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US 5,475,117 AGranted
Process for optically active 2-alkyl-2,5-diazabicyclo[2.2.1]heptanes
AssigneePfizer Inc.
InventorsTamim F. Braish, Darrell E. Fox
Life of this patent
Estimating the term…
Abstract
1S,4S and 1R,4R-2-Alkyl-2,5-diazabicyclo[2.2.1]heptanes useful as intermediates in the synthesis of certain antibacterial quinolones, are prepared respectively, from trans-4-hydroxy-L-proline and trans-4-hydroxy-D-proline via multistep procedures.
Claims26
A process for the preparation of an optically active 2,5-diazabicyclo[2.2.1]heptane of the stereochemical formula ##STR5## wherein R is (C.sub.1 -C.sub.6)alkyl;
- R.sup.2 is (C.sub.1 -C.sub.6)alkyl, trifluoromethyl or ##STR6## and X and X.sup.1 are each independently hydrogen, (C.sub.1 -C.sub.6)alkyl, bromo, chloro, trifluoromethyl, methoxy or nitro;
- which comprises hydride reduction of an optically active carboxamide of the absolute stereochemical formula ##STR7## wherein R.sup.4 is independently a value of R.sup.2 as defined above, in a reaction inert solvent.
A process for the preparation of a 2,6-diazabicyclo[2.2.1]heptane of the relative or absolute stereochemical formula ##STR10## wherein R is (C.sub.1 -C.sub.6)alkyl;
- R.sup.2 is (C.sub.1 -C.sub.6)alkyl, trifluoromethyl or ##STR11## and X and X.sup.1 are each independently hydrogen, (C.sub.1 -C.sub.6)alkyl, bromo, chloro, trifluoromethyl, methoxy or nitro;
- which comprises the steps of
- (a) esterification of a hydroxyproline of the absolute stereochemical formula ##STR12## with an alcohol of the formula
- R.sup.1 OH,
- wherein R.sup.1 is (C.sub.1 -C.sub.6)alkyl, to form a carboxylate ester of the formula ##STR13## wherein R.sup.1 is (C.sub.1 -C.sub.6)alkyl;
- (b) stepwise N-sulfonylation followed by O-sulfonylation to form a sulfonate of the formula ##STR14## wherein R.sup.4 is independently a value of R.sup.2 as defined above;
- or concurrent N- or O-sulfonylation to form a sulfonate of the formula (XII) wherein R.sup.2 and R.sup.4 have the same value;
- (c) amidification of said sulfonate with an amine of the formula
- RNH.sub.2
- to form a carboxamide of the formula ##STR15## (d) hydride reduction of said carboxamide in a reaction inert solvent to form said compound of the formula (VIII).
7 more elements
Dependencies are inferred from the claim text.