Process of making gyrase and topoisomerase inhibitors
AssigneeVertex Pharmaceuticals Incorporated
InventorsDean Shannon, Tiansheng Wang, Simon Giroux
Life of this patent
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Abstract
The present application is directed to compounds, intermediates and methods for preparing compounds of formula (I) or a pharmaceutically acceptable salts thereof, wherein R is H or F, and each of R3, R4, and R5 are as defined herein. The compounds of formula (I) and pharmaceutical compositions comprising said compounds and salts inhibit bacterial gyrase and/or Topo IV and are useful in treating bacterial infections.
Claims24
A method for preparing a compound of formula (I)
- or a pharmaceutically acceptable salt thereof, wherein R is F;
- and each of R3, R4, and R5 is independently an optionally substituted alkyl or an optionally protected hydroxyl group;
- comprising providing a phenylpyrimidine compound of formula (II)
- wherein R is F, and each of R3, R4, and R5 is independently an optionally substituted alkyl or an optionally protected hydroxyl group;
- and reacting the phenylpyrimidine compound of formula (II) with a urea derivative of formula A or B:
- wherein R6 is an optionally substituted alkyl, optionally substituted aryl, optionally substituted saturated or unsaturated carbocycle, or optionally substituted saturated or unsaturated heterocycle;
- to provide a compound of formula (I);
- and
- optionally reacting the compound of formula (I) with a suitable acid to provide a pharmaceutically acceptable salt of the compound of formula (I).
A method for preparing a compound of formula (I)
- or a pharmaceutically acceptable salt thereof, wherein R is F;
- and each of R3, R4, and R5 is independently an optionally substituted alkyl or an optionally protected hydroxyl group;
- comprising providing a dihydrofuranyl nitrobenzene compound of formula
- wherein R is F, and
- converting the compound of formula (VIIIa) or (VIIIb), or a combination thereof, to the compound of formula (I) or a pharmaceutically acceptable salt thereof.
2-[5-(4-amino-2-fluoro-5-nitro-3-tetrahydrofuran-2-yl-phenyl)pyrimidin-2-yl]propan-2-ol.
2-[5-(4,5-diamino-2-fluoro-3-tetrahydrofuran-2-yl-phenyl)pyrimidin-2-yl]propan-2-ol.
Dependencies are inferred from the claim text.