96142-63-1

Upstream product

• 23474-98-8 2-amino-5-chlorobenzenethiol 
• 105560-93-8 methyl (2R,3S)-3-(4-methoxyphenyl)glycidate 

Downstream Products

• 156415-89-3 ethyl (+)-(2S,3S)-8-chloro-2,3,4,5-tetrahydro-3-hydroxy-2-(4-methoxyphenyl)-4-oxo-1,5-benzothioazepin-5-acetate 
• 156415-92-8 (+)-(2S,3S)-8-chloro-2,3-dihydro-3-hydroxy-2-(4-hydroxyphenyl)-1,5-benzothioazepin-4(5H)-one 
• 130884-49-0 (+)-(2S,3S)-cis-8-chloro-5-<2-(dimethylamino)ethyl>-2,3-dihydro-2-(4-methoxyphenyl)-3-<(4-nitrobenzyl)oxy>-1,5-benzothiazepin-4(5H)-one 
• 96125-47-2 (+)-(2S,3S)-cis-8-chloro-5-<2-(dimethylamino)ethyl>-2,3-dihydro-2-(4-methoxyphenyl)-3-(valeryloxy)-1,5-benzothiazepin-4(5H)-one 
• 96125-53-0 8-chlorodiltiazem 
• 131099-95-1 (+)-(2S,3S)-cis-8-chloro-5-<2-(dimethylamino)ethyl>-2,3-dihydro-3-methoxy-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one 
• 112525-50-5 (+)-(2S,3S)-3-acetoxy-5-<2-(N-benzyl-N-methylamino)ethyl>-2-(4-benzyloxyphenyl)-8-chloro-2,3-dihydro-2-(4-hydroxyphenyl)-1,5-benzothioazepin-4(5H)-one 
• 112525-30-1 (+)-(2S,3S)-5-<2-(N-benzyl-N-methylamino)ethyl>-2-(4-benzyloxyphenyl)-8-chloro-2,3-dihydro-3-hydroxy-2-(4-hydroxyphenyl)-1,5-benzothioazepin-4(5H)-one 
• 112525-45-8 (+)-(2S,3S)-3-acetoxy-2-(4-benzyloxyphenyl)-8-chloro-5-<2-(dimethylamino)ethyl>-2,3-dihydro-1,5-benzothioazepin-4(5H)-one 
• 112525-54-9 (+)-(2S,3S)-3-acetoxy-5-<2-(N-benzyloxycarbonyl-N-methylamino)ethyl>-2-(4-benzyloxyphenyl)-8-chloro-2,3-dihydro-2-(4-hydroxyphenyl)-1,5-benzothioazepin-4(5H)-one 
• 112544-49-7 (+)-(2S,3S)-5-<2-(N-benzyloxycarbonyl-N-methylamino)ethyl>-2-(4-benzyloxyphenyl)-8-chloro-2,3-dihydro-3-hydroxy-2-(4-hydroxyphenyl)-1,5-benzothioazepin-4(5H)-one 
• 1027373-55-2 [(2S,3S)-3-Acetoxy-2-(4-benzyloxy-phenyl)-8-chloro-4-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazepin-5-yl]-acetic acid 
• 156415-90-6 methyl (+)-(2S,3S)-2-(4-benzyloxyphenyl)-8-chloro-3-hydroxy-2,3,4,5-tetrahydro-4-oxo-1,5-benzothioazepin-5-acetate 
• 156415-91-7 (+)-(2S,3S)-2-(4-benzyloxyphenyl)-8-chloro-2,3,4,5-tetrahydro-3-hydroxy-4-oxo-1,5-benzothioazepin-5-acetic acid 

Relevant academic research and scientific papers

Facile ionic liquid-mediated protocol for the regioselective synthesis of 1,5-benzothiazepines

An efficient one-step ionic liquid-mediated green protocol for the regioselective synthesis of (+)=(±)-cis-2-(4-methoxy/benzyloxyphenyl)-3- hydroxy-2,3-dihydro-1,5- benzothiazepin-4-[5H]-ones has been developed from the reaction between substituted 2-aminobenzenethiol and methyl-(±)-trans-3- (4-methoxy/benzyloxy phenyl)glycidate, under nitrogen atmosphere, at 60±2 °C. The reaction has been performed in ionic liquids (viz, 1-butyl-3-methylimidazolium bromide/hexafluorophosphate), and the yields of the 1,5-benzothiazepine derivatives were found to be excellent. The cis-stereoisomer was obtained as the major product along with a trans-isomer as minor product.

Method for preparing (+)-(2S,3S)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-5H-1,5-benzothiazepine-4-one and chlorinated derivatives thereof

2-Aminothiophenol is reacted with methyl (-)-(2R,3S)-2,3-epoxy-3-(4-methoxyphenyl)propionate, and the intermediate methyl (2S,3S)-3-[(2-aminophenyl)thio]-2-hydroxy-3-(4-methoxyphenyl)propionate is cyclized in the presence of methanesulfonic acid, in the same vessel and without isolating said intermediate product, using e.g. chlorobenzene as a solvent.

Process for preparing 1,5-benzothiazepin derivatives

The invention relates to a process for preparing a preferably stereoisomerically pure 1,5-benzothiazepin derivative with the general formula (I) by the cyclization of an ester of the corresponding 2-hydroxy-3-(4-R3-phenyl)--3-(2-aminoarylthio)propanoic acid with the general formula (II) in the presence of a base and in an aprotic, polar solvent where R1 and R2, each independently, represent hydrogen, halogen, or an alkyl group with 1-6 carbon atoms or together with the phenyl group to which they are attached from a naphtalene group, R4 represents a residual group with 1-20 carbon atoms and R3 a hydrogen atom, a hydroxy group or an alkoxy group with 1-6 carbon atoms, at which a 2-hydroxy-3-(4-R3-phenyl)-3-(2-aminoarylthio)propanoic acid ester with the general formula (II) is cyclized in the presence of an alkali metal alkanolate as base. The invention also relates to a process for the preparation of alkylated and/or acylated 1,5-benzothiazepin derivatives and to the new compounds of (2X,3Y)-2-phenyl-3-hydroxy-2,3-dihydro-1,5-benzothiazepin-4(5H)-one, (2X,3Y)-2-phenyl-3-hydroxy-5-[2-(dimethylamino)ethyl]-2,3-di hydro-1,5-benzothiazepin-4(5H)-one and (2X,3Y)-2-phenyl--3-acetyloxy-5-[2-(dimethylamino)ethyl]-2,3-dihydro-1,5-benz othiazepin-4(5H)-one, where X and Y each independently represent the R or S configuration. Application of 1,5-benzothiazepin derivatives, obtained according to the process of the present invention, in the preparation of pharmaceuticals and particularly in the preparation of diltiazem.