Synthesis of 1,2,3,4-tetrahydro-5H-[1]benzopyrano[3,4-c]pyridin-5-ones. I. 3-unsubstituted compounds

Synthesis of 1,2,3,4-tetrahydro-5H-[1]benzopyrano[3,4-c]pyridin-5-ones via a Pechmann condensation of 3-carbethoxy-1-methyl-4-piperidone with various phenols is described. The limitations of this method are discussed. Synthesis of the parent ring system 3a via reduction of 1,2,3,4-tetrahydro-3-(phenylmethyl)-8-[(1-phenyl-1H-tetrazol-5-yl)oxy]-5H-[1]benzopyrano[3,4-c]pyridin-5-one ( 5 ) is also described.     

Sensitive spectrophotometric determination of vanadium with 2-(5-bromo-2-pyridylazo)-5-diethyl-aminophenol (5-Br-PADAP)

A new sensitive and highly selective method is described for the spectrophotometric determination of microgram amounts of vanadium(V). First, vanadium is isolated by extraction withN-benzoyl-N-phenylhydroxylamine (BPHA) in chloroform from about 4M hydrochloric acid medium. Then, chloroform is evaporated and the residue mineralized with mixture of cone. perchloric and nitric acid. Finally, a colour reaction of vanadium(V) separated with 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol (5-Br-PADAP) in an acetate buffer (pH 4.5) gives a molar absorptivity of 5.48×10⁴l·mol^–1·cm^–1 at 585 nm. The proposed method was applied for the determination of traces of vanadium in aluminium samples. The results obtained show a good precision and accuracy of the method.     

The syntheses of 5-amino-3-t-butylisothiazole and 3-amino-5-t-butylisothiazole

A general synthesis of 3-amino-3-alkylpropenenitriles is described. These intermediates are further transformed to 5-amino-3-alkylisothiazoles. Also described is the synthesis of the novel isomer, 3-amino-5-t-butyl-isothiazole.     

Synthesis of N-(1,2,4-triazol-5-yl)amidines from 5-amino-1,2,4-triazole and nitriles using tributylborane

A method is proposed for the synthesis of N-(1,2,4-triazol-5-yl)amidines not previously described in the literature from 5-amino-1,2,4-triazole and nitriles using tributylborane as an auxiliary reagent. The structures of the products were indicated by physicochemical methods.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 10, pp. 2353–2355, October, 1989.     

Studies on the preparation and exchange reactions of 5-deuterated uracils

The mechanism of base catalyzed proton exchange at the 5-position of uracil and its N-methylated derivatives has been studied. These reactions proceed by addition — elimination across the 5,6-double bond when the 1-nitrogen is substituted with a methyl group, or with anchimeric assistance of the N-1 anion if the 1-position is unsubstituted. The base catalyzed hydrolyses of 1,3-dimethyluracil and 3-methyluracil also appear to proceed through hydrated intermediates. A facile method for an acid catalyzed preparation of 5-deuterated uracils is described as well as a simple and accurate method for analysis of deuterium content.     

Synthesis of 7-alkyl-2,4-dimethoxy-5-oxo-5H-pyrano[4,3-d]pyrimidines

A convenient synthesis of 7-alkyl-2,4-dimethoxy-5-oxo-5H-pyrano[4,3-d]pyrimidines from methyl 2,4-dimethoxy-6-phenylselenylmethyl (or 6-phenylthiomethyl)-5-pyrimidinecarboxylate with alkylaldehydes is described.     

Pseudoesters and Derivatives. XXXI1. Synthesis of 5-Ethylthio-, 5-Ethylsulfinyl- and 5-Ethylsulfonylfuran-2(5H)-ones

Convenient syntheses of 5-(ethylthio) furan-2(5H)-ones 2a-k from the appropriate 5-methoxyfuran-2(5H)-one 1a-g are described. The oxidation to the corresponding sulfoxides 5a-c and sulfones 6a-f is also reported.     

Reactions of methyl 3-hydroxythiophene-2-carboxylate. Part 4. Synthesis of methyl 5-azolyl-3-hydroxythiophene-2-carboxylates

The indirect introduction of an azolyl group in position 5 of compound 1 by an easy two-step procedure taking place at room temperature is described. A similar procedure yields the 4-chloro derivatives of these 5-azolyl compounds. The same method is applied for the introduction of a 5-azido group and from the 5-azido compounds, 5-v-triazolyl derivatives are obtained by a known method.     

An unexpected aminolysis in the synthesis of 5-substituted 3-(1H-tetrazol-5-yl)pyrazolo[1, 5-a]quinazolines

A synthetic route to 5-substituted 3-(1H-tetrazol-5-yl)pyrazolo[1, 5-a]quinazolines is described. An unexpected displacement of a 4-morpholinyl group from the 5-position of this system occurred during tetrazole formation by the ammonia produced by in situ generation of hydrazoic acid from ammonium chloride and sodium azide.     

Synthesis of (5R)- and (5S)-5-Methyl-5, 6-dihydrouridine Derivatives

The hydrogenation of 2′, 3′-O-isopropylidene-5-methyluridine (1) in water over 5% Rh/Al₂O₃ gave (5 R)- and (5 S)-5-methyl-5, 6-dihydrouridine (2) , separated as 5′-O-(p-tolylsulfonyl)- (3) and 5′-O-benzoyl- (5) derivatives by preparative TLC. on silica gel and ether/hexane developments. The diastereoisomeric differentiation at the C(5) chiral centre depends upon the reaction media and the nature of the protecting group attached to the ribosyl moiety. The synthesis of iodo derivatives (5 R)- and (5 S)- 4 is also described. The diastereoisomers 4 were converted into (5 R)- and (5 S)-2′, 3′,-O-isopropylidene-5-methyl-2, 5′-anhydro-5, 6-dihydrouridine (7) .     

Synthesis of 5-Substituted 1,3-Dimethylpyrazolo[4,3-e][1,2,4]triazines

A novel method for the synthesis of a new series of 5-substituted 1,3-dimethyl pyrazolo[4,3-e][1,2,4]triazines is described. The new synthetic strategy is based on the classical Bischler 1,2,4-benzotriazine synthesis. This approach involves the preparation of 5-hydrazinopyrazole from 5-chloro-1,3-dimethyl-4-nitropyrazole followed by acylation and nitro group reduction to form the corresponding 4-amino-3-(acylhydrazino)pyrazoles. Intramolecular oxidative cyclization of the latter derivatives, using polyphosphoric acid, produced the respective target pyrazolotriazines.     

Synthesis of 2,3-dihydro-5H-oxazolo[2,3-B]quinazolin-5-ones

Iodide-catalyzed ring expansion of 2-[(1-aziridinylcarbonyl)amino]benzoic acid methyl ester (2) gave 2,3-dihydro-5H-oxazolo[2,3-b]quinazolin-5-one (3) in quantitative yield. Treatment of the dimethyl analog of 2 (9) with sodium iodide in acetone gave a mixture of the 2,3-dihydro-2,2-dimethyl- (10) and 2,3-dihydro-3,3-dimethyl-5H-oxazolo[2,3-b]quinazolin-5-ones (11). However, rearrangement of 9 with sulfuric acid produced only 10. Synthesis of 11 by another route for comparison is described, and the known syntheses of 2,3-dihydro-5H-oxazolo[2,3-b]quinazolin-5-ones are reviewed.     

UNUSUAL FORMATION OF 2-BUTYL-5-ALKYLOXYMETHYLFURAN

An unexpected reaction of 5-O-allyl-3-deoxy-1,2-O-isopropylidene-α-D-glycero-pent-3-eno-furanose (1) and its 5-O-benzyl derivative (5) with n-butyl lithium is described.     

Preparation of pyrylium salts from 2-phenyl-5H-phenaleno [ 1,9-bc] pyran-5-one

The preparation of 2-phenyl-5H-phenaleno[ 1,9-bc]pyran-5-one ( 7 ) is described. Compound 7 undergoes reactions typical of pyrones and was therefore a useful intermediate for the preparation of pyrylium salts. Several pyrylium dyes were prepared from 7 and the long-wavelength absorptions of these dyes were compared with those of the corresponding flavylium dyes.     

Aza-Claisen Rearrangement: Synthesis of 5′-branched 5′-aminothymidines

The syntheses of both diastereoisomers of 5′-ethyl-substituted thymidine dimers, the (5′R)- and (5′S)-configurated 33a and 33b respectively, in which the natural phosphodiester linkage is replaced by an amide group (C(3′)-CH₂CONH-CH(5′)(Et)), arc described. Their fully protected derivatives 35a and 35b , respectively, are suitable for incorporation into antisense oligonucleotides. Unexpectedly, an attempted Pd^II-catalysed aza-Claisen rearrangement of trichloroacetimidate 7 provided the diastereoisomerically pure cyclopropane derivative 17 , whose structure was confirmed by X-ray analysis.     

Tetronic acids and derivatives. Part V. Synthesis of 5-hydroxy-1H-pyrazoles via 4-hydrazino-5H-furan-2-ones. Reaction of hydrazines on tetronic acids

The conversion of tetronic acids 1 to 3(1-hydroxy alkyl)-5-hydroxy-1H-pyrazole derivatives 3, 5, 7 and 12 is described. The formation is shown to proceed via base-catalyzed rearrangement of the intermediate 4-hydrazino-5H-furan-2-one derivatives.     

The Use of 4-Cyanoaminomethylene-2-phenyl-5(4h)-oxazolone in the Synthesis of Some Heteroarylaminomethylene Substituted 5(4H)-Oxazolones

The use of 4-cyanoaminomethylene-2-phenyl-5(4H)-oxazolone in the synthesis of some 4-heteroarylaminomethylene-2-phenyl-5(4H)-oxazolones was studied. Synthesis of 4-(1,2,4-oxadiazol-3-yl)aminomethylene-2-phenyl-5(4H)-oxazolone is described.     

Reactions of 2H-3,1-benzoxazine-2,4-(1H)dione (isatoic anhydride) with anions of 1,4-dihydro-5H-pyrazol-5-ones: Synthesis of pyrazolo[5,1-b]quinazolin-9-ones

Reactions of 2H-3,1-benzoxazine-2,4-(1H)dione (isatoic anhydride) (1) with anions of 1,4-dihydro-5H-pyrazol-5-ones (2) gave pyrazolo[5,1-6]quinazolin-9-ones (3) via the nucleophilic attack of the anion 2b rather than 2a. However, in the case of 5-methoxyisatoic anhydride ( 10c) , both products 3e and 11c were obtained. A new synthetic method of preparation of 5-(alkylthio)-2-aminobenzoic acids (18) was described. These acids (18) were used to synthesize a series of substituted pyrazolo[5,1-b]quinazolin-9-ones (3) .     

Synthesis of morphine-d5 and codeine-d8

The synthesis of morphine labeled with deuterium in the N-methyl group and at positions 1 and 6 is described. Reduction of N-carboethoxy-1-bromonorcodeinone (IV) with lithium aluminum deuteride in tetrahydrofuran-d₅ yielded the codeine-d₅. O-Demethylation with sodium propylmercaptide-dimethyl formamide afforded morphine-d₅, which could be remethylated with perdeuterioiodomethane to give codeine-d₈. The labeled compounds are useful as standards for field ionization mass spectrometric analysis.     

A Cascade Synthesis of Hetero‐arylated Triarylmethanes Through a Double 5‐endo‐dig Cyclization Sequence

A sequential two‐step method for the synthesis of hetero‐arylated triarylmethanes through a Ag‐catalyzed sequential double cyclization–nucleophilic addition cascade is described. This methodology basically involves an initial 5‐endo‐dig cyclization of o‐alkynyl anilines to provide 2‐substituted indole derivatives, which then react with 2‐(2‐enynyl)‐pyridines to afford indolizine‐containing unsymmetrical triarylmethanes through another 5‐endo‐dig cyclization.