153415-36-2Relevant articles and documents
NOVEL PROCESS FOR PRODUCTION OF CABERGOLINE
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Page/Page column 21, (2008/06/13)
A process for preparing cabergoline (I) from ergoline-8β-carboxylic acid ester (XIII) comprising the following steps. (a) reacting an ergoline-8β-carboxylic acid ester of formula (XIII), wherein R1 represents a C1-4 alkyl group, in the presence of a catalyst (i) with a compound of formula (XIV), X-COOR2 (XIV) wherein R2 is an optionally substituted straight or branched C1-6 alkyl group, X represents a bromine or chlorine atom, or (ii) with a compound of formula (XV), O(COOR2)2 (XV) wherein R2 is a group as defined above; (b) reacting the obtained carbamate derivative of formula (XVI) with 3-(dimethylamino)-propylamine (DMAPA) in the presence of a catalyst; (c) reacting the obtained ergoline-8β-carboxamide derivative of formula (XVII) with ethyl isocyanate (EtNCO) in the presence of ligand(s) and Ib and IIb metal group salt catalysts; (d) reacting the obtained protected N-acylurea derivative of formula (XVIII) with a strong aqueous inorganic acid (aq./acid); (e) reacting the obtained secondary amine (XIX) with an electrophyl allyl alcohol derivative in the presence of a palladium or nickel containing catalyst and optionally in the presence of ligand(s) to form cabergoline (I). The intermediates of (XVI), (XVII), (XVIII) and (XIX) are novel. The polymorphic amorphous form of Cabergoline (I) and the production thereof.
