ABSTRACT
An efficient, catalytic hypervalent iodine-mediated oxidative 1,2-shift of 1,1'-disubstituted olefins is described. This methodology provides concise access to homobenzylic ketones with electron-donating substituents. In the case of cyclic systems, this transformation results in ring-expanded ß-benzocycloalkanones, which are useful for further elaboration.
Subject(s)
Alkenes/chemistry , Ketones/chemical synthesis , Oxidants/chemistry , Sulfuric Acids/chemistry , Catalysis , Combinatorial Chemistry Techniques , Ketones/chemistry , Molecular Structure , Oxidation-ReductionABSTRACT
Fmoc-O-benzyl-l-phosphoserine is an important building block in the synthesis of Forigerimod, a phosphopeptide being investigated for Systemic Lupus Erythematosus (SLE). An efficient one-pot process was developed using inexpensive, readily available starting materials. This general procedure was used to prepare a variety of protected phosphoamino acids.
Subject(s)
Phosphoamino Acids/chemical synthesis , Molecular Structure , Oxidants/chemistry , Peptides/chemistryABSTRACT
The synthesis of a new kinase inhibitor template 2-anilino-7-aryl-pyrrolo[2,1-f][1,2,4]triazine is described which includes a late stage orthogonally reactive key intermediate amenable to rapid diversification as well an optimized in situ triflate displacement to install the C2-aniline. Furthermore, an efficient scalable process approach will be highlighted which begins with tert-butyl carbazate to provide the key N-N bond and generates the pyrrolotriazine core through a stable bromoaldehyde intermediate followed by condensation with ammonium carbonate.
Subject(s)
Protein Kinase Inhibitors/chemical synthesis , Pyrroles/chemistry , Triazines/chemical synthesis , Molecular StructureABSTRACT
Imidoyl chlorides, generated from secondary acetamides and oxalyl chloride, can be harnessed for a selective and practical deprotection sequence. Treatment of these intermediates with 2 equiv of propylene glycol and warming enables the rapid release of amine hydrochloride salts in good yields. Notably, the reaction conditions are mild enough to allow for a swift deprotection with no observed epimerization of the amino center.
ABSTRACT
Tramadol is a centrally acting opioid analgesic structurally related to codeine and morphine. O-Alkyl, N-desmethyl, and non-phenol containing derivatives of tramadol were synthesized to probe their effect on metabolic stability and both in vitro and in vivo potency.
Subject(s)
Analgesics, Opioid/chemistry , Analgesics, Opioid/pharmacology , Tramadol/analogs & derivatives , Tramadol/pharmacology , Analgesics, Opioid/metabolism , Animals , Humans , Microsomes, Liver/drug effects , Microsomes, Liver/metabolism , Molecular Structure , Pain/drug therapy , Protein Binding , Rats , Structure-Activity Relationship , Tramadol/chemistry , Tramadol/metabolismABSTRACT
A new synthesis of enamides from ketones is disclosed that involves a phosphine-mediated reductive acylation of oximes. The resulting enamides are isolated in good yields (up to 89%) and excellent purity, permitting a subsequent hydrogenation to access enantiopure acetamides at catalyst loadings practical for large-scale applications.
Subject(s)
Amides/chemical synthesis , Combinatorial Chemistry Techniques , Ketones/chemistry , Catalysis , Molecular StructureABSTRACT
[reaction: see text] An efficient method has been developed to prepare all four isomers of the hydroxyl derivatives of sibutramine by addition of Grignard reagents (R)- or (S)-5 to a single enantiomer of sulfinyl imine (R)-1 simply by tuning the reaction solvent. The phenomenon of the reversed diastereoselectivity in CH(2)Cl(2) and THF implied that the reaction may proceed through a chelated cyclic transition state in CH(2)Cl(2) and nonchelated acyclic transition state in THF.