# US 4,391,752 A · Process for preparing 5H-pyrrolo[2,1-c]-[1,4]thiazepine-1,5-diones

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- Number: US 4,391,752 A
- Document ID: US4391752A
- Status: Granted
- Kind: A
- Application number: 06/376,356
- Filed: 1982-05-10
- Granted: 1983-07-05
- Earliest claimed: 1980-02-26
- Assignees: John Wyeth & Brother Limited
- Inventors: Roger Crossley
- Web page: https://patentgrep.com/patent/US4391752A

## CPC

- C07D 513/04: Ortho-condensed systems
- C07D 207/16: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## 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.

## Claims

### Claim 1

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.

### Claim 2 (depends on 1)

A process as claimed in claim 1 wherein Y is hydrogen which is carried out in tertiary amine solvent.

### Claim 3 (depends on 1)

A process as claimed in claim 1 wherein B.sup..sym. is an alkylammonium cation.

### Claim 4 (depends on 1, 4)

A process as claimed in claim 1 in which the compound of formula VII is prepared by a process according to claim 4.