Process for preparing 1,5-benzothiazepine derivative
AssigneeTanabe Seiyaku Co., Ltd.
InventorsShinichi Yamada, Ryuzo Yoshioka, Takeji Shibatani
Life of this patent
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Abstract
A novel process for preparing 1,5-benzothiazepine derivative II!: ##STR1## wherein Ring A and Ring B are substituted or unsubstituted benzene ring, and R.sup.3 is H, (di-lower alkylamino)-lower alkyl or substituted or unsubstituted piperazinyl-lower alkyl, or a salt thereof, in high yield and in a single step from a novel 3-(2-amino-substituted or unsubstituted phenylthio)-2-hydroxy-3-substituted or unsubstituted phenylpropionamide compound. Said 1,5-benzothiazepine derivative II! is useful as an intermediate for preparing medicaments such as diltiazem hydrochloride.
Claims22
A process for preparing a 1,5-benzothiazepine derivative of the formula II!:
- ##STR101## wherein Ring A and Ring B are a substituted or unsubstituted benzene ring, and R.sup.3 is a hydrogen atom, a (di-lower alkylamino)-lower alkyl group or a substituted or unsubstituted piperazinyl-lower alkyl group, or a salt thereof, which comprises subjecting a propionamide derivative of the formula I!:
- ##STR102## wherein R.sup.1 and R.sup.2 are the same or different and each are a hydrogen atom, a carbamoyl group, a lower alkyl group, a lower alkanoyl group, a lower alkylaminocarbonyl group, an amino acid residue, or an aryl group having optionally a substituent, or combine with each other at their termini together with the adjacent nitrogen atom to which they bond to form a heterocyclic group having optionally a substituent, and Ring A, Ring B and R.sup.3 are the same as defined above, to intramolecular cyclization reaction, and if necessary, converting the product into a salt thereof.
A process for preparing a 3-lower alkanoyloxy-5-di-lower alkylamino-lower alkyl or a substituted or unsubstituted piperazinyl-lower alkyl!-1,5-benzothiazepine derivative of the formula III!:
- ##STR103## wherein Ring A and Ring B are a substituted or unsubstituted benzene ring, R.sup.31 is a (di-lower alkylamino)-lower alkyl group or a substituted or unsubstituted piperazinyl-lower alkyl group, and R.sup.5 is a lower alkanoyl group, or a pharmaceutically acceptable salt thereof, which comprises subjecting a propionamide derivative of the formula I!:
- ##STR104## wherein R.sup.1 and R.sup.2 are the same or different and each are a hydrogen atom, a carbamoyl group, a lower alkyl group, a lower alkanoyl group, a lower alkylaminocarbonyl group, an amino acid residue, or an aryl group having optionally a substituent, or combine with each other at their termini together with the adjacent nitrogen atom to which they bond to form a heterocyclic group having optionally a substituent, R.sup.3 is a hydrogen atom, a (di-lower alkylamino)-lower alkyl group or a substituted or unsubstituted piperazinyl-lower alkyl group, and Ring A and Ring B are the same as defined above, or a salt thereof, to intra-molecular cyclization reaction to give a 1,5-benzothiazepine derivative of the formula II!:
- ##STR105## wherein Ring A, Ring B and R.sup.3 are the same as defined above, and when R.sup.3 of the compound II! is a hydrogen atom, introducing a (di-lower alkylamino)-lower alkyl group or a substituted or unsubstituted piperazinyl-lower alkyl group into the 5-position of the compound II!, acylating the 3-hydroxy group of the resulting compound with a lower alkanoyl group, and if necessary, converting the product into a pharmaceutically acceptable salt thereof.
A process according to clam 1, wherein the intramolecular cyclization reaction is carried out in an alcohol, an aromatic hydrocarbon, an ether or a mixture thereof.
Dependencies are inferred from the claim text.