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4-Thiocarbamoyl-5-aminoisoxazole 4 was used as a convenient starting material for preparing both isoxazolo[5,4-d]pyrimidine-4(5H)thiones 5 and 4-aminoisothiazolo[4,3-d]isoxazole 6. The structure of the latter compound was definitively assigned by X-ray analysis.

The synthetic route to N-alkyl-N'-(4-diazo-5-pyrazolyl)ureas (4) starting from pyrazolo[4,3-c][1,2,5] oxadiazin-3(5H)-one (1) is described. Compounds (4) undergo thermal and photochemical reactions affording pyrazolo[3,4-d][1,2,3]triazoles (5) and pyrazolo[3,4-d]oxazoles (7) respectively

The reaction of pyrimido[5,4-c][1,2,5]oxadiazin-3(5H)-one with carbon nucleophiles afforded pteridine-2,4-diones bearing a variety of substituents unequivocally positioned in the pyrazine ring

An efficient synthesis of pyrazolo[3,4-d]thiazoles (6) was achieved by treatment of N-(4-amino-5-pyrazolyl)thiocarboxamides (4) with sodium nitrite in acidic medium followed by irradiation with uv light

Trichloromethyl chloroformate reacts with N-(1-alkyl/aryl-5-pyrazolyl) thiocarboxamides (2a-j) to give pyrazolo[3,4-d][1,3]thiazin-4-ones (3) while it reacts with N-(3-methyl-5-pyrazolyl)thiobenzamide (2m) to give the pyrazolo[1,5-c] [1,3,5]thiadiazine-4-one (4). Heating under reflux in formic acid of homologues (3g-i) bearing a tert-butyl group linked to pyrazole N-1 atom afforded the dealkylated derivatives (3k-m)

Thiation of N-(1-tert-butyl-3-methylpyrazol-5-yl)carboxamides 2 with the Lawesson reagent afforded the corresponding thiocarboxamides 3. Heating of 3 in formic acid gave the N-dealkylated thiocarboxamides 4 which were cyclized into 4H-pyrazolo[1,5-c][1,3,5]thiadiazine-4-thiones 5 by treatment with thiophosgene.

Ortho-aminobenzonitriles 1 react with β-ketoesters and alkyl malonates, in the presence of stoichiometric amounts of tin(IV) chloride, to give 4-aminoquinolines 2 and 4-amino-2-quinolones 3 respectively. Similarly β-enaminonitriles 7 afford 4-aminopyridines 8 and 4-amino-2-pyridones 9.

The syntheses of 4-, 5-, and 6- substituted imidazo[4,5-c]pyrazoles, compounds of potential biological activity, are reported.

The utilization of poly(N-acryloylmorpholine) as a new soluble polymeric support for the liquid phase synthesis of oligonucleotides is described.

The synthesis of imidazo[4,5-c]pyrazol-5-ones (6) is reported. 5-Amino-4-ethoxycarbonylaminopyra-zoles 3a-g when heated at 200° for 2 hours afford 6a-g. In a similar manner imidazo[4,5-c]pyrazol-5-one (6a) is readily obtained from 4-amino-5-ethoxycarbonylaminopyrazole (5a).

β-Alkoxycarbonyl-β-enaminoketoesters 1a,b react with hydrazines to give pyrazole ortho-dicarboxylic acid derivatives 3, 4 and 5. Similarly 1a reacts with hydroxylamine to give isoxazole 6 and with amidines and guanidine to give pyrimidine ortho-dicarboxylic acid monoesters 7a-c. The total or partial hydrolysis of selected heterocycles afforded the dicarboxylic acids 8, 9 and 10 and the dicarboxylic acid monoesters 11 and 12.

Condensation of pyrazolyl isothiocyanates 2 with N-substituted hydrazines provided the 2-methyl/phenyl-4-(pyrazol-5-yl)thiosemicarbazides 3. Cyclization of 3 with formic acid-acetic anhydride or with triethyl orthoacetate-acetic anhydride provided 4-(pyrazol-5-yl)-l,2,4-triazole-3-thiones 4a-f and 5-methyl-4-(pyrazol-5-yl)-1,2,4-triazole-3-thiones 4g-I respectively.

A new route to the synthesis of pyrazole and pyrimidine C-nucleosides, involving as the key step a metal catalysed reaction of β-D-ribofuranosyl ketoesters with alkyl cyanoformates, is described, 2,3,5-Tri-O-benzoyl-β-D-ribofuranosyl cyanide (1) reacts with α-bromoesters, in the presence of zinc dust, to give β-D-ribofuranosyl-enaminoesters 2 which are easily hydrolised to β-ketoesters 3. The reactions of compounds 3 with alkyl cyanoformates, in the presence of catalytic amounts of [Cu(acac)2], afford C-glycosyl enaminoketosters 4. These compounds react with benzylhydrazine and acetamidine to give pyrazole and pyrimidine C-nucleosides 5 and 6 respectively.

β-Enaminoketoesters, obtained by metal-catalyzed reaction between alkyl acetoacetates and alkyl cyanoformates, are useful starting materials for rapid access to β-acetyl-dehydroaspartic acid derivatives which could be transformed into (±)-2-azetidinones bearing a 1-hydroxy-ethyl substituent through suitable reductive processes.

In this work we report our results concerning the study on the in vitro antiproliferative activity of 18 Baylis-Hillman adducts and some derivatives against a panel of humor tumor cell lines. A brief qualitative structure-activity relationship study indicated that carbon-carbon double bond and the presence of an electron-withdrawing substituent at the aromatic ring are essential for the activity. A quinoline-phthalide derivative has exhibited a potent effect on the proliferation of all cell lines. It is interesting to note their special cytotoxic activity against NCIADR cell line.

A palladium-mediated carbonylative cyclization reaction of Baylis–Hillman adducts is disclosed. This simple, efficient and straightforward sequence leads to the formation of an array of 3-alkenylphthalides with different substitution patterns on the aromatic ring, with good chemical yields and selectivities.

A novel experimental procedure to obtain α-benzyl-β-keto esters from the Heck reaction between arenediazonium tetrafluoroborate salts and Baylis–Hillman (BH) adducts in the presence of Pd(OAc) 2 as catalyst is described. The methodology is simple, straightforward and the use of arenediazonium salts as opposed to conventional arylhalides/triflates over the usual Heck reaction is highlighted.

Tin(IV) chloride selectively promotes the nucleophilic attack of methyl acetoacetate to the cyano instead of the olefinic carbon atom of α,β-unsaturated nitriles to give enaminoketoesters. In the presence of an excess of ketoester a second C–C bond formation occurs followed by cyclisation affording substituted pyridines in a selective cascade sequence.

The utilization of ultrasound radiation in the Baylis–Hillman reaction with several aldehydes (aromatics and aliphatics) and different α,β-unsaturated reactants is described. For all aldehydes tested, the utilization of ultrasound sources augmented the reaction rate and the chemical yields. The use of ultrasound with two different catalysts (tri-n-butylphosphine and 1,4-diazabicyclo[2.2.2]octane [DABCO]) was also investigated. It was clearly demonstrated that DABCO is much more effective for catalyzing a Baylis–Hillman reaction under the influence of ultrasound than is tri-n-butylphosphine. No effect on reaction rate was observed when the concentration of DABCO was increased.