Chinoin Zrt

Chinoin Gyogyszer Es Vegyeszeti Termekek Gyara Rt.

Zoltán Bischof

Gábor Havasi

Ádám Bódis

Zsuzsanna Kardos

Irén Hortobágyi

Tibor Kiss

István Lászlófi

István Lászlofi

Mária Kömüves-Mars

The subject of the invention is process for the preparation of the prostaglandin amides of the general formula I, 

Processes for the preparation of prostaglandin amides

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. 

Process for the preparation of travoprost

The subject of the invention is process for the preparation of the prostaglandin amides of the general formula I, &#x2014;where in the formula the bonds marked with dotted lines may be single or double bonds, in the case of double bounds at positions 5,6 and 13,14 they may be in cis or in trans orientation, Q stands for a hydroxyl-group and Z stands for a hydroxyl- or oxo-group, Rand Rindependently represent hydrogen atom or a straight or branched Calkyl- or aralkyl-group, optionally substituted with &#x2014;ONOgroup, or an aralkyl- or aryl-group, which contains heteroatom, Rrepresents a straight or branched, saturated or unsaturated Chydrocarbon group, or a Calkylcycloalkyl- or cycloalkyl-group, or an optionally with alkyl group or halogen atom substituted phenyl-, Calkylaryl- or hetaryl-group, Y represents (CH)group or 0 atom or S atom, and where n=0-3. 

The invention relates to a process for the preparation of travoprost of formula (I), comprising that, the compound of formula (II), is stereoselectively reduced, the resulting compound of formula (III), is if desired crystallized, the lactone group of the compound of formula (III) is reduced, the p-phenyl-benzoyl protecting group of the thus obtained compound of formula (IV), is removed, the resulting triol of formula (V), is, if desired after crystallization, transformed by Wittig reaction into the acid of formula (VI), which is then esterified. 

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Budapest, Hungary

Zoltán Bischof