Process for preparing 5H-pyrrolo[2,1-c]-[1,4]thiazepine-1,5-diones
AssigneeJohn Wyeth & Brother Limited
InventorRoger Crossley
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Abstract
The invention relates to the preparation of 1-bromo-2-D-alkylpropanoyl-L-proline derivatives and analogous compounds which are useful as chemical intermediates to angiotensin converting enzyme (ACE) inhibitors and to the stereospecific synthesis of such ACE inhibitors having the formula: ##STR1## wherein R.sup.1 is lower alkyl and R.sup.4 and R.sup.5 are both hydrogen or together with the carbons to which they are attached represent a benzene ring optionally substituted by defined substituents. Intermediates of formula ##STR2## are also disclosed wherein R.sup.1, R.sup.4, R.sup.5 are as defined above and B.sup.30 is a cation.
Claims4
A process for preparing a compound of formula XI ##STR21## wherein R.sup.1 is lower alkyl, R.sup.4 and R.sup.5 either both represent hydrogen or together with the carbon atoms to which they are attached represent a fused benzene ring optionally substituted by a group selected from hydroxy, lower alkyl, lower alkoxy and halogen, which comprises selecting a process from the group consisting of
- (a) reacting a compound of formula ##STR22## substantially free from the L,L isomer, wherein R.sup.1, R.sup.4 and R.sup.5 are as defined above with a haloformate ester and a sulphide of formula XII
- Y--SH (XII)
- wherein Y represents hydrogen or an alkali metal, with the proviso that when Y is hydrogen the reaction is carried out in the presence of base, and cyclising the product by heating, and
- (b) cyclising by heating a compound of formula (XIII) ##STR23## substantially free of L,L stereoisomer wherein R.sup.1, R.sup.4 and R.sup.5 are as defined above and B.sup..sym. is a cation.
A process as claimed in claim 1 in which the compound of formula VII is prepared by a process according to claim 4.
Dependencies are inferred from the claim text.