Intermediate for preparing a pharmaceutically active compound

Details Intermediate for preparing a pharmaceutically active compound Intermediate for preparing a pharmaceutically active compound

1996-11-20

1998-02-17

Higel, Floyd D.

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

5483421, C07D23364

Patent

active

057192936

DESCRIPTION:

BRIEF SUMMARY
This application is a 371 of PCT/U.S. application Ser. No. 95/05664 filed May 4, 1995.


FIELD OF THE INVENTION

The present invention relates to the bisulfite addition compound of a key intermediate useful in the preparation of an angiotensin II (AII) receptor antagonist.


BACKGROUND OF THE INVENTION

PCT Application WO 94/06776 published Mar. 31, 1994 describes a process for preparing 1-alkylaryl-2-alkyl-5-formylimidazoles which comprises reacting a 2-halo-2-propenal-3-alkyl ether, such as 2-bromo-3-(1-methylethoxy)-2-propenal, with a N-(1-iminoalkyl)aminoalkylaryl compound, such as N-(1-iminopentyl)-4-(aminomethyl)benzoic acid. In particular, the PCT application details the preparation of key intermediate in the preparation of )methyl-2-propenoic acid, a highly potent AII receptor antagonist (Weinstock, et al., J. Med. Chem,, 34:1514-1517 (1991)). Although the process described in PCT Application WO 94/06776 produces the key intermediate in high yield and high purity, the isolation of said intermediate involves a lengthy procedure consisting of multiple extractions, a slurry with montmorillonite K-10 clay, and a distillation/crystallization sequence. Thus, there is a need for an alternate method for the isolation of when preparing this intermediate on a commercial scale for use in the synthesis of (2-thienyl)methyl-2-propenoic acid.
It has now been found that purified obtained by converting the intermediate to its bisulfite addition compound, recrystaliizing the addition compound and then reconverting said addition compound to bisulfite addition compound itself can be used directly in the preparation -{(4-carboxyphenyl)methyl-1H-imidazol-5-yl!-2-(2-thienyl)methyl-2-propenoa te, which is the immediate precussor to )methyl-2-propenoic acid. The ease of work-up and the efficiency of the isolation process which makes use of the bisulfite addition compound of advantageous from a commercial viewpoint.


SUMMARY OF THE INVENTION

The present invention provides for a compound according to the formula (I) : ##STR2## and hydrates, solvates, and salts thereof.


DETAILED DESCRIPTION OF THE INVENTION

This invention relates to a compound of the formula (I): ##STR3## and hydrates, solvates, and salts thereof.
The specific compound of this invention is the bisulfite addition compound hydrates, solvates, and salts thereof.
Generally, the compound of formula (I) is prepared by reacting a compound of formula (II): ##STR4## with sodium bisulfite.
Specifically, the compound of the formula (I) is prepared by the method described in Scheme I. ##STR5##
According to Scheme I, reacting N-(1-iminopentyl)-4-(aminomethyl)benzoic acid (formula (I) compound in Scheme I) with 2-bromo-3-(1 -methylethoxy)-2-propenal (formula (2) compound in Scheme I) in the presence of a base, for example, potassium carbonate. (See PCT Application WO 94/06776.) The resulting 5-formyl imidazole compound (formula (II) compound), without isolation, is then reacted with sodium bisulfite to yield the intermediate sodium salt of the bisulfite addition compound (formula (3) in Scheme I). Treatment of the formula (3) compound with aqueous hydrochloric acid (pH 1.0-1.5) resulted in the formation of the formula (4), Scheme I, compound, which is also a formula (I) compound. regenerated by reacting the formula (4) Scheme (I) compound with a mixture of water, acetic acid and hydrochloric acid under nitrogen.
The compound of formula (I) may exist in hydrated or solvated form. Any and all such hydrates and solvates are included within the scope of this invention.
Salts of the compound of formula (I), such as the formula (3) Scheme (I) compound, may be prepared by known methods from inorganic bases, including alkali metal and alkaline earth bases, for example, lithium, sodium and potassium hydroxides, bicarbonates, and carbonates, and organic bases, such as triethylamine, butylamine, piperazine, choline and diethanolamine.
Use of the compound of this invention provides a new method for isolating and purifying a key intermediate in the synthesis of a potent angiotens

REFERENCES:
patent: 4355040 (1982-10-01), Furukawa et al.
patent: 5185351 (1993-02-01), Finkelstein et al.
patent: 5254546 (1993-10-01), Ardecky et al.
J. Marc, "Advanced Organic Chemistry " published 1992 by John Wiley & sons (N.Y.), see p. 895, section 6-12.

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