Thieno benzothiazepines

Syntheses of benzo[/]thieno[3,2-i7][l,4]thiazepin-9(10H)-one 323 (2001BMC1123) and thieno[3,4- 7]-[l,4]benzothiazepine 324 (Figure 5 (1999JHC659)) start from the corresponding open chain amino acids. 

Benzo[e]thieno[3,2- ]thiepin-10(5Ef)-one 388 can be smoothly reduced with sodium borohydride to the corresponding alcohol, which forms the chloro substituted compound under standard treatment with thionyl chloride (1991CPB2564). Dihydro derivatives of pyrrolo-benzothiazepine 377 have been reported starting from ketone 373 by a carbonyl reduction, bromination and amination sequence (Scheme 76, Section 5.1.1 (1998JMC3763, 2002JMC344, 2004JMC143)). 

Several patents report the synthesis of thieno[2,3-6][l, 5]benzothiazepin-4(5//)-ones (45) as potential antidepressant agents. These derivatives were synthesized from 2-(2-thienylthio)anilines (40), which were converted into the corresponding isocyanates 44 by reaction with COCl2 and then cyclized by treatment with A1C13. /V-Dialkylaminoalkyl derivatives 46 were pre-... 

The synthesis of thieno[3,4-6][ 1,5]benzothiazepin-10(9/7)-ones (60) was carried out by cyclizing mercaptans 59 in the presence of polyphosphoric acid the reaction afforded compounds 60 and benzothiazoles 61 in approximately equal amounts. Lactams 60 were transformed into 10-piperazinyl derivatives 63 directly on treatment in refluxing toluene with piperazines or through the formation of iminochloride intermediates 62, which then reacted with an excess of piperazines under the same experimental... 

Condensation of 5 with methyl tetrahydro-4-oxothiophene-3-carboxyl-ate (64) led to the formation of the ring-closed enamino thiolactone 65. Chemical transformation of 65 with sodium hydride/methyl iodide gave 67, whereas 4H, 10//-thieno[3,4-c][l,5]benzothiazepin-10-one (66) was obtained upon aromatization of the thiophene ring by the action of sulfuryl chloride (Scheme 18) (80JOC497). 

One of the most common synthetic approaches to the construction of heterocyclic compounds involves the reaction of /3-keto esters with bifunctional nucleophiles. Thus a variety of reactions of (1) with different bifunctional heteronucleophiles, including hydrazine, substituted aminotriazoles, 2-aminopyridines, o-phenylenediamines, and o-aminothiophenol, lead to polynuclear condensed thieno compounds (e.g. 2-8) of potential medicinal interest featuring the pyrazolone, pyrimidinone, benzodiazepine, and benzothiazepine nuclei. Cannabinoid analogs can be prepared through cyclization of the condensation products of (1) with bifunctional oxygenated nucleophiles such as substituted resorcinols. ... 

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