Abstract: Processes for the preparation of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]-amino]-2-pyrimidinyl]amino]benzonitrile of formula (I), a N-oxide, a pharmaceutically acceptable acid addition salt, a quaternary amine or a stereochemically isomeric form thereof are provided, said processes comprise: a) reacting 4-(2-cyanoethenyl)-2,6-dimethylbenzenamine with an intermediate of formula (III) in the presence of a suitable solvent; b) reacting an intermediate of formula (IV) with acrylonitrile in the presence of a suitable palladium catalyst, a suitable base and a suitable solvent; c) dehydrating the corresponding amide of the compound of formula (I).

Abstract: Processes for the preparation of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]-amino]-2-pyrimidinyl]amino]benzonitrile of formula (I), a N-oxide, a pharmaceutically acceptable acid addition salt, a quaternary amine or a stereochemically isomeric form thereof are provided, said processes comprise: a) reacting 4-(2-cyanoethenyl)-2,6-dimethylbenzenamine with an intermediate of formula (III) ?in the presence of a suitable solvent; b) reacting an intermediate of formula (IV) ?with acrylonitrile in the presence of a suitable palladium catalyst, a suitable base and a suitable solvent; c) dehydrating the corresponding amide of the compound of formula (I).

Abstract: Processes for the preparation of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]-amino]-2-pyrimidinyl]amino]benzonitrile of formula (I), a N-oxide, a pharmaceutically acceptable acid addition salt, a quaternary amine or a stereochemically isomeric form thereof are provided, said processes comprise: a) reacting 4-(2-cyanoethenyl)-2,6-dimethylbenzenamine with an intermediate of formula (III) ?in the presence of a suitable solvent; b) reacting an intermediate of formula (IV) ?with acrylonitrile in the presence of a suitable palladium catalyst, a suitable base and a suitable solvent; c) dehydrating the corresponding amide of the compound of formula (I).

Abstract: Processes for the preparation of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]-amino]-2-pyrimidinyl]amino]benzonitrile of formula (I), a N-oxide, a pharmaceutically acceptable acid addition salt, a quaternary amine or a stereochemically isomeric form thereof are provided, said processes comprise: a) reacting 4-(2-cyanoethenyl)-2,6-dimethylbenzenamine with an intermediate of formula (III) in the presence of a suitable solvent; b) reacting an intermediate of formula (IV) with acrylonitrile in the presence of a suitable palladium catalyst, a suitable base and a suitable solvent; c) dehydrating the corresponding amide of the compound of formula (I).

Abstract: The object of the present invention is a novel mandelate salt of a substituted tetracyclic tetrahydrofuran derivative according to Formula (I) the N-oxide forms and the stereochemically isomeric forms thereof, wherein R1 and R2 each independently are hydrogen or C1-6alkyl and R3 and R4 each independently are hydrogen or halogen. In the foregoing definitions C1-6alkyl defines straight and branched saturated hydrocarbon radicals having from 1 to 6 carbon atoms such as, for example, methyl, ethyl, propyl, butyl, 1-methylpropyl, 1,1-dimethylethyl, pentyl or hexyl. The novel mandelate salt is not light-sensitive and is far more stable than the prior art salts at room temperature, enhanced temperature and at relative high humidities and in aqueous media.

Abstract: The present invention concerns processes for the preparation of each of the 4 diastereomers of formula (I) in stereochemically pure form from either of two enantiomerically pure precursors. The tetracyclic ringsystem having trans-fused five and seven membered rings is formed in an acid-catalysed cyclization reaction. The invention further relates to the thus obtained cis-fused tetracyclic alcohol intermediates, the methanamine end-products, the methanamine end-products for use as a medicine, in particular as CNS active medicines.

Abstract: The object of the present invention is a novel mandelate salt of a substituted tetracyclic tetrahydrofuran derivative according to Formula (I) the N-oxide forms and the stereochemically isomeric forms thereof, wherein R1 and R2 each independently are hydrogen or C1-6alkyl and R3 and R4 each independently are hydrogen or halogen. In the foregoing definitions C1-6alkyl defines straight and branched saturated hydrocarbon radicals having from 1 to 6 carbon atoms such as, for example, methyl, ethyl, propyl, butyl, 1-methylpropyl, 1,1-dimethylethyl, pentyl or hexyl. The novel mandelate salt is not light-sensitive and is far more stable than the prior art salts at room temperature, enhanced temperature and at relative high humidities and in aqueous media.