# US 5,344,937 A · Alkyl substituted nitroimidazole acetic acids

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- Number: US 5,344,937 A
- Document ID: US5344937A
- Status: Granted
- Kind: A
- Application number: 08/049,915
- Filed: 1993-04-20
- Granted: 1994-09-06
- Earliest claimed: 1993-04-20
- Assignees: Eli Lilly and Company
- Inventors: Charles J. Barnett; Thomas M. Wilson
- Web page: https://patentgrep.com/patent/US5344937A

## CPC

- C07D 233/92: attached in position 4 or 5
- A61P 9/12: Antihypertensives
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

This invention provides the substantially pure (R) enantiomer of a compound of the Formula II: ##STR1## The compounds of Formula II are useful in the preparation of the substantially pure (R) enantiomer of angiotensin II antagonists of Formula III: ##STR2## wherein R.sub.1, Ar, R.sub.2 and X are variables.

## Claims

### Claim 1

A method of preparing the compounds of the formula, ##STR20## wherein the configuration is substantially the (R) enantiomer, and R.sub.1 is C.sub.4 -C.sub.9 straight chain alkyl, C.sub.4 -C.sub.9 straight chain trifluoroalkyl, C.sub.4 -C.sub.9 straight chain alkenyl, or C.sub.4 -C.sub.9 straight chain trifluoroalkenyl; or a (-)-cinchonidine salt thereof, comprising:
(a) reacting a racemic mixture of the compound of the formula ##STR21## wherein R.sub.1 is C.sub.4 -C.sub.9 straight chain alkyl, C.sub.4 -C.sub.9 straight chain trifluoroalkyl, C.sub.4 -C.sub.9 straight chain alkenyl, or C.sub.4 -C.sub.9 straight chain trifluoroalkenyl; with (-)-cinchonidine in an alcoholic solvent in the presence or absence of C.sub.1 -C.sub.4 alkyl amine to produce a crystalline salt;
(b) isolating the crystalline salt; and
(c) optionally converting the crystalline salt to the free acid thereby producing a substantially pure (R) enantiomer of the formula: ##STR22## wherein R.sub.1 is C.sub.4 -C.sub.9 straight chain alkyl, C.sub.4 -C.sub.9 straight chain trifluoroalkyl, C.sub.4 -C.sub.9 straight chain alkenyl, or C.sub.4 -C.sub.9 straight chain trifluoroalkenyl.

### Claim 2 (depends on 1)

The method of claim 1 further comprising dissolving said salt in a second solvent comprising an aqueous alcohol, and crystallizing said salt from the second solvent to provide a recrystallized salt.

### Claim 3 (depends on 1)

The method of claim 1 wherein the racemic mixture is (RS)-.alpha.-hexyl-4-nitro-1H-imidazole-1-acetic acid.

### Claim 4 (depends on 1)

The method of claim 1 wherein step (a) is carried out with one-half equivalent of (-)-cinchonidine and one-half equivalent of triethylamine.