Synthesis of 2H-pyrano[2,3-b]quinolines. Part II. Preparation and 1H-nmr investigations of 4-hydroxy-2-methyl-3,4-dihydro-2H-pyrano[2,3-b]quinolines

Diastereoisomers of 4-hydroxy-2-methyl-3,4-dihydro-2H-pyrano[2,3-b]quinolines 8 and 9 were synthesized starting from the appropriate 2-chloroquinoline-3-carboxaldehydes 1. The relative configuration of the 1,3-diol intermediates 4 and 5 was determined on the basis of the ¹³C-nmr spectra of their acetonides. The relative stereochemistry of title compounds was confirmed by using homonuclear NOE and selective decoupling experiments, as well as by analysis of the coupling patterns observed in their ¹H-nmr spectra.     

Convenient Synthesis of 2,2-Dimethyl-3,4-dihydro-2H-pyrano[2,3-b]quinolines

A convenient general synthesis of 2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]quinolines using the Wittig reaction is described. The o-nitrobenzaldehydes (1a–d) on reaction with phosphorane 2 provided ( E )-ethyl-α-(2,2-dimethylprop-2-ene)-2-nitrocinnamates (3a–d) in excellent yields, which on cyclization with polyphosphoric acid followed by reductive cyclization using Fe/HCl afforded dihydropyranoquinolines (5a–d). Alternatively, the pyranoquinolines 5a–d were also synthesised from esters 3a–d by employing domino reductive cyclization in a single step.     

Condensed Pyridazines. Part I. Synthesis of 2-Oxo-2H-pyrano[2,3-D]-pyridazine and 2-Oxo-2H-pyrano[2,3-c] pyridazine

The reaction of 4,7-diehlorofuro[2,3-d]pyridazine (1) with potassium cyanide in DMSO gave two products, (E)-3,6-diehloro-5-(2-cyanovinyl)-4-hydroxypyridazine (II) and 5,8-dichloro-2-oxo-2H-pyrano[2,3-d]pyridazine (III) as a result of ring opening or ring expansion. A new ring system, 2-oxo-2H-pyrano[2,3-c]pyridazines (IX, XII, XIII) was obtained from 5,8-dichloro-3-methyl-2-oxo-2H-pyrano[2,3-d]pyridazine (VI).     

Synthesis of 2H-pyrano[2,3-d]pyrimidine derivatives

Two series of 2H-pyrano[2,3-d]pyrimidine-2,5(6H)-dione derivatives have been prepared. Thus, the reaction of 6-hydroxy-pyrimidin-4(3H)-ones (1 a–c) with bis-2,4,6-trichlorphenyl malonates (2 a–d) or diethyl malonates (3 a–d) afforded good yields of 4-hydroxy-2H-pyrano[2,3-d]pyrimidine-2,5(6H)-diones (4 a-l). Application of our modifiedPechmann reaction^9–11 using -aminocrotonate (5) or -keto esters (6, 7) in the presence of ammonium acetate yielded the 2H-pyrano[2,3-d]pyrimidinediones8 a–h.Dedicated to Prof. Dr.Karl Schlögl, University of Vienna, on the occasion of his 60th birthday.     

Acetylene chemistry. Part 28. New C-2 substituted furo[2,3-b]quinolines via Pd-catalyzed reaction

Four new C-2 substituted furo[2,3-b]quinolines have been synthesized via Pd-catalyzed reaction. The present study was to provide furo[2,3-b]quinolines for biological studies on the influence of the side chain length and its polarity of the biological activity particularly against phytopathogenic bacteria and fungi.     

3,4-Dihydro-2-phenyl-2H-pyrano[2,3-b]pyridines. Novel aza analogs of flavans

Complementary approaches to the synthesis of the title compounds 1 are described. Metallation of 3,5-di-bromo-2-methoxypyridine ( 5b ) by bromine/lithium exchange gave selectively the 3-lithio intermediate 6 which was trapped with substituted cinnamaldehydes 7 , providing allylic alcohols 8 in good yields. Methyl ether cleavage and concomitant cyclization occurred on exposure to concentrated hydrobromic acid in hot acetic acid. The resulting 2-phenyl-2H-pyrano[2,3-b]pyridines were hydrogenated over Raney nickel to the title compounds which had antiviral activity. Alternatively, 1 were synthesized by Heck reaction of appropriately substituted 3-halo-2-methoxypyridines ( 5 or 24 ) with vinyl carbinol 15 to furnish ketones 16 or 26 which, upon reduction of the carbonyl group, were cyclized directly to 1 .     

A new synthesis of 2,3-dihydrofuro[2,3-b], [2,3-c] and [3,2-c]quinolines

A new synthesis of three isomeric dihydrofuroquinolines is described. This route via ortholithiation of O-quinolyl carbamates is considerably more effective than that which proceeds via lithiation of alkoxyquinolines.     

Synthesis of 9-chloropyrazolo[4,3-b]quinolines

A series of 1-methyl-4-arylaminopyrazole-3- and -5-carboxylic acids were synthesized by the reaction of 1-methyl-4-halopyrazole-3- and -5-carboxylic acids with aromatic amines in the presence of a copper catalyst; treatment with phosphorus oxychloride converted them to the corresponding 9-chlorosubstituted 1-methyl-1H- and 2-methyl-2H-pyrazolo[4,3-b]quinolines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1123–1125, August, 1984.     

Synthesis of substituted 2-amino-3-cyano-7,9-dimethyl-4H-pyrano[2",3":4,5]thieno[2,3-b]pyridines

4,6-Dimethyl-2H-thieno[2,3-b]pyridin-3-one reacts with 2-aryl-1,1-dicyanoethylenes or an aromatic aldehyde/ketone (cyclohexanone and piperidone derivatives) and malononitrile to give substituted 2-amino-3-cyano-7,9-dimethyl-4H-pyrano[2",3":4,5]thieno[2,3-b]pyridines.     

Pyrimido[5,4-b]quinolines. I. Synthesis of substituted tricyclic systems related to riboflavin

Two alternative synthetic routes were investigated for the synthesis of 2,4,10-substituted-7,8-dimethylpyrimido[5,4-b]quinolines: (1) cyclization of 5-(3,4-xylidino)-2,4-disubstituted-pyrimidine-6-carboxylic acids, and (2) cyclization of N-5-(2,4-disuhstituted-pyrimidinyl)-4,5-dimethylanthranilic acids. Route (1) invariably led to isomeric mixtures of the corresponding 7,8- and 8,9-dimethylpyrimido[5,4-b]quinolines which were difficult to separate, while route (2) yielded only the desired 7,8-dimelhyl derivatives. The required intermediates were synthesized by Ullman-type condensation of the appropriate pyrimidine and benzene derivatives. Cyclization with polyphosphoric acid, or phosphorus oxychloride (under various conditions) led to a number of new pyrimido[5,4-b]quinoline derivatives, with oxo, methoxy and/or chloro substituents in the 2,4 and 10 positions. A mild, but effective chlorination procedure was developed for the chlorination of the 10-(oxo) position without the cleavage of methoxyl groups at positions 2 and 4.     

Synthesis of 2,10,11-Trisubstituted Indolo[3,2-b]quinolines

A new method has been developed for the synthesis of derivatives of indolo[3,2-b]quinolines-11 based on N-oxidization of 2-nitro-10-substituted indolo[3,2-b]quinolines with subsequent conversion of the mixtures obtained into 2-nitro-11-substituted indolo[3,2-b]quinolinones-11. A series of 2-nitro-11-substituted indolo[3,2-b]quinolines was prepared.     

A Useful Synthesis of 2-Methyl-2,3-dihydrofuro [2,3-b] Quinolines

A convenient, general synthesis of 2-methyl-2,3-dihydrofuro [2,3-b] quinolines is described from o-nitrobenzaldehydes. The benzaldehydes (la-c) on reaction with phosphorane 2 provide (E)-ethyl-α-allylcinnamates (3a-c) in high yields. These esters 3a-c on reduction followed by acid catalysed cyclisation give 2,3-dihydrofuro [2,3-b] quinolines (5a-c).     

Synthesis of [1,4]dioxino[2,3-c]quinolines and [1,4]dioxepino-[2,3-c]quinolines and their 1-sulfur analogues

The synthesis of [1,4]dioxino[2,3-c]quinolines and [1,4]dioxepino[2,3-c]quinolines with restrained conformation of the piperidine ring, which represent 1,2,3,4-tetrahydroquinolines containing two heteroatom substituents at positions 3 and 4, is described. In addition, the application of this approach for the synthesis of 1-sulfur analogues is discussed. Both series are helpful tools for three-dimensional quantitative structure-activity relationship studies in the field of modulators of multidrug resistance.     

Synthesis of furo[2,3-b]pyridine

Two routes were employed to synthesize unsubstituted furo[2,3-b]pyridine (IV). The first method started with ethyl 5-aminofuro[2,3-b] pyridine-2-carboxylate (1) and involved successive deamination, hydrolysis, and decarboxylation. The second method began with 5-nitrofuro[2,3-b ]-pyridine-2-carboxylic acid (V) and consisted of successive decarboxylation, reduction, and deamination reactions.     

Fluorine-containing heterocycles: Part III. Synthesis of some new furo[2,3-b]-, pyrazolo[3,4-b]- and thieno[2,3-b]pyridines with anticipated biological activities

3-Cyano-6-(2-thienyl)-4-trifluoromethylpyridine-2(1H)-one (1) and its thiono analog 2 were prepared by the reaction of (2-thenoyl)-ω,ω,ω-trifluoroacetone with cyanoacetamide or cyanothioacetamide, respectively. Interaction of compound 1 with ethyl chloroacetate or chloroacetamide led to the regioselective formation of O-alkylated pyridines 3 and 10. The latter compounds underwent some successive reactions to furnish the promising furopyridines (4 and 7–9) and pyrazolopyridines (12–15). The reaction of 2 with chloroacetamides or chloroacetonitrile furnished 2-functionalized 3-amino-6-(2-thienyl)-4-trifluoromethyl-thieno[2,3-b]pyridines (16a, b) which were used as key intermediates in the synthesis of the title thienopyridines. Structures of the newly synthesized compounds were established on the basis of their elemental and spectral (IR, ¹H NMR and mass) analyses.     

Synthesis of pyrido[2,1-b]- and thiazolo[2,3-b]purines

Some pyrido[2,1-b]- and thiazolo[2,3-b]purines, tricyclic compounds structurally related to [1,2,4]triazolo[1,5-c]quinazolines 1 have been synthesized with a view to study their possible adenosine and benzodiazepine receptors affinity.