Preparation of norbornyl sulfonamide derivatives

Details Preparation of norbornyl sulfonamide derivatives Preparation of norbornyl sulfonamide derivatives

1991-06-18

1992-06-23

Raymond, Richard L.

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

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

560 12, 562427, 564 89, 564 93, C07C31120, C07D49308

Patent

active

051244624

DESCRIPTION:

BRIEF SUMMARY
FIELD OF THE INVENTION

This invention relates to a process for preparing norbornyl sulfonamide derivatives useful as intermediates for the preparation of bicycloheptane carboxylic acid derivatives of general formula: ##STR3## wherein R.sup.2 is phenyl or substituted phenyl; Y is oxygen, methylene, or substituted methylene; m is 0 or 1; and n is 3 or 4.
The norbornyl sulfonamide derivative of the invention is shown by formula (I): ##STR4## wherein R' is optionally protected --CH.sub.2 OH or --COOH; R.sup.2 is phenyl or substituted phenyl; and Y is oxygen, methylene, or substituted methylene.
Because typical compounds of formula (I) where Y is methylene are known as "norbornane derivatives", the compounds of formula (I) are referred to as "norbornyl sulfonamide derivatives" throughout this specification irrespective of what Y represents.


BACKGROUND OF THE INVENTION

The above-mentioned bicycloheptane carboxylic acid derivatives are clinically important thromboxane A.sub.2 (TXA.sub.2) receptor antagonists. TXA.sub.2 is a member of prostanoids which are synthesized enzymatically from arachidonic acid via prostaglandin H.sub.2 (PGH.sub.2) as an intermediate, and are known to exhibit many significant biological activities such as aggregation of platelets and contraction of smooth muscles of various organs. Therefore, TXA.sub.2 receptor antagonists have been expected to be therapeutically and prophylactically effective on TXA.sub.2 -associated diseases. Such diseases include myocardial infarction, cerebral infarction, pulmonary embolism, thrombosis, encyopyelitis, renal dysfunction, asthma caused by bronchoconstriction, and the like. It may be also useful to prevent the vascular contraction after a subarchnoidal bleeding, TXA.sub.2 shocks after the artery reperfuse of circulation systems or digestive organs, shocks caused by bleeding, septicemia, wound, cardiac dysfunction, endotoxin, acute pancreatitis, burn, or the like. It may be also effective for the prevention of thrombocytopenia during extracorporeal circulation.
In view of the above, the present inventors made extensive studies and found a class of bicyclheptane carboxylic acid derivatives having antagonistic activities against TXA.sub.2 [see, Japanese Patent Publication (Kokai) No. 139161/1988]. The carboxylic acids were so far prepared by a process in which a sulfonamide derivative of formula (I) was prepared from 2-alkoxycarbonyl-3-carboxy-norbornane of formula (IV) by means of Curtius Rearrangement according to the following reaction scheme. ##STR5## In the reaction scheme, R.sup.1 is an ester-forming group; R.sup.2 is a phenyl or substituted phenyl; Z is an amino-protecting group; and Y is as defined above. However, the above-mentioned method is not suitable to apply to the total process for the mass-production of the bicycloheptane carboxylic acid derivatives because: amino group.
Therefore, it has been highly desired to establish a safe and efficient method for preparing the sulfonamide derivative of formula (I), which in turn makes an advance in the mass-production of the biologically active bicycloheptane carboxylic acid derivatives.
The inventors made extensive investigations with the aim of solving these problems and have now found that the sulfonamide derivative (I) can be obtained efficiently and easily by making a sulfonyl halide react with a norbornyl amine prepared by treating a norbornane derivative having carbamoyl group at the 3-position under the reaction conditions for the "Hofmann Rearrangement" in situ.


DISCLOSURE OF THE INVENTION

Thus, the present invention provides a process for the preparation of a norbornyl sulfonamide derivative of formula (I), which process comprises treating a norbornanoic acid amide of formula (II): ##STR6## wherein R is optionally protected --CH.sub.2 OH or --COOR.sup.1 ; R.sup.1 is hydrogen or ester-forming group; and Y is oxygen, methylene, or substituted methylene under the reaction conditions for the Hofmann Rearrangement, and then with a substituted sulfonyl halide of formula (III): successively.

REFERENCES:
patent: 5002972 (1991-03-01), Narisada et al.

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