Process for the preparation of chiral triazolones
AssigneeSandoz Ltd.
InventorsMichael Oberhuber, Joerg Salchenegger, Dominic De Souza, Martin Albert, Thorsten Wilhelm, Martin Langner, Hubert Sturm, Hans-Peter Spitzenstaetter
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Abstract
A process for the preparation of a chiral compound, in particular posaconazole, wherein the process comprises mixing and reacting the compounds of formula (I) Y3—NH2; of formula (IIa) 0=C═N—Y0 and/or of formula (IIb) and of formula (III) in a solvent in any order to obtain a reaction mixture containing a chiral compound of formula (IV) and/or formula (V).
Claims36
A process for the preparation of a chiral compound, comprising
- (1.1) providing a compound of formula (I)
- Y3—NH2 (I)
- or a salt thereof,
- wherein Y3 is an optionally substituted aryl residue;
- (1.2) providing a phosgene derivative of formula (IIb)
- wherein Y1N— and Y2N— are the same or different optionally substituted nitrogen heterocycle moieties, preferably selected from the group consisting of imidazolyl and benzimidazolyl;
- (1.3) providing a compound of formula (III)
- or a salt thereof,
- wherein R1 is an alkyl residue preferably having from 1 to 6 carbon atoms,
- and
- wherein —R is —H or a suitable hydroxyl protecting group preferably selected from the group consisting of —SiRaRbRc and optionally substituted alkyl, aryl, alkaryl or aralkyl residues, where Ra, Rb and Rc are the same or different and selected from the group consisting of optionally suitably substituted alkyl and aryl residues;
- (2) mixing and reacting the compounds of formulae (I), (IIb), and (III) in a solvent in any order to obtain a reaction mixture containing a chiral compound of formula (IV) and/or formula (V)
An optionally crystalline chiral compound of formula (IVa)
- or a salt thereof,
- wherein R1 is an alkyl residue preferably having from 1 to 6 carbon atoms, more preferably from 1 to 4 carbon atoms, more preferably 1 or 2 carbon atoms, most preferably 2 carbon atoms, R1 in particular being ethyl, and wherein —R is —H or the hydroxyl protecting group —SiRaRbRc, where Ra, Rb and Rc are the same or different and selected from the group consisting of optionally suitably substituted alkyl and aryl residues, with —R preferably being —H or —Si(CH3)3, —R in particular being —H, and wherein said compound is most preferably a compound of formula (IVb)
A composition comprising a preferably crystalline chiral compound of formula (Va)
- or a salt thereof, wherein R1 is an alkyl residue preferably having from 1 to 6 carbon atoms, more preferably from 1 to 4 carbon atoms, more preferably 1 or 2 carbon atoms, most preferably 2 carbon atoms,
- said composition preferably comprising a compound of formula (Vb)
- wherein preferably at least 95%, more preferably at least 97%, more preferably at least 99% of the molecules of said preferably crystalline compound are present as isomer of formula (Vc)
- preferably as isomer of formula (Vd)
- said composition containing at most 70 weight-ppm, preferably at most 50 weight-ppm, more preferably at most 30 weight-ppm, more preferably at most 10 weight-ppm, said composition in particular being free of a compound of formula (Ve)
- preferably a compound of formula (Vf)
- wherein —R is —CH2—C6H5, —R preferably being selected from the group consisting of
- —SiRaRbRc and optionally substituted alkyl, aryl, alkaryl or aralkyl residues,
- where Ra, Rb and Rc are the same or different and selected from the group consisting of optionally suitably substituted alkyl and aryl residues, —R more preferably being a hydroxyl protecting group.
34-36. (canceled)
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Dependencies are inferred from the claim text.