2,3,4,5-TETRAHYDRO-1H-3-BENZAZEPINES HAVING ANTI-PSYCHOTIC ACTIVITY, AND SYNTHESIS OF .ALPHA.-SUBSTITUTED-ARYLACETAMIDES

• Main Authors: CHANG, WEI K, BERGER, JOEL G, ZHOU, GUOWEI, KOZLOWSKI, JOSEPH A
• Format: Patent
• Language: English; French
• Published: 04.07.2006
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; APPARATUS THEREFOR; CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOIDCHEMISTRY; CHEMISTRY; GENERAL METHODS OF ORGANIC CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PERFORMING OPERATIONS; PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; THEIR RELEVANT APPARATUS; TRANSPORTING

A novel process for the preparation of .alpha.-substituted arylacetamides wherein the substituent is an aromatic group or a 1-alkenyl or 1-cycloalkenyl group and wherein the nitrogen atom carries no hydrogen atoms comprises the reaction of an arylacetamide having one or two hydrogen atoms on the .alpha.-carbon atom, wherein the nitrogen atom carries no hydrogen atoms, with a strong base in an inert aprotic organic solvent, followed by reaction with a zerovalent transition metal catalyst and then with a compound of the formula R4-X, wherein R4 is selected from aromatic groups, 1 - alkenyl groups and 1-cycloalkenyl groups and X is a particular leaving group, especially a triflate group. The .alpha .- substituted arylacetamides are useful as intermediates in the preparation (by reduction) of .alpha.-substituted arylethylamines, e.g., 1- substituted-2,3,4,5-tetrahydro-1H-3-benzazepines, having pharmacological activity. Certain benzazepines wherein the 1-substituent R4 is 1-(1-cycloalkenyl) are novel.