1365254-35-8

Upstream product

• 100-46-9 benzylamine 
• 91142-84-6 2-[2-(2-oxopropyl)phenyl]acetic acid 
• 1365254-28-9 3-benzyl-4-methyl-1,3,4,5-tetrahydro-3-benzazepin-2-one 
• 1365254-15-4 3-benzyl-4-methyl-1,3-dihydro-3-benzoazepin-2-one 
• 1298062-70-0 4-methyl-1,3-dihydro-2H-3-benzazepin-2-one 

Relevant academic research and scientific papers

Asymmetric synthesis of potent and selective σ1 receptor ligands with tetrahydro-3-benzazepine scaffold

A new strategy for the synthesis of tetrahydro-3-benzazepinones 6 by reductive amination of keto acid 3 and subsequent carbonyl diimidazole (CDI) mediated cyclization was developed. Use of enantiomerically pure (R)-1-phenylethylamine led to the formation of diastereomeric lactams (R α-R)-6d and (Rα-S)-6e in a 80:20 ratio. Diastereoselective alkylation of (Rα-R)-6d, BH 3-mediated reduction and exchange of the N-phenylethyl substituent provided enantiomerically pure tetrahydro-3-benzazepines with various substituents in the 1-, 3-, and 4-positions. High I1 affinity was achieved with a benzyl, cyclohexylmethyl, or 1-phenylethyl moiety at the N-atom. Whereas (R)-configuration of the N-substituent is crucial for high I1 affinity, the configuration of the 3-benzazepine ring system does not influence the I1 affinity considerably. Introduction of additional substituents in the 1-position led to almost complete loss of σ1 affinity. Potent σ1 ligands show high selectivity against the σ2 subtype and the NMDA receptor. The key step in the synthesis of enantiomerically pure tetrahydro-3-benzazepines is the diastereoselective, consecutive, three-step transformation of keto acids into lactams. Relationships between the structure and the σ1 affinity are elaborated.

Microwave assisted synthesis of 3-benzazepin-2-ones as building blocks for 2,3-disubstituted tetrahydro-3-benzazepines

Microwave assisted condensation of primary amines with keto acids 1a-c provided directly 3,4-disubstituted 1,3-dihydro-3-benzazepin-2-ones 2. Whereas small amine size, such as NH3 afforded high yields of secondary lactams 2a, 2d, and 2g, primary amines with larger substituents in α-position led to lower yields of 2 or even to regioisomeric indanone derivatives 4. However, subsequent alkylation of 2a, 2d, and 2g with various alkyl halides provided the corresponding N-substituted 3-benzazepin-2-ones 2 in good yields. Hydrogenation of 2 followed by BH3 reduction led to 3-benzazepines 9. 3-Benzyl-2-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine (9c) reveals high σ1 affinity and selectivity over σ2 and NMDA receptors.