Pyrolytic behavior of substituted N‐aminoheteroaromatics: Synthesis of pyrazolo[1,5‐a]pyridine and 3‐substituted 3‐oxopropionitrile derivatives

Flash vacuum pyrolysis (FVP) of 1,7‐bis‐(3‐aroylideneamino)‐4,6,10,12‐tetramethyl‐2,8‐dioxo‐1,7‐diazacyclododeca‐3,5,9,11‐tetraene‐3,9‐dicarbonitriles 11a‐c at 650°C and 0.02 Torr yielded 5,7‐dimethyl‐3‐(4‐methylbenzoyl)‐pyrazolo[1,5‐a]pyridine‐4‐carbonitrile 14 , 4,6‐dimethyl‐2‐oxo‐1,2‐dihydropyridine‐3‐carbonitrile 16 and 3‐aryl‐3‐oxo‐propionitriles 17a,b . A plausible mechanism is suggested to account for the formation of the products.     

Synthesis of some novel 2,6‐disubstituted pyridazin‐3‐ones as TMC120 analogues

Different analogues of TMC120 derived from pyridazin‐3(2H)‐one rings were synthesized by coupling of 3,6‐dichloropyridazine with arylacetonitriles, phenols and/or aniline derivative followed by hydrolysis and alkylation with different benzyl bromide derivatives.     

Reactions of 2‐amino‐4h‐1‐benzopyran‐4‐one with 4‐oxo‐4h‐1‐benzopyran‐3‐carbaldehydes

The title aldehyde 1 reacts smoothly with the enamine moiety of 2 ‐aminochromone 2 to produce hitherto unreported 3‐(2‐hydroxybenzoyl)‐5H‐1‐benzopyrano[2,3‐b]pyridin‐5‐one (azaxanthone) 5 . This reaction has been extended for the synthesis of bisazaxanthone 9.     

Regioselective one pot synthesis of 2‐alkyl/aryl‐4h‐benzo[1,4] thiazine‐3‐one via microwave irradiation

A series of 2‐alkyl/aryl‐4H‐benzo[1,4]thiazine‐3‐ones have been synthesized by microwave irradiation of ethyl‐2‐bromo‐2‐alkyl/aryl acetate and 2‐amino thiophenol in the presence of 1,8‐diazabicyclo‐[5.4.0] undec‐7‐ene and N‐methylpiperidine. All compounds were characterized by ¹H NMR, ¹³C NMR and elemental analyses, and by X‐ray crystallography in the case of 2‐methyl‐4H‐benzo[1,4]thiazin‐3‐one.     

Synthesis of 1‐(substituted phenylcarbonyl/sulfonylamino)‐1,2,3,6‐tetrahydropyridine‐5‐carboxylic acid diethylamides as potential anti‐inflammatory agents

Fifteen novel 1‐(substituted phenylcarbonyl/sulfonylamino)‐1,2,3,6‐tetrahydro‐ pyridine‐5‐carboxylic acid diethylamide ( 7, 15 ) were synthesized in fair to good yields via sodium borohydride reduction of the corresponding 1‐(substituted phenylcarbonyl/ sulfonylimino)‐3‐diethylcarbamoyl pyridinium ylides ( 6, 14 ) in absolute ethanol.     

The reaction of aryl and heteroarylhydrazines with aryl‐trifluoromethyl β‐diketones

We report the results obtained when five aromatic or heteroaromatic hydrazines react with six β‐diketones bearing trifluoromethyl and aryl substituents. Forty‐two compounds have been isolated corresponding to two isomeric trifluoromethyl pyrazoles and the intermediate 5‐CF₃, 5‐OH pyrazolines. The results have provided useful information for establishing the mechanism of the synthesis of pyrazoles.     

Reaction of 3‐aminoquinoline‐2,4‐diones with isocyanates. Synthesis of novel 3‐(3′‐alkyl/arylureido)quinoline‐2,4‐diones and their cyclic carbinolamide isomers

3‐Alkyl/aryl‐3‐amino‐1H,3H‐quinoline‐2,4‐diones react with alkyl/aryl isocyanates to give novel 3‐alkyl/aryl‐3‐ureido‐1H,3H‐quinoline‐2,4‐diones or 3a‐alkyl/aryl‐9b‐hydroxy‐3,3a,5,9b‐tetrahydro‐1H‐imidazo[4,5‐c]quinoline‐2,4‐diones. In some cases, a mixture of both products was obtained and separated by fractional crystallization. All compounds were characterized by their ¹H, ¹³C, ir and ms data and some of them also by ¹⁵N nmr data.     

Chemoselective reaction of formalin with 2‐(5‐substituted‐2‐hydroxybenzylamino)phenols: Synthesis of 6‐substituted 3‐(2‐hydroxyphenyl)‐3,4‐dihydro‐2H‐benzo[e][1,3]oxazines

Reaction of 2‐(5‐substituted‐2‐hydroxybenzylamino)phenols ( 2 ) with formalin in ethanol under reflux has chemoselectively led to 2‐(6‐substituted‐2H—benzo[e][1,3]oxazin‐3(4H)‐yl)phenols ( 3 ) in good yield involving the ring closure of the hydroxyl group of the C‐aryl ring and not that of the N‐aryl ring.     

A simple and efficient synthesis of novel N,N′‐bis (1H‐pyrrol‐1‐yl)‐1‐[2‐(2‐aryl‐5‐methyl‐3‐oxo‐2,4‐dihydro‐3H‐1,2,4‐triazol‐4‐yl)ethyl]‐1H‐1,2,3‐triazole‐4,5‐dicarboxamides

One‐pot reaction of 3‐aryl‐5‐methyl‐1,3,4‐oxadiazolin‐2‐ones 1a‐g with ethanolamine yielded the 4‐(2‐hydroxyethyl)‐2‐aryl‐5‐methyl‐2,4‐dihydro‐3H‐1,2,4‐triazolin‐3‐ones 2a‐g which were converted to the azido compounds 6a‐g . These azides on 1,3‐dipolar cycloaddition with DMAD afforded the dimethyl‐1‐[2‐(2‐aryl‐5‐methyl‐3‐oxo‐1,2,4‐triazol‐4‐yl)ethyl]‐1H‐1,2,3‐triazol‐4,5‐dicarboxylates 7a‐g which on conversion to bishydrazides 8a‐g and further cyclisation with 2,5‐hexanedione afforded the title compounds 9a‐g . This new short route for the so far unkown bis‐(triazolinone‐triazole)ethanes involves mild and convergent 1,3‐dipolar cycloaddition reaction yielding overall good yields of the products.     

The [3 + 2] cycloaddition route to 5‐carbomethoxy‐4h‐1,2,3‐triazolo[1,5‐a][1]benzazepines from baylis‐hillman acetates of 2‐azidobenzaldehydes

A new, simple synthesis of 5‐carbomethoxy‐4H‐1,2,3‐triazolo[1,5‐a][1]benzazepines from the reaction of several Baylis‐Hillman acetates of 2‐azidobenzaldehydes with alkynide Grignard reagents such as phenylethynyl‐, 1‐propynyl‐ and ethynylmagnesium bromides followed by cycloaddition reaction has been described.     

Regioselective synthesis of novel spiroheterocyclic framework via the 1,3‐dipolar cycloaddition

A series of novel dispiro[oxindole‐fused pyrimidine]pyrrolidine ring systems 4a‐f were synthesized by the regioselective 1,3‐dipolar cycloaddition reaction of the 2‐arylmethylene‐7‐benzyl‐9‐(benzylidene)tetrahydropyrido[4,3‐d]thiazolo[3,2‐a]pyrimidin‐3‐ones 1a‐f with azomethine ylides, generating by the decarboxylative route from isatin 2 and sarcosine 3 , in moderate to good yields. The regiochemistry of designed dispiroheterocyclic compounds 4a‐f was established by single crystal X‐ray structure and spectroscopic techniques.     

Microwave assisted synthesis of novel 6,7,8‐trimethoxy N‐substituted‐4‐aminoquinazoline compounds

A fast, efficient and convenient reaction of 6,7,8‐trimethoxy‐4‐chloroquinazoline and aryl (or benzyl) amines was achieved under microwave irradiation in isopropyl alcohol, providing a simple method for synthesis of novel 6,7,8‐trimethoxy N‐substituted‐4‐aminoquinazoline compounds in good yield in short time. The title compounds were evaluated for their in vitro anti‐proliferative activities against PC3 cell by MTT method.     

Towards the syntheses of N‐H and N‐alkylated derivatives of meridianins

Novel N‐H and N‐alkylated derivatives of meridianins have been synthesized as potential antitumor agents by a two‐step conversion of N‐tosyl‐3‐acetylindoles or N‐alkyl‐3‐acetylindoles to the corresponding enaminones using DMF‐DMA, with or without added pyrrolidine. Further cyclization with guanidine gave the corresponding 2‐aminopyrimidines. The structures of the compounds, thus obtained, were proved by ¹H and ¹³C NMR spectroscopy, NOE experiments and X‐ray analysis.     

Structure determination of N‐methyl‐tetrahydro‐5H‐indazol‐5‐ones

This paper communicates the (regio) synthesis and a convenient NMR structural assignment method for N‐methyl‐tetrahydro‐5H‐indazol‐5‐one isomers. The cyclization reaction of 7‐(hydroxymethylene)‐1,4‐dioxaspiro[4,5]decan‐8‐one ( 3 ) with methylhydrazine yields, after de‐protection predominately the N‐2 methyl isomer 2 . Analysis of the product ratio and structural assignments are based on NMR data including NOE difference experiments and subsequently confirmed with X‐ray crystallography. These findings are in sharp contrast with the literature. The experimental conditions used to optimize the synthesis of the individual isomers are discussed.     

Microwave induced efficient synthesis of (un)substituted benzaldehyde (5‐aryl‐1,3,4‐thiadiazol‐2‐yl)hydrazones using silica‐supported dichlorophosphate as a recoverable dehydrant

(Un)substituted benzaldehyde (5‐aryl‐1,3,4‐thiadiazol‐2‐yl)hydrazones were efficiently synthesized by reactions of (un)substituted benzaldehyde thiocarbohydrazones with aromatic carboxylic acids by using silica‐supported dichlorophosphate as a recoverable dehydrant under microwave irradiation. The protocol has advantages of short reaction time, high yield, easy work‐up procedure and no environmental pollution.     

A practical synthesis of 5‐(4′‐methylbiphenyl‐2‐yl)‐1H‐tetrazole

Practical synthesis of 5‐(4′‐methylbiphenyl‐2‐yl)‐1H‐tetrazole, key intermediate in several angiotensin II receptor antagonists from 2‐fluorobenzonitrile in excellent yields and very high purity is described.     

A facile synthesis of pyrazolo[3,4‐D]pyridazines Via the 1,3‐dipolar cycloaddition of 3‐arylsydnones. Synthesis and computational studies of 1‐aryl‐4,5‐dihydro‐1H‐pyrazolo[3,4‐D]pyridazine‐3,6‐diones and their 3,6‐dichloro derivatives.

The synthetic utility of 1,3‐dipolar cycloaddition of DMAD to sydnones has been exploited in the preparation of new 1‐aryl‐4,5‐dihydro‐1H‐pyrazolo[3,4‐d]pyridazine‐3,6‐diones 7a‐j and their aromatic 3,6‐dichloro analogues 8a‐j . The lactam‐lactim tautomerism of compound 7a has been studied by the semi emperical (PM3) and ab initio methods.