Synthesis of 2-Carbamoylthieno[3,2-d]thiazoles

A preparation procedure was developed for previously unknown 2-carbamoylthieno[3,2-d]-thiazoles consisting in cyclization effected by K₃Fe(CN)₆ of monothiooxamides obtained from 2-methyl-4-aminothiophene, chloroacetamides, and sulfur in the presence of triethylamine.     

Efficient synthesis of novel pyrido[3,2-d]pyrimidine-2,4-diones

A series of pyrido[3,2-d]pyrimidine-2,4-diones 5a-g have been synthesized through conversion of 2,3-pyridinedicarboxylic anhydride 1 into half-ester 2, subsequent Curtius rearrangement and further reaction with amino acids.     

Synthesis of novel substituted naphthoquino[b]-benzo[e][1,4]diazepines via Pictet-Spengler cyclization

Synthesis of novel 4,5-dihydro-1H-1,4-naphthoquino[b]-benzo[e][1,4]diazepine derivatives via Pictet-Spengler cyclization is reported. Reaction of 2,3-diamino-naphthoquinones with aldehydes in the presence of BF₃·Et₂O gives benzodiazepine-naphthoquinones in good yields.     

Synthesis of 2-mercapto-substituted thieno[2,3-d]thiazoles and ben zothieno[3,2-d] thiazoles

2-Mercaptothieno[2, 3-d]thiazoles were synthesized from bis(2-nitro-3-thienyl) disulfide by successive reduction of, initially, the disulfide bond and the nitro group in the presence of carbon disulfide without isolation of the intermediate 2-nitro-3-mercaptothiophene. 2-Mercaptobenzo-[b]thieno[3, 2-d]thiazole was synthesized by reaction of 3-aminobenzo[b]thiophene hydrochloride with sulfur monochloride and cleavage of the resulting benzo[b]thienothiazothionium chloride with sodium sulfide in the presence of carbon disulfide.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1355–1356, October, 1976.     

Photochemical synthesis of benzoxazolo[3,2-b]isoquinolin-11-one and isoquinolino[3,2-b][1,3]benzoxazin-11-one under basic conditions

Irradiation of N-phenyl substituted isoquinolines in acetonitrile containing 1 M NaOH in a multilamp reactor (MLR) furnished benzoxazolo[3,2-b]isoquinolin-11-ones. In contrast, irradiation of the N-benzyl substituted isoquinoline derivative under the same conditions afforded the hydrolysed N-benzylbenzamide derivative. The isoquinolinobenzoxazine was obtained by irradiating the N-benzyl substituted isoquinoline derivative at higher basic conditions. The required isoquinolines were synthesized under solvent-free, solid supported microwave conditions.     

Synthesis of substituted thieno[2,3-d]thiazoles and indolo[3,2-d]thiazoles

Alkylene-, halo-, and aryl-substituted 2-methylthieno[2,3-d]thiazoles were obtained by the action of phosphorus pentasulfide on the corresponding 2-acetylamino-3-bromo- or 2-acetylamino-3-hydroxythiophenes in an organic solvent with heating. 2-Oximes of halo- and methyl-substituted isatins were converted by reduction and acylation into 2-hydroxy-3-acetylaminoin-doles, from which 2-methylindolo[3,2-d]-thiazoles were obtained by the action of phosphorous pentasulfide with heating in xylene.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 410–417, March, 1987.     

Facile asymmetric construction of a functionalized dodecahydrobenz[a]indolo[3,2-h]quinolizine template

We report a highly diastereoselective approach for the synthesis of a functionalized dodecahydrobenz[a]indolo[3,2-h]quinolizine ring system that is present as the heterocyclic core of the manadomanzamine alkaloids. We have achieved complete control over the relative and absolute stereochemistries at the three contiguous stereocentres at ring positions 1, 10 and 24 in only two linear synthetic steps. The introduction of useful functionality to the heterocyclic skeleton is significant as this may allow for future derivatization, and application of this route in an asymmetric synthesis of the manadomanzamine natural products.     

An expedient approach for the synthesis of pyrrolo[3,2-d]pyrimidines (9-deazaxanthines) and furo[3,2-d]pyrimidine via radical cyclization

A new efficient route for the synthesis of substituted 9-deazaxanthines in excellent yields via aza-Claisen rearrangement followed by radical cyclization has been achieved. This methodology has also been applied to the synthesis of furo[3,2-d]pyrimidine.     

Synthesis of a novel tricyclic 1,6,7,8-tetrahydro-2H-cyclopenta[b]furo[3,2-d]pyridine derivative,the 5-aza analog of ramelteon

The 5-aza analog of ramelteon 3, a novel tricyclic 1,6,7,8-tetrahydro-2H-cyclopenta[b]furo[3,2-d]pyridine derivative, was synthesized by hetero-Diels–Alder reaction and chemoselective Dieckmann condensation.     

The first example of tetrahydrothieno[3,2-d]azocines synthesis

A novel and efficient one-pot synthesis of thieno[3,2-d]azocines based on tamden transformation of tetrahydropyridine ring was elaborated.     

A novel ionic liquid mediated synthesis of 4(1H)-quinolones, 5H-thiazolo[3,2-a]pyrimidin-5-one and 4H-pyrimido[2,1-b]benzothiazol-4-ones

A new, convenient, environmentally benign two-step synthesis of 4(1H)-quinolones, 5H-thiazolo[3,2-a]pyrimidin-5-one and 4H-pyrimido[2,1-b]benzothiazol-4-ones have been developed by first condensing substituted arylamine/2-aminothiazole/2-aminobenzenethiazole with Meldrum’s acid and trimethylorthoformate in 1-butyl-3-methylimidazolium bromide at a moderate temperature to afford 5-{(substituted aryl/4-methylthiazolyl/substituted benzothiazolyl)methylene}-2,2-dimethyl-1,3-dioxane-4,6-dione. The resulting compounds upon cyclization in 1-butyl-3-methyl tetrafluoroborate/triflate at a moderate temperature gave the title compounds in excellent yields.     

Practical one-pot protocol for the syntheses of 2-chloro-pyrrolo[3,2-d]pyrimidines

A novel one-pot protocol for the syntheses of 2-chloro-pyrrolo[3,2-d]pyrimidines was described. A series of 2-chloro-pyrrolo[3,2-d]pyrimidines were prepared from readily available starting materials in moderate to good yields using this methodology.     

Synthesis and rearrangement of cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-8/9-ones: an access to cycloalkyl[1,2-d]oxazolo[3,2-a]pyrimidin-5-ones

2-Substituted-4a-hydroxy-9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-9-ones 2a-c were synthesized by an one-step cyclocondensation from the 5-substituted-2-amino-2-oxazolines 1a-c with ethyl 2-oxocyclohexanecarboxylate in ethanol at room temperature, and easily dehydrated to provide 2-substituted-9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-9-ones 3. In refluxing xylene, the reaction conducted with various ethyl 2-oxocycloalkanecarboxylates led to the two isomeric 2-substituted-8/9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-8/9-ones 3 and 2-substituted-5H-cycloalkyl[1,2-d]oxazolo[3,2-a]pyrimidin-5-ones 4. The structure of some compounds was unambiguously established using X-ray crystallography. According to results from the DSC analysis of compound 2a, formation of the thermodynamically stable pyrimidinones 4 could be related to an intramolecular rearrangement of kinetically controlled pyrimidinones 3.     

One pot synthesis of imidazo[2,1-b]thiazoles and benzo[d]thiazolo[3,2-a]imidazoles

A series of imidazo[2,1-b]thiazole and benzo[d]thiazolo[3,2-a]imidazole analogues were synthesized by stirring an equimolar mixture of dibenzoylacetylene with imidazole/thiazole derivatives in toluene or acetonitrile at room temperature. The products were generated in good yields and characterized by standard analytical techniques such as IR, ¹H NMR, ¹³C NMR and mass spectrometry. The structure of products 19, 20, 22, 24 and 25 were also unambiguously confirmed by single crystal X-ray analysis.     

A novel and efficient synthesis of pyrimido[4,5-d]pyrimidine-2,4,7-trione and pyrido[2,3-d:6,5-d] dipyrimidine-2,4,6,8-tetrone derivatives

An efficient and direct procedure for the synthesis of pyrimido[4,5-d]pyrimidine-2,4,7-trione derivatives has been described under microwave-assisted conditions. Reaction of 6-amino-1,3-dimethyluracil with aromatic aldehydes resulted in the formation of pyrido[2,3-d:6,5-d] dipyrimidine-2,4,6,8-tetrone derivatives.     

A straightforward synthesis of indazolo[3,2-a]isoquinolin-6-amines

4-Substituted 1-bromoisoquinolin-3-amines were subjected to Suzuki coupling with o-nitrophenylboronic acid to yield 1-(2-nitrophenyl) isoquinolinamines, which participated in Cadogan cyclization with triethyl phosphite under microwave irradiation in a sealed vial to yield fluorescent indazolo[3,2-a]isoquinolin-6-amines. The new compounds were also functionalized by transformation of the amino group.     

Synthesis of pyrido[2,3-d]pyridazines and pyrazino[2,3-d]-pyridazines—novel classes of GABAA receptor benzodiazepine binding site ligands

Novel syntheses of 2,3,8-trisubstituted pyrido[2,3-d]pyridazines and 2,3,5-trisubstituted pyrazino[2,3-d]pyridazines are described. Two complementary routes to pyrido[2,3-d]pyridazines were developed, the first of which began by constructing the pyridine ring, and the second of which started by constructing the pyridazine ring. Pyrazino[2,3-d]pyridazines were prepared in a route employing an aza-Wadsworth-Emmons cyclization as the key step. The resulting compounds were found to be high affinity ligands for the GABA_A receptor benzodiazepine binding site.     

Preparation of novel pyridine-fused tris-heterocycles; pyrido[4,3-e]pyrrolo-/pyrido[4,3-e]furano[2,3-c]pyridazines and pyrido[3,4-b]pyrrolo[3,2-d]pyrrole

Three novel pyrido-fused tris-heterocycles have been prepared based on a Suzuki coupling and subsequent cyclisation approach. Pyrido[4,3-e]pyrrolo[2,3-c]pyridazine (3b, 77%) and pyrido[4,3-e]furano[2,3-c]pyridazine (5b, 76%) were obtained by intramolecular diazocoupling. Successful diazocoupling of furan (5b) is thus reported for the first time by NOBF₄ generation of the diazonium intermediate. N-TIPS-pyrido[3,4-b]pyrrolo[3,2-d]pyrrole (TIPS-4b) was synthesised by thermal cyclisation of pyridyl nitrene in considerably higher yield (71%) than previously experienced from similar cyclisations, due to TIPS-activation.     

Synthesis and reactivity of pyrrolo[3,2-d][1,3]oxazine-2,4-dione. Access to new pyrrolo[3,2-e][1,4]diazepine-2,5-diones

A convenient synthesis of pyrrolo[3,2-d][1,3]oxazine-2,4-dione 4 is described and its reactivity towards various nucleophiles studied. The regioselective ring opening of anhydride 4 or its N-alkylated analog 25 in the presence of alanine or proline afforded, respectively, imidazolidinedione 22 and N-protected pyrrolo[3,2-e][1,4]diazepines 30 and 31 in a one-pot process. In a last part of this study, an alternative route to produce a library of eight non protected pyrrolo[3,2-e][1,4]diazepine-2,5-diones 35a–h is described to overcome the limited reactivity of anhydride 4.