Process for preparing beta-lactamase inhibitor hydroxylurea intermediates
AssigneeMerck Sharp & Dohme Corp.
InventorsJianguo Yin, Zhijian Liu, Nobuyoshi Yasuda, Mark Weisel
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Abstract
The present invention relates to processes for the preparation of N-protected (2S,5R)-6-hydroxy-7-oxo-N-piperidin-4-yl-1,6-diazabicyclo[3.2.1]octane-2-carboxamide intermediates. Such compounds have application in the preparation of beta-lactamase inhibitors such as 7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamides and esters, in particular, the beta lactamase inhibitor, (2S,5R)-7-oxo-N-piperidin-4-yl-6-(sulfoxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide. The present invention also encompasses intermediates useful in the disclosed processes and methods for their preparation.
Claims14
A process for preparing a compound of Formula I, or a salt thereof:
- comprising
- (A) reacting a compound of Formula II:
- with a catalyst system and silylating agent under hydrogenation conditions to obtain a compound of Formula III;
- wherein each R group is independently a C1-6 alkyl or phenyl;
- and
- (B) hydrolyzing the compound of Formula III to form the compound of Formula I, wherein
- PG1 is an amine protecting group which forms with the amino nitrogen to which it is attached a carbamate, a benzylamine, or a sulfonamide;
- and
- PG2 is an oxygen protecting group selected from benzyl (Bn), substituted benzyl, trityl, and substituted trityl.
A compound of Formula III:
- or a salt thereof, wherein each R group is independently a C1-6 alkyl or phenyl;
- and
- PG1 is an amine protecting group which forms with the amino nitrogen to which it is attached a carbamate, a benzylamine, or a sulfonamide.
Dependencies are inferred from the claim text.