The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.
The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.
Patent No.:
Date of Patent:
Jul. 22, 1986
Filed:
Jan. 22, 1985
John K Thottathil, Trenton, NJ (US);
Jerome L Moniot, Chester, NJ (US);
E. R. Squibb & Sons, Inc., Princeton, NJ (US);
Abstract
A method is provided for preparing phosphinic acid prodrug intermediates which are useful in preparing phosphinic acid angiotensin-converting enzyme inhibitors which method includes the step of coupling a phosphonous acid or its ester of the structure ##STR1## wherein R is H or lower alkyl and R.sup.1 is lower alkyl, aryl, arylalkyl, cycloalkyl or cycloalkylalkyl, with an alkylating agent of the structure ##STR2## wherein Hal is Cl, Br or I, n is 0 or 1, R.sup.2 is H or lower alkyl, and Z is H, lower alkyl, --CO.sub.2 R.sup.3 (wherein R.sup.3 is H or lower alkyl), ##STR3## (wherein R.sup.4 is H, lower alkyl, aryl or arylalkyl), --CN, or ##STR4## (wherein R.sup.5 and R.sup.6 may be the same or different and are selected from the group consisting of H, lower alkyl, aryl, aryl-lower alkyl, cycloalkyl or cycloalkylalkyl and at least one of R.sup.5 and R.sup.6 is other than H, or R.sup.5 and R.sup.6 can be taken with the N-atom to form a 5-, 6- or 7-membered heterocyclic ring which 5-, 6- or 7-membered N-containing ring may or may not contain a CO.sub.2 R.sup.3 group and which 5- or 6-membered N-containing ring may or may not be fused to an aryl ring), in the presence of a silylating agent, to form the phosphinic acid intermediate of the structure ##STR5## wherein R, R.sup.1, R.sup.2, n and Z are as defined above.