Process for the preparation of travoprost
AssigneeChinoin GyóGyszer éS VegyéSzeti TerméKek GyáRa Zrt.
InventorsZoltán Bischof, Ádám Bódis, Mária Kömüves-Mars, Gábor Havasi
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Abstract
The subject of the invention is process the preparation of travoprost of formula (I) characterized by that the free acid of formula (II) is a.) activated with 2-chloro-1,3-dimethyl-imidazolinium chloride (DMC) and the resulting activated carboxylic acid intermediate is reacted with isopropyl alcohol, or b.) reacted with alkyl haloformate and the resulting mixed anhydride is reacted with isopropyl alcohol, or c.) activated with a straight or branched C1-8 dialkyl dicarbonate and reacted with isopropanol in the presence of water-free magnesium salt.
Claims21
Process for the preparation travoprost of formula (I)
- wherein the free acid of formula (II)
- is
- a.) activated with 2-chloro-1,3-dimethylimidazolinium chloride (DMC) and the resulting activated carboxylic acid intermediate is reacted with optionally activated isopropyl alcohol, or
- b.) activated with a straight or branched C1-6 alkyl haloformate and the resulting mixed anhydride is reacted with optionally activated isopropyl alcohol, or
- c.) activated with a straight or branched C1-8 dialkyl dicarbonate and reacted with optionally activated isopropyl alcohol in the presence of water-free magnesium salt.
Process for the preparation of prostaglandin esters of the general formula (III),
- wherein:
- the bonds in dotted lines may be single or double bonds, in the case of double bonds in positions 5,6 and 13,14 respectively, they may be in cis or in trans orientation,
- Q and Z stand for hydroxyl group,
- R1 stands for straight or branched C1-10 alkyl group,
- R3 stands for straight or branched, saturated or unsaturated C4-6 hydrocarbon group, or a C4-10 alkylcycloalkyl or cycloalkyl group, or a phenyl, C7-10 alkylaryl, or hetaryl group optionally substituted with alkyl group, halogen atom or trifluoromethyl group,
- wherein an acid of the general formula (IV),
- in which Q, Z, and R3 are as defined above,
- a.) is activated with 2-chloro-1,3-dimethylimidazolinium chloride (DMC) and the resulting activated carboxylic acid intermediate is reacted in the presence of base with an optionally activated alcohol of the general formula R1OH, where the meaning of R1 is as defined above, or
- b.) is activated with a straight or branched C1-6 alkyl haloformate and the resulting mixed anhydride is reacted with an optionally alcohol of the general formula R1OH, where the meaning of R1 is as defined above, or
- c.) is activated with a straight or branched C1-8 dialkyl dicarbonate and then in the presence of water-free magnesium salt reacted with an optionally activated alcohol of the general formula R1OH, where the meaning of R1 is as defined above.
Dependencies are inferred from the claim text.