Method of preparing 7-oxabicycloheptyl substituted heterocyclic amide prostaglandin analogs useful in the treatment of thrombotic and vasospastic disease
AssigneeE. R. Squibb & Sons, Inc.
InventorsJagabandhu Das, David Kronenthal
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Abstract
A method is provided for preparing 7-oxabicycloheptyl substituted heterocyclic aide prostaglandin analogs which are thromboxane A.sub.2 (TXA.sub.2) receptor antagonists or combined thromboxane A.sub.2 receptor antagonists/thromboxane synthetase inhibitors useful, for example, in the treatment of thrombotic and/or vasospastic disease, wherein a vinyl bromide of the formula, for example, ##STR1## wherein m, n, R.sup.1 and R.sup.2 are as defined herein is treated with a cyclizing agent to forth the corresponding oxazole.
Claims1
A method for preparing a chloromethylamide of the structure ##STR38## wherein m is 1, 2or 3;
- n is 0, 1, 2, 3 or 4;
- (CH.sub.2).sub.n is unsubstituted or is substituted with one or two alkyl groups;
- R.sup.1 is lower alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, saturated heterocycle, or aromatic heterocycle;
- and
- R.sup.2 is hydrogen, lower alkyl, aryl, or aralkyl, or R.sup.1 and R.sup.2 together with the N to which they are linked form a 5- to 8- membered ring;
- and which comprises treating a hydroxymethyl compound of the structure ##STR39## with a methanesulfonyl chloride in the presence of an organic base to form the mesylated compound of the structure ##STR40## and treating the mesylated compound with an alkali metal chloride or a quanternary ammonium chloride salt in the presence of dimethylformamide or dichloromethane to form the desired chloromethylamide compound.
Dependencies are inferred from the claim text.