Merck Patent Gesellschaft MIT Beschrankter Haftung

Merck Patent Gesellschaft MIT Beschraenkter Haftung

E. Merck

Rolf Pohlke

Herbert Thomas

Peter Andrews

Jurgen Seubert

Friedrich Loebich

Christoph Seyfried

Werner Mehrhof

Wolfgang Fischer

Hans-Jochen Schliep

Wighard Strehlow

Karl Heinz Becker

Helmut Mueller-Calgan

Jurgen Thyssen

The invention relates to a process for the preparation of alkylenebis(2-pyridylamine) compounds by reacting 2-halopyridine derivatives with alkylenediamines and to the use of these compounds in a Karl Fischer reagent as are indicated for the determination of water content.

Process for the preparation of alkylene-bis(2-pyridylamine) compounds

Isoquinolines of the formula ##STR1## wherein R.sup.1 is H, OH, alkyl; R.sup.2 is H, or an unsubstituted or substituted carbonyl, carbonyloxy or thiocarbonyl group; R.sup.3 is H, alkyl or hydroxy alkyl; R.sup.4 is H, alkyl or phenyl; R.sup.5 is O, H,H or H and alkyl, phenyl, halo or hydroxy; R.sup.6 and R.sup.7 are optional substituents; and R.sup.8 is H or alkyl, R.sup.2 being a thiocarbonyl or carbonyloxy group when R.sup.1 and R.sup.3 to R.sup.8 are H and X is O; and their physiologically acceptable salts, are antihelmintics, especially against cestodes and trematodes; some also possessing CNS activity, e.g., psychotropic and blood pressure regulating activity.

Ring substituted pyrazino-isoquinoline derivatives and their preparation

Isoquinolines of the formula ##STR1## wherein R.sup.1 is H or alkyl of 1 - 4 carbon atoms, R.sup.2 is H and R.sup.3 is OH or R.sup.2 and R.sup.3 collectively are a C--C bond, and physiologically acceptable acid addition salts thereof have anti-depressant activity and can be prepared by solvolyzing or hydrogenolyzing a compound of the formula ##STR2## or an acid addition salt thereof, wherein R.sup.4 is R.sup.1 or R.sup.6, R.sup.5 is OR.sup.7 or, when R.sup.4 is R.sup.6, R.sup.3 ; R.sup.6 and R.sup.7 are radicals which can be split off solvolytically or hydrogenolytically and R.sup.1 and R.sup.2 are as above; and the optional step of dehydrating a resulting carbinol (R.sup.2 is H, R.sup.3 is OH) and/or treating a resulting compound (R.sup.1 is H) with a N-alkylating agent and/or converting a resulting base to a physiologically acceptable acid addition salt by treatment with and acid.

Isoquinolines and anti-depressants containing them

Isoquinolines of the formula ##STR1## wherein R.sup.1 is H, OH, alkyl; R.sup.2 is H, or an unsubstituted or substituted carbonyl, carbonyloxy or thiocarbonyl group; R.sup.3 is H, alkyl or hydroxy alkyl; R.sup.4 is H, alkyl or phenyl; R.sup.5 is O, H,H or H and alkyl, phenyl, halo or hydroxy; R.sup.6 and R.sup.7 are optional substituents; and R.sup.8 is H or alkyl, R.sup.2 being a thiocarbonyl or carbonyloxy group when R.sup.1 and R.sup.3 to R.sup.8 are H and X is 0; and their physiologically acceptable salts, are antihelmintics, especially against cestodes and trematodes; some also possessing CNS activity, e.g., psychotropic and blood pressure regulating activity.

4-OXO-HEXAHYDRO-PYRAZINOISOQUINOLINE DERIVATIVES ARE OBTAINED IN GOOD YIELD BY A SINGLE-STEP PROCESS WHICH COMPRISES HYDROLYZING A 2-ACYL-4-OXO-1,2,3,6,7,11B-HEXAHYDRO-4H-pyrazino[2,1-a]isoquinoline with an oxygen-containing acid or acid salt of inorganic pentavalent phosphorus or hexavalent sulfur.

Process for the preparation of 4-oxo-hexahydro-pyrazinoisoquinoline

2-Benzoyl-4-oxo-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinoline is used as an anthelmintic against cestodes and trematodes, preferably in admixture with a pharmaceutically acceptable carrier.

Anthelmintic

(-)-2-Benzoyl-4-oxo-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinoline is prepared by benzoylation of (-)-4-oxo-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinoline, or cyclization of a compound of the formula ##SPC1## Wherein X is F, Cl, Br, I or O-tosyl and which has the optical configuration of the final product, or cyclization of a compound of the formula ##SPC2## wherein Y is OH, alkoxy, F, Cl, Br or I under HY-removing reaction conditions and which has the optical configuration of the final product, which is an anthelmintic.

Pyrazinoisoquinolines as anthelmintic agents

Novel isoquinoline derivatives of the formula ##SPC1## Wherein R.sub.1 is H or, together with R.sub.2, a C--N bond; R.sub.2 is H, R.sub.8 or, together with R.sub.1, a C--N bond; R.sub.3 is H, methyl or ethyl; R.sub.4 and R.sub.5 each are H or collectively a C--C bond; and R.sub.6 and R.sub.7 each are H or methoxy; R.sub.8 being acyl of 1-10 carbon atoms or alkyl of 1-17 carbon atoms optionally mono- or polysubstituted by phenyl, OH, ArCOO--, ArCONH--, piperidino, 3,4-dehydropiperidino, morpholino, carboxy, carbomethoxy and/or carbethoxy, Ar being 3,4,5-trimethoxyphenyl; and the physiologically acceptable acid addition salts and quaternary ammonium salts thereof, have cardiovascular activity and can be prepared by acylating a corresponding primary amine lacking the COAr group with 3,4,5-trimethoxybenzoic acid or a functional derivative thereof.

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Darmstadt, Germany

Rolf Pohlke