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US 4,764,608 AGranted
Process for the manufacture of spiro-linked pyrrolidine-2,5-dione derivatives
AssigneeKyorin Pharmaceutical Co., Ltd.
InventorsKuniyoshi Masuzawa, Kyuya Okamura, Kazunori Kasuga, Shizuyoshi Fujimori, Susumu Kinoshita, Hiroshi Matsukubo
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Abstract
This invention relates to novel processes for the manufacture of spiro-linked pyrrolidine-2,5-diones of formula; ##STR1## which have a potent inhibitory activity on aldose reductase and are useful for reduction and prevention of chronic diabetic complications. The invented processes are useful as improved and convenient method for a large scale manufacture.
Claims2
A process for the synthesis of a spiro-linked pyrrolidine-2,5-dione of the formula:
- ##STR5## wherein X.sub.1 and X.sub.2 each independently represent a hydrogen atom, a halogen atom, a lower alkyl group or an alkoxy group;
- Y is a methylene group, an oxygen atom or a sulfur atom;
- R.sub.1, R.sub.2, R.sub.3 and R.sub.4 each independently represent a hydrogen atom, a lower alkyl group or the carbon atoms of which groups together form a benzene ring, comprising:
- reacting acetone cyanohydrin with a compound of the formula:
- ##STR6## wherein Ra is a lower alkyl group and X.sub.1, X.sub.2, Y and R.sub.1 -R.sub.4 each have the above-stated meanings;
- and
- heating, in the presence of an acid, the product obtained from the acetone cyanohydrin addition step of the formula:
- ##STR7##
5 more elements
A process for the synthesis of a spiro-linked pyrrolidine-2,5-dione of the formula:
- ##STR8## wherein X.sub.1 and X.sub.2 each independently represent a hydrogen atom, a halogen atom, a lower alkyl group or an alkoxy group;
- Y is a methylene group, an oxygen atom or a sulfur atom;
- R.sub.1, R.sub.2, R.sub.3 and R.sub.4 each independently represent a hydrogen atom, a lower alkyl group or the carbon atoms of which groups together form a benzene ring, comprising:
- adding nitromethane to a compound of the formula:
- ##STR9## wherein Ra is a lower alkyl group and X.sub.1, X.sub.2, Y and R.sub.1 -R.sub.4 each have the above-stated meanings;
- dehydrating the compound obtained by nitromethane addition of the formula:
- ##STR10## wherein Ra, X.sub.1, X.sub.2, Y and R.sub.1 -R.sub.4 are each as defined above;
- and
- heating, in the presence of an acid, the dehydrated compound of the formula:
- ##STR11## wherein Ra, X.sub.1, X.sub.2, Y and R.sub.1 -R.sub.4 are each as stated above, thereby obtaining said product spiro-linked pyrrolidine-2,5-dione compound.
7 more elements
Dependencies are inferred from the claim text.