Crystal structure of (1S*,2R*)-7-benzyloxy-2-methyl-3-tosyl-2,3,4,5-tetrahydro-1H-3-benzazepin-1-ol: elucidation of the relative configuration of potent allosteric GluN2B selective NMDA receptor antagonists

Tetra­hydro-3-benzazepines with a hy­droxy group in the 1-position and a methyl group in the 2-position were designed as conformationally restricted ifenprodil analogues. The enanti­omerically pure 3-benzazepine (S,R)-4 representing a constitutional isomer of ifenprodil shows high affinity towards the ifenprodil binding site (Ki = 26 nM) and high antagonistic activity at the NMDA receptor (IC50 = 9.0 nM). The crystal structure analysis of the inter­mediate sulfonamide (S,R)-2 was performed in order to assign unequivocally the relative configuration of the methyl and hy­droxy groups.
In the title compound, C25H27NO4S, which crystallized as a racemate, the relative configuration of the adjacent OH and CH3 groups on the azepine ring is trans. The seven-membered azepin ring has a chair-like conformation. The planar aromatic rings of the benzyl and tosyl­ate moiety are inclined to the planar 3-benzazepine ring by 78.39 (15) and 77.03 (14)°, respectively, and to each another by 13.82 (15)°. In the crystal, mol­ecules are linked via O—H⋯O and C—H⋯O hydrogen bonds, forming double-stranded chains along the a-axis direction. The chains are linked via C—H⋯π inter­actions, forming a three-dimensional architecture.