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

作者：Sarkar Soumya; Husain Syed Masood; Schepmann Dirk; Froehlich Roland; Wuensch Bernhard

来源：Tetrahedron, 2012, 68(12): 2687-2695.

DOI：10.1016/j.tet.2012.01.052

• Keto acids
• 3-Benzazepin-2-ones
• Indanones
• Microwave irradiation
• sigma Affinity
• X-ray structure

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 alpha-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 sigma(1) affinity and selectivity over sigma(2) and NMDA receptors.

• 出版日期2012-3-25