Novel GluN2B selective NMDA receptor antagonists: Relative configuration of 7-methoxy-2-methyl-2,3,4,5-tetrahydro-1H-3-benzazepin-1-ols

Abstract

The title compounds, C22H29NO2 (3) and C22H29NO2 (4) [systematic names: (1S∗,2R∗)-7-methoxy-2-methyl-3-(4-phenylbutyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-1-ol and (1R∗,2R∗)-7-methoxy-2-methyl-3-(4-phenylbutyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-1-ol, are diastereomers with the relative configuration of the adjacent hydroxyl and methyl groups at the seven-membered azepine ring being trans in (3) and cis in (4). In the crystals the orientation of these groups is -anti-periplanar (3) and +syn-clinal (4). In both cases, the crystals studied proved to be of a racemic mixture, with relative configurations (R∗,S∗)-3 and (R∗,R∗)-4. In both compounds, the seven-membered azepine ring has a chair-like conformation, and the 4-phenylbutyl side chain adopts a extended conformation in (R∗,S∗)-3, but a twisted conformation in (R∗,R∗)-4. In the crystal of (S∗,R∗)-3, molecules are linked via C - H⋯O hydrogen bonds, forming slabs parallel to the ac plane. In the crystal of (R∗,R∗)-4, molecules are linked via O - H⋯N hydrogen bonds, forming chains propagating along the c-axis direction. The chains are linked by C - H⋯O hydrogen bonds, forming slabs parallel to the ac plane.