Citric Acid‐catalyzed Synthesis of 2,4‐Disubstituted Thiazoles from Ketones via C–Br,C–S,and C–N Bond Formations in One Pot: A Green Approach

An improved and greener protocol has been developed for the synthesis of 2,4‐disubstituted thiazoles via C–Br, C–S, and, C–N bond formations in a single step from readily available ketones, N‐bromosuccinimide (NBS), and thiourea catalyzed by citric acid in a mixture of ethanol and water (3:1) under reflux conditions. This method has the advantages of freedom from the isolation of lachrymatory α‐bromoketones, ease of carrying out, cleaner reaction profile, broad substrate scope, freedom from chromatographic purification, and suitability for large‐scale synthesis.     

Synthesis of Substituted Pyridyl‐Pyrimidines as Potential Protein–Protein Interaction Inhibitors

An efficient synthetic method for the preparation of pyridyl‐pyrimidines as potential inhibitors of protein–protein interactions is described. The key transformation is the reaction of a pyrimidine enaminone with phenyl ethyl acetate and NH⁴OAc to yield the desired pyridyl‐pyrimidine.     

First Report on the Abnormal Dearylation/Alkylation Reaction in One‐Pot Hantzch Synthesis with 6‐Amino‐1,3‐Dimethyl Uracil

Abstract

First report on the abnormal dearylation/dealkylation reaction occurring during dehydrogenation in one‐pot, three‐component condensation of dihydropyrido[2,3‐d]pyrimidines.     

An approach to fused pyrimidine derivativesvia Schiff bases of aromaticortho-nitrocarbaldehydes. An investigation of substituent effects on the reaction course

The synthesis of fused pyrimidines from the Schiff bases of aromatic ortho-nitrocarbaldehydes is reported. The Schiff bases after selective reduction of the nitro group on 10% Pd/C, followed by condensation of the amines formed with orthoesters, are transformed to the corresponding imidates. Heating of the latter in a sealed tube with an excess of ammonia (or with ammonia in ethanol) gives fused pyrimidines. The influence of various substituents in the aromatic ring of the imine moiety of the Schiff bases on the overall yield of fused pyrimidine derivatives has been investigated. Moderate electron-withdrawing groups gave the best results.Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, PL-01-224 Warszawa, PolandTranslated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 799–805, June, 2000.     

An efficient base-mediated intramolecular condensation of 2-(disubstituted amino)-benzonitriles to 3-aminoindoles

A concise and versatile method for the preparation of 3-aminoindoles from 2-(disubstituted amino)-benzonitriles is described, and in situ functionalizations were illustrated.     

Highly flexible and efficient synthesis of the GABAB enhancer 4-(2-hexylsulfanyl-6-methyl-pyrimidin-4-ylmethyl)-morpholine

In the course of establishing a flexible synthesis of 2,4,6-substituted pyrimidines, we discovered that 2-hexyl-isothiourea hydrobromide reacts at ambient temperature and in a mildly exothermic fashion with 5,5-diethoxy-pent-3-yn-2-one upon treatment with 2 equiv of triethylamine in tetrahydrofuran to afford 4-diethoxymethyl-2-hexylsulfanyl-6-methyl-pyrimidine in 80% isolated yield. The methodology was developed in the search for an improved synthesis of the GABA_B enhancer 4-(2-hexylsulfanyl-6-methyl-pyrimidin-4-ylmethyl)-morpholine.     

Novel Regiospecific Method for Synthesis of 2‐(3,5‐Diaryl‐4,5‐dihydro‐1H‐pyrazol‐1‐yl)‐4,6‐diarylpyrimidines

The facile, regiospecific, one‐pot synthesis of 2‐(3,5‐diaryl‐4,5‐dihydro‐1H‐pyrazol‐1‐yl)‐4,6‐diarylpyrimidines derivatives has been described, involving a [3+2] and [3+3] cyclocondensation between the α,β‐unsaturated ketones and aminoguanidine bicarbonate.     

New Strategy for the Oxidation of Hantzsch 1,4‐Dihydropyridines and Dihydropyrido[2,3‐d]pyrimidines Catalyzed by DMSO under Aerobic Conditions

A novel metal‐salt‐oxidant‐free, efficient, and economical method for the oxidation of Hantzsch 1,4‐dihydropyridines that uses aerial oxygen and solvent‐grade dimethylsulfoxide is described. Also, the synthesis of pyrido[2,3‐d]pyrimidines is achieved from in situ oxidation of dihydropyrido[2,3‐d]pyrimidines that arise from the reaction of 6‐aminouracils and cyano olefins in dimethylsulfoxide.     

C-3 β-lactam carbocation equivalents: versatile synthons for C-3 substituted β-lactams

An efficient and operationally simple strategy for the synthesis of differently C-3 monosubstituted (9) and disubstituted (10) monocyclic β-lactams is described. This involves reaction of β-lactam carbocation equivalents (8) with an active aromatic, aliphatic and heterocyclic substrates in the presence of a Lewis acid.     

Synthesis and reactions of 2-substituted 1-phenyl-4-oxo-1,4-dihydropyrido-[2,3-d]pyrimidines

2-Methyl-4-oxo-1-phenyl-1,4-dihydropyrido[2,3-d]pyrimidine was acylated by succinic and trifluoroacetic anhydrides and also underwent the Claisen reaction with diethyl oxalate and ethyl oxanilate to give acyl derivatives at the methyl group, which, according to UV, IR, and¹H NMR spectra, exist as enaminocarbonyl and iminoenol tautomers with intramolecular hydrogen bonds.Perm State Pharmaceutical Academy, Perm 614600, Russia. e-mail: GIO@pharm.perm.su. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1119–1122, August, 2000.