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US 7,019,140 B2Granted
Process for the synthesis of pergolide
AssigneeAntibioticos S.p.A.
InventorsWalter Cabri, Paolo Paissoni, Jacopo Roletto, Piera Fonte, Sara Olmo
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Abstract
A process for the synthesis of pergolide (Formula (I)) (D-6-n-propyl-8βmethylmercaptomethylergo line) from acid 9,10-dihydrolysergic is herein disclosed. The process can be carried out without isolating most intermediates and is particularly convenient both from the yield and safety standpoint. Moreover, pergolide thereby obtained is highly pure and can be conveniently transformed into pergolide mesylate
Claims15
A process for the synthesis of pergolide 1
- comprising the following steps:
- a) reaction of 9,10-dihydrolysergic acid 6
- with propyl iodide to give D-6-methyl-6-n-propyl-8(3-propyloxycarbonyl-6-ergolinium iodide 14;
- b) reduction of intermediate 14 to give D-6-methyl-6-n-propyl-8(3-hydroxymethyl-6-ergolinium iodide 12;
- c) demethylation of intermediate 12 with nucleophiles to give D-6-n-propyl-8(3-hydroxymethylergoline 4;
- d) reaction of D-6-n-propyl-8p-hydroxymethylergoline 4 with an alkylsulfonyl halide or a toluenesulfonyl halide RS02X, in which R is a straight or branched Cl—C alkyl chain, or a C6H5CH2 residue, whereas X is a halogen selected from fluorine, chlorine, bromine and iodine
- to give D-6-n-propyl-8p-alkylsulfonyloxymethylergoline or D-6-npropyl-8(3-tosyloxymethylergoline 5, in which R has the meanings defined above;
- e) reaction of compound of formula 5 with sodium thiomethoxide to give pergolide 1.
5 more elements
The quaternary salt of formula 14
Dependencies are inferred from the claim text.