ABSTRACT
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] 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.