Functionalized 2,5-Disubstituted Benzazepines: Stereoselective Synthesis of 3-Methyl-5-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-2-carbonitrile and Related Derivatives
| Autor: | David E. Uehling, Suganthini S. Nanthakumar, Jeff E. Cobb, Randy D. Rutkowske |
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| Rok vydání: | 2004 |
| Předmět: | |
| Zdroj: | Synlett. :1394-1398 |
| ISSN: | 1437-2096 0936-5214 |
| Popis: | A stereoselective synthesis of 2-carbonitrile and 2-aminomethyl-substituted 5-phenylbenzazepine derivatives was developed starting from [4-hydroxy-3-(methyloxy)phenyl]acetic acid. The key step in the synthesis is a stereoselective addition of cyanide to 3-methyl-1-phenyl-2,3-dihydro-1H-3-benzazepine (4) to give a 15:1 trans/cis mixture of 2-carbonitrile-5-phenyl benzazepine diastereomers 5a/5b in 83% yield. The stereochemistry of the major product was deduced by 1 H NMR NOESY analysis. The carbonitrile diastereomers could be separated and further manipulated by reduction to the corresponding aminomethyl derivatives 3a and 3b in a stereoselective manner. The aminomethyl benzazepine template 3 has potential to serve as a handle for the synthesis of a variety of derivatives modified at the 2-position of the benzazepine scaffold, as illustrated by an acylation of the primary amine of 3 followed by mild deprotection of the 7-phenol functionality. |
| Databáze: | OpenAIRE |
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