ABSTRACT
Chemoselective reduction of nitro groups in the presence of activated heteroaryl halides was achieved via catalytic hydrogenation with a commercially available sulfided platinum catalyst. The optimized conditions employ low temperature, pressure, and catalyst loading (<0.1 mol % Pt) to afford heteroaromatic amines with minimal hydrodehalogenation byproducts.
Subject(s)
Amines/chemical synthesis , Hydrocarbons, Halogenated/chemistry , Amines/chemistry , Catalysis , Hydrogenation , Molecular Structure , StereoisomerismABSTRACT
Under conventional heat (135-145 degrees C) or microwave irradiation and 1 equiv of acetic anhydride, ortho-substituted aryl-oximes undergo a novel sp3 C-H activated cyclization to produce the corresponding isoindoles, and aliphatic oximes afford the corresponding dihydropyrroles. The cyclization occurs with various substrates in good yield (46-82%) leading to unique spiro-fused and cyclic imines. An initial mechanistic investigation suggests the reaction occurs via a nitrenium or vinyl nitrene intermediate. [reaction: see text]
Subject(s)
Combinatorial Chemistry Techniques , Imines/chemical synthesis , Oximes/chemistry , Spiro Compounds/chemical synthesis , Acetic Anhydrides/chemistry , Cyclization , Hot Temperature , Imines/chemistry , Indoles/chemistry , Microwaves , Models, Chemical , Pyrroles/chemistry , Vinyl Compounds/chemistryABSTRACT
We report the first case of a pharmaceutical cocrystal formed between an inorganic acid and an active pharmaceutical ingredient (API), which enabled us to develop a stable crystalline and bioavailable solid dosage form for pharmaceutical development where otherwise only unstable amorphous free form or salts could have been used.
Subject(s)
Phosphates/chemistry , Phosphoric Acids/chemistry , Crystallization , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Structure , Phosphates/pharmacologyABSTRACT
An improved protocol for N-acetyl enamine formation is disclosed which involves LiBr-mediated addition of MeLi to substituted nitriles. The resulting enamides are isolated in high yields and excellent purity which permits subsequent hydrogenation at very low catalyst loading.
ABSTRACT
[reaction: see text] The reaction of a variety of indoles with N-thioalkyl- and N-thioarylphthalimides to produce 3-thioindoles is reported. Catalytic quantities of halide-containing salts are crucial to the success of this reaction. This highly efficient reaction provides sulfenylated indoles from bench-stable, readily available starting materials in good to excellent yields.
Subject(s)
Combinatorial Chemistry Techniques , Hydrocarbons, Halogenated/chemistry , Indoles/chemistry , Indoles/chemical synthesis , Sulfenic Acids/chemistry , Catalysis , Indicators and Reagents , Molecular Structure , Sulfenic Acids/chemical synthesisABSTRACT
A general procedure for the synthesis of 4-arylpiperidines via the coupling of 4-(N-BOC-piperidyl)zinc iodide with aryl halides and triflates is presented. The reaction requires cocatalysis with both Cl(2)Pd(dppf) and a copper(I) species. An improved, safer procedure for the activation of zinc dust is also presented.
ABSTRACT
[reaction: see text] A new synthesis of thioethers is described. The reaction of boronic acids with aryl, heteroaryl, and alkyl N-thioimides in the presence of catalytic quantities of a Cu(I) carboxylate affords good to excellent yields of thioethers. This reaction takes place in the absence of a base under mild conditions (THF, 45-50 degrees C, 2.5-12 h) and represents an interesting complement to known methods for thioether synthesis.
Subject(s)
Boronic Acids/chemistry , Copper/chemistry , Imides/chemistry , Sulfides/chemical synthesis , Catalysis , Disulfides/chemistry , Molecular Structure , Sulfides/chemistry , TemperatureABSTRACT
[reaction: see text] We describe herein a new base-mediated process for the formation of N-arylpyridinones 2 and their use for the preparation of naphthyridones and quinolines. The cyclization of various hindered enamines with methyl propiolate proceeds efficiently in the presence of NaOH to afford the corresponding N-arylpyridinones. These substrates were then found to undergo subsequent cyclizations to afford highly functionalized naphthyridones and quinolines.