Simple Synthesis of 7‐Formyl‐indole

A simple route to 7‐formyl‐indole (5) is described in which appropriately functionalized o‐nitrotoluenes (1) are converted to 7‐hydroxymethyl‐indole (4) using the Batcho–Leimgruber process. Condensation of 3‐methyl‐2‐nitrobenzyl alcohol (1a) with N,N‐dimethylformamide dimethyl acetal yields the enamine 2a, which upon catalytic hydrogenation affords 4 in 22% yield. When the hydroxyl function in 1 is protected with pivaloyl or tetrahydropyranyl group, the yields of 4 are increased to 39% and 48%, respectively. Finally, 4 is oxidized with pyridinium chlorochromate (PCC) to afford 5 in 86% yield.     

Simple Analogues of Acyclonucleosides: Synthesis of N‐Substituted Pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidine Derivatives

The synthesis of N‐substituted pyridothienopyrimidines bearing ethoxymethyl, benzyloxymethyl, methylthiomethyl, benzoylmethyl, allyl, sec‐butyl, and 2‐acetyloxyethyl chains as a sugar mimic was described. The O‐substituted pyridothienopyrimidines were obtained during some reactions.     

Synthesis of 4,4‐Disubstituted‐4H‐benzo[d][1,3]oxathiin‐2‐ones,a New Class of Compounds

4,4‐Dialkyl and 4,4‐diaryl‐4H‐benzo[d][1,3]oxathiin‐2‐ones were synthesized by the reaction of 2‐(mercapto‐phenyl)‐dialkyl‐ (or diaryl)‐methanol with CDI in excellent yield. The 2‐(mercaptophenyl)‐dialkyl‐ (or diaryl)‐methanols were prepared by the reaction of commercially available methylthiosalicylate with an appropriate alkyl or aryl Grignard reagent.     

Synthesis and Antimicrobial Activity of 1‐[(Substituted Carbamoyl)Amino]‐1H,3H‐1λ5‐[1,3,2]oxazaphospholo[3,4‐a]benzimidazol‐1‐ones

1‐[(Substituted carbamoyl)amino]‐1H,3H‐1λ⁵‐[1,3,2]oxazaphospholo[3,4‐a]benzimidazol‐1‐ones were synthesized by reacting benzimidazole 2‐methanol (4) with different chlorides of carbamidophosphoric acids (3) in the presence of triethylamine at 40–45°C. Their ¹H, ¹³C, and ³¹P NMR spectral data were discussed. The title compounds were tested for their activity against the fungi Aspergillus niger and Fusarium solani and bacteria Staphylococcus aureus and Escherichia coli. These compounds showed moderate antibacterial activity when compared with antifungal activity.     

Synthesis of 7,8‐Dihydrothieno[3′,2′:4,5]pyrrolo[1,2‐a]pyrazin‐5(6H)‐ones Using a Modification of Four‐Component Ugi Reaction

We describe an efficient synthesis of novel 7,8‐dihydrothieno [3′,2′:4,5]pyrrolo[1,2‐a]pyrazin‐5(6H)‐one heterocyclic structures. The target compounds were prepared by a novel modification of four‐component Ugi reaction of heterocyclic bifunctional keto acids, isonitriles, and amines. We demonstrate the usefulness and versatility of the developed approach, which is amenable to production of combinatorial libraries.     

Synthesis of New (4‐Acetonylidene‐2,6,8,9‐tetramethyl‐7H‐imidazo[1,5,4‐e,f][1,5]benzodiazepine) Derivatives

Imidazobenzodiazepine derivatives were obtained by cyclization of the condensation products 7‐amino‐2,5,6‐trimethylbenzimidazole with acetylacetone and ethyl acetoacetate. By careful examination of spectroscopic data and the open‐chain intermediate isolation, we have identified the formed compound structure.     

Synthesis of Some 3‐Substituted Isochromen‐1‐ones

An alternative method for the synthesis of 3‐substituted isocoumarins from homophthalic acid and ester is described.     

Microwave‐Assisted Synthesis of 10‐(Phthalimidoalkyl)‐halosubstitutedpyrido [3,2‐b][1,4]‐benzothiazine in Dry Media

N‐Alkylation of 10H‐9‐fluoropyrido[3,2‐b][1,4]‐benzothiazine 5a, 10H‐7‐fluoropyrido[3,2‐b][1,4]‐benzothiazine 5b, and 10H‐7‐chloropyrido[3,2‐b][1,4]‐benzothiazine 5c with different N‐(bromoalkyl)phthalimides using anhydrous K₂CO₃ and tetrabutylammonium bromide (TBAB) under dry conditions with microwave irradiation leads to the formation of 10‐(phthalimidoalkyl)‐halosubstitutedpyrido[3,2‐b][1,4]‐benzothiazine (6a–f) along with some unidentified product. Compound 5a is a new azaphenothiazine derivative and was obtained from hitherto unknown 2‐acetylamino‐3‐fluorophenyl‐3′‐nitro‐2′‐pyridylsulfide 4a via Smiles rearrangement. Compound 4a is required for the synthesis and has been prepared starting from 2‐amino‐3‐fluorobenzenethiol 1a in three steps.     

Synthesis of Ethyl 8‐Aryl‐8‐hydroxy‐3‐oxo‐8H[1,2,4]oxadiazolo‐[3,4‐c][1,4]thiazine‐5‐carboxylates by Ring‐Expansion Rearrangement

The title compounds were prepared by the ring–ring interconversion of ethyl 5‐nitroso‐6‐arylimidazo[2,1‐b]thiazole‐3‐carboxylates with hydrochloric acid. The effect of electron‐withdrawing substituent in the thiazole ring on the general applicability of the ring–ring interconversion has been also evaluated.     

Studies in Thio‐Claisen Rearrangement: Regioselective Synthesis of Thiopyrano[2,3‐b]pyran‐2‐ones and Thieno[2,3‐b]pyran‐2‐ones

Abstract

4‐Mercapto‐6‐methyl‐2‐pyrone was alkylated with different allylic and propargylic halides under phase transfer catalyzed condition in the presence of TBAB or BTEAC catalyst in chloroform–aqueous NaOH (1%) at room temperature. The S‐alkylated thiopyran‐2‐ones were then refluxed in quinoline or in chlorobenzene to give 4‐chloromethylthiopyrano[2,3‐b]pyran‐2‐one and 4‐hydroxymethylthiopyrano[2,3‐b]pyran‐2‐one or several thieno[2,3‐b]pyran‐2‐ones.     

Facile Synthesis of Pyrazolo[3,4‐d]pyrimidines and Pyrimido[4,5‐d]pyrimidin‐4‐one Derivatives

Pyrazolopyrimidine and pyrimidopyrimidine derivatives have shown a wide range of biological activities such as acting as A₁ adenosine receptors, kinase insert domain receptor (KDR), Rous sarcoma oncogene (Src), epidermal growth factor receptor (EGFR), antiproliferative, dihydrofolate reductase (DHFR), antimicrobial, antifungal, and lipid peroxidation. Because of this wide range of activities, we have synthesized pyrazolo[3,4‐d]pyrimidines and pyrimido[4,5‐d]pyrimidin‐4‐one derivatives.     

Efficient Synthesis of Substituted 2‐Amino‐3‐carbethoxythiophenes

A microwave‐assisted method for the synthesis of a variety of thiophene o‐aminoesters (2a–l) has been developed, starting from an appropriate aldehyde, methyl ketone or acetoacetate ester with ethyl cyanoacetate in the presence of elemental sulfur.     

Synthesis of 4‐Substituted‐ and 1,4‐Disubstituted‐4‐Hydroxypyrrolidin‐2‐ones

This report describes the synthesis of 4‐substituted‐ and 1,4‐disubstituted‐4‐hydroxypyrrolidin‐2‐ones by cyclization of intermediate γ‐aminoesters prepared from alkylbenzylamines, α‐bromoketones, and lithio ethyl acetate.     

Catalytic Oxidative Cyclocondensation of o‐Aminophenols to 2‐Amino‐3H‐phenoxazin‐3‐ones

The catalytic oxidative cyclocondensation of the o‐aminophenols 1a–f was investigated. The oxidants used were air/laccase, H₂O₂/horseradish peroxidase, H₂O₂/ebselen (3), and TBHP/diphenyl diselenide 4. The products obtained were 2‐amino‐3H‐phenoxazin‐3‐one—questiomycin A, its derivative 2b, and cinnabarinic acid and actinocin (2c,d). Substrates with methyl groups at 4 and 5 positions of benzene ring were converted to different dihydrophenoxazinones 2g,h. Compounds having chlorine atoms at the same positions underwent oxidation to planar phenoxa-zinones 2e,f with elimination of one hydrochloride molecule.     

Synthesis of Substituted 2‐Amino‐cyclobutanones

A series of weakly nucleophilic nitrogen derivatives including carbamates, amides, sulfonamides, and anilines were reacted with 1,2‐bis(trimethylsilyloxy)cyclobutene under acidic conditions to afford various substituted 2‐aminocyclobutanone derivatives 3a–i in modest to excellent yields.     

Design and Synthesis of Novel Amino Acid‐Bearing Macrocyclic Calix[4]Arenes

Abstract

A new family of macrocyclic calix[4]arenes (4a–d) potentially capable of chiral recognition were synthesized by incorporating the chirality inducing moieties, bis α‐amino acylated polyethylene glycols, or tripeptide bis‐Phe Cystine(OMe)₂ to the lower rim.     

A Facile Synthesis of [Tetrahydrofuran‐3H] Terazosin

Abstract

An efficient synthesis of [³H] terazosin at high specific activity from prazosin is described.     

Unprecedented N→C[1,4] Boc migration: synthesis of 3-carboxyl functionalized 7-azaindolo[2,1-c][1,4]benzoxazine ring system

Use of 1 equiv excess n-BuLi in synthesis of azaindolo[2,1-c][1,4]benzoxazine heterocycles furnished the corresponding 3-(tert-butyloxycarbonyl) derivatives presumably via an unprecedented intramolecular N→C[1,4] Boc migration. Thus, treatment of N-Boc-2-aminopicoline 1a with 3 equiv of n-BuLi at ?15 °C, to generate the dianion Li₂-1a, followed by the reactions with Weinreb amides 2a–h at ?40 °C, and then allowing the reaction mixture to warm upto rt in a controlled manner (?40 to 0 °C, 2 h; 0 °C to rt, 16 h) led to formation of a series of Boc-group migrated products 7a–h generally in good yield (～70% isolated yield). Surprisingly, going from cyclopentylene to cyclohexylene cases (2d–e to 2g–h), the desired [1,4] Boc migration was found to be a minor fate (yield ～20%). In these instances, N→ortho-C[1,3] Boc-migrated compounds 9g–h (to ortho-aryl position) were obtained as major products. Plausible mechanisms have been invoked for the formation of tetracyclic heterocycle 3a, as well as for the observed N→C[1,4] Boc-group migration phenomena supported by data from anion quenching experiments.