvent‐free condensation and reduction) starting from 5‐amino‐1‐tert‐butyl‐1H‐pyrrole‐3‐carbonitrile is described. The syntheses proceed via isolated N‐(pyrrol‐2‐yl)imines, which are also key synthetic intermediates of other valuable compounds. The crystal structures of the reduced compounds showed a reduction in the symmetry compared with the corresponding precursors, viz. Pbcm to P from compound (7a) to (8a) and P2₁/c to P from compound (7b) to (8b), probably due to a severe change in the molecular conformations, resulting in the loss of planarity observed in the nonreduced compounds. In all of the crystals, the supramolecular assembly is controlled mainly by strong (N,C)—H…N hydrogen bonds. However, in the case of (7a)–(7c), C—H…Cl interactions are strong enough to help in the three‐dimensional architecture, as observed in Hirshfeld surface maps.     

Reduction of 3‐Aminoquinoline‐2,4(1H,3H)‐diones and Deamination of the Reaction Products

3‐Aminoquinoline‐2,4‐diones were stereoselectively reduced with NaBH₄ to give cis‐3‐amino‐3,4‐dihydro‐4‐hydroxyquinolin‐2(1H)‐ones. Using triphosgene (=bis(trichloromethyl) carbonate), these compounds were converted to 3,3a‐dihydrooxazolo[4,5‐c]quinoline‐2,4(5H,9bH)‐diones. The deamination of the reduction products using HNO₂ afforded mixtures of several compounds, from which 3‐alkyl/aryl‐2,3‐dihydro‐1H‐indol‐2‐ones and their 3‐hydroxy and 3‐nitro derivatives were isolated as the products of the molecular rearrangement.     

An Expeditious Access to Enantiomerically Pure cis‐Dialkyl‐Substituted γ‐ and δ‐Lactones

A facile general route to enantiomerically pure 3,4‐cis‐dialkyl‐substituted γ‐lactones and 4,5‐cis‐dialkyl‐substituted δ‐lactones by TiCl₄‐mediated Evans asymmetric aldolization as the key step is exemplified by synthesis of cis‐(3R,4R)‐3‐methyldecan‐4‐olide and (4R,5R)‐aerangis lactone.     

Photocycloaddition of 2H‐1‐Benzopyran‐3‐carbonitriles and 2H‐1‐Benzothiopyran‐3‐carbonitriles to Alkenes and Alkenynes

Both (intermolecular) photocycloadditions of 2H‐1‐benzopyran‐ and 2H‐1‐benzothiopyran‐3‐carbonitriles to 2,3‐dimethylbut‐2‐ene and 2‐methylbut‐1‐en‐3‐yne, and (intramolecular) photoisomerization of 4‐(alkenyl)benzopyran‐3‐carbonitriles were investigated. In contrast to 2H‐1‐benzopyran‐3‐carbonitrile ( 1 ), its thia analog 4 reacts with 2,3‐dimethylbut‐2‐ene selectively, to afford only cyclobuta derivative 7 . In the presence of 2‐methylbut‐1‐en‐3‐yne, both 1 and 4 behave alike to afford the all‐cis‐cyclobuta diastereoisomers, 15 and 8 , respectively, as main products, as well as minor amounts of cyclobutenes 17 and 10 , respectively, which result from the addition of the terminal C‐atom of the acetylenic bond to C(3) of the heterocycle. 4‐Methyl‐2H‐1‐benzopyran‐3‐carbonitrile ( 5 ) does not undergo photoaddition to the alkene or the alkenyne mentioned above, whereas the corresponding intramolecular [2+2] photocycloaddition of 4‐(pent‐4‐enyl)benzopyran‐3‐carbonitrile ( 6b ) to tetracycle 20 proceeds quantitatively.     

The Reaction of 2‐X‐1, 2‐Difluoroalk‐1‐enyldifluoroboranes with Xenon Difluoride. A Methodical Approach to 1, 2‐Difluoroalk‐1‐enylxenon(II) Salts

2‐X‐1, 2‐Difluoroalk‐1‐enylxenon(II) salts were prepared by the reaction of XeF₂ with XCF=CFBF₂ (X = F, trans‐H, cis‐Cl, trans‐Cl, cis‐CF₃, cis‐C₂F₅) but no organoxenon(II) compounds were obtained when the trans‐isomers of boranes, trans‐XCF=CFBF₂ (X = CF₃, C₄F₉, C₄H₉, Et₃Si), were used under similar conditions.     

Supramolecular aggregation in three 4‐aryl‐6‐(1H‐indol‐3‐yl)‐3‐methyl‐1‐phenyl‐1H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitriles

Both 6‐(1H‐indol‐3‐yl)‐3‐methyl‐4‐(4‐methylphenyl)‐1‐phenyl‐1H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitrile and 6‐(1H‐indol‐3‐yl)‐3‐methyl‐4‐(4‐methoxyphenyl)‐1‐phenyl‐1H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitrile crystallize from dimethylformamide solutions as stoichiometric 1:1 solvates, viz. C₂₉H₂₁N₅·C₃H₇NO, (I), and C₂₉H₂₁N₅O·C₃H₇NO, (II), respectively; however, 6‐(1H‐indol‐3‐yl)‐3‐methyl‐1‐phenyl‐4‐(3,4,5‐trimethoxyphenyl)‐1H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitrile, C₃₁H₂₅N₅O₃, (III), crystallizes in the unsolvated form. The heterocyclic components of (I) are linked by C—H...π(arene) hydrogen bonds to form cyclic centrosymmetric dimers, from which the solvent molecules are pendent, linked by N—H...O hydrogen bonds. In (II), the heterocyclic components are linked by a combination of C—H...N and C—H...π(arene) hydrogen bonds into chains containing two types of centrosymmetric ring, and the pendent solvent molecules are linked to these chains by N—H...O hydrogen bonds. Molecules of (III) are linked into simple C(12) chains by an N—H...O hydrogen bond, and these chains are weakly linked into pairs by an aromatic π–π stacking interaction.     

13‐cis‐β,β‐Carotene and 15‐cis‐β,β‐carotene

13‐cis‐β,β‐Carotene, C₄₀H₅₆, crystallizes with a complete molecule in the asymmetric unit, whereas 15‐cis‐β,β‐carotene, also C₄₀H₅₆, has twofold symmetry about an axis through the central bond of the polyene chain. The polyene methyl groups are arranged on one side of the polyene chains for each molecule and the 6‐s‐cisβ end groups, with the cyclohexene rings in half‐chair conformations, are twisted out of the planes of the polyene chains by angles ranging from 41.37 (17) to 52.2 (4)°. The molecules in each structure pack so that the arms of one occupy the cleft of the next, and there is significant π–π stacking of the almost‐parallel polyene chains of the 15‐cis isomer, which approach at distances of 3.319 (1)–3.591 (1) Å.     

Chiral 2‐endo‐Substituted 9‐Oxabispidines: Novel Ligands for Enantioselective Copper(II)‐Catalyzed Henry Reactions

A flexible approach, applicable on a gram scale, to chiral 2‐endo‐substituted 9‐oxabispidines was developed. The key intermediate, a cis‐configured 6‐aminomethylmorpholine‐2‐carbonitrile, was prepared from (R)‐3‐aminopropane‐1,2‐diol and 2‐chloroacrylonitrile. The 2‐endo substituent was introduced by Grignard addition, cyclization, and exo‐selective reduction, thus furnishing the enantiomerically pure bi‐ and tricyclic 9‐oxabispidines in 19–59 % yield. The CuCl₂ complex of the tricyclic 9‐oxabispidine, which carries an 2‐endo,N‐anellated piperidine ring, is an excellent catalyst for enantioselective Henry reactions giving the S‐configured β‐nitro alcohols in 91–98 % ee (13 examples). Surprisingly, the analogous copper complexes of the bicyclic 9‐oxabispidines delivered the enantiocomplementary R‐configured products in 33–57 % ee. The respective transition states were discussed.     

3,6‐Di­chloro‐4‐[2‐(4‐thia­morpholino)­ethanesulfanyl]­pyridazine and 3,6‐bis­(pyrazol‐1‐yl)‐4‐[2‐(4‐thia­mor­pho­lino)­ethanesulfanyl]­pyridazine

The trans–trans conformations adopted by the derivatized bis­(bidentate) chelating N₄‐donor ligand 3,6‐bis­(pyrazol‐1‐yl)‐4‐[2‐(4‐thia­morpholino)­ethanesulfanyl]­pyridazine, C₁₆H₁₉N₇S₂, and an intermediate in its formation, 3,6‐di­chloro‐4‐[2‐(4‐thia­morpholino)­ethanesulfanyl]­pyridazine, C₁₀H₁₃Cl₂N₃S₂, con­trast with the cis–cis conformation found previously for 3,6‐bis­(thio­phen‐2‐yl)­pyridazine [Ackers, Blake, Hill & Hubberstey (2002). Acta Cryst. C 58 , o640–o641], which places all four heteroatoms on the same side of the mol­ecule.     

Crystal packing of two 5‐substituted 2‐methyl‐4‐nitro‐1H‐imidazoles

Infinite chains connected by N—H...N hydrogen bonding form the primary packing motif in two closely related 4‐nitroimidazole derivatives, viz. 5‐bromo‐2‐methyl‐4‐nitro‐1H‐imidazole, C₄H₄BrN₃O₂, (I), and 2‐methyl‐4‐nitro‐1H‐imidazole‐5‐carbonitrile, C₅H₄N₄O₂, (II). These chains are almost identical, even though in (II) there are two symmetry‐independent molecules in the asymmetric unit. The differences appear in the interactions between the chains; in (I), there are strong C—Br...O halogen bonds, which connect the chains into a two‐dimensional grid, while in (II), the cyano group does not participate in specific interactions and the chains are only loosely connected into a three‐dimensional structure.     

Synthesis and reactions of 6‐methylsulfanyl‐2,4‐dithioxo‐1,2,3,4‐tetrahydropyrimidin‐5‐carbonitrile

The synthesis of 6‐methylsulfanyl‐2,4‐dithioxo‐1,2,3,4‐tetrahydropyrimidine‐5‐carbonitrile 4 is described. Compound 4 was reacted with various alkylants. The reaction with chloroacetic acid derivatives results in the formation of thieno[2,3‐d]pyrimidines 8 . When methyl iodide was used 2,4,6‐tris(methylsul‐fanyl)pyrimidine‐5‐carbonitrile 5 was obtained. The substitution of the methylsulfanyl groups in compound 5 by several N‐nuclophiles leads to amino substituted pyrimidines.     

(4S,5S)‐4‐[(1R)‐1,2‐Di­hydroxy­ethyl]‐5‐tri­decyl‐1,3‐oxazolidin‐2‐one

The title compound, C₁₈H₃₅NO₄, is a new bioactive amphiphilic lipid with a cis‐substituted 1,3‐oxazolidin‐2‐one head group. In the crystal structure, the mol­ecules form intercalating bilayers in which the oxazolidinone head groups are joined together by hydrogen bonds into chains.     

Synthesis and Characterization of 11‐Amino‐3‐methoxy‐8‐substituted‐12‐aryl‐8,9‐dihydro‐7H‐chromeno[2,3‐b]quinolin‐10(12H)‐one Derivatives

A series of 2‐amino‐7‐methoxy‐4‐aryl‐4H‐chromene‐3‐carbonitrile compounds 2 were obtained by condensation of 3‐methoxyphenol with β‐dicyanostyrenes 1 in absolute ethanol containing piperidine. The intermediate enamines 3 were prepared by compounds 2 with 5‐substituted‐1,3‐cyclohexanedione using p‐toluenesuflonic acid (TsOH) as catalyst. The title compounds 11‐amino‐3‐methoxy‐8‐substituted‐12‐aryl‐8,9‐dihydro‐7H‐chromeno[2,3‐b]quinolin‐10(12H)‐one 4 were synthesized by cyclization of the intermediate enamines 3 in THF with K₂CO₃ /Cu₂Cl₂ as catalyst. The structures of all compounds were characterized by elemental analysis, IR, MS, and ¹H NMR spectra. The crystal structure of compound 4i was determined by single‐crystal X‐ray diffraction analysis.     

Five bicyclo[3.3.0]octa‐2,6‐dienes

A series of five compounds containing the bicyclo[3.3.0]octa‐2,6‐diene skeleton are described, namely tetramethyl cis,cis‐3,7‐dihydroxybicyclo[3.3.0]octa‐2,6‐diene‐2,4‐exo,6,8‐exo‐tetracarboxylate, C₁₆H₁₈O₁₀, (I), tetramethyl cis,cis‐3,7‐dihydroxy‐1,5‐dimethylbicyclo[3.3.0]octa‐2,6‐diene‐2,4‐exo,6,8‐exo‐tetracarboxylate, C₁₈H₂₂O₁₀, (II), tetramethyl cis,cis‐3,7‐dimethoxybicyclo[3.3.0]octa‐2,6‐diene‐2,4‐exo,6,8‐exo‐tetracarboxylate, C₁₈H₂₂O₁₀, (III), tetramethyl cis,cis‐3,7‐dimethoxy‐1,5‐dimethylbicyclo[3.3.0]octa‐2,6‐diene‐2,4‐exo,6,8‐exo‐tetracarboxylate, C₂₀H₂₆O₁₀, (IV), and tetramethyl cis,cis‐3,7‐diacetoxybicyclo[3.3.0]octa‐2,6‐diene‐2,4‐exo,6,8‐exo‐tetracarboxylate, C₂₀H₂₂O₁₂, (V). The bicyclic core is substituted in all cases at positions 2, 4, 6 and 8 with methoxycarbonyl groups and additionally at positions 3 and 7 with hydroxy [in (I) and (II)], methoxy [in (III) and (IV)] or acetoxy [in (V)] groups. The conformations of the methoxycarbonyl groups at positions 2 and 4 are exo for all five compounds. Each C₅ ring of the bicyclic skeleton is almost planar, but the rings are not coplanar, with dihedral angles of 54.93 (7), 69.85 (5), 64.07 (4), 80.74 (5) and 66.91 (7)° for (I)–(V), respectively, and the bicyclooctadiene system adopts a butterfly‐like conformation. Strong intramolecular hydrogen bonds exist between the –OH and C=O groups in (I) and (II), with O...O distances of 2.660 (2) and 2.672 (2) Å in (I), and 2.653 (2) and 2.635 (2) Å in (II). The molecular packing is stabilized by weaker C—H...O(=C) interactions, leading to dimers in (I)–(III) and to a chain structure in (V). The structure series presented in this article shows how the geometry of the cycloocta‐2,6‐diene skeleton changes upon substitution in different positions and, consequently, how the packing is modified, although the intermolecular interactions are basically the same across the series.     

Stereocomplementary Synthesis of cis‐ and trans‐2‐(p‐Bromophenyl)‐5‐methylthiazolidin‐4‐ones: Useful Umpolung‐type Suzuki–Miyaura Cross‐coupling Partner and Donor

Novel cis‐ and trans‐2‐(p‐bromophenyl)‐5‐methylthiazolidin‐4‐ones, S,N‐containing heterocyclic compounds, were provided in a cis‐stereocomplementary and trans‐stereocomplementary synthetic manner. cis‐Selective cyclo‐condensation proceeded between 2‐sulfanylpropanoic acid (thiolactic acid) and an imine derived from 4‐bromobenzaldehyde and methylamine, whereas Ti(OiPr)₄ and Ti(OiBu)₄‐promoted trans‐selective cyclo‐condensation proceeded between benzyl 2‐sulfanylpropanoate and the imine. The obtained cis‐ and trans ‐ 2‐(p‐bromophenyl)‐5‐methylthiazolidin‐4‐ones were successfully converted to 2‐(3‐furyl)phenyl derivatives and bis(pinacolato)diborane derivatives utilizing Suzuki–Miyaura and Miyaura–Ishiyama cross‐coupling reactions, respectively, in an umpolung manner.     

tert‐Butyl (6S)‐4‐hydroxy‐6‐isobutyl‐2‐oxo‐1,2,5,6‐tetra­hydropyridine‐1‐carboxyl­ate and tert‐butyl (4R,6S)‐4‐hydroxy‐6‐iso­butyl‐2‐oxopiperidine‐1‐carboxyl­ate

X‐ray studies reveal that tert‐butyl (6S)‐6‐iso­butyl‐2,4‐dioxo­piperidine‐1‐carboxyl­ate occurs in the 4‐enol form, viz. tert‐butyl (6S)‐4‐hydroxy‐6‐iso­butyl‐2‐oxo‐1,2,5,6‐tetra­hydropyri­dine‐1‐carboxyl­ate, C₁₄H₂₃NO₄, when crystals are grown from a mixture of di­chloro­methane and pentane, and has an axial orientation of the iso­butyl side chain at the 6‐position of the piperidine ring. Reduction of the keto functionality leads predominantly to the corresponding β‐hydroxy­lated δ‐lactam, tert‐butyl (4R,6S)‐4‐hydroxy‐6‐iso­butyl‐2‐oxo­piperidine‐1‐car­boxyl­ate, C₁₄H₂₅NO₄, with a cis configuration of the 4‐hydroxy and 6‐iso­butyl groups. The two compounds show similar molecular packing driven by strong O—H⋯O=C hydrogen bonds, leading to infinite chains in the crystal structure.     

The heteroscorpionate ligand 2,2‐bis(3,5‐dimethylpyrazol‐1‐yl)‐1,1‐diphenylethanol and an easy preparation of its tungsten complex

The heteroscorpionate ligand 2,2‐bis(3,5‐dimethylpyrazol‐1‐yl)‐1,1‐diphenylethanol, C₂₄H₂₆N₄O, features in the solid state an intramolecular O—H…N hydrogen bond. A heteroscorpionate tungsten complex, cis‐[2,2‐bis(3,5‐dimethylpyrazolyl)‐1,1‐diphenylethanolato]chloridodioxidotungsten(VI) tetrahydrofuran monosolvate, [W(C₂₄H₂₅N₄O)ClO₂]·C₄H₈O, was prepared by the simple mixing of solutions of the ligand and WOCl₄ in tetrahydrofuran. The tungsten complex was isolated after standing for several weeks. The complex exhibits a κ³N,N′,O‐coordination of the ligand. This simple synthetic procedure allows access to the cis isomer in high yield without additional purification steps. The Hirshfeld surface analysis shows a change of the intermolecular contacts due to the coordination of the WO₂Cl unit with the ligand molecule.     

Preparation and structural analysis of (±)‐cis‐ethyl 2‐sulfanylidenedecahydro‐1,6‐naphthyridine‐6‐carboxylate and (±)‐trans‐ethyl 2‐oxooctahydro‐1H‐pyrrolo[3,2‐c]pyridine‐5‐carboxylate

Bicycle ring closure on a mixture of (4aS,8aR)‐ and (4aR,8aS)‐ethyl 2‐oxodecahydro‐1,6‐naphthyridine‐6‐carboxylate, followed by conversion of the separated cis and trans isomers to the corresponding thioamide derivatives, gave (4aSR,8aRS)‐ethyl 2‐sulfanylidenedecahydro‐1,6‐naphthyridine‐6‐carboxylate, C₁₁H₁₈N₂O₂S. Structural analysis of this thioamide revealed a structure with two crystallographically independent conformers per asymmetric unit (Z′ = 2). The reciprocal bicycle ring closure on (3aRS,7aRS)‐ethyl 2‐oxooctahydro‐1H‐pyrrolo[3,2‐c]pyridine‐5‐carboxylate, C₁₀H₁₆N₂O₃, was also accomplished in good overall yield. Here the five‐membered ring is disordered over two positions, so that both enantiomers are represented in the asymmetric unit. The compounds act as key intermediates towards the synthesis of potential new polycyclic medicinal chemical structures.     

A Green Synthesis of 7‐amino‐5‐(4‐aroyl)‐1,3‐dimethyl‐2,4‐dioxo‐1,2,3,4,5,8‐hexahydropyrido[2,3‐d]pyrimidine‐6‐carbonitrile Derivatives by a One‐pot Three‐component Reaction

The synthesis of polyfunctionalized 7‐amino‐5‐(4‐aroyl)‐1,3‐dimethyl‐2,4‐dioxo‐1,2,3,4,5,8‐hexahydropyrido[2,3‐d ]pyrimidine‐6‐carbonitrile derivatives by a green approach was achieved via one‐pot three‐component reaction of arylglyoxals, malononitrile, and 1,3‐dimethyl‐6‐aminouracil in the presence of urea as organocatalyst in EtOH:H₂O (1:1) at 60°C. This protocol provides a mild and fast procedure to structurally diverse bicyclic pyridopyrimidines in good to excellent yields.