Benzothiazepine amide 3,1 -Benzothiazepines

Pyrrolo[2,1 -d][ 1,5]benzothiazepine-6-carboxylic acid (27) was obtained via base-catalyzed cyclization of pyrrole-2-carboxaldehydes 26 and 28, each synthesized by Vilsmeier-Haack formylation of their respective pyrroles 24 and 25, prepared in turn by condensation of 18, respectively, with ethyl bromoacetate and chloroacetonitrile in the presence of sodium ethylate at room temperature. When treated with piperidine in refluxing benzene for 48 hours, 26 and 28 afforded ester 29 and nitrile 31 from which, in an alkaline medium, acid 27 could be obtained. Under similar experimental conditions, acid 27 was also formed from amide 30 (Scheme... 

Dihydrothieno[2,3-6][l,5]benzothiazepines (42) were synthesized from 2-(2-thienylthio)aniline (40). Compound 40 was acylated by treatment with acetic anhydride or benzoyl chloride to give N-acyl derivatives (41), which afforded compounds 42 by cyclization with phosphorus oxychloride and subsequent reduction with sodium borohydride or Zn/HCl. N-Dimethylaminopropyl derivatives 43 were prepared by reaction with di-methylaminopropyl chloride in the presence of sodium amide (Scheme 13) (67CZP124935 68CCC1846). 

The preparation of some novel pyrimido[4,5-6][l,4]benzothiazepines has been described employing a Bischler-Napieralski-type cyclisation on pyrimidine amide derivatives... 

Acid-catalyzed hydrolysis of the amide acetal (64) of 2-thiolbenzamide (63) yielded the 1,4-benzothiazepin-5(4 -one (65) (Scheme 21) <88CB2147>. 

A series of selective D2 dopamine receptor agonists were discovered and optimized to obtain benzothiazepine amide 161, a lead compound that possessed good in vitro physical properties, metaboHc stabihty, and in vivo pharmacokinetics (14JME3450). A number of 8-alkoxy-4,5-dihydrobenzo[l)] [l,2,4]triazolo[4,3-(/][l,4]thiazepine derivatives were synthesized, with compound 162 showing potent anticonvulsant activity (14JEIM272). 

Nitrobenzoic acid and its derivatives are commonly used in the synthesis of benzodiazepines and benzothiazepines. Formation of the desired seven-membered ring is usually achieved through an intramolecular amidation. 

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