Process for manufacturing picolinate borinic esters
AssigneeAnacor Pharmaceuticals, Inc.
InventorsKirk Maples, Stephen Baker, Glenn Stahl, Michael DiPierro, Christopher Tokar, Premchandran Ramiya, Siead Zegar
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Abstract
The present invention relates to the field of boron-containing compounds, particularly boron compounds and pharmaceutical compositions thereof that exhibit with antibacterial and/or anti-inflammatory activities, and uses thereof. Methods for preparing and using these boron compounds and pharmaceutical compositions thereof, are also provided.
Claims66
A method for manufacturing a compound of Formula I
- and its pharmaceutically acceptable salts, hydrates, and solvates, said method comprising:
- (a) reacting nucleophilic equivalents of R1 and R2 with a trialkylborate to form an alkyl borinic acid ester;
- (b) treating the borinic acid ester with an absorbent;
- and
- (c) combining the treated borinic acid ester with a picolinic acid under conditions effective to form the compound
- wherein
- R1 and R2 are selected independently from the group consisting of alkyl, heteroalkyl, aryl and heteroaryl;
- R3-R6 are members independently selected from the group consisting of hydrogen, hydroxy, amino, carboxy, cyano, halo, nitro, sulfo, thio, carbamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl, and
- R5 and R6 together with the ring to which they are attached form an optionally substituted aromatic ring.
A method for producing 2-({[bis(3-chloro-4-methylphenyl)boryl]oxy}carbonyl)pyridin-3-ol, and its pharmaceutically acceptable salts, hydrates, and solvates, comprising:
- reacting 3-chloro-4-methylphenyl magnesium bromide with trimethylborate under conditions effective to form methyl bis(3-chloro-4-methylphenyl)borinate;
- treating the methyl bis(3-chloro-4-methylphenyl)borinate with an absorbent;
- and
- reacting the methyl bis(3-chloro-4-methylphenyl)borinate with 3-hydroxypicolinic acid under conditions effective to form 2-({[bis(3-chloro-4-methylphenyl)boryl]oxy}carbonyl)pyridin-3-ol.
A method for producing 2-({[bis(3-chloro-4-methylphenyl)boryl]oxy}carbonyl)pyridin-3-ol, and its pharmaceutically acceptable salts, hydrates, and solvates, comprising:
- reacting 3-chloro-4-methylphenyl magnesium bromide with trimethylborate under conditions effective to form methyl bis(3-chloro-4-methylphenyl)borinate;
- treating the methyl bis(3-chloro-4-methylphenyl)borinate with ethanol and a first absorbent to form a mixture which is heated;
- treating 3-hydroxypicolinic acid with a second absorbent;
- filtering the mixture of the second absorbent and the 3-hydroxypicolinic acid and the mixture of the first absorbent and the methyl bis(3-chloro-4-methylphenyl)borinate;
- and
- reacting the filtered bis(3-chloro-4-methylphenyl)borinate with the filtered 3-hydroxypicolinic acid under conditions effective to form 2-({[bis(3-chloro-4-methylphenyl)boryl]oxy}carbonyl)pyridin-3-ol.
The compound 2-({[bis(3-chloro-4-methylphenyl)boryl]oxy)carbonyl)pyridin-3-ol in substantially anhydrous crystalline form.
Dependencies are inferred from the claim text.